RESUMEN
Melia azedarach is a species of enormous value of pharmaceutical industries. Although the chloroplast genome of M. azedarach has been explored, the information of mitochondrial genome (Mt genome) remains surprisingly limited. In this study, we used a hybrid assembly strategy of BGI short-reads and Nanopore long-reads to assemble the Mt genome of M. azedarach. The Mt genome of M. azedarach is characterized by two circular chromosomes with 350,142 bp and 290,387 bp in length, respectively, which encodes 35 protein-coding genes (PCGs), 23 tRNA genes, and 3 rRNA genes. A pair of direct repeats (R1 and R2) were associated with genome recombination, resulting in two conformations based on the Sanger sequencing and Oxford Nanopore sequencing. Comparative analysis identified 19 homologous fragments between Mt and chloroplast genome, with the longest fragment of 12,142 bp. The phylogenetic analysis based on PCGs were consist with the latest classification of the Angiosperm Phylogeny Group. Notably, a total of 356 potential RNA editing sites were predicted based on 35 PCGs, and the editing events lead to the formation of the stop codon in the rps10 gene and the start codons in the nad4L and atp9 genes, which were verified by PCR amplification and Sanger sequencing. Taken together, the exploration of M. azedarach gap-free Mt genome provides a new insight into the evolution research and complex mitogenome architecture.
Asunto(s)
Genoma Mitocondrial , Filogenia , Recombinación Genética , Secuencias Repetitivas de Ácidos Nucleicos/genética , Genoma del Cloroplasto , Genoma de Planta , Edición de ARNRESUMEN
Using a three-dimensional classical ensemble model, nonsequential double ionization (NSDI) of Ar atoms by counter-rotating two-color elliptical polarization (TCEP) fields is investigated. The major axes of the two elliptical fields are aligned in different directions. The relative alignment of the two elliptical fields strongly affects the waveform of the combined electric field and the ultrafast dynamics of NSDI in TCEP fields. Numerical results show that the correlated electron momentum distributions in the x direction evolve from a V-shaped structure near the axis to a distribution concentrated on the diagonal with the angle between the two elliptical major axes increasing. The asymmetry of the energy sharing between the two electrons during recollision results in the V-shaped structure in the correlated momentum spectrum. Back analysis indicates that the recollision times of a part of the trajectories move from the peak to the valley of the combined electric field with the angle between the two elliptical major axes increasing. Therefore, for the case of a larger angle between the two elliptical major axes, the electrons experience a longer time to escape away from the vicinity of the parent ion and thus the stronger Coulomb effect from the parent ion makes the momentum difference between two electrons small, which results in a distribution concentrated on the diagonal. This provides an effective avenue to control the electron ultrafast dynamics in NSDI.
RESUMEN
We experimentally study two-body Coulomb explosions of CO2, O2, and CH3Cl molecules in intense femtosecond laser pulses. We observe an obvious variation in the ionic angular distribution of the fragments with respect to the kinetic energy releases (KERs). Using a classical model based on ab initio potential energy curves, we find that the dependence of the ionic angular distribution on the KER is relevant to the fact that the accurate potential energy deviates significantly from the value determined by applying the Coulomb interaction approximation at a relatively small internuclear distance of the molecule. We show that the KER-dependent ionic angular distribution provides an effective way to determine the critical internuclear distance at which the Coulomb interaction approximation holds or breaks down without relying on the knowledge of the accurate potential energy curves.
RESUMEN
BACKGROUND: Allyl isothiocyanate (AITC) is a natural product with high volatility that is used as a biofumigant to alleviate soil-borne plant diseases, and problems such as root knot nematodes (RKNs) that necessitate continuous cropping. However, little research has assessed the effects of AITC fumigation on medicinal plants. RESULTS: AITC significantly reduced the population of RKNs in soil (p < 0.0001) and showed an excellent RKN disease control effect within 6 months after sowing Panax notoginseng (p < 0.0001). The seedling survival rate of 2-year-old P. notoginseng was approximately 1.7-fold higher after soil treatment with AITC (p = 0.1008). 16S rRNA sequencing indicated that the AITC treatment affected bacterial richness rather than diversity in consecutively cultivated (CC) soil. Furthermore, biomarkers with statistical differences between AITC-treated and untreated CC soil showed that Pirellulales (order), Pirellulaceae (family), Pseudomonadaceae (family), and Pseudomonas (genus) played important roles in the AITC-treated group. In addition, the microbiome functional phenotypes predicted using the BugBase tool suggested that AITC treatment is more conducive to improving CC soil through changes in the bacterial community structure. Crucially, our research also suggested that AITC soil treatment significantly increases soil organic matter (p = 0.0055), total nitrogen (p = 0.0054), and available potassium (p = 0.0373), which promotes the survival of a succeeding medicinal plant (Polygonatum kingianum). CONCLUSION: AITC is an ecologically friendly soil treatment that affects the top 10 bacterial richness but not diversity. It could also provide a basis for a useful agricultural soil management measure to alleviate soil sickness.
Asunto(s)
Plantas Medicinales , Suelo , Suelo/química , Fumigación , ARN Ribosómico 16S/genética , Microbiología del Suelo , Bacterias/genéticaRESUMEN
BACKGROUND: Cases of multiple cerebral aneurysms are rare. In this case report, we describe a male patient with multiple, enlarging, and ruptured aneurysms. The two aneurysms were believed to be dissecting aneurysms. CASE DESCRIPTION: A 47-year-old man presented with left limb paralysis. Magnetic resonance imaging revealed a cerebral infarction. Digital subtraction angiography (DSA) identified an aneurysm and occlusion in the right middle cerebral artery (MCA). The MCA aneurysm was remarkably enlarged on the eighth day after cerebral ischemia and was treated using endovascular techniques. Two weeks after the endovascular treatment, the patient experienced a severe headache and became comatose, and a subarachnoid re-hemorrhage was confirmed. The fourth DSA revealed an enlarging dissecting aneurysm in the posterior cerebral artery. The patient died without further treatment. CONCLUSION: Some dissecting aneurysms rapidly enlarge and rupture.
Asunto(s)
Aneurisma Roto , Disección Aórtica , Hemorragia Subaracnoidea , Humanos , Masculino , Persona de Mediana Edad , Hemorragia Subaracnoidea/diagnóstico por imagen , Hemorragia Subaracnoidea/etiología , Aneurisma Roto/diagnóstico por imagen , Angiografía de Substracción Digital , Disección Aórtica/complicaciones , Disección Aórtica/diagnóstico por imagen , Infarto CerebralRESUMEN
Wasabi (Eutrema japonicum) is a root vegetable that is cultivated at large scales in southwestern China. In November 2021, approximately 40% of plants in a forested plantation in Dadishui, Yunnan Province, China (25.47°N, 103.22°E), showed leaf spot symptoms. The early symptoms were small black spots that gradually expanded into irregular brown to black lesions (0.5-1.5 cm), which were restricted by leaf veins. Yellow halos were observed at the outer edges of necrotic lesions. To identify the causal agent, we collected 20 diseased leaves and obtained fungal isolates from symptomatic leaf tissues. Following surface sterilization with 75% ethanol for 30 s, the tissues were cultured on potato dextrose agar (PDA) plates and incubated at 25°C under a 12 h light/12 h dark light cycle. After 7 days of incubation, a total of 12 isolates were obtained through single-spore culture. All isolates had similar colony morphology, and produced fluffy white mycelia and yellow pigment after 1 week of PDA culture at 25°C, and blackish- brown mycelium, tan pigment, and conidia after 2 weeks. The conidia were hyaline and cylindrical, with an average size of 4.6 µm × 2.2 µm. These morphological characteristics similar to the description of Leptosphaeria biglobosa (Shoemaker et. al, 2001) and Leptosphaeria maculans (Vincenot et al. 2008). Genomic DNA was extracted from mycelium of isolate SK-1, which was harvested from 10-day-old PDA culture using a FAST plant genomic DNA Extraction Kit (Biomed, China), following the manufacturer's instructions. The species-specific primers LbigF, LmacF, and LmacR (Liu et al. 2006) were used for identification via polymerase chain reaction (PCR). A 444-bp fragment characteristic of L. biglobosa 'brassicae' (Lbb), and a 330-bp of L. maculans 'brassicae' (Lmb) were amplified, respectively. Internal transcribed spacer (ITS) sequences (592 bp), part of the 5' end of beta-tubulin (968 bp), and actin (899 bp) were also amplified using the primers ITS1/ITS4, BT1/BT2, and ACTF/ACTR (Vincenot et al. 2008), respectively. PCR was performed in a volume of 25 µL containing 12.5 µL 2 × T5 Super PCR Mix (Tsingke Biotech, Beijing, China), 1 µL 10 µM primer (Tsingke Biotech), 1 µL DNA template, and an aliquot of sterile water to attain the total volume. The thermal cycler settings were 5 min at 98°C; 35 cycles of 10 s at 98°C, 10 s at 58°C, and 30 s at 72°C; and extension for 2 min at 72°C. The ITS sequence of isolate SK-1 (GenBank accession no. OQ216838), the partial ß-tubulin gene sequence (OQ241183), and the actin gene sequence (OQ241184) indicated 100% query cover and 100% identity with L. biglobosa (DQ458906), Lbb strain B3.6 (AY748995), and Lbb strain 2379-4 (AY748949), respectively. Phylogenetic analysis (King et al. 2022) also identified of isolate SK-1 as Lbb. To determinate its pathogenicity, isolate SK-1 was grown on PDA incubated at 28°C for 2 weeks, and conidial suspensions were prepared at a concentration of 106 conidia/mL. Then, 15 leaves of 4-month-old E. japonicum seedlings were needle-wounded on the front and inoculated by syringe injection of 10 µL of the appropriate conidial suspension. We used 10 µL of the sterilized distilled water as the control under forest growth conditions. All inoculation sites were covered with cotton strips and moistened with 1.0 mL sterile water to maintain humidity. After 12 days of incubation, the leaves developed symptoms similar to those observed in the field, and the fungus was reisolated from diseased leaves, whereas the controls remained healthy. Based on these results, we identified L. biglobosa 'brassicae' as the causal agent of leaf spot on E. japonicum in China. This fungus has been reported to cause blackleg in many Brassica crops in China such as Brassica napus (Fitt et al. 2006), Brassica oleracea (Zhou et al. 2019), B. juncea var. tumida (Deng et al. 2020), Brassica rapa subsp. pekinensis (Yu et al. 2021). To the best of our knowledge, this is the first report of L. biglobosa causing leaf spots in E. japonicum in China. Our data provide a basis for disease management in E. japonicum production in China.
RESUMEN
Nonsequential double ionization (NSDI) of Argon atoms by counter-rotating two-color elliptically polarized (TCEP) fields is investigated with a three-dimensional classical ensemble model. Different from two-color circularly polarized fields, the combined electric field in TCEP pulses has no symmetry and the ionized electron mainly returns to the parent ion from one direction. Thus the electron momentum distributions show strong asymmetry. Numerical results show with the increase of the relative phase between the two elliptical fields, the return angle of the travelling electron, i.e., the angle between the return direction of the electron and the +x direction, gradually decreases. Moreover, the dominant behavior of electron pairs evolves from anti-correlation to correlation with the relative phase increasing. This provides an avenue to control the return angle and electron correlation behavior by the relative phase between the two elliptical fields.
RESUMEN
With a three-dimensional classical ensemble method, we theoretically investigated the correlated electron dynamics in nonsequential double ionization (NSDI) driven by the spatially inhomogeneous fields. Our results show that NSDI in the spatially inhomogeneous fields is more efficient than that in the spatially homogeneous fields at the low laser intensities, while at the high intensities NSDI is suppressed as compared to the homogeneous fields. More interestingly, our results show that the electron pairs from NSDI exhibit a much stronger angular correlation in the spatially inhomogeneous fields, especially at the higher laser intensities. The correlated electron momentum distribution shows that in the inhomogeneous fields the electron pairs favor to achieve the same final momentum, and the distributions dominantly are clustered in the more compact regions. It is shown that the electron's momentum is focused by the inhomogeneous fields. The underlying dynamics is revealed by back-tracing the classical trajectories.
RESUMEN
BACKGROUND: Oxidative stress and neurocyte apoptosis are crucial pathophysiological process in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Geniposide (GNP) has been reported to exert neuroprotective effects by reducing oxidative injury and neurocyte apoptosis. However, the effect of GNP has not been clarified in EBI after SAH. The study was performed to evaluate the neuroprotective effects and mechanisms of GNP in EBI after SAH. METHODS AND RESULTS: A total of 60 male Wistar rats were randomly divided into five groups. The prechiasmatic cistern SAH model was used in this study. SAH grade was evaluated using a grading system. Neurological function was evaluated using the Garcia scores. Brain edema was measured by the wet-dry method. Blood-brain barrier (BBB) permeability was measured by the extravasation of Evans Blue (EB). The neurocyte apoptosis was observed using TUNEL assay. The levels of malondialdehyde (MDA) and superoxide dismutase (SOD), as well as the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), hemeoxygenase-1 (HO-1), glutathione S-transferase (GST) and quinone oxidoreductase-1 (NQO-1) were performed. The results showed that GNP reduced brain edema, attenuated BBB permeability, inhibited neurocyte apoptosis and improved neurological function. Moreover, GNP also decreased the levels of ROS and MDA, elevated Nrf2 expression in the temporal cortex and up-regulated the expression of NQO-1, HO-1 and GST after SAH. CONCLUSIONS: GNP could ameliorate oxidative stress and neurocyte apoptosis to exert neuroprotective effects by Nrf2 pathway.
Asunto(s)
Edema Encefálico , Lesiones Encefálicas , Fármacos Neuroprotectores , Hemorragia Subaracnoidea , Animales , Apoptosis , Encéfalo/metabolismo , Edema Encefálico/tratamiento farmacológico , Edema Encefálico/metabolismo , Glutatión Transferasa/metabolismo , Iridoides , Masculino , Factor 2 Relacionado con NF-E2/metabolismo , Fármacos Neuroprotectores/metabolismo , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo , Ratas , Ratas Sprague-Dawley , Ratas Wistar , Hemorragia Subaracnoidea/tratamiento farmacológico , Hemorragia Subaracnoidea/metabolismoRESUMEN
Estimating whether to treat the rupture risk of small intracranial aneurysms (IAs) with size ≤ 7 mm in diameter is difficult but crucial. We aimed to construct and externally validate a convenient machine learning (ML) model for assessing the rupture risk of small IAs. One thousand four patients with small IAs recruited from two hospitals were included in our retrospective research. The patients at hospital 1 were stratified into training (70%) and internal validation set (30%) randomly, and the patients at hospital 2 were used for external validation. We selected predictive features using the least absolute shrinkage and selection operator (LASSO) method and constructed five ML models applying diverse algorithms including random forest classifier (RFC), categorical boosting (CatBoost), support vector machine (SVM) with linear kernel, light gradient boosting machine (LightGBM), and extreme gradient boosting (XGBoost). The Shapley Additive Explanations (SHAP) analysis provided interpretation for the best ML model. The training, internal, and external validation cohorts included 658, 282, and 64 IAs, respectively. The best performance was presented by SVM as AUC of 0.817 in the internal [95% confidence interval (CI), 0.769-0.866] and 0.893 in the external (95% CI, 0.808-0.979) validation cohorts, which overperformed compared with the PHASES score significantly (all P < 0.001). SHAP analysis showed maximum size, location, and irregular shape were the top three important features to predict rupture. Our SVM model based on readily accessible features presented satisfying ability of discrimination in predicting the rupture IAs with small size. Morphological parameters made important contributions to prediction result.
Asunto(s)
Aneurisma Intracraneal , Humanos , Aneurisma Intracraneal/complicaciones , Aneurisma Intracraneal/diagnóstico por imagen , Estudios Retrospectivos , Aprendizaje Automático , Máquina de Vectores de Soporte , AlgoritmosRESUMEN
Electron correlation in nonsequential double ionization (NSDI) of molecules by counter-rotating two-color circularly polarized (TCCP) fields is investigated with a three-dimensional classical ensemble model. Numerical results indicate that the two electrons from NSDI of molecules in counter-rotating TCCP fields show strong angular correlation and the angular correlation behavior sensitively depends on the internuclear distance. With the internuclear distance increasing, the dominant behavior of electron pairs evolves from correlation to anti-correlation. It leaves a clear imprint on the ion momentum distributions, which exhibit an inverted Y-shape distribution at a small internuclear distance and a triangle-shape distribution at a large internuclear distance. Back analysis indicates that the asymmetric electron energy sharing by soft recollision and longer time delay of double ionization are responsible for more anti-correlated emissions at large internuclear distances.
RESUMEN
Understanding biogeographic patterns of community assemblages is a core objective in ecology, but for soil communities these patterns are poorly understood. To understand the spatial patterns and underlying mechanisms of ß-diversity in soil communities, we investigated the ß-diversity of soil nematode communities along a 3,200-km transect across semi-arid and arid grasslands. Spatial turnover and nested-resultant are the two fundamental components of ß-diversity, which have been attributed to various processes of community assembly. We calculated the spatial turnover and nested-resultant components of soil nematode ß-diversity based on the ß-partitioning framework. Distance matrices for the dissimilarity of soil nematode communities were computed using the 'Sørensen' method. We fitted negative exponential models to compare the distance decay patterns in nematode community similarity with geographic distance and plant community distance in three vegetation types (desert, desert steppe and typical steppe) and along the whole transect. Variation partitioning was used to distinguish the contribution of geographic distance and environmental variables to ß-diversity and the partitioned components. Geographic distance and environmental filtering jointly drove the ß-diversity patterns of nematode community, but environmental filtering explained more of the variation in ß-diversity in the desert and typical steppe, whereas geographic distance was important in the desert steppe. Nematode community assembly was explained more by the spatial turnover component than by the nested-resultant component. For nematode feeding groups, the ß-diversity in different vegetation types increased with geographic distance and plant community distance, but the nested-resultant component of bacterial feeders in the desert ecosystem decreased with geographic distance and plant community distance. Our findings show that spatial variation in soil nematode communities is regulated by environmental processes at the vegetation type scale, while spatial processes mainly work on the regional scale, and emphasize that the spatial patterns and drivers of nematode ß-diversity differ among trophic levels. Our study provides insight into the ecological processes that maintain soil biodiversity and biogeographic patterns of soil community assemblage at large spatial scales.
Asunto(s)
Nematodos , Suelo , Animales , Biodiversidad , Ecosistema , PraderaRESUMEN
With a three-dimensional classical ensemble method, we theoretically investigated frustrated double ionization (FDI) of atoms with different laser wavelengths. Our results show that FDI can be more efficiently generated with shorter wavelengths and lower laser intensities. With proper laser parameters more FDI events can be generated than normal double ionization events. The physical condition under which FDI events happen is identified and explained. The energy distribution of the FDI products - atomic ions in highly excited states - shows a sensitive wavelength dependency.
RESUMEN
BACKGROUND: Long non-coding RNAs (LncRNAs) have been reported to play important roles in the pathogenesis and development of many diseases, including cerebral ischemia and reperfusion (I/R) injury. In this study, we aimed to investigate the role of LncRNA-Potassium Voltage-Gated Channel Subfamily Q Member 1 opposite strand/antisense transcript 1 (KCNQ1OT1) in cerebral I/R induced neuronal injury, and its underlying mechanisms. METHODS: Primary mouse cerebral cortical neurons treated with oxygen-glucose deprivation and reoxygenation (OGD/R) in vitro and mice subjected to middle cerebral artery occlusion (MCAO) and reperfusion were used to mimic cerebral I/R injury. Small inference RNA (siRNA) was used to knockdown KCNQ1OT1 or microRNA-153-3p (miR-153-3p). Dual-luciferase assay was performed to detect the interaction between KCNQ1OT1 and miR-153-3p and interaction between miR-153-3p and Fork head box O3a (Foxo3). Flow cytometry analysis was performed to detect neuronal apoptosis. qRT-PCR and Western blotting were performed to detect RNA and protein expressions. RESULTS: KCNQ1OT1 and Foxo3 expressions were significantly increased in neurons subjected to I/R injury in vitro and in vivo, and miR-153-3p expression were significantly decreased. Knockdown of KCNQ1OT1 or overexpression of miR-153-3p weakened OGD/R-induced neuronal injury and regulated Foxo3 expressions. Dual-luciferase analysis showed that KCNQ1OT1 directly interacted with miR-153-3p and Foxo3 is a direct target of miR-153-3p. CONCLUSIONS: Our results indicate that LncRNA-KCNQ1OT1 promotes OGD/R-induced neuronal injury at least partially through acting as a competing endogenous RNA (ceRNA) for miR-153-3p to regulate Foxo3a expression, suggesting LncRNA-KCNQ1OT1 as a potential therapeutic target for cerebral I/R injury.
Asunto(s)
Corteza Cerebral/metabolismo , Proteína Forkhead Box O3/metabolismo , Infarto de la Arteria Cerebral Media/terapia , MicroARNs/metabolismo , Neuronas/metabolismo , ARN Largo no Codificante/metabolismo , Daño por Reperfusión/metabolismo , Reperfusión/efectos adversos , Animales , Hipoxia de la Célula , Células Cultivadas , Corteza Cerebral/patología , Proteína Forkhead Box O3/genética , Regulación de la Expresión Génica , Glucosa/deficiencia , Infarto de la Arteria Cerebral Media/genética , Infarto de la Arteria Cerebral Media/metabolismo , Infarto de la Arteria Cerebral Media/patología , Masculino , Ratones Endogámicos C57BL , MicroARNs/genética , Neuronas/patología , ARN Largo no Codificante/genética , Daño por Reperfusión/genética , Daño por Reperfusión/patología , Transducción de SeñalRESUMEN
This study evaluated the preventative effects of metformin (Met) on glucocorticoid (GC)-induced osteoporosis in a rat model, compared with alendronate (Aln). Twenty-eight 3-month-old female Sprague-Dawley rats were randomly assigned into four groups: normal control (Ctr), methylprednisolone (MP, 13 mg/kg/day, sc, 5 days per week), MP plus Aln orally (1 mg/kg/day), and MP plus Met orally (200 mg/kg/day). After 9 weeks, serum bone metabolic biochemistry, bone densitometry and histomorphometry were performed. The GC-induced osteoporosis model was characterized by decreased osteocalcin, increased tartrate-resistant acid phosphatase-5b (TRAP-5b), and decreased bone mineral density (BMD) in the femur and fifth lumbar vertebra (L5). Histomorphometrically, MP significantly decreased trabecular bone volume, decreased bone formation and increased bone resorption in proximal metaphysis, compared with the controls. Aln and Met increased the BMDs of femur (0.305 ± 0.011 vs. 0.280 ± 0.012, P < 0.05; 0.304 ± 0.019 vs. 0.280 ± 0.012, P < 0.05) and L5 (0.399 ± 0.029 vs. 0.358 ± 0.022, P < 0.05; 0.397 ± 0.022 vs. 0.358 ± 0.022, P < 0.05), compared with the model group. Met increased osteocalcin and decreased TRAP-5b, but Aln only decreased TRAP-5b, compared with model group. In histomorphometry of tibial proximal metaphysis, Aln and Met increased trabecular bone volume (39.21 ± 2.46 vs. 30.98 ± 5.83, P < 0.05; 38.97 ± 5.56 vs. 30.98 ± 5.83, P < 0.05), while Met increased the bone formation dynamic parameters and decreased bone resorption dynamic parameters, but Aln just decreased bone resorption dynamic parameters, compared with model group significantly. These findings suggest that metformin prevents GC-induced bone loss by suppressing bone resorption and stimulating bone formation in trabecular bone. The action mode of metformin was different from alendronate, which only suppressed bone resorption.
Asunto(s)
Glucocorticoides/efectos adversos , Metformina/uso terapéutico , Osteoporosis/inducido químicamente , Osteoporosis/tratamiento farmacológico , Sustancias Protectoras/uso terapéutico , Alendronato/farmacología , Animales , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Densidad Ósea/efectos de los fármacos , Femenino , Fémur/efectos de los fármacos , Fémur/fisiología , Fémur/fisiopatología , Lípidos/sangre , Vértebras Lumbares/efectos de los fármacos , Vértebras Lumbares/patología , Vértebras Lumbares/fisiopatología , Metformina/farmacología , Metilprednisolona/farmacología , Osteocalcina/sangre , Osteoporosis/sangre , Osteoporosis/fisiopatología , Sustancias Protectoras/farmacología , Ratas Sprague-Dawley , Fosfatasa Ácida Tartratorresistente/sangreRESUMEN
BACKGROUND/AIMS: Assistance with tumor-associated vascularization is needed for the growth and invasion of non-small cell lung cancer (NSCLC). Recently, it was shown that placental growth factor (PLGF) expressed by NSCLC cells had a critical role in promoting the metastasis of NSCLC cells. However, the underlying molecular mechanisms remain elusive. METHODS: Here, we first established a NSCLC model in mice that allows us not only to isolate tumor cells from non-tumor cells in the tumor, but also to trace tumor cells in living animals. Levels of PLGF, its unique receptor Flt-1, as well as transforming growth factor ß1 (TGFß1) was examined in tumor cells and tumor-associated macrophages (TAM) by RT-qPCR. A transwell well co-culture system and HUVEC assay were applied to study the crosstalk between NSCLC cells and TAM. RESULTS: NSCLC cells produced and secreted PLGF to signal to tumor-associated macrophages (TAM) through surface expression of Flt-1 on macrophages. In a transwell co-culture system, PLGF secreted by NSCLC cells triggered macrophage polarization to a TAM subtype that promote growth of NSCLC cells. Moreover, polarized TAM seemed to secrete TGFß1 to enhance the growth of endothelial cells in a HUVEC assay. CONCLUSION: The cross-talk between TAM and NSCLC cells via PLGF/Flt-1 and TGFß receptor signaling may promote the growth and vascularization of NSCLC.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Comunicación Celular , Neoplasias Pulmonares , Macrófagos , Proteínas de Neoplasias/metabolismo , Neovascularización Patológica , Factor de Crecimiento Placentario/metabolismo , Células A549 , Carcinoma de Pulmón de Células no Pequeñas/irrigación sanguínea , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Células Endoteliales de la Vena Umbilical Humana , Humanos , Neoplasias Pulmonares/irrigación sanguínea , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Macrófagos/metabolismo , Macrófagos/patología , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patologíaRESUMEN
Temozolomide (TMZ) is currently the first-line drug used for clinical postoperative or non-surgical chemotherapy for glioma, but acquired and intrinsic resistance to TMZ limits its application. The anti-proliferative effect of formononetin on human glioma cells had been confirmed. To improve therapeutic effects of TMZ, we studied the effect of formononetin in combination with TMZ on C6 glioma cells. The anti-proliferative effect of C6 cells was tested by 3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT) assay. The synergy was evaluated by Chou-Talalay method. Morphological changes were observed by hematoxylin-eosin (HE) staining. The effect of formononetin in combination with TMZ on apoptosis of C6 cells was investigated by flow cytometry. The effect of formononetin in combination with TMZ on migration of cells was investigated by wound healing assay and transwell assay. The expression of proteins related to apoptosis and migration were detected by Western blot. These results showed that formononetin or TMZ alone could inhibit the growth of C6 cells in dose-dependent manner and formononetin in combination with TMZ had synergy effect on C6 cells. Further changes in cell morphology could be observed in drug combination by HE staining. Drug combination enhanced the expression of Bax, Cleaved Caspase-3, Cleaved Caspase-9, decreased the expression of Bcl-2, and promoted tumor cells apoptosis. In addition, the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) were down-regulated via drug combination which resulted into inhibiting migration of C6 cell. In conclusion, formononetin in combination with TMZ can play a synergistic role in anti-C6 cells, the mechanisms of synergy depended on multiple pathways.
Asunto(s)
Antineoplásicos/farmacología , Neoplasias Encefálicas/tratamiento farmacológico , Glioma/tratamiento farmacológico , Isoflavonas/farmacología , Temozolomida/farmacología , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Sinergismo Farmacológico , RatasRESUMEN
Using a classical ensemble method, we revisit the topic of recollision and nonsequential double ionization with elliptically polarized laser fields. We focus on how the recollision mechanism transitions from short trajectories with linear polarization to long trajectories with elliptical polarization. We propose how this transition can be observed by meansuring the carrier-envelop-phase dependence of the correlated electron momentum spectra using currently available few-cycle laser pulses.
RESUMEN
To solve the fundamental dilemma in data storage applications, it is crucial to manipulate the magnetic anisotropy energy (MAE). Herein, using first-principles calculations, we predict that the system of double-vacancy graphene decorated by iridium atoms possesses high stability, giant MAE, perpendicular-anisotropy and long-range ferromagnetic coupling. More importantly, the amplitude of MAE can be manipulated by electric fields. This is due to the change in the occupation number of Ir-5d orbitals. The present hybrid system could be a high-performance nanoscale information storage device with ultralow energy consumption.
RESUMEN
Changes in ambient temperature profoundly affect plant growth and performance. Therefore, the molecular basis of plant acclimation to temperature fluctuation is of great interest. In this study, we discovered that GLYCINE-RICH RNA-BINDING PROTEIN 7 (GRP7) contributes to cold and heat tolerance in Arabidopsis thaliana. We found that exposure to a warm temperature rapidly induces GRP7 condensates in planta, which can be reversed by transfer to a lower temperature. Cell biology and biochemical assays revealed that GRP7 undergoes liquid-liquid phase separation (LLPS) in vivo and in vitro. LLPS of GRP7 in the cytoplasm contributes to the formation of stress granules that recruit RNA, along with the translation machinery component eukaryotic initiation factor 4E1 (eIF4E1) and the mRNA chaperones COLD SHOCK PROTEIN 1 (CSP1) and CSP3, to inhibit translation. Moreover, natural variations in GRP7 affecting the residue phosphorylated by the receptor kinase FERONIA alter its capacity to undergo LLPS and correlate with the adaptation of some Arabidopsis accessions to a wider temperature range. Taken together, our findings illustrate the role of translational control mediated by GRP7 LLPS to confer plants with temperature resilience.