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1.
Plant J ; 118(5): 1486-1499, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38457289

RESUMEN

The petals of rose (Rosa sp.) flowers determine the ornamental and industrial worth of this species. The number of petals in roses was previously shown to be subject to fluctuations in ambient temperature. However, the mechanisms by which rose detects and responds to temperature changes are not entirely understood. In this study, we identified short interstitial telomere motifs (telo boxes) in the second intron of AGAMOUS (RcAG) from China rose (Rosa chinensis) that play an essential role in precise temperature perception. The second intron of RcAG harbors two telo boxes that recruit telomere repeat binding factors (RcTRBs), which interact with CURLY LEAF (RcCLF) to compose a repressor complex. We show that this complex suppresses RcAG expression when plants are subjected to low temperatures via depositing H3K27me3 marks (trimethylation of lysine 27 on histone H3) over the RcAG gene body. This regulatory mechanism explains the low-temperature-dependent decrease in RcAG transcript levels, leading to the production of more petals under these conditions. Our results underscore an interesting intron-mediated regulatory mechanism governing RcAG expression, enabling rose plants to perceive temperature cues and establish petal numbers.


Asunto(s)
Flores , Histonas , Intrones , Proteínas de Plantas , Rosa , Rosa/genética , Rosa/metabolismo , Flores/genética , Flores/metabolismo , Flores/crecimiento & desarrollo , Histonas/metabolismo , Histonas/genética , Intrones/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Frío , Metilación , Proteínas de Dominio MADS/genética , Proteínas de Dominio MADS/metabolismo , Lisina/metabolismo
2.
New Phytol ; 243(4): 1387-1405, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38849320

RESUMEN

Flowering is a vital agronomic trait that determines the economic value of most ornamental plants. The flowering time of rose (Rosa spp.) is photoperiod insensitive and is thought to be tightly controlled by light intensity, although the detailed molecular mechanism remains unclear. Here, we showed that rose plants flower later under low-light (LL) intensity than under high-light (HL) intensity, which is mainly related to the stability of PHYTOCHROME-INTERACTING FACTORs (RcPIFs) mediated by OPEN STOMATA 1-Like (RcOST1L) under different light intensity regimes. We determined that HL conditions trigger the rapid phosphorylation of RcPIFs before their degradation. A yeast two-hybrid screen identified the kinase RcOST1L as interacting with RcPIF4. Moreover, RcOST1L positively regulated rose flowering and directly phosphorylated RcPIF4 on serine 198 to promote its degradation under HL conditions. Additionally, phytochrome B (RcphyB) enhanced RcOST1L-mediated phosphorylation of RcPIF4 via interacting with the active phyB-binding motif. RcphyB was activated upon HL and recruited RcOST1L to facilitate its nuclear accumulation, in turn leading to decreased stability of RcPIF4 and flowering acceleration. Our findings illustrate how RcPIF abundance safeguards proper rose flowering under different light intensities, thus uncovering the essential role of RcOST1L in the RcphyB-RcPIF4 module in flowering.


Asunto(s)
Flores , Proteínas de Plantas , Complejo de la Endopetidasa Proteasomal , Proteolisis , Rosa , Fosforilación , Flores/fisiología , Rosa/fisiología , Proteínas de Plantas/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Proteolisis/efectos de la radiación , Regulación de la Expresión Génica de las Plantas , Luz , Fitocromo B/metabolismo , Unión Proteica , Núcleo Celular/metabolismo
3.
Mar Drugs ; 22(2)2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38393053

RESUMEN

The marine red microalga Porphyridium can simultaneously synthesize long-chain polyunsaturated fatty acids, including eicosapentaenoic acid (C20:5, EPA) and arachidonic acid (C20:4, ARA). However, the distribution and synthesis pathways of EPA and ARA in Porphyridium are not clearly understood. In this study, Porphyridium cruentum CCALA 415 was cultured in nitrogen-replete and nitrogen-limited conditions. Fatty acid content determination, transcriptomic, and lipidomic analyses were used to investigate the synthesis of ARA and EPA. The results show that membrane lipids were the main components of lipids, while storage lipids were present in a small proportion in CCALA 415. Nitrogen limitation enhanced the synthesis of storage lipids and ω6 fatty acids while inhibiting the synthesis of membrane lipids and ω3 fatty acids. A total of 217 glycerolipid molecular species were identified, and the most abundant species included monogalactosyldiglyceride (C16:0/C20:5) (MGDG) and phosphatidylcholine (C16:0/C20:4) (PC). ARA was mainly distributed in PC, and EPA was mainly distributed in MGDG. Among all the fatty acid desaturases (FADs), the expressions of Δ5FAD, Δ6FAD, Δ9FAD, and Δ12FAD were up-regulated, whereas those of Δ15FAD and Δ17FAD were down-regulated. Based on these results, only a small proportion of EPA was synthesized through the ω3 pathway, while the majority of EPA was synthesized through the ω6 pathway. ARA synthesized in the ER was likely shuttled into the chloroplast by DAG and was converted into EPA by Δ17FAD.


Asunto(s)
Microalgas , Porphyridium , Porphyridium/genética , Porphyridium/metabolismo , Microalgas/genética , Microalgas/metabolismo , Lipidómica , Ácidos Grasos/análisis , Ácido Graso Desaturasas/metabolismo , Ácido Eicosapentaenoico , Lípidos de la Membrana , Perfilación de la Expresión Génica , Nitrógeno/metabolismo
4.
Sensors (Basel) ; 24(8)2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38676196

RESUMEN

As a natural satellite of the Earth, the moon is a prime target for planetary remote sensing exploration. However, lunar polarization studies are not popular in the planetary science community. Polarimetry of the lunar surface had not been carried out from a spacecraft until the Korean lunar exploration program was initiated. In previous polarization observations of the moon, images of different polarization states were obtained by a rotating linear polarizer. This method is not well suited for future polarization observations from space-based spacecraft. To this end, we present a new kind of polarized observation of the moon using a division of a focal-plane polarization camera and propose a pipeline on the processing method of the polarization observation of the moon. We obtain a map of the degree of white-light polarization on the nearside of the moon through polarization observation, data processing, and correction. The observation and data processing methods presented in this study have the potential to serve as a reference for analyzing polarization observation data from future orbiting spacecraft. These are expected to lead to new discoveries in the fields of astronomy and planetary science.

5.
Molecules ; 29(11)2024 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-38893392

RESUMEN

Neurodegenerative diseases represent a cluster of conditions characterized by the progressive degeneration of the structure and function of the nervous system. Despite significant advancements in understanding these diseases, therapeutic options remain limited. The medicinal mushroom Ganoderma lucidum has been recognized for its comprehensive array of bioactive compounds with anti-inflammatory and antioxidative effects, which possess potential neuroprotective properties. This literature review collates and examines the existing research on the bioactivity of active compounds and extracts from Ganoderma lucidum in modulating the pathological hallmarks of neurodegenerative diseases. The structural information and preparation processes of specific components, such as individual ganoderic acids and unique fractions of polysaccharides, are presented in detail to facilitate structure-activity relationship research and scale up the investigation of in vivo pharmacology. The mechanisms of these components against neurodegenerative diseases are discussed on multiple levels and elaborately categorized in different patterns. It is clearly presented from the patterns that most polysaccharides of Ganoderma lucidum possess neurotrophic effects, while ganoderic acids preferentially target specific pathogenic proteins as well as regulating autophagy. Further clinical trials are necessary to assess the translational potential of these components in the development of novel multi-target drugs for neurodegenerative diseases.


Asunto(s)
Enfermedades Neurodegenerativas , Fármacos Neuroprotectores , Reishi , Enfermedades Neurodegenerativas/tratamiento farmacológico , Humanos , Reishi/química , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/uso terapéutico , Animales , Triterpenos/farmacología , Triterpenos/química , Triterpenos/uso terapéutico , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/uso terapéutico , Polisacáridos/química , Polisacáridos/farmacología , Polisacáridos/uso terapéutico
6.
J Transl Med ; 21(1): 26, 2023 01 14.
Artículo en Inglés | MEDLINE | ID: mdl-36641471

RESUMEN

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a deadly gastrointestinal malignancy, and chemotherapy resistance is a key factor leading to its poor prognosis. M2 tumor-associated macrophages (M2-TAMs) may be an important cause of chemoresistance in ESCC, but its exact mechanism is still unclear. METHODS: In order to study the role of M2-TAMs in ESCC chemoresistance, CCK-8, clone formation assay, flow cytometric apoptosis assay, qRT-PCR, western blotting, and serum-free sphere formation assays were used. In vivo animal experiments and human ESCC tissues were used to confirm the findings. RESULTS: In vitro and in vivo animal experiments, M2-TAMs reduced the sensitivity of ESCC cells to cisplatin. Mechanistically, M2-TAMs highly secreted TGF-ß1 which activated the TGFßR1-smad2/3 pathway to promote and maintain the stemness characteristic of ESCC cells, which could inhibit the sensitivity to cisplatin. Using TGFß signaling inhibitor SB431542 or knockdown of TGFßR1 could reverse the cisplatin resistance of ESCC cells. In 92 cases of human ESCC tissues, individuals with a high density of M2-TAMs had considerably higher levels of TGF-ß1. These patients also had worse prognoses and richer stemness markers. CONCLUSION: TGF-ß1 secreted from M2-TAMs promoted and maintained the stemness characteristic to induce cisplatin resistance in ESCC by activating the TGFß1-Smad2/3 pathway.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Animales , Humanos , Carcinoma de Células Escamosas de Esófago/patología , Cisplatino/farmacología , Cisplatino/uso terapéutico , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/patología , Línea Celular Tumoral , Proliferación Celular
7.
BMC Pregnancy Childbirth ; 23(1): 351, 2023 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-37179315

RESUMEN

BACKGROUND: Noninvasive prenatal testing (NIPT) is increasingly used in the clinical prenatal screening of twin pregnancies, and its screening performance for chromosomal abnormalities requires further evaluation. For twin pregnancies with indications for prenatal diagnosis, there is a lack of clinical data to assess the prenatal diagnosis rate (PDR). The aim of this study was to evaluate the screening performance of NIPT for foetal chromosomal abnormalities in twin pregnancies and the PDR in the second and third trimesters. METHODS: Ultrasound scans were carried out for all twin pregnancies between 11 and 13+ 6 gestational weeks. For twin pregnancies with nuchal translucency thickness˂3.0 mm and no foetal structural malformations, NIPT was performed after blood sampling, followed by routine ultrasound monitoring. Women with twin pregnancies who underwent NIPT at the prenatal diagnostic centre of Xiangya Hospital from January 2018 to May 2022 were included in the study. Genetic counselling was offered to each pregnant woman when the NIPT result indicated a high risk of abnormalities or abnormal ultrasonographic (USG) findings were detected. We followed up twin pregnancies for NIPT results, USG findings, prenatal diagnosis results and pregnancy outcomes. RESULTS: In 1754 twin pregnancies, the sensitivity, specificity and positive predictive value of NIPT for trisomy 21 were 100%, 99.9% and 75%, and the corresponding values for sex chromosome aneuploidy (SCA) were 100%, 99.9% and 50%, respectively. For the 14 twin pregnancies for which the NIPT results indicated a high risk of abnormalities, the PDR was 78.6% (11/14). For the 492 twin pregnancies for which the NIPT results indicated a low risk of abnormalities, the rate of USG findings in the second and third trimesters was 39.4% (194/492); of these pregnancies, prenatal diagnosis was recommended for 16.7% (82/492), but it was actually performed in only 8.3% (41/492), and the PDR was 50% (41/82). There was no significant difference in the PDR between the NIPT high-risk and low-risk groups. CONCLUSIONS: The screening performance of NIPT for SCA in twin pregnancies needs to be further evaluated. When abnormal NIPT results or USG findings are used as the main prenatal diagnostic indicator in the second and third trimesters, the PDR is poor.


Asunto(s)
Pruebas Prenatales no Invasivas , Embarazo , Femenino , Humanos , Estudios Retrospectivos , Embarazo Gemelar , Trisomía , Diagnóstico Prenatal/métodos , Aberraciones Cromosómicas , Aneuploidia
8.
Chem Biodivers ; 20(4): e202200421, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36867116

RESUMEN

The presence of 25-OH moiety has been proved to enhance the bioactivity of dammarane saponins in many cases. However, such modification by previous strategies had compromised yield and purity of target products. Herein ginsenoside Rf was specifically transformed into 25-OH-(20S)-Rf with a conversion rate of 88.03 % by a Cordyceps Sinensis-mediated biocatalytic system. The formulation of 25-OH-(20S)-Rf was calculated by HRMS, whilst its structure was validated by 1 H-NMR, 13 C-NMR, HSQC, and HMBC analysis. Time-course experiments unveiled straightforward hydration of the double bond on Rf with undetectable side reactions and maximum production of 25-OH-(20S)-Rf on the 6th day, which collectively suggested the suitable timing of harvesting this target compound. In vitro bioassay of (20S)-Rf and 25-OH-(20S)-Rf against lipopolysaccharide-induced macrophages indicated a significant boost of anti-inflammatory effects after the C24-C25 double bond was hydrated. Therefore, the biocatalytic system in this article could be leveraged to deal with macrophage-mediated inflammation under defined circumstances.


Asunto(s)
Biocatálisis , Cordyceps , Ginsenósidos , Antiinflamatorios/farmacología , Cordyceps/química , Cordyceps/enzimología , Ginsenósidos/química , Ginsenósidos/farmacología
9.
Plant Physiol ; 186(2): 1186-1201, 2021 06 11.
Artículo en Inglés | MEDLINE | ID: mdl-33693800

RESUMEN

As day-neutral (DN) woody perennial plants, the flowering time of roses (Rosa spp.) is assumed to be independent of the photoperiodic conditions; however, light responses of rose plants are not well understood. Chinese rose (Rosa chinensis) plants were grown under two light intensities (low light [LL], 92 µmol·m-2·s-1; or high light [HL], 278 µmol·m-2·s-1), and either with or without an end-of-day far-red (EOD-FR) treatment. Flowering was significantly delayed in the LL condition compared with the HL, but was not affected by EOD-FR treatment. The time until flowering positively corresponded with the mRNA and protein levels of phytochrome-interacting factors (PIFs; RcPIFs). The heterologous expression of RcPIF1, RcPIF3, or RcPIF4 in the Arabidopsis (Arabidopsis thaliana) pifq quadruple mutant partially rescued the mutant's shorter hypocotyl length. Simultaneous silencing of three RcPIFs in R. chinensis accelerated flowering under both LL and HL, with a more robust effect in LL, establishing RcPIFs as flowering suppressors in response to light intensity. The RcPIFs interacted with the transcription factor CONSTANS (RcCO) to form a RcPIFs-RcCO complex, which interfered with the binding of RcCO to the promoter of FLOWERING LOCUS T (RcFT), thereby inhibiting its expression. Furthermore, this inhibition was enhanced when RcPIFs were stabilized by LL, leading to delayed flowering under LL compared with HL. Our results not only revealed another layer of PIF functioning in the flowering of woody perennial plants, but also established a mechanism of light response in DN plants.


Asunto(s)
Fitocromo/metabolismo , Proteínas de Plantas/metabolismo , Rosa/genética , Arabidopsis/genética , Arabidopsis/fisiología , Flores/genética , Flores/fisiología , Flores/efectos de la radiación , Expresión Génica , Hipocótilo/genética , Hipocótilo/fisiología , Hipocótilo/efectos de la radiación , Mutación , Fotoperiodo , Proteínas de Plantas/genética , Rosa/fisiología , Rosa/efectos de la radiación , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Transgenes
10.
J Am Soc Nephrol ; 32(8): 1871-1879, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34049960

RESUMEN

BACKGROUND: Bilateral renal agenesis (BRA) is a lethal con genital anomaly caused by the failure of normal development of both kidneys early in embryonic development. Oligohydramnios on fetal ultrasonography reveals BRA. Although the exact causes are not clear, BRA is associated with mutations in many renal development genes. However, molecular diagnostics do not pick up many clinical patients. Nephronectin (NPNT) may be a candidate protein for widening diagnosis. It is essential in kidney development, and knockout of Npnt in mice frequently leads to kidney agenesis or hypoplasia. METHODS: A consanguineous Han family experienced three cases of induced abortion in the second trimester of pregnancy, due to suspected BRA. Whole-exome sequencing (WES)-based homozygosity mapping detected underlying genetic factors, and a knock-in mouse model confirmed the renal agenesis phenotype. RESULTS: WES and evaluation of homozygous regions in II:3 and II:4 revealed a pathologic homozygous frameshift variant in NPNT (NM_001184690:exon8:c.777dup/p.Lys260*), which leads to a premature stop in the next codon. The truncated NPNT protein exhibited decreased expression, as confirmed in vivo by the overexpression of WT and mutated NPNT. A knock-in mouse model homozygous for the detected Npnt mutation replicated the BRA phenotype. CONCLUSIONS: A biallelic loss-of-function NPNT mutation causing an autosomal recessive form of BRA in humans was confirmed by the corresponding phenotype of knock-in mice. Our results identify a novel genetic cause of BRA, revealing a new target for genetic diagnosis, prenatal diagnosis, and preimplantation diagnosis for families with BRA.


Asunto(s)
Anomalías Congénitas/diagnóstico , Anomalías Congénitas/genética , Proteínas de la Matriz Extracelular/genética , Enfermedades Renales/congénito , Riñón/anomalías , Alelos , Animales , Mapeo Cromosómico , Anomalías Congénitas/patología , Modelos Animales de Enfermedad , Proteínas de la Matriz Extracelular/metabolismo , Femenino , Mutación del Sistema de Lectura , Técnicas de Sustitución del Gen , Células HEK293 , Homocigoto , Humanos , Riñón/patología , Enfermedades Renales/diagnóstico , Enfermedades Renales/genética , Enfermedades Renales/patología , Mutación con Pérdida de Función , Masculino , Linaje , Fenotipo , Secuenciación del Exoma
11.
Glob Chang Biol ; 26(3): 1697-1713, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31479179

RESUMEN

Global dimming, a decadal decrease in incident global radiation, is often accompanied with an increase in the diffuse radiation fraction, and, therefore, the impact of global dimming on crop production is hard to predict. A popular approach to quantify this impact is the statistical analysis of historical climate and crop data, or use of dynamic crop simulation modelling approach. Here, we show that statistical analysis of historical data did not provide plausible values for the effect of diffuse radiation versus direct radiation on rice or wheat yield. In contrast, our field experimental study of 3 years demonstrated a fertilization effect of increased diffuse radiation fraction, which partly offset yield losses caused by decreased global radiation, in both crops. The fertilization effect was not attributed to any improved canopy light interception but mainly to the increased radiation use efficiency (RUE). The increased RUE was explained not only by the saturating shape of photosynthetic light response curves but also by plant acclimation to dimming that gradually increased leaf nitrogen concentration. Crop harvest index slightly decreased under dimming, thereby discounting the fertilization effect on crop yields. These results challenge existing modelling paradigms, which assume that the fertilization effect on crop yields is mainly attributed to an improved light interception. Further studies on the physiological mechanism of plant acclimation are required to better quantify the global dimming impact on agroecosystem productivity under future climate change.


Asunto(s)
Oryza , Fotosíntesis , Producción de Cultivos , Productos Agrícolas , Triticum
12.
Bioorg Med Chem Lett ; 30(21): 127504, 2020 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-32827631

RESUMEN

25-OH ginsenosides are potent and rare prodrugs in natural sources. However current strategies for such modification always end up in undesirable side products and unsatisfied yield that hinders them from further applications. Herein, ginsenoside Rg1 was thoroughly converted into 20(S/R)-Rh1 and 25-OH-20(S/R)-Rh1 by Cordyceps Sinensis in an optimum medium. The chemical correctness of either 25-OH-20(S/R)-Rh1 epimers was validated by LC-IT-TOF-MSn and 13C NMR spectrometry. The biocatalytic pathway was established as Rg1 â†’ 20(S/R)-Rh1 â†’ 25-OH-20(S/R)-Rh1. The molar bioconversion rate for total 25-OH-20(S/R)-Rh1 was calculated to be 82.5%, of which S-configuration accounted for 43.2% while R-configuration 39.3%. These two 25-OH derivatives are direct hydration products from 20(S/R)-Rh1 without other side metabolites, suggesting this is a highly regioselective process. In conclusion, this biocatalytic system could be harnessed to facilitate the preparation of diversified 25-OH ginsenosides with high yields of the target compound and simple chemical background in the reaction mixture.


Asunto(s)
Cordyceps/metabolismo , Ginsenósidos/metabolismo , Biotransformación , Cordyceps/química , Ginsenósidos/química , Conformación Molecular , Estereoisomerismo
13.
J Sep Sci ; 43(12): 2436-2446, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32227667

RESUMEN

Four types of middle-pressure chromatogram isolated gels are evaluated for adsorption or desorption characteristics of ginsenosides from Panax ginseng. Among them, SP207SS and SP2MGS were selected for dynamic investigations based on their static adsorption or desorption capacity of total ginsenoside. Their adsorption kinetics was better explained by pseudosecond-order model and isotherms were preferably fitted to Langmuir model. Dynamic breakthrough experiments indicated an optimum sample loading speed of 4 bed volume/h for either SP207SS or SP2MGS. Desorption speed was determined to be 2 bed volume/h according to desorption amount of total ginsenoside in their effluents. Eight ginsenosides were identified and quantified by high performance liquid chromatography-triple quadropole-mass spectrometry in total ginsenoside extract and different fractions during stepwise dynamic elution. For SP207SS, 27.62% of loaded ginsenosides was detected in 40% ethanol fraction, while 59.12% of them were found in 60% ethanol fraction. As on SP2MGS, the number went to 53.71 and 44.43%, respectively. Recovery rate of ginsenosides were calculated to 78.65% for SP207SS and 89.53% for SP2MGS, respectively. Intriguingly, content of Rg1 and Re in 40% ethanol fraction from SP207SS became 20.1 and 18.6 times higher than that in total ginsenoside extract by one-step elution, which could be leveraged for the facile enrichment of these two ginsenosides from natural sources.


Asunto(s)
Ginsenósidos/análisis , Panax/química , Adsorción , Cromatografía Líquida de Alta Presión , Geles/química , Geles/aislamiento & purificación , Presión
14.
J Biol Chem ; 293(25): 9662-9673, 2018 06 22.
Artículo en Inglés | MEDLINE | ID: mdl-29610274

RESUMEN

In mammalian cells, autophagy plays crucial roles in restricting further spread of invading bacterial pathogens. Previous studies have established that the Salmonella virulence factors SseF and SseG are required for intracellular bacterial survival and replication. However, the underlying mechanism by which these two effectors facilitate bacterial infection remains elusive. Here, we report that SseF and SseG secreted by Salmonella Typhimurium (S. Typhimurium) inhibit autophagy in host cells and thereby establish a replicative niche for the bacteria in the cytosol. Mechanistically, SseF and SseG impaired autophagy initiation by directly interacting with the small GTPase Rab1A in the host cell. This interaction abolished Rab1A activation by disrupting the interaction with its guanine nucleotide exchange factor (GEF), the TRAPPIII (transport protein particle III) complex. This disruption of Rab1A signaling blocked the recruitment and activation of Unc-51-like autophagy-activating kinase 1 (ULK1) and decreased phosphatidylinositol 3-phosphate biogenesis, which ultimately impeded autophagosome formation. Furthermore, SseF- or SseG-deficient bacterial strains exhibited reduced survival and growth in both mammalian cell lines and mouse infection models, and Rab1A depletion could rescue these defects. These results reveal that virulence factor-dependent inactivation of the small GTPase Rab1A represents a previously unrecognized strategy of S Typhimurium to evade autophagy and the host defense system.


Asunto(s)
Proteínas Bacterianas/metabolismo , Interacciones Huésped-Patógeno , Infecciones por Salmonella/microbiología , Salmonella typhimurium/patogenicidad , Virulencia , Proteínas de Unión al GTP rab1/fisiología , Animales , Autofagia , Proteínas Bacterianas/genética , Aparato de Golgi/metabolismo , Aparato de Golgi/microbiología , Factores de Intercambio de Guanina Nucleótido/genética , Factores de Intercambio de Guanina Nucleótido/metabolismo , Células HeLa , Humanos , Ratones , Ratones Noqueados , Salmonella typhimurium/crecimiento & desarrollo , Factores de Virulencia/genética , Factores de Virulencia/metabolismo
15.
J Am Chem Soc ; 141(19): 7758-7764, 2019 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-30844265

RESUMEN

Z-DNA, a left-handed duplex, has been shown to form in vivo and regulate expression of the corresponding gene. However, its biological roles have not been satisfactorily understood, mainly because Z-DNA is easily converted to the thermodynamically favorable B-DNA. Here we present a new idea to form stable Z-DNA under normal physiological conditions and achieve detailed analysis on its fundamental features. Simply by mixing two complementary minicircles of single-stranded DNA with no chemical modification, the hybridization spontaneously induces topological constraint which twines one-half of the double-stranded DNA into stable Z-DNA. The formation of Z-conformation with high stability has been proved by using circular dichroism spectroscopy, Z-DNA-specific antibody binding assay, nuclease digestion, etc. Even at a concentration of MgCl2 as low as 0.5 mM, Z-DNA was successfully obtained, avoiding the use of high salt conditions, limited sequences, ancillary additives, or chemical modifications, criteria which have hampered Z-DNA research. The resultant Z-DNA has the potential to be used as a canonical standard sample in Z-DNA research. By using this approach, further developments of Z-DNA science and its applications become highly promising.


Asunto(s)
ADN de Forma Z/química , ADN de Forma Z/genética , Secuencia de Bases , ADN Forma B/química , ADN Forma B/genética , Termodinámica
16.
Molecules ; 20(10): 19291-309, 2015 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-26512632

RESUMEN

Compound K (CK), a highly active and bioavailable derivative obtained from protopanaxadiol ginsenosides, displays a wide variety of pharmacological properties, especially antitumor activity. However, the inadequacy of natural sources limits its application in the pharmaceutical industry. In this study, we firstly discovered that Cordyceps sinensis was a potent biocatalyst for the biotransformation of ginsenoside Rb1 into CK. After a series of investigations on the biotransformation parameters, an optimal composition of the biotransformation culture was found to be lactose, soybean powder and MgSO4 without controlling the pH. Also, an optimum temperature of 30 °C for the biotransformation process was suggested in a range of 25 °C-50 °C. Then, a biotransformation pathway of Rb1→Rd→F2→CK was established using high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS). Our results demonstrated that the molar bioconversion rate of Rb1 to CK was more than 82% and the purity of CK produced by C. sinensis under the optimized conditions was more than 91%. In conclusion, the combination of C. sinensis and the optimized conditions is applicable for the industrial preparation of CK for medicinal purposes.


Asunto(s)
Cordyceps/metabolismo , Ginsenósidos/biosíntesis , Ginsenósidos/metabolismo , Micelio/metabolismo , Biotransformación , Cordyceps/crecimiento & desarrollo , Medios de Cultivo , Ginsenósidos/aislamiento & purificación , Concentración de Iones de Hidrógeno , Hidrólisis , Redes y Vías Metabólicas , Micelio/crecimiento & desarrollo
17.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 40(7): 748-53, 2015 Jul.
Artículo en Zh | MEDLINE | ID: mdl-26267687

RESUMEN

OBJECTIVE: To identify the screening time and prepare a screening schedule for outpatients with acute fatty liver of pregnancy (AFLP).
 METHODS: AFLP patients who admitted to Xiangya Hospital and the Second Xiangya Hospital, Central South University, Hunan, China between November, 2006 and December, 2013, were retrospectively studied. The diagnosis of 78 AFLP patients met the domestic clinical and laboratory criteria and the Swansea criteria. Clinical and laboratory data obtained on admission were used for analysis. Contrastive analysis was conducted within our data and other large medical centers or general hospitals. 
 RESULTS: The difference between domestic clinical and laboratory criteria and Swansea criteria in diagnosing AFLP patients in the 2 hospitals mentioned above was significant (P<0.05). The maternal mortality was 14.10% (11/78) and perinatal mortality was 17.95 % (14/78). The mean gestational age at delivery was 35.6 weeks. Based on the clinical and laboratory data, more than 85% of AFLP patients showed abnormal levels of transaminase, bilirubin, and white blood cells, as well as coagulation dysfunction. Gastrointestinal symptoms, such as abdominal pain and vomiting, jaundice, renal impairment and ascites or bright liver on ultrasound scan, were showed in 50%-85% of AFLP patients. Less than 50% of patients suffered from low blood sugar, high blood ammonia or hepatic encephalopathy.
 CONCLUSION: The 34th gestation week might be important time for screening AFLP outpatients. Gastrointestinal symptoms, blood routine, liver function, and coagulant function tests are recommended as the first grade screening indicators. Renal function, blood sugar test, and abdominal ultrasound could be the second grade screening indicators for AFLP outpatients.


Asunto(s)
Hígado Graso/diagnóstico , Tamizaje Masivo/métodos , Complicaciones del Embarazo/diagnóstico , China , Femenino , Edad Gestacional , Humanos , Pacientes Ambulatorios , Embarazo , Estudios Retrospectivos , Factores de Tiempo
18.
Langmuir ; 30(24): 7168-76, 2014 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-24920223

RESUMEN

Microgel particles of cross-linked poly(NIPAM-co-acrylic acid) with different acrylic acid contents are investigated in solution and in the adsorbed state. As a substrate, silicon with a poly(allylamine hydrochloride) (PAH) coating is used. The temperature dependence of the deswelling of the microgel particles was probed with atomic force microscopy (AFM). The inner structure of the adsorbed microgel particles was detected with grazing incidence small angle neutron scattering (GISANS). Small angle neutron scattering (SANS) on corresponding microgel suspensions was performed for comparison. Whereas the correlation length of the polymer network shows a divergence in the bulk samples, in the adsorbed microgel particles it remains unchanged over the entire temperature range. In addition, GISANS indicates changes in the particles along the surface normal. This suggests that the presence of a solid surface suppresses the divergence of internal fluctuations in the adsorbed microgels close to the volume phase transition.

19.
Artículo en Inglés | MEDLINE | ID: mdl-38954566

RESUMEN

Estimating blood pressure (BP) values from physiological signals (e.g., photoplethysmogram (PPG)) using deep learning models has recently received increased attention, yet challenges remain in terms of models' generalizability. Here, we propose taking a new approach by framing the problem as tracking the "changes" in BP over an interval, rather than directly estimating its value. Indeed, continuous monitoring of acute changes in BP holds promising implications for clinical applications (e.g., hypertensive emergencies). As a solution, we first present a self-contrastive masking (SCM) model, designed to perform pair-wise temporal comparisons within the input signal. We then leverage the proposed SCM model to introduce ΔBPNet, a model trained to detect elevations/drops greater than a given threshold in the systolic blood pressure (SBP) over an interval, from PPG. Using data from PulseDB, 1) we evaluate the performance of ΔBP-Net on previously unseen subjects, 2) we test ΔBP-Net's ability to generalize across domains by training and testing on different datasets, and 3) we compare the performance of ΔBP-Net with existing PPG-based BP-estimation models in detecting over-threshold SBP changes. Formulating the problem as a binary classification task (i.e., over-threshold SBP elevation/ drop or not), ΔBP-Net achieves 75.97%/73.19% accuracy on data from subjects unseen during training. Additionally, the proposed ΔBP-Net outperforms ΔSBP estimations derived from existing PPG-based BP-estimation methods. Overall, by shifting the focus from estimating the value of SBP to detecting overthreshold "changes" in SBP, this work introduces a new potential for using PPG in clinical BP monitoring, and takes a step forward in addressing the challenges related to the generalizability of PPG-based BP-estimation models.

20.
Foods ; 13(9)2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38731716

RESUMEN

It is now widely recognized that gut microbiota plays a critical role not only in the development and progression of diseases, but also in its susceptibility to dietary patterns, food composition, and nutritional intake. In this comprehensive review, we have compiled the latest findings on the effects of food nutrients and bioactive compounds on the gut microbiota. The research indicates that certain components, such as unsaturated fatty acids, dietary fiber, and protein have a significant impact on the composition of bile salts and short-chain fatty acids through catabolic processes, thereby influencing the gut microbiota. Additionally, these compounds also have an effect on the ratio of Firmicutes to Bacteroides, as well as the abundance of specific species like Akkermansia muciniphila. The gut microbiota has been found to play a role in altering the absorption and metabolism of nutrients, bioactive compounds, and drugs, adding another layer of complexity to the interaction between food and gut microbiota, which often requires long-term adaptation to yield substantial outcomes. In conclusion, understanding the relationship between food compounds and gut microbiota can offer valuable insights into the potential therapeutic applications of food and dietary interventions in various diseases and health conditions.

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