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1.
Circ Res ; 135(2): e4-e23, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38860377

RESUMEN

BACKGROUND: Cell phenotype switching is increasingly being recognized in atherosclerosis. However, our understanding of the exact stimuli for such cellular transformations and their significance for human atherosclerosis is still evolving. Intraplaque hemorrhage is thought to be a major contributor to plaque progression in part by stimulating the influx of CD163+ macrophages. Here, we explored the hypothesis that CD163+ macrophages cause plaque progression through the induction of proapoptotic endothelial-to-mesenchymal transition (EndMT) within the fibrous cap. METHODS: Human coronary artery sections from CVPath's autopsy registry were selected for pathological analysis. Athero-prone ApoE-/- and ApoE-/-/CD163-/- mice were used for in vivo studies. Human peripheral blood mononuclear cell-induced macrophages and human aortic endothelial cells were used for in vitro experiments. RESULTS: In 107 lesions with acute coronary plaque rupture, 55% had pathological evidence of intraplaque hemorrhage in nonculprit vessels/lesions. Thinner fibrous cap, greater CD163+ macrophage accumulation, and a larger number of CD31/FSP-1 (fibroblast specific protein-1) double-positive cells and TUNEL (terminal deoxynucleotidyl transferase-dUTP nick end labeling) positive cells in the fibrous cap were observed in nonculprit intraplaque hemorrhage lesions, as well as in culprit rupture sections versus nonculprit fibroatheroma sections. Human aortic endothelial cells cultured with supernatants from hemoglobin/haptoglobin-exposed macrophages showed that increased mesenchymal marker proteins (transgelin and FSP-1) while endothelial markers (VE-cadherin and CD31) were reduced, suggesting EndMT induction. Activation of NF-κB (nuclear factor kappa ß) signaling by proinflammatory cytokines released from CD163+ macrophages directly regulated the expression of Snail, a critical transcription factor during EndMT induction. Western blot analysis for cleaved caspase-3 and microarray analysis of human aortic endothelial cells indicated that apoptosis was stimulated during CD163+ macrophage-induced EndMT. Additionally, CD163 deletion in athero-prone mice suggested that CD163 is required for EndMT and plaque progression. Using single-cell RNA sequencing from human carotid endarterectomy lesions, a population of EndMT was detected, which demonstrated significant upregulation of apoptosis-related genes. CONCLUSIONS: CD163+ macrophages provoke EndMT, which may promote plaque progression through fibrous cap thinning.


Asunto(s)
Antígenos CD , Antígenos de Diferenciación Mielomonocítica , Macrófagos , Placa Aterosclerótica , Receptores de Superficie Celular , Humanos , Antígenos de Diferenciación Mielomonocítica/metabolismo , Antígenos de Diferenciación Mielomonocítica/genética , Animales , Antígenos CD/metabolismo , Antígenos CD/genética , Macrófagos/metabolismo , Macrófagos/patología , Placa Aterosclerótica/patología , Placa Aterosclerótica/metabolismo , Receptores de Superficie Celular/metabolismo , Receptores de Superficie Celular/genética , Ratones , Células Cultivadas , Células Endoteliales/metabolismo , Células Endoteliales/patología , Masculino , Ratones Noqueados para ApoE , Ratones Endogámicos C57BL , Apoptosis , Femenino , Transición Epitelial-Mesenquimal , Vasos Coronarios/patología , Vasos Coronarios/metabolismo
2.
Nucleic Acids Res ; 52(5): 2711-2723, 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38281192

RESUMEN

Class IIa Histone deacetylases (HDACs), including HDAC4, 5, 7 and 9, play key roles in multiple important developmental and differentiation processes. Recent studies have shown that class IIa HDACs exert their transcriptional repressive function by interacting with tissue-specific transcription factors, such as members of the myocyte enhancer factor 2 (MEF2) family of transcription factors. However, the molecular mechanism is not well understood. In this study, we determined the crystal structure of an HDAC4-MEF2A-DNA complex. This complex adopts a dumbbell-shaped overall architecture, with a 2:4:2 stoichiometry of HDAC4, MEF2A and DNA molecules. In the complex, two HDAC4 molecules form a dimer through the interaction of their glutamine-rich domain (GRD) to form the stem of the 'dumbbell'; while two MEF2A dimers and their cognate DNA molecules are bridged by the HDAC4 dimer. Our structural observations were then validated using biochemical and mutagenesis assays. Further cell-based luciferase reporter gene assays revealed that the dimerization of HDAC4 is crucial in its ability to repress the transcriptional activities of MEF2 proteins. Taken together, our findings not only provide the structural basis for the assembly of the HDAC4-MEF2A-DNA complex but also shed light on the molecular mechanism of HDAC4-mediated long-range gene regulation.


Asunto(s)
ADN , Histona Desacetilasas , Factores de Transcripción MEF2 , Proteínas Represoras , ADN/química , ADN/metabolismo , Regulación de la Expresión Génica , Genes Reporteros , Factores de Transcripción MEF2/química , Factores de Transcripción MEF2/metabolismo , Factores Reguladores Miogénicos/química , Factores Reguladores Miogénicos/genética , Factores Reguladores Miogénicos/metabolismo , Proteínas Represoras/química , Proteínas Represoras/metabolismo , Humanos , Histona Desacetilasas/química , Histona Desacetilasas/metabolismo
3.
Plant Physiol ; 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39041422

RESUMEN

The WRINKLED1 (WRI1) and LAFL [LEAFY COTYLEDON1 (LEC1), ABSCISIC ACID INSENSITIVE3 (ABI3), FUSCA3 (FUS3), and LEC2] transcription factors play essential roles in governing seed development and oil biosynthesis. To gain a comprehensive understanding of the transcriptional regulation of WRI1 and LAFL, we conducted genome-wide association studies for the expression profiles of WRI1 and LAFL in developing seeds at 20 and 40 days after flowering (DAF) using 302 rapeseed (Brassica napus) accessions. We identified a total of 237 expression quantitative trait nucleotides (eQTNs) and 51 expression QTN-by-environment interactions (eQEIs) associated with WRI1 and LAFL. Around these eQTNs and eQEIs, we pinpointed 41 and 8 candidate genes with known transcriptional regulations or protein interactions with their expression traits, respectively. Based on RNA-seq and ATAC-seq data, we employed the XGBoost and Basenji models which predicted 15 candidate genes potentially regulating the expression of WRI1 and LAFL. We further validated the predictions via tissue expression profile, haplotype analysis, and expression correlation analysis, and verified the transcriptional activation activity of BnaC03.MYB56 (R2R3-MYB transcription factor 56) on the expression of BnaA09.LEC1 by dual-luciferase reporter and yeast one-hybrid assays. BnaA10.AGL15 (AGAMOUS-LIKE 15), BnaC04.VAL1 (VIVIPAROUS1/ABSCISIC ACID INSENSITIVE3-LIKE 1), BnaC03.MYB56, and BnaA10.MYB56 were co-expressed with WRI1 and LAFL at 20 DAF in M35, a key module for seed development and oil biosynthesis. We further validated the positive regulation of MYB56 on seed oil accumulation using Arabidopsis (Arabidopsis thaliana) mutants. This study not only delivers a framework for future eQEI identification but also offers insights into the developmental regulation of seed oil accumulation.

4.
BMC Genomics ; 25(1): 431, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38693480

RESUMEN

Ophthalmic manifestations have recently been observed in acute and post-acute complications of COVID-19 caused by SARS-CoV-2 infection. Our precious study has shown that host RNA editing is linked to RNA viral infection, yet ocular adenosine to inosine (A-to-I) RNA editing during SARS-CoV-2 infection remains uninvestigated in COVID-19. Herein we used an epitranscriptomic pipeline to analyze 37 samples and investigate A-to-I editing associated with SARS-CoV-2 infection, in five ocular tissue types including the conjunctiva, limbus, cornea, sclera, and retinal organoids. Our results revealed dramatically altered A-to-I RNA editing across the five ocular tissues. Notably, the transcriptome-wide average level of RNA editing was increased in the cornea but generally decreased in the other four ocular tissues. Functional enrichment analysis showed that differential RNA editing (DRE) was mainly in genes related to ubiquitin-dependent protein catabolic process, transcriptional regulation, and RNA splicing. In addition to tissue-specific RNA editing found in each tissue, common RNA editing was observed across different tissues, especially in the innate antiviral immune gene MAVS and the E3 ubiquitin-protein ligase MDM2. Analysis in retinal organoids further revealed highly dynamic RNA editing alterations over time during SARS-CoV-2 infection. Our study thus suggested the potential role played by RNA editing in ophthalmic manifestations of COVID-19, and highlighted its potential transcriptome impact, especially on innate immunity.


Asunto(s)
COVID-19 , Edición de ARN , SARS-CoV-2 , Humanos , COVID-19/genética , COVID-19/virología , SARS-CoV-2/genética , Adenosina/metabolismo , Inosina/metabolismo , Inosina/genética , Transcriptoma , Ojo/metabolismo , Ojo/virología
5.
Biol Reprod ; 110(5): 895-907, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38267362

RESUMEN

It is known that the oocyte has a limited capacity to acquire and metabolize glucose, and it must rely on cumulus cells (CCs) to take up glucose and produce pyruvate for use to produce ATP through oxidative phosphorylation. We therefore propose that miRNAs might regulate glucose metabolism (GM) in CCs and might be used as markers for oocyte quality assessment. Here, mouse CC models with impaired glycolysis or pentose phosphate pathway (PPP) were established, and miRNAs targeting the key enzymes in glycolysis/PPP were predicted using the miRNA target prediction databases. Expression of the predicted miRNAs was compared between CCs with normal and impaired glycolysis/PPP to identify candidate miRNAs. Function of the candidate miRNAs was validated by transfecting CCs or cumulus-oocyte-complexes (COCs) with miRNA inhibitors and observing effects on glucose metabolites of CCs and on competence of oocytes. The results validated that miR-23b-3p, let-7b-5p, 34b-5p and 145a-5p inhibited glycolysis, and miR-24-3p, 3078-3p,183-5p and 7001-5p inhibited PPP of CCs. Our observation using a more physiologically relevant model (intact cultured COCs) further validated the four glycolysis-targeting miRNAs we identified. Furthermore, miR-let-7b-5p, 34b-5p and 145a-5p may also inhibit PPP, as they decreased the production of glucose-6-phosphate. In conclusion, miRNAs play critical roles in GM of CCs and may be used as markers for oocyte quality assessment. Summary sentence:  We identified and validated eight new miRNAs that inhibit glycolysis and/or pentose phosphate pathways in cumulus cells (CCs) suggesting that miRNAs play critical roles in glucose metabolism of CCs and may be used for oocyte quality markers.


Asunto(s)
Células del Cúmulo , Glucosa , Glucólisis , MicroARNs , Animales , Células del Cúmulo/metabolismo , MicroARNs/metabolismo , MicroARNs/genética , Ratones , Glucosa/metabolismo , Femenino , Glucólisis/fisiología , Vía de Pentosa Fosfato , Oocitos/metabolismo
6.
Int J Obes (Lond) ; 48(6): 849-858, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38341506

RESUMEN

OBJECTIVE: Fatty acids play a critical role in the proper functioning of the brain. This study investigated the effects of a high-fat (HF) diet on brain fatty acid profiles of offspring exposed to maternal gestational diabetes mellitus (GDM). METHODS: Insulin receptor antagonist (S961) and HF diet were used to establish the GDM animal model. Brain fatty acid profiles of the offspring mice were measured by gas chromatography at weaning and adulthood. Protein expressions of the fatty acid transport pathway Wnt3/ß-catenin and the target protein major facilitator superfamily domain-containing 2a (MFSD2a) were measured in the offspring brain by Western blot. RESULTS: Maternal GDM increased the body weight of male offspring (P < 0.05). In weaning offspring, factorial analysis showed that maternal GDM increased the monounsaturated fatty acid (MUFA) percentage of the weaning offspring's brain (P < 0.05). Maternal GDM decreased offspring brain arachidonic acid (AA), but HF diet increased brain linoleic acid (LA) (P < 0.05). Maternal GDM and HF diet reduced offspring brain docosahexaenoic acid (DHA), and the male offspring had higher DHA than the female offspring (P < 0.05). In adult offspring, factorial analysis showed that HF diet increased brain MUFA in offspring, and male offspring had higher brain MUFA than female offspring (P < 0.05). The HF diet increased brain LA in the offspring. Male offspring had higher level of AA than female offspring (P < 0.05). HF diet reduced DHA in the brains of female offspring. The brain protein expression of ß-catenin and MFSD2a in both weaning and adult female offspring was lower in the HF + GDM group than in the CON group (P < 0.05). CONCLUSIONS: Maternal GDM increased the susceptibility of male offspring to HF diet-induced obesity. HF diet-induced adverse brain fatty acid profiles in both male and female offspring exposed to GDM.


Asunto(s)
Encéfalo , Diabetes Gestacional , Dieta Alta en Grasa , Ácidos Grasos , Efectos Tardíos de la Exposición Prenatal , Animales , Embarazo , Femenino , Diabetes Gestacional/metabolismo , Ratones , Dieta Alta en Grasa/efectos adversos , Encéfalo/metabolismo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Masculino , Ácidos Grasos/metabolismo , Modelos Animales de Enfermedad , Fenómenos Fisiologicos Nutricionales Maternos
7.
New Phytol ; 243(1): 362-380, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38730437

RESUMEN

Plants typically activate distinct defense pathways against various pathogens. Heightened resistance to one pathogen often coincides with increased susceptibility to another pathogen. However, the underlying molecular basis of this antagonistic response remains unclear. Here, we demonstrate that mutants defective in the transcription factor ETHYLENE-INSENSITIVE 3-LIKE 2 (OsEIL2) exhibited enhanced resistance to the biotrophic bacterial pathogen Xanthomonas oryzae pv oryzae and to the hemibiotrophic fungal pathogen Magnaporthe oryzae, but enhanced susceptibility to the necrotrophic fungal pathogen Rhizoctonia solani. Furthermore, necrotroph-induced OsEIL2 binds to the promoter of OsWRKY67 with high affinity, leading to the upregulation of salicylic acid (SA)/jasmonic acid (JA) pathway genes and increased SA/JA levels, ultimately resulting in enhanced resistance. However, biotroph- and hemibiotroph-induced OsEIL2 targets OsERF083, resulting in the inhibition of SA/JA pathway genes and decreased SA/JA levels, ultimately leading to reduced resistance. Our findings unveil a previously uncharacterized defense mechanism wherein two distinct transcriptional regulatory modules differentially mediate immunity against pathogens with different lifestyles through the transcriptional reprogramming of phytohormone pathway genes.


Asunto(s)
Ciclopentanos , Regulación de la Expresión Génica de las Plantas , Oryza , Oxilipinas , Enfermedades de las Plantas , Inmunidad de la Planta , Proteínas de Plantas , Rhizoctonia , Ácido Salicílico , Xanthomonas , Oxilipinas/metabolismo , Ácido Salicílico/metabolismo , Ciclopentanos/metabolismo , Oryza/microbiología , Oryza/genética , Oryza/inmunología , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/inmunología , Xanthomonas/fisiología , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Rhizoctonia/fisiología , Inmunidad de la Planta/efectos de los fármacos , Mutación/genética , Resistencia a la Enfermedad/genética , Regiones Promotoras Genéticas/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Unión Proteica/efectos de los fármacos
8.
Opt Express ; 32(3): 4525-4536, 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38297652

RESUMEN

In this study, we present a simulation-based analysis of radio-over-fiber (ROF) transmission links incorporating both phase modulation (PM) and a single ring resonator (RR) as the modulation transformer (MT). This configuration offers cost-effectiveness, enhanced operational stability, facile reconfiguration, and heightened robustness. The optimization of the RR involves a comprehensive adjustment of the power coupler coupling coefficient (k) and the roundtrip optical phase shift (φ) to attain superior characteristics in terms of power output, bandwidth, dispersion, and nonlinearity, individually. The simulation encompasses the transmission of diverse data formats, including QPSK, 16QAM, and 16QAM-based OFDM, modulated by the PM-RR system. The results reveal a 0.25 dB improvement in nonlinearity tolerance, increased power, and superior fading mitigation compared to the conventional intensity modulation (IM) approach. Furthermore, through careful tuning of the phase response, the Q factor of the PM-RR system exhibits an enhancement exceeding 40% over a 100 km fiber length when compared to the Mach-Zehnder modulator (MZM) system.

9.
Opt Express ; 32(11): 19814-19824, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38859107

RESUMEN

The intriguing photonic spin Hall effect (PSHE) of reflected Laguerre-Gaussian (LG) beams can be exhibited on the systems with optical anti-parity-time (Anti-PT) symmetry. During the reflection, the left/right circularly polarized (LCP/RCP) components of reflected LG beams are considered. By controlling parameters of the Anti-PT systems, the PSHE of reflected LCP/RCP can be identical and symmetrical with respect to incident-reflected plane (IRP). Due to gain/non-Hermitian effects of designed Anti-PT systems, special PSHE near the strong gain points (SGP) and exceptional points (EPs) can be obtained simulatively. Through analyses in PSHE of reflected LCP on four similar Anti-PT systems, specific conclusions that can even be extended to more general cases. Moreover, simulations of PSHE by simultaneously varying the incident angles * and imaginary/real dielectric constants Im/Re[ε] of the Anti-PT systems, specal PSHE and other novel optical phenomena with real applications can be revealed. So Anti-PT systems not only provide novel ways to regulate the PSHE of reflected LG beams, but also offer possibilities for new optical characteristics of devices.

10.
J Exp Bot ; 2024 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-38824403

RESUMEN

Rapeseed (Brassica napus) is an important oilseed crop worldwide. Plant vascular tissues are responsible for material transport and provide mechanical support. The lateral roots (LRs) absorb sufficient water and nutrients. The genetic basis of vascular tissues and LRs development in rapeseed remains unknown. This study characterized an EMS-mutagenized rapeseed mutant, T16, which showed dwarf stature, reduced LRs, and leaf wilting. Scanning electron microscopy observations showed that the internode-cell shortened. Observations of the tissue sections revealed defects in the development of vascular bundles in the stems and petioles. Genetic analysis revealed that the phenotypes of T16 were controlled by a single semi-dominant nuclear gene. Map-based cloning and genetic complementarity confirmed that BnaA03.IAA13 is the functional gene, a G-to-A mutation in second exon changed the glycine at the 79th position to glutamic acid, disrupting the conserved degron motif VGWPP. Transcriptome analysis in roots and stems showed that auxin and cytokinin signaling pathways were disordered in T16. Evolutionary analysis showed that AUXIN/INDOLE-3-ACETIC ACID was conserved during plant evolution. The heterozygote of T16 significantly reduced the plant height while maintaining other agronomic traits. Our findings provide novel insights into the regulatory mechanisms of vascular tissues and LRs development, and provide a new germplasm resource for rapeseed breeding.

11.
BMC Cancer ; 24(1): 422, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38580944

RESUMEN

BACKGROUND: As comprehensive surgical management for gastric cancer becomes increasingly specialized and standardized, the precise differentiation between ≤T1 and ≥T2 gastric cancer before endoscopic intervention holds paramount clinical significance. OBJECTIVE: To evaluate the diagnostic efficacy of contrast-enhanced gastric ultrasonography in differentiating ≤T1 and ≥T2 gastric cancer. METHODS: PubMed, Web of Science, and Medline were searched to collect studies published from January 1, 2000 to March 16, 2023 on the efficacy of either double contrast-enhanced gastric ultrasonography (D-CEGUS) or oral contrast-enhanced gastric ultrasonography (O-CEGUS) in determining T-stage in gastric cancer. The articles were selected according to specified inclusion and exclusion criteria, and the quality of the included literature was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 scale. Meta-analysis was performed using Stata 12 software with data from the 2 × 2 crosslinked tables in the included literature. RESULTS: In total, 11 papers with 1124 patients were included in the O-CEGUS analysis, which revealed a combined sensitivity of 0.822 (95% confidence interval [CI] = 0.753-0.875), combined specificity of 0.964 (95% CI = 0.925-0.983), and area under the summary receiver operating characteristic (sROC) curve (AUC) of 0.92 (95% CI = 0.89-0.94). In addition, five studies involving 536 patients were included in the D-CEGUS analysis, which gave a combined sensitivity of 0.733 (95% CI = 0.550-0.860), combined specificity of 0.982 (95% CI = 0.936-0.995), and AUC of 0.93 (95% CI = 0.91-0.95). According to the I2 and P values ​​of the forest plot, there was obvious heterogeneity in the combined specificities of the included papers. Therefore, the two studies with the lowest specificities were excluded from the O-CEGUS and D-CEGUS analyses, which eliminated the heterogeneity among the remaining literature. Consequently, the combined sensitivity and specificity of the remaining studies were 0.794 (95% CI = 0.710-0.859) and 0.976 (95% CI = 0.962-0.985), respectively, for the O-CEDUS studies and 0.765 (95% CI = 0.543-0.899) and 0.986 (95% CI = 0.967-0.994), respectively, for the D-CEGUS studies. The AUCs were 0.98 and 0.99 for O-CEGUS and D-CEGUS studies, respectively. CONCLUSION: Both O-CEGUS and D-CEGUS can differentiate ≤T1 gastric cancer from ≥T2 gastric cancer, thus assisting the formulation of clinical treatment strategies for patients with very early gastric cancer. Given its simplicity and cost-effectiveness, O-CEGUS is often favored as a staging method for gastric cancer prior to endoscopic intervention.


Asunto(s)
Medios de Contraste , Estadificación de Neoplasias , Neoplasias Gástricas , Ultrasonografía , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/patología , Humanos , Ultrasonografía/métodos , Sensibilidad y Especificidad , Curva ROC , Estómago/diagnóstico por imagen , Estómago/patología
12.
J Nutr ; 154(2): 590-599, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38159812

RESUMEN

BACKGROUND: Polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA), are critical for proper fetal brain growth and development. Gestational diabetes mellitus (GDM) could affect maternal-fetal fatty acid metabolism. OBJECTIVE: This study aimed to explore the effect of GDM and high-fat (HF) diet on the DHA transport signaling pathway in the placenta-brain axis and fatty acid concentrations in the fetal brain. METHODS: Insulin receptor antagonist (S961) and HF diet were used to establish an animal model of GDM. Eighty female C57BL/6J mice were randomly divided into control (CON), GDM, HF, and HF+GDM groups. The fatty acid profiles of the maternal liver and fetal brain were analyzed by gas chromatography. In addition, we analyzed the protein amounts of maternal liver fatty acid desaturase (FADS1/3), elongase (ELOVL2/5) and the regulatory factor sterol-regulatory element-binding protein (SREBP)-1c, and the DHA transport signaling pathway (Wnt3/ß-catenin/MFSD2a) of the placenta and fetal brain using western blotting. RESULTS: GDM promoted the decrease of maternal liver ELOVL2, ELOVL5, and SREBP-1c. Accordingly, we observed a significant decrease in the amount of maternal liver arachidonic acid (AA), DHA, and total n-3 PUFA and n-6 PUFA induced by GDM. GDM also significantly decreased the amount of DHA and n-3 PUFA in the fetal brain. GDM downregulated the Wnt3/ß-catenin/MFSD2a signaling pathway, which transfers n-3 PUFA in the placenta and fetal brain. The HF diet increased n-6 PUFA amounts in the maternal liver, correspondingly increasing linoleic acid, gamma-linolenic acid, AA, and total n-6 PUFA in the fetal brain, but decreased DHA amount in the fetal brain. However, HF diet only tended to decrease placental ß-catenin and MFSD2a amounts (P = 0.074 and P = 0.098, respectively). CONCLUSIONS: Maternal GDM could affect the fatty acid profile of the fetal brain both by downregulating the Wnt3/ß-catenin/MFSD2a pathway of the placental-fetal barrier and by affecting maternal fatty acid metabolism.


Asunto(s)
Diabetes Gestacional , Ácidos Grasos Omega-3 , Humanos , Animales , Ratones , Femenino , Embarazo , Diabetes Gestacional/metabolismo , Ácidos Grasos/metabolismo , Placenta/metabolismo , beta Catenina/metabolismo , Ratones Endogámicos C57BL , Ácidos Grasos Omega-3/metabolismo , Ácidos Grasos Insaturados/metabolismo , Ácidos Docosahexaenoicos/metabolismo , Ácido Araquidónico , Encéfalo/metabolismo
13.
BMC Cancer ; 24(1): 727, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38877445

RESUMEN

BACKGROUND: The Naples Prognostic Score (NPS), integrating inflammatory and nutritional biomarkers, has been reported to be associated with the prognosis of various malignancies, but there is no report on intrahepatic cholangiocarcinoma (ICC). This study aimed to explore the prognostic value of NPS in patients with ICC. METHODS: Patients with ICC after hepatectomy were collected, and divided into three groups. The prognosis factors were determined by Cox regression analysis. Predictive efficacy was evaluated by the time-dependent receiver operating characteristic (ROC) curves. RESULTS: A total of 174 patients were included (Group 1: 33 (19.0%) patients; Group 2: 83 (47.7%) patients; and Group 3: 58 (33.3%) patients). The baseline characteristics showed the higher the NPS, the higher the proportion of patients with cirrhosis and Child-Pugh B, and more advanced tumors. The Kaplan-Meier curves reflect higher NPS were associated with poor survival. Multivariable analysis showed NPS was an independent risk factor of overall survival (NPS group 2 vs. 1: HR = 1.671, 95% CI: 1.022-3.027, p = 0.009; NPS group 3 vs. 1: HR = 2.208, 95% CI: 1.259-4.780, p = 0.007) and recurrence-free survival (NPS group 2 vs. 1: HR = 1.506, 95% CI: 1.184-3.498, p = 0.010; NPS group 3 vs. 1: HR = 2.141, 95% CI: 2.519-4.087, P = 0.001). The time ROC indicated NPS was superior to other models in predicting prognosis. CONCLUSIONS: NPS is a simple and effective tool for predicting the long-term survival of patients with ICC after hepatectomy. Patients with high NPS require close follow-up, and improving NPS may prolong the survival time.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Hepatectomía , Humanos , Colangiocarcinoma/cirugía , Colangiocarcinoma/mortalidad , Colangiocarcinoma/patología , Masculino , Femenino , Persona de Mediana Edad , Pronóstico , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/patología , Anciano , Curva ROC , Estudios Retrospectivos , Estimación de Kaplan-Meier , Adulto , Factores de Riesgo
14.
Biomacromolecules ; 25(5): 2701-2714, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38608139

RESUMEN

Over decades of development, while phosphoramidite chemistry has been known as the leading method in commercial synthesis of oligonucleotides, it has also revolutionized the fabrication of sequence-defined polymers (SDPs), offering novel functional materials in polymer science and clinical medicine. This review has introduced the evolution of phosphoramidite chemistry, emphasizing its development from the synthesis of oligonucleotides to the creation of universal SDPs, which have unlocked the potential for designing programmable smart biomaterials with applications in diverse areas including data storage, regenerative medicine and drug delivery. The key methodologies, functions, biomedical applications, and future challenges in SDPs, have also been summarized in this review, underscoring the significance of breakthroughs in precisely synthesized materials.


Asunto(s)
Materiales Biocompatibles , Sistemas de Liberación de Medicamentos , Oligonucleótidos , Compuestos Organofosforados , Polímeros , Medicina Regenerativa , Medicina Regenerativa/métodos , Materiales Biocompatibles/química , Polímeros/química , Sistemas de Liberación de Medicamentos/métodos , Humanos , Oligonucleótidos/química , Compuestos Organofosforados/química , Animales
15.
World J Urol ; 42(1): 454, 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39073634

RESUMEN

BACKGROUND: The morphology of tumor thrombus varies from person to person and it may affect surgical methods and tumor prognosis. However, studies on the morphology of tumor thrombus are limited. The purpose of our study was to evaluate the impact of tumor thrombus morphology on surgical complexity. METHODS: We retrospectively reviewed the clinical data of 229 patients with renal cell carcinoma combined with inferior vena cava (IVC) tumor thrombus who underwent surgical treatment at Peking University Third Hospital between January 2014 and December 2021. The patients were divided into floating morphology (107 patients) and filled morphology (122 patients) tumor thrombi groups. Chi-square and Mann-Whitney U tests were used for categorical and continuous variables, respectively. Postoperative complications were evaluated using the Clavien-Dindo surgical complication classification method. RESULTS: Patients with filled morphology tumor thrombus required more surgical techniques than those with floating morphology tumor thrombus, which was reflected in more open surgeries (P < 0.001), more IVC interruptions (P <0.001), lesser use of the delayed occlusion of the proximal inferior vena cava (DOPI) technique (P < 0.001), and a greater need for cut-off of the short hepatic vein (P < 0.001) and liver dissociation (P = 0.001). Filled morphology significantly increased the difficulty of surgery in patients with renal cell carcinoma with tumor thrombus, reflected in longer operation time (P < 0.001), more surgical blood loss (P <0.001), more intra-operative blood transfusion (P < 0.001), and longer postoperative hospital stay (P < 0.001). Filled morphology tumor thrombus also led to more postoperative complications (53% vs. 20%; P < 0.001). CONCLUSION: Compared with floating morphology thrombus, filled morphology thrombus significantly increased the difficulty of surgery in patients with renal cell carcinoma with IVC tumor thrombus.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Células Neoplásicas Circulantes , Vena Cava Inferior , Trombosis de la Vena , Humanos , Carcinoma de Células Renales/cirugía , Carcinoma de Células Renales/patología , Neoplasias Renales/cirugía , Neoplasias Renales/patología , Vena Cava Inferior/patología , Vena Cava Inferior/cirugía , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , China/epidemiología , Células Neoplásicas Circulantes/patología , Trombosis de la Vena/patología , Trombosis de la Vena/cirugía , Anciano , Nefrectomía/métodos , Complicaciones Posoperatorias/epidemiología , Adulto
16.
Artículo en Inglés | MEDLINE | ID: mdl-38536076

RESUMEN

Three yeast strains belonging to the ascomycetous yeast genus Pichia were isolated from two soil samples from Yunnan and Guizhou provinces and a marine water sample from Liaoning province, PR China. Phylogenetic analyses based on the sequences of the D1/D2 domains of the large subunit(LSU) rRNA gene and the internal transcribed spacer (ITS) region indicate that these three strains, together with 12 additional strains isolated from various substrates collected in different regions or countries of the world, represent a novel species of the genus Pichia, for which the name Pichia kurtzmaniana sp. nov. (holotype: strain CGMCC 2.7213) is proposed. The novel species differs from its close relatives Candida californica by eight (1.5 %) and 26 (11.1 %) mismatches in the D1/D2 domains and the ITS region, respectively; and from Pichia chibodasensis by 11 (2.1 %) and 20 (8.7 %) mismatches in the D1/D2 domains and the ITS region, respectively. In addition, eight Candida species which belong to the Pichia clade are transferred to the genus Pichia, resulting in the proposal of the following new combinations: Pichia cabralensis comb. nov., Pichia californica comb. nov., Pichia ethanolica comb. nov., Pichia inconspicua comb. nov., Pichia phayaonensis comb. nov., Pichia pseudolambica comb. nov., Pichia rugopelliculosa comb. nov., and Pichia thaimueangensis comb. nov.


Asunto(s)
Candida , Pichia , Técnicas de Tipificación Bacteriana , Composición de Base , China , ADN Bacteriano/genética , Ácidos Grasos/química , Filogenia , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN
17.
Artículo en Inglés | MEDLINE | ID: mdl-38415711

RESUMEN

A yeast strain (CGMCC 2.6937T) belonging to the ascomycetous yeast genus Saturnispora was recently isolated from soil collected in Xinghuacun, Shanxi Province, PR China. The strain produces one or two ellipsoid or spherical ascospores in asci formed by the conjugation between a cell and its bud. Phylogenetic analyses of the internal transcribed spacer (ITS) region and the D1/D2 domain of the large subunit rRNA gene suggest that this strain is conspecific with strains NYNU 14639 isolated from rotten wood collected in Funiu Mountain, Henan province and ES13S05 from soil collected in Nantou County, Taiwan. The CGMCC 2.6937T group is most closely related to Saturnispora dispora and Saturnispora zaruensis. However, strain CGMCC 2.6937T differs from S. dispora by 17 (3.2 %, 13 substitutions and four gaps) and 77 (18.8 %, 52 substitutions and 25 gaps) mismatches, and from S. zaruensis by 15 (2.9 %, 12 substitutions and three gaps) and 64 (15.6 %, 44 substitutions and 20 gaps) mismatches, in the D1/D2 domain and ITS region, respectively. The results suggest that the CGMCC 2.6937T group represents an undescribed species in the genus Saturnispora, for which the name Saturnispora sinensis sp. nov. is proposed. The holotype strain is CGMCC 2.6937T.


Asunto(s)
Ascomicetos , Filogenia , Microbiología del Suelo , Madera , Ascomicetos/clasificación , Ascomicetos/genética , Composición de Base , Análisis de Secuencia de ADN , Madera/microbiología , Técnicas de Tipificación Micológica
18.
J Org Chem ; 89(1): 740-747, 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-38101804

RESUMEN

An efficient transition-metal-free fluorination synthesis of N-H-free 3-heteroaryl-oxindoles with Selectfluor was depicted. Under mild reaction conditions, a series of 3-heteroaryl-fluorooxindoles were produced in yield of 62-88% using Selectfluor as a fluorine source.

19.
Inorg Chem ; 63(25): 11821-11831, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38848310

RESUMEN

A series of ruthenium complexes (Ru1-Ru4) bearing new NNN-pincer ligands were synthesized in 58-78% yields. All of the complexes are air and moisture stable and were characterized by IR, NMR, and high-resolution mass spectra (HRMS). In addition, the structures of Ru1-Ru3 were confirmed by X-ray crystallographic analysis. These Ru(II) complexes exhibited high catalytic efficiency and broad functional group tolerance in the N-methylation reaction of amines using CH3OH as both the C1 source and solvent. Experimental results indicated that the electronic effect of the substituents on the ligands considerably affects the catalytic reactivity of the complexes in which Ru3 bearing an electron-donating OMe group showed the highest activity. Deuterium labeling and control experiments suggested that the dehydrogenation of methanol to generate ruthenium hydride species was the rate-determining step in the reaction. Furthermore, this protocol also provided a ready approach to versatile trideuterated N-methylamines under mild conditions using CD3OD as a deuterated methylating agent.

20.
Inorg Chem ; 63(19): 8822-8831, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38696545

RESUMEN

This study presents the rare examples of S-heteroaryl tetradentate Pt(S^C^N^O) luminescent complexes (PtSZ and PtSZtBu) containing a Pt-S bond. The presence of the Pt-S bond allows the novel Pt(S^C^N^O) complexes to exhibit temperature-dependent phosphorescent emission behavior. The PtSZtBu exhibits dual-emission phenomena and biexponential transient decay spectra above 250 K, indicating the presence of two minimal excited states in the potential energy surface (PES) of the T1 state. Through complementary experimental and computational studies, we have identified changes in orbital composition between Pt(dxy)-S(px) and Pt(dyz)-S(pz) in excited states with increasing temperature. This results in two energy minima, enabling the excited states to decay selectively and radiatively at different temperatures. Consequently, this leads to remarkable steady-state and transient emission spectra changes. Our work not only provides valuable insights for the development of novel Pt-S bond-based tetradentate Pt(II) complexes but also enhances our understanding of the distinctive properties governed by the Pt-S bond.

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