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The timely degradation of proteins that regulate the cell cycle is essential for oocyte maturation. Oocytes are equipped to degrade proteins via the ubiquitin-proteasome system. In meiosis, anaphase promoting complex/cyclosome (APC/C), an E3 ubiquitin-ligase, is responsible for the degradation of proteins. Ubiquitin-conjugating enzyme E2 S (UBE2S), an E2 ubiquitin-conjugating enzyme, delivers ubiquitin to APC/C. APC/C has been extensively studied, but the functions of UBE2S in oocyte maturation and mouse fertility are not clear. In this study, we used Ube2s knockout mice to explore the role of UBE2S in mouse oocytes. Ube2s-deleted oocytes were characterized by meiosis I arrest with normal spindle assembly and spindle assembly checkpoint dynamics. However, the absence of UBE2S affected the activity of APC/C. Cyclin B1 and securin are two substrates of APC/C, and their levels were consistently high, resulting in the failure of homologous chromosome separation. Unexpectedly, the oocytes arrested in meiosis I could be fertilized and the embryos could become implanted normally, but died before embryonic day 10.5. In conclusion, our findings reveal an indispensable regulatory role of UBE2S in mouse oocyte meiosis and female fertility.
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Puntos de Control de la Fase M del Ciclo Celular , Meiosis , Animales , Femenino , Ratones , Ciclosoma-Complejo Promotor de la Anafase/genética , Ciclosoma-Complejo Promotor de la Anafase/metabolismo , Oocitos/metabolismo , Ubiquitinas/metabolismoRESUMEN
Aryl chlorides are among the most versatile synthetic precursors, and yet inexpensive and benign chlorination techniques to produce them are underdeveloped. We propose a process to generate aryl chlorides by chloro-group transfer from chlorophenol pollutants to arenes during their mineralization, catalyzed by Cu(NO3)2/NaNO3 under aerobic conditions. A wide range of arene substrates have been chlorinated using this process. Mechanistic studies show that the Cu catalyst acts in cooperation with NOx species generated from the decomposition of NaNO3 to regulate the formation of chlorine radicals that mediate the chlorination of arenes together with the mineralization of chlorophenol. The selective formation of aryl chlorides with the concomitant degradation of toxic chlorophenol pollutants represents a new approach in environmental pollutant detoxication. A reduction in the use of traditional chlorination reagents provides another (indirect) benefit of this procedure.
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Cloruros , Clorofenoles , Contaminantes Ambientales , Contaminantes Químicos del Agua , Catálisis , Cloruros/síntesis química , Clorofenoles/química , Clorofenoles/toxicidad , Contaminantes Ambientales/química , Contaminantes Ambientales/toxicidad , Halogenación , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/toxicidadRESUMEN
BACKGROUND: Phosphorus plays a key role in plant adaptation to adversity and plays a positive role in the yield and quality formation of apples. Genes of the SPX domain-containing family are widely involved in the regulation of phosphorus signalling networks. However, the mechanisms controlling phosphorus deficiency are not completely understood in self-rooted apple stock. RESULTS: In this study, 26 members of the apple SPX gene family were identified by genome-wide analysis, and further divided into four subfamilies (SPX, SPX-MFS, SPX-EXS, and SPX-RING) based on their structural features. The chromosome distribution and gene duplications of MdSPXs were also examined. The promoter regions of MdSPXs were enriched for multiple biotic/abiotic stresses, hormone responses and typical P1BS-related elements. Analysis of the expression levels of 26 MdSPXs showed that some members were remarkably induced when subjected to low phosphate (Pi) stress, and in particular MdSPX2, MdSPX3, and MdPHO1.5 exhibited an intense response to low Pi stress. MdSPX2 and MdSPX3 showed significantly divergent expression levels in low Pi sensitive and insensitive apple species. Protein interaction networks were predicted for 26 MdSPX proteins. The interaction of MdPHR1 with MdSPX2, MdSPX3, MdSPX4, and MdSPX6 was demonstrated by yeast two-hybrid assay, suggesting that these proteins might be involved in the Pi-signaling pathway by interacting with MdPHR1. CONCLUSION: This research improved the understanding of the apple SPX gene family and contribute to future biological studies of MdSPX genes in self-rooted apple stock.
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Evolución Molecular , Malus , Familia de Multigenes , Fósforo , Proteínas de Plantas , Estrés Fisiológico , Malus/genética , Malus/metabolismo , Estrés Fisiológico/genética , Fósforo/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Filogenia , Regiones Promotoras Genéticas , Duplicación de Gen , Mapas de Interacción de ProteínasRESUMEN
Arabidopsis RESISTANCE TO POWDERY MILDEW 8.1 (RPW8.1) is an important tool for engineering broad-spectrum disease resistance against multiple pathogens. Ectopic expression of RPW8.1 leads to enhanced disease resistance with cell death at leaves and compromised plant growth, implying a regulatory mechanism balancing RPW8.1-mediated resistance and growth. Here, we show that RPW8.1 constitutively enhances the expression of transcription factor WRKY51 and activates salicylic acid and ethylene signalling pathways; WRKY51 in turn suppresses RPW8.1 expression, forming a feedback regulation loop. RPW8.1 and WRKY51 are both induced by pathogen infection and pathogen-/microbe-associated molecular patterns. In ectopic expression of RPW8.1 background (R1Y4), overexpression of WRKY51 not only rescues the growth suppression and cell death caused by RPW8.1, but also suppresses RPW8.1-mediated broad-spectrum disease resistance and pattern-triggered immunity. Mechanistically, WRKY51 directly binds to and represses RPW8.1 promoter, thus limiting the expression amplitude of RPW8.1. Moreover, WRKY6, WRKY28 and WRKY41 play a role redundant to WRKY51 in the suppression of RPW8.1 expression and are constitutively upregulated in R1Y4 plants with WRKY51 being knocked out (wrky51 R1Y4) plants. Notably, WRKY51 has no significant effects on disease resistance or plant growth in wild type without RPW8.1, indicating a specific role in RPW8.1-mediated disease resistance. Altogether, our results reveal a regulatory circuit controlling the accumulation of RPW8.1 to an appropriate level to precisely balance growth and disease resistance during pathogen invasion.
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Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/metabolismo , Resistencia a la Enfermedad/genética , Retroalimentación , Arabidopsis/metabolismo , Muerte Celular , Enfermedades de las Plantas/genética , Regulación de la Expresión Génica de las Plantas/genéticaRESUMEN
We report the continuous-wave (cw) difference-frequency generation (DFG) in a ZnGeP2 (ZGP) crystal that produces tunable long-wavelength infrared (LWIR) lasing. Particularly, we experimentally demonstrate the feasibility to drive DFG in ZGP by all-fiber near-infrared fiber lasers consisting of a 1.3â µm tunable cw random Raman fiber laser (RRFL) and a 1.5â µm erbium-doped fiber amplifier seeded by a tunable distributed feedback (DFB) laser, making the whole system compact and robust. As a result, the demonstrated LWIR DFG presents a broadband spectral tuning range spanning from 9.5 to 11.5â µm, and the output powers in the spectral range of 9.5-11â µm are larger than 40â µW pumped by watt-level fiber lasers. Meanwhile, as a typical application, a proof-of-concept demonstration of gas sensing of SF6 is executed based on the generated cw LWIR source. Our work demonstrates that the combination of ZGP crystal and fiber lasers can provide an effective and robust approach for the generation of cw LWIR radiation with useful power and broadband wavelength tunability.
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Pseudaminic acid (Pse) is found in the polysaccharide structures of the cell surface of various Gram-negative pathogenic bacteria including Acinetobacter baumannii and considered as an important component of cell surface glycans including oligosaccharides and glycoproteins. However, the glycosyltransferase that is responsible for the Pse glycosylation in A. baumannii remains unknown yet. In this study, through comparative genomics analysis of Pse-positive and negative A. baumannii clinical isolates, we identified a potential glycosyltransferase, KpsS1, located right downstream of the Pse biosynthesis genetic locus. Deletion of this gene in an Pse-positive A. baumannii strain, Ab8, impaired the glycosylation of Pse to the surface CPS and proteins, while the gene knockout strain, Ab8ΔkpsS1, could still produce Pse with 2.86 folds higher amount than that of Ab8. Furthermore, impairment of Pse glycosylation affected the morphology and virulence potential of A. baumannii, suggesting the important role of this protein. This study will provide insights into the further understanding of Pse in bacterial physiology and pathogenesis.
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Acinetobacter baumannii , Glicosiltransferasas , Acinetobacter baumannii/metabolismo , Glicosilación , Glicosiltransferasas/metabolismo , Glicosiltransferasas/genética , Azúcares Ácidos/metabolismo , Azúcares Ácidos/química , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/química , VirulenciaRESUMEN
We successfully synthesized two new supramolecular frameworks, namely {[Cu2(L1)(H2O)2]·(H2O)}n (1) and {[Ag(L2)(bpp)]2n·2(H2O)}n (2) (H2L1 = 2-hydroxy-5-sulfobenzoic acid, HL2 = 8-hydroxyquinoline-2-sulfonic acid) under hydrothermal condition. These single-crystal structures were determined via X-ray single crystal diffraction analyses. Solids 1 and 2 acted as photocatalysts and performed good photocatalytic activities for MB degradation under UV light irradiation.
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BACKGROUND AND AIMS: Uric acid (UA) and C-reactive protein (CRP) may interact synergistically to accelerate the initiation and progression of cardiovascular disease (CVD). This study investigated the effects of a combination of high UA and high CRP on the risks of CVD. METHODS AND RESULTS: A total of 90,270 participants recruited from the Kailuan study were included, who were divided into four groups according to the presence/absence of hyperuricemia and inflammation. Cox regression was applied to evaluate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of CVD. C-statistics, net classification index (NRI), and integrated discrimination improvement (IDI) were used to compare the incremental predictive of UA, CRP, and their combined effects on CVD. Mediation analysis was to explore the impact of CRP on the association between UA and CVD. Over a median follow-up of 14.95 years, we identified 11398 incident CVD cases. Compared to the low UA/low CRP group, the high UA/low CRP, low UA/high CRP and high UA/high CRP groups showed progressively higher risks of CVD, HR (95% CI): 1.18(1.10-1.27), 1.27(1.21-1.33) and 1.50 (1.33-1.69), respectively. The incorporation of UA and CRP into the traditional China-PAR model led to improvement in the C-statistic, NRI, and IDI, and was better than incorporation of either UA or CRP alone. Mediation analysis showed that CRP mediated the association between UA and CVD, accounting for 11.57% of the total effects. CONCLUSIONS: High UA/high CRP is associated with increased risks of CVD. Incorporation of both UA and CRP provided additional value for risk stratification.
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Biomarcadores , Proteína C-Reactiva , Enfermedades Cardiovasculares , Factores de Riesgo de Enfermedad Cardiaca , Hiperuricemia , Mediadores de Inflamación , Regulación hacia Arriba , Ácido Úrico , Humanos , Proteína C-Reactiva/análisis , Ácido Úrico/sangre , Masculino , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/diagnóstico , Persona de Mediana Edad , Femenino , Estudios Prospectivos , Biomarcadores/sangre , China/epidemiología , Medición de Riesgo , Hiperuricemia/sangre , Hiperuricemia/epidemiología , Hiperuricemia/diagnóstico , Factores de Tiempo , Adulto , Incidencia , Mediadores de Inflamación/sangre , Pronóstico , Anciano , Análisis de MediaciónRESUMEN
Endothelial damage caused by persistent glucose and lipid metabolism disorders is the main reason of diabetic vascular diseases. Daidzein exerts positive effects on vascular dysfunction. Peroxisome proliferator-activated receptors (PPARs) regulate critically glucose and lipid metabolism. However, the interaction of daidzein to PPARs is still insufficiently explored. In this study, the cell proliferation was detected by EdU. The intrinsic activity and binding affinity of daidzein for human PPARs (hPPARs) were estimated by transactivation reporter gene test and HPLC-UV method, respectively. Daidzein significantly reversed high glucose (HG, at 30 mmol/l)-induced injury in HUVECs, which was inhibited by both PPARα and PPARγ antagonist, but no PPARß antagonist. Daidzein selectively activated hPPARα and hPPARγ1, but weakly hPPARß. Additionally, daidzein also bound to both hPPARα and hPPARγ1. The findings suggested that daidzein may be a PPARα and PPARγ dual-agonist. The amelioration of daidzein on HUVECs from hyperglycemia may be mediated by the activation of PPARα and PPARγ receptors.
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Isoflavonas , PPAR alfa , PPAR gamma , Humanos , PPAR alfa/metabolismo , Células Endoteliales , GlucosaRESUMEN
Neijiang (NJ) and Yacha (YC) are two indigenous pig breeds in the Sichuan basin of China, displaying higher resistance to diseases, lower lean ratio, and slower growth rate than the commercial Western pig breed Yorkshire (YS). The molecular mechanisms underlying the differences in growth and development between these pig breeds are still unknown. In the present study, five pigs from NJ, YC, and YS breeds were subjected to the whole genome resequencing, and then the differential single-nucleotide polymorphisms (SNPs) were screened using a 10-kb window sliding in 1-kb step using the Fst method. Finally, 48,924, 48,543, and 46,228 nonsynonymous single-nucleotide polymorphism loci (nsSNPs) were identified between NJ and YS, NJ and YC, and YC and YS, which highly or moderately affected 2,490, 800, and 444 genes, respectively. Moreover, three nsSNPs were detected in the genes of acetyl-CoA acetyltransferase 1 (ACAT1) insulin-like growth factor 2 receptor (IGF2R), insulin-like growth factor 2 and mRNA-binding protein 3 (IGF2BP3), which potentially affected the transformation of acetyl-CoA to acetoacetyl-CoA and the normal functions of the insulin signaling pathways. Moreover, serous determinations revealed significantly lower acetyl-CoA content in YC than in YS, supporting that ACAT1 might be a reason explaining the differences in growth and development between YC and YS breeds. Contents of phosphatidylcholine (PC) and phosphatidic acid (PA) significantly differed between the pig breeds, suggesting that glycerophospholipid metabolism might be another reason for the differences between Chinese and Western pig breeds. Overall, these results might contribute basic information to understand the genetic differences determining the phenotypical traits in pigs.
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Porcinos , Animales , Acetilcoenzima A , Genoma , Polimorfismo de Nucleótido Simple , Porcinos/genética , Porcinos/crecimiento & desarrolloRESUMEN
Many rice microRNAs have been identified as fine-tuning factors in the regulation of agronomic traits and immunity. Among them, Osa-miR535 targets SQUAMOSA promoter binding protein-like 14 (OsSPL14) to positively regulate tillers but negatively regulate yield and immunity. Here, we uncovered that Osa-miR535 targets another SPL gene, OsSPL4, to suppress rice immunity against Magnaporthe oryzae. Overexpression of Osa-miR535 significantly decreased the accumulation of the fusion protein SPL4TBS -YFP that contains the target site of Osa-miR535 in OsSPL4. Consistently, Osa-miR535 mediated the cleavage of OsSPL4 mRNA between the 10th and 11th base pair of the predicted binding site at the 3' untranslated region. Transgenic rice lines overexpressing OsSPL4 (OXSPL4) displayed enhanced blast disease resistance accompanied by enhanced immune responses, including increased expression of defense-relative genes and up-accumulated H2 O2 . By contrast, the knockout mutant osspl4 exhibited susceptibility. Moreover, OsSPL4 binds to the promoter of GH3.2, an indole-3-acetic acid-amido synthetase, and promotes its expression. Together, these data indicate that Os-miR535 targets OsSPL4 and OsSPL4-GH3.2, which may parallel the OsSPL14-WRKY45 module in rice blast disease resistance.
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Magnaporthe , Oryza , Proteínas Portadoras/metabolismo , Resistencia a la Enfermedad/genética , Regulación de la Expresión Génica de las Plantas , Magnaporthe/metabolismo , Oryza/metabolismo , Enfermedades de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMEN
BACKGROUND: Punica granatum is a fundamentally important fruit tree that has important economic, medicinal and ornamental properties. At present, there are few reports on the mitochondrial genome of pomegranate. Hence, in this study the P. granatum mitogenome was sequenced and assembled to further understanding of organization, variation, and evolution of mitogenomes of this tree species. RESULTS: The genome structure was multi-chromosomes with seven circular contigs, measuring 382,774 bp in length with a 45.91% GC content. It contained 74 genes, including 46 protein-coding genes, 25 tRNA genes, and three rRNA genes. There were 188 pairs of dispersed repeats with lengths of 30 or greater, primarily consisting of reverse complementary repeats. The mitogenome analysis identified 114SSRs and 466 RNA editing sites. Analyses of codon usage, nucleotide diversity and gene migration from chloroplast to mitochondrial were also conducted. The collinear and comparative analysis of mitochondrial structures between P. granatum and its proximal species indicated that P. granatum 'Taishanhong' was closely related to P. granatum 'Qingpitian' and Lagerstroemia indica. Phylogenetic examination based on the mitogenome also confirmed the evolutionary relationship. CONCLUSION: The results offered crucial information on the evolutionary biology of pomegranate and highlighted ways to promote the utilization of the species' germplasm.
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Genoma del Cloroplasto , Genoma Mitocondrial , Granada (Fruta) , Granada (Fruta)/genética , Filogenia , Genoma Mitocondrial/genética , Secuencia de BasesRESUMEN
Arabidopsis RESISTANCE TO POWDERY MILDEW 8.2 (RPW8.2) is specifically induced by the powdery mildew (PM) fungus (Golovinomyces cichoracearum) in the infected epidermal cells to activate immunity. However, the mechanism of RPW8.2-induction is not well understood. Here, we identify a G. cichoracearum effector that interacts with RPW8.2, named Gc-RPW8.2 interacting protein 1 (GcR8IP1), by a yeast two-hybrid screen of an Arabidopsis cDNA library. GcR8IP1 is physically associated with RPW8.2 with its REALLY INTERESTING NEW GENE finger domain that is essential and sufficient for the association. GcR8IP1 was secreted and translocated into the nucleus of host cell infected with PM. Association of GcR8IP1 with RPW8.2 led to an increase in RPW8.2 in the nucleus. In turn, the nucleus-localized RPW8.2 promoted the activity of the RPW8.2 promoter, resulting in transcriptional self-amplification of RPW8.2 to boost immunity at infection sites. Additionally, ectopic expression or host-induced gene silencing of GcR8IP1 supported its role as a virulence factor in PM. Altogether, our results reveal a mechanism of RPW8.2-dependent defense strengthening via altered partitioning of RPW8.2 and transcriptional self-amplification triggered by a PM fungal effector, which exemplifies an atypical form of effector-triggered immunity.
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Proteínas de Arabidopsis , Arabidopsis , Ascomicetos , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Resistencia a la Enfermedad , Ascomicetos/fisiología , Enfermedades de las Plantas/microbiologíaRESUMEN
The effect of driving wavelengths on high harmonic generation (HHG) have long been a fundamental research topic. However, despite of abundant efforts, the investigation of wavelength scaling of HHG in solids is still confined within the scope of theoretical predictions. In this work, we for the first time to the best of our knowledge, experimentally reveal wavelength scaling of HHG yields and cutoff energy in three typical solid media (namely pristine crystals GaSe, CdTe and polycrystalline ZnSe), driven in a broad mid-infrared (MIR) range from 4.0 to 8.7â µm. It is revealed that when the driving wavelength is shorter than 6.5-7.0â µm, HHG yields decrease monotonously with the MIR driving wavelengths, while they rise abruptly by 1-3 orders of magnitude driven at longer wavelength and exhibit a crest at 7.5â µm. In addition, the cutoff energies are found independent on driving wavelengths across the broad MIR pump spectral range. We propose that the interband mechanism dominates the HHG process when the driving wavelength is shorter than 6.5-7.0â µm, and as the driving wavelength increases, intraband contribution leads to an abrupt rise of the HHG yields, which is verified by the HHG polarization measurement driven at 3.0 and 7.0â µm. This work not only experimentally demonstrate the wavelength scaling of HHG in solids, but more importantly blazes the trail for optimizing the HHG performance by choosing a driving wavelength and provides experimental method to distinguish the interband and intraband dynamics.
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Background: As an emerging arrhythmia monitor, ambulatory smartwatch electrocardiogram (ECG) provides an option for home-based monitoring of delayed new-onset arrhythmic events after transcatheter aortic valve replacement (TAVR). We aimed to validate the diagnostic efficacy of a consumer smartwatch ECG in TAVR recipients, while further explore the occurrence rate of both tachy- and brady-arrhythmia for 30 days after discharge to support risk management. Methods: Consecutive TAVR recipients from February 26th, 2021 to December 13th, 2021 were enrolled prospectively, receiving simultaneous 24-hour Holter and 12-lead ECG compared with smartwatch ECG during hospitalization and daily smartwatch ECG collection for 30 days after discharge. Results: Among 110 patients, the efficacy of smartwatch ECG presented sensitivity and specificity in diagnosing atrial fibrillation (AF) as 1.00 and 0.97, left bundle branch block (LBBB) as 0.61 and 0.88, and right bundle branch block (RBBB) as 0.60 and 0.97, respectively, compared with 24-hour Holter; presented sensitivity and specificity in diagnosing AF as 0.88 and 1.00, LBBB as 0.90 and 0.96, and RBBB as 0.83 and 0.94, respectively, compared with 12-lead ECG. At 30-day follow-up, new-onset arrhythmia included new-onset severe conduction disturbance (SCD) (23.6%), new-onset AF (21.8%), new-onset permanent LBBB (14.5%) and new-onset permanent RBBB (0.9%); 69.2% (36/52) of early new-onset LBBB recovered at 30-day follow-up. Conclusions: The diagnostic efficacy of consumer smartwatch ECG in arrhythmic events among TAVR population was acceptable, which provided a recommendable option for home-based management. Clinical Trial Registration: "Continuously ambulatory rhythm monitoring and predictors of electrocardio-related adverse events in 30 days after transcatheter aortic valve replacement"; Identifier: ChiCTR2000041244; http://www.chictr.org.cn/showproj.aspx?proj=66324.
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In parametric conversion, phase-matching techniques such as birefringence and quasi phase-matching (PM) with the designed crystal angle or periodically poled polarities are employed to fulfill the requirement of momentum conservation. However, directly using phase-mismatched interactions in nonlinear media with large quadratic nonlinear coefficient remains unheeded. Here, for the first time to the best of our knowledge, we study the phase-mismatched difference-frequency generation (DFG) in an isotropic cadmium telluride (CdTe) crystal, with the comparison of other DFG processes based on birefringence-PM, quasi-PM, and random-quasi-PM. Long-wavelength mid-infrared (LWMIR) phase-mismatched DFG with an ultra-broadband spectral tuning range of 6-17â µm based on CdTe is demonstrated. Thanks to the giant quadratic nonlinear coefficient (â¼109 pm/V) and good figure of merit in the parametric process, the output power up to 100 µW is obtained, which is comparable to or even better than the DFG output from a polycrystalline ZnSe with the same thickness facilitated by random-quasi-PM. A proof-of-concept demonstration in gas sensing of CH4 and SF6 is conducted based on the phase-mismatched DFG as a typical application. Our results demonstrate the feasibility of phase-mismatched parametric conversion in producing useful LWMIR power and ultra-broadband tunability in a simple and convenient way without the necessity of controlling the polarization, phase-matching angle, or pole periods, which could find applications in the fields of spectroscopy and metrology.
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Endometrial carcinoma (EC) morbidity and mortality have been increasing in recent years. Otubain 2 (OTUB2) was shown to be upregulated in EC patients, so the aim of this study was to explore the role of OTUB2 in EC. Cell Counting Kit-8 (CCK-8), colony formation, enzyme-linked immunosorbent assay, the wound healing assay, and Transwell invasion assays were used to investigate the specific role of OTUB2 in EC tumorigenesis. Real-time polymerase chain reaction and western blot analysis were used to detect the expression of OTUB2 in EC tissues and cells. OTUB2 is upregulated in EC patients and cell lines and is associated with a poor prognosis. The overexpression of OTUB2 promoted glycolysis and induced the proliferation, migration, and invasion of endometrial cancer cells. The silencing of OTUB2 had the opposite effect. In addition, the silencing of OTUB2 significantly suppressed the expression levels of PKM2. Importantly, inhibition of the PKM2/PI3K/AKT signaling pathway significantly reversed the promoting effect of OTUB2 overexpression on EC. OTUB2 regulated the proliferation and invasion of EC cells by regulating the PKM2/PI3K/AKT signaling pathway. OTUB2 may serve as a potential prognostic and therapeutic target in EC.
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Neoplasias Endometriales , Proteínas Proto-Oncogénicas c-akt , Femenino , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Línea Celular Tumoral , Movimiento Celular , Transducción de Señal , Neoplasias Endometriales/metabolismo , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Tioléster Hidrolasas/metabolismoRESUMEN
Phenolic organic compounds are widely used industrial chemicals that exist extensively in the environment and have a significant impact on human health. 4-Nitrophenol (4-NP) is a typical phenolic organic compound found in aqueous environments. Efficient detection of 4-NP in wastewater is highly challenging due to the complexity of testing environmental samples. Herein, a luminescent lanthanide metal-organic framework (MOF) sensor based on the Eu3+ ion {[Eu(HL)(L)(H2O)]·2H2O}n (EuMOF; H2L = 5-(4H-1,2,4-triazol-4-yl)benzene-1,3-dicarboxylic acid) was successfully synthesized for efficient 4-NP detection in wastewater. Fluorescence sensing experiments revealed that 4-NP could greatly quench the EuMOF fluorescence. Subsequently, EuMOF was applied to 4-NP detection in distilled water, tap water, river water, and treated industrial wastewater, exhibiting high sensitivity, a fast response within 30 s, high selectivity, excellent reusability, and a low detection limit. Finally, the fluorescence quenching mechanism was explored and attributed to competitive absorption of irradiated light between 4-NP and the ligand.
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Hepatocellular carcinoma (HCC) is a common malignancy affecting many people worldwide. Baicalin is a flavonoid extracted from the dried root of Scutellaria baicalensis Georgi. It can effectively inhibit the occurrence and development of HCC. Nonetheless, the mechanism through which Baicalin inhibits HCC growth and metastasis remain unknown. This work discovered that Baicalin inhibited HCC cell proliferation, invasion, metastasis while inducing cell cycle arrest at the G0/G1 phase and apoptosis. In vivo HCC xenograft results indicated that Baicalin inhibited HCC growth. Western blotting analysis indicated that Baicalin suppressed the expressions of ROCK1, p-GSK-3ß, and ß-catenin, whereas it up-regulated the expressions of GSK-3ß and p-ß-catenin. Baicalin also reduced the expressions of Bcl-2, C-myc, Cyclin D1, MMP-9, and VEGFA, while increasing the expression of Bax. Molecular docking revealed that Baicalin docked in the binding site of the ROCK1 agonist, with a binding energy of -9 kcal/mol between the two. In addition, lentivirus-mediated suppression of ROCK1 expression improved the inhibitory effect of Baicalin on the proliferation, invasion, and metastasis of HCC and the expression of proteins associated with ROCK1/GSK-3ß/ß-catenin signaling pathway. Moreover, restoring ROCK1 expression decreased the anti-HCC efficacy of Baicalin. These findings suggest that Baicalin may decrease HCC proliferation and metastasis by suppressing ROCK1/GSK-3ß/ß-catenin signaling.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , beta Catenina/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Línea Celular Tumoral , Simulación del Acoplamiento Molecular , Transducción de Señal , Flavonoides/farmacología , Proliferación Celular , Quinasas Asociadas a rhoRESUMEN
The peel color of pomegranates is an important exterior quality that determines market value. Anthocyanins are biosynthesized in the cytosol and then transported to the vacuole for storage. However, the molecular mechanism that determines the color variation between red and white pomegranates remains unclear. In this study, we identified an R2R3-MYB protein (PgMYB1) that interacts with the PgGSTF6 promoter and regulates its transcriptional expression, thus promoting the accumulation of anthocyanins in pomegranate. The expression of PgMYB1 and PgGSTF6 was positively correlated with the anthocyanin content in red and white pomegranates. Further investigation showed that the knockdown of PgMYB1 in red pomegranate 'Taishanhong' (TSH), by the virus-induced gene-silencing system, inhibited anthocyanin accumulation. Together, our results indicate that PgMYB1 controls the transport of anthocyanin via PgGSTF6 and thus promotes anthocyanin accumulation in red pomegranates. Our results have a certain reference value for further clarifying the regulation of anthocyanin synthesis and transport in pomegranate fruits.