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REPAT (response to pathogen) is an immune-associated gene family that plays important roles in insect immune response to pathogens. Although nine REPAT genes have been identified in Spodoptera frugiperda (Lepidoptera: Noctuidae) currently, their functions and mechanisms in the immune response to pathogens still remain unclear. Therefore, SfREPAT38, a pathogen response gene (REPAT) of S. frugiperda, was characterised and its function was analysed. The results showed that SfREPAT38 contains a signal peptide and a transcription activator MBF2 (multi-protein bridging factor 2) domain. Quantitative real-time polymerase chain reaction analysis showed that SfREPAT38 was highly expressed in the sixth-instar larvae (L6) and was the highest in expression in the midgut of L6. We found that the expression of SfREPAT38 could be activated by challenge with four microbial pathogens (Bacillus thuringiensis, Metarhizium anisopliae, Spodoptera exigua nuclearpolyhedrosis and Escherichia coli), except 12 h after E. coli infection. Furthermore, the SfREPAT38 expression levels significantly decreased at 24, 48 and 72 h after SfREPAT38 dsRNA injection or feeding. Feeding with SfREPAT38 dsRNA significantly decreased the weight gain of S. frugiperda, and continuous feeding led to the death of S. frugiperda larvae from the fourth day. Moreover, SfREPAT38 dsRNA injection resulted in a significant decrease of weight gain on the fifth day. Silencing SfREPAT38 gene down-regulated the expression levels of immune genes belonging to the Toll pathway, including SPZ, Myd88, DIF, Cactus, Pell and Toll18W. After treatment with SfREPAT38 dsRNA, S. frugiperda became extremely sensitive to the B. thuringiensis infection, and the survival rate dramatically increased, with 100% mortality by the eighth day. The weight of S. frugiperda larvae was also significantly lower than that of the control groups from the second day onwards. In addition, the genes involved in the Toll signalling pathway and a few antibacterial peptide related genes were down-regulated after treatment. These results showed that SfREPAT38 is involved in the immune response of S. frugiperda larvae through mediating Toll signalling pathway.
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Proteínas de Insectos , Larva , Transducción de Señal , Spodoptera , Animales , Spodoptera/inmunología , Spodoptera/genética , Spodoptera/crecimiento & desarrollo , Larva/crecimiento & desarrollo , Larva/inmunología , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Inmunidad Innata , Receptores Toll-Like/genética , Receptores Toll-Like/metabolismoRESUMEN
KEY MESSAGE: R2R3 MYB transcription factor GhMYB18 is involved in the defense response to cotton aphid by participating in the synthesis of salicylic acid and flavonoids. R2R3 MYB transcription factors (TFs) play crucial roles in plant growth and development as well as response to abiotic and biotic stresses. However, the mechanism of R2R3 MYB TFs in cotton response to aphid infestation remains largely unknown. Here, an R2R3 MYB transcription factor GhMYB18 was identified as a gene up-regulated from upland cotton (Gossypium hirsutum L.) under cotton aphid (Aphis gossypii Glover) infestation. GhMYB18, which has transcription activity, was localized mainly to nucleus and cell membranes. Transient overexpression of GhMYB18 in cotton activates salicylic acid (SA) and phenylpropane signaling pathways and promoted the synthesis of salicylic acid and flavonoids, which leads to enhancing the tolerance to cotton aphid feeding. In contrast, silencing of GhMYB18 increased the susceptibility of G. hirsutum to aphid. Additionally, GhMYB18 significantly promoted the activities of defense-related enzymes including catalase (CAT), peroxidase (POD), polyphenol oxidase (PPO) and phenylalanine ammonia-lyase (PAL). These results collectively suggest that GhMYB18 is involved in cotton defense response to cotton aphid attacks through regulating the synthesis of salicylic acid and flavonoids.
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Áfidos , Gossypium , Proteínas de Plantas , Animales , Áfidos/fisiología , Flavonoides/metabolismo , Gossypium/metabolismo , Ácido Salicílico/farmacología , Ácido Salicílico/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas de Plantas/metabolismoRESUMEN
Cardiovascular disease caused by atherosclerosis remains the main reason of death in the worldwide scale. Although oxidative stress plays a key role in the initiation and progression of atherosclerosis, current antioxidant drugs have limited efficacy. To resolve this problem, we constructed Nox2 siRNA-loaded nanobubbles (PNBs-siNox2) coated with platelet membranes to utilize their antioxidant stress activity and targeting effect for atherosclerosis treatment. After platelet membranes modification, the capacity of PNBs-siNox2 to target collagen, foam cells, or human umbilical vein endothelial cells (HUVECs) was significantly increased. Moreover, our study demonstrated that under ultrasonic irradiation, biomimetic nanobubbles were more effective at targeting atherosclerotic plaques and delivering genes into cells. In the present study, we provided a biomimetic gene loading strategy based on nanoplatform for noninvasive, precise and efficient therapy of atherosclerosis, which further improved the efficiency of gene transfection and effectively slowed the progression of atherosclerotic plaques when combined with ultrasound.
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Aterosclerosis , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/genética , Placa Aterosclerótica/terapia , Antioxidantes/farmacología , Biomimética , Aterosclerosis/terapia , Aterosclerosis/genética , Células Endoteliales de la Vena Umbilical HumanaRESUMEN
Side-chain liquid crystalline polymer (SCLCP) usually contains a simple and flexible homopolymer as main chain, while its effect on the self-assembly behavior is often ignored. In this work, in order to increase the structural complexity and investigate the interaction between the main chain and mesogens, perfluorinated segments are introduced into the main chain using a photoinduced Step Transfer-Addition & Radical-Termination polymerization method, producing a novel series of SCLCPs containing 4-methoxyphenyl benzoate mesogens, soft hydrocarbon spacers, and a strictly alternating perfluoroalkyl and alkyl backbone. By adjusting the length of spacers or perfluoroalkyl segments, several mesophases with complex chain packing structures are achieved. This design strategy that constructing highly ordered liquid crystalline (LC) structures from SCLCPs with precise chemical structure provides a facile way toward novel LC nanomaterials.
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OBJECTIVES: A new method based on the adhesion of SonoVue to plasmids was assessed to achieve targeted gene delivery into the vascular endothelium. METHODS: pEGFP-Salusin-α and pcDNA3.1-Salusin-α plasmids were transfected into the arterial endothelium of different rabbit groups. Western blotting was performed to analyze the expression of EGFP and salusin-α in the common carotid arteries of rabbits from different groups, and ELISA was performed to detect plasma salusin-α levels in rabbits from each group; simultaneously, blood parameters of different groups of rabbits were measured. RESULTS: Green fluorescence was observed in the right common carotid artery of rabbits transfected with pEGFP-Salusin-α, but not in the endothelial cells of not-transfected control rabbits. The expression of salusin-α in the transfected animals was higher than that in the control not-transfected animals (P < .05). In rabbits transfected with pcDNA3.1-Salusin-α plasmid, salusin-α expression was higher than in the not-transfected control animals (P < .05). However, there was no significant difference in plasma salusin-α levels between transfected animals and controls (P > .05). Blood parameters were also measured in both groups. CONCLUSIONS: Our data confirm the establishment of a new method using SonoVue for targeted gene delivery into the arterial endothelium. Our study outcomes propose a new method of intervention in atherosclerosis and a new tool for targeted gene delivery.
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Aterosclerosis , Endotelio Vascular , Animales , Células Endoteliales , Péptidos y Proteínas de Señalización Intercelular , Fosfolípidos , Conejos , Hexafluoruro de AzufreRESUMEN
As a member of the PGAMs family, PGAM2 has been proved to catalyze the reversible reaction of 3-phosphoglycerate (3-PGA) to 2-phosphoglycerate (2-PGA) in the glycolytic pathway. However, it is unclear whether PGAM2 has a role in regulating differentiation in goat intramuscular preadipocytes. Here, this study was carried to clone the open reading frame (ORF) of goat PGAM2, elucidate its molecular and expressional characteristics, and evaluate the involvement in adipogenesis of intramuscular preadipocytes. According to our findings, the cloned goat PGAM2 gene was 784 bp in full length, including 762 bp of ORF and encoding a protein of 253 amino acids. The expressional level of PGAM2 peaked at 48 hours after induced adipogenic differentiation and was highest in the skeletal muscle of triceps. Moreover, overexpression of PGAM2 transfected by its overexpression plasmid promotes lipid accumulation of goat intramuscular adipocyte as shown by Oil Red O and bodipy staining, accompanied by up-regulating the mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ) (p < 0.001), sterol regulatory element-binding protein 1 (SREBP1) (p < 0.001), CCAAT/Enhancer-binding protein α (C/EBPα) (p < 0.01) and lipoprotein lipase (LPL) (p < 0.01). Taken together, these findings indicate that PGAM2 is a positive regulator for goat intramuscular adipocytes and provide new insights into improvement intramuscular fat deposition in goat meat.
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The acoustic emission (AE) method is a popular and well-developed method for passive structural health monitoring of metallic and composite structures. The current study focuses on the analysis of one of its processes, sound source or signal propagation. This paper discusses the principle of plate wave signal sensing using piezoelectric transducers, and derives an analytical expression for the response of piezoelectric transducers under the action of stress waves, to obtain an overall mathematical model of the acoustic emission signal from generation to reception. The acoustic emission caused by fatigue crack extension is simulated by a finite element method, and the actual acoustic emission signal is simulated by a pencil lead break experiment. The results predicted by the mathematical model are compared with the experimental results and the simulation results, respectively, and show good agreement. In addition, the presence of obvious S0 mode Lamb waves is observed in the simulation results and experimental results, which further verifies the correctness of the analytical model prediction.
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Acústica , Sonido , Modelos Teóricos , TransductoresRESUMEN
BACKGROUND: The relationship between sleep duration and anthropometric indices are still unclear. This study aimed to explore the association between sleep duration and body mass index (BMI), percentage of body fat (PBF) and visceral fat area (VFA) among Chinese adults, further to explore gender difference in it. METHODS: We analyzed part of the baseline data of a cohort study among adult attendees at two health-screening centers in China. Sleep duration was self-reported and categorized into short (< 7 h/day), optimal (7-9 h/day) and long sleep (≥ 9 h/day). BMI, PBF and VFA were assessed by bioelectric impedance analysis. Demographic characteristics, chronic diseases and medication history, physical activity, smoking and alcohol drinking behaviors were measured by an investigator-administrated questionnaire. RESULTS: A total of 9059 adult participants (63.08% were females) were included in the analysis. The participants aged from 19 to 91 years with the mean age of 45.0 ± 14.6 years. Short sleep was independently associated with elevated odds of general obesity (defined using BMI) and visceral obesity (defined using VFA) among the total study population, and gender differences were observed in these associations. Among women, short sleep was associated with 62% increased odds of general obesity (OR = 1.62, 95% CI: 1.24-2.12) and 22% increased odds of visceral obesity (OR = 1.22, 95% CI: 1.02-1.45). Among men, long sleep duration was associated with 21% decreased odds of visceral obesity (OR = 0.79, 95% CI: 0.64-0.99). No association was observed between sleep duration and PBF in both sexes. CONCLUSIONS: Sleep duration was associated with increased odds of general and visceral obesity, and this association differed between men and women. No association was observed between sleep duration and PBF among either males or females.
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Tejido Adiposo/metabolismo , Índice de Masa Corporal , Obesidad/epidemiología , Sueño/fisiología , Adulto , Anciano , Anciano de 80 o más Años , China/epidemiología , Estudios Transversales , Femenino , Humanos , Grasa Intraabdominal/metabolismo , Masculino , Persona de Mediana Edad , Obesidad Abdominal/epidemiología , Factores Sexuales , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: Few studies have compared bioelectrical body and visceral fat indices with anthropometric measures, or evaluated their optimal cutoffs in relation to hypertension among Asians. We compared the efficiencies of bioelectrical indices (percentage of body fat, PBF; visceral fat area, VFA) with anthropometric measures (body mass index, BMI; waist-hip ratio, WHR) for hypertension and re-evaluated the optimal cutoffs of each index by age and gender. METHODS: We conducted a cross-sectional survey among 8234 adults for health examination. PBF, VFA, BMI, WHR, and data on hypertension and behaviors were collected. Receiver operating characteristic (ROC) curve and areas under curves (AUCs) were used to analyze the efficiencies of the indices for hypertension, optimal cutoffs were estimated using the Youden index. RESULTS: A total of 8234 individuals aged 21-91 with median age 44 (interquartile range [IQR] 33-56) years were included and 40.56% were men. The overall prevalence of hypertension was 27.47%. The studied indices were all associated with hypertension in all age-specific groups both among men and women except for WHR in 21-29 years old men and PBF in in 21-29 years old women. Among males, there were no statistical differences in powers of four indices for hypertension in all age-specific groups, except for 40-49 years, in which WHR was better than VFA. Among females, no differences were found among the indices in 30-39 and 70-79 years groups, while WHR was the best in 21-29 years group, VFA was better than PBF in 30-39 and 50-59 years groups, BMI was better than PBF and WHR in 60-69 years group. The optimal cutoffs of PBF, VFA, BMI and WHR ranged from 23.9 to 28.7%, 86.4 to 106.9cm2, 23.5 to 27.1 kg/m2, 0.92 to 0.96 across the age categories in males, and 32.8 to 36.3%, 75.9 to 130.9cm2, 21.9 to 26.4 kg/m2, 0.84 to 0.95 across the age categories in females, respectively. CONCLUSIONS: The obesity indices' efficiencies for hypertension varied by age and gender, and their cutoff values varied across the age categories and gender. Specific indices and cutoffs based on person's age and gender should be used to identify individuals with hypertension.
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Adiposidad , Antropometría , Hipertensión/diagnóstico , Grasa Intraabdominal/fisiopatología , Obesidad/diagnóstico , Adulto , Distribución por Edad , Factores de Edad , Anciano , Anciano de 80 o más Años , Presión Sanguínea , China/epidemiología , Estudios Transversales , Impedancia Eléctrica , Femenino , Encuestas Epidemiológicas , Humanos , Hipertensión/epidemiología , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Obesidad/fisiopatología , Valor Predictivo de las Pruebas , Prevalencia , Factores de Riesgo , Distribución por Sexo , Factores Sexuales , Adulto JovenRESUMEN
A phytochemical investigation of the leaves of the medicinal plant Isodon rubescens led to the isolation of the two new degraded abietane lactone diterpenoids rubesanolides F (1) and G (2). Their structures were elucidated based on the analyses of the HRESIMS and 1D/2D NMR spectral data, and their absolute configurations were determined by ECD spectrum calculations and X-ray single crystal diffraction methods. Compounds 1 and 2, with a unique γ-lactone subgroup between C-8 and C-20, were found to form a carbonyl carbon at C-13 by removal of the isopropyl group in an abietane diterpene skeleton. Rubesanolide G (2) is a rare case of abietane that possesses a cis-fused configuration between rings B and C. The two isolates were evaluated for their biological activities against two cancer cell lines (A549 and HL60), three fungal strains (Candida alba, Aspergillus niger and Rhizopus nigricans) and three bacterial strains (Escherichia coli, Staphylococcus aureus and Bacillus subtilis).
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Abietanos , Antiinfecciosos , Antineoplásicos Fitogénicos , Bacterias/crecimiento & desarrollo , Hongos/crecimiento & desarrollo , Isodon/química , Lactonas , Neoplasias/tratamiento farmacológico , Hojas de la Planta/química , Células A549 , Abietanos/química , Abietanos/aislamiento & purificación , Abietanos/farmacología , Antiinfecciosos/química , Antiinfecciosos/aislamiento & purificación , Antiinfecciosos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Células HL-60 , Humanos , Lactonas/química , Lactonas/aislamiento & purificación , Lactonas/farmacología , Neoplasias/metabolismo , Neoplasias/patologíaRESUMEN
BACKGROUND: To investigate the similarities and differences of renal clinical and renal pathology between IgA nephropathy (IgAN) and IgA vasculitis nephritis (IgAVN) in children. METHODS: A total of 237 children with IgAN and 190 children with IgAVN were included. The general conditions, clinical characteristics, final diagnosis, clinical and pathological classification of the children were intercepted at the time of admission, and the retrospective comparative analysis was carried out. RESULTS: The results showed that the median course of disease in IgAN group was longer than that in IgAVN group (p = 0.02). Patients with IgAN had a significantly higher duration of infection than the patients with IgAVN (p = 0.03). The white blood cell count (WBC), hemoglobin (HGB) in IgAN group were significantly lower than that in IgAVN group (p = 0.02). The serum creatinine in IgAN group was higher than that in IgAVN group (p = 0.02). Patients with IgAN and IgAVN had statistically significant differences in pathological typing between clinical types: hematuria and proteinuria, nephrotic syndrome and chronic nephritis (p = 0.004). DISCUSSION: The clinical manifestations of IgAN and IgAVN were similar, but the onset of IgAN was hidden and the clinical manifestations were relatively serious. Renal pathology was mainly glomerulosclerosis and renal tubular atrophy. IgAVN was characterized by acute onset and good renal function. Renal pathology was dominated by endothelial hyperplasia and crescent formation. These differences did not support the hypothesis that the two diseases are the same.
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Glomerulonefritis por IGA , Vasculitis por IgA , Nefritis , Niño , Humanos , Vasculitis por IgA/complicaciones , Glomerulonefritis por IGA/complicaciones , Estudios Retrospectivos , RiñónRESUMEN
Schwann cells are the main supportive cells of the peripheral nerves. Schwann cells suffer inhibition of autophagy under hyperglycemia treatment in diabetic peripheral neuropathy (DPN). However, the exact mechanism is still not fully elucidated. We first observed the decrease of autophagy markers (LC3-II/LC3-I, P62) in the sciatic nerves of diabetic mice vs. normal mice, accompanied with the loss of myelinated nerve fibers and abnormal myelin sheath. In line with this, LC3-II/LC3-I and P62 were also significantly reduced in high glucose-treated rat Schwann cell 96 (RSC96) cells compared with normal glucose-treated cells. Furthermore, we found that trichostatin A [an inhibitor of histone deacetylase (HDAC)] evidently improved LC3-II/LC3-I in high glucose-treated RSC96 cells, without an effect on P62 expression. Again, HDAC1 and HDAC5 were revealed to be increased in RSC96 cells stimulated with high glucose. Inhibition of HDAC1 but not HDAC5 by small hairpin RNA vector enhanced LC3-II/LC3-I in high glucose-cultured RSC96 cells. In addition, LC3-II conversion regulators [autophagy-related protein (Atg)3, Atg5, and Atg7] were detected in high glucose-treated and HDAC1-knockdown RSC96 cells, and Atg3 was proven to be the key target of HDAC1. The presuppression of Atg3 offset the improvement of LC3-II/LC3-I resulting from HDAC1 inhibition in high glucose-treated RSC96 cells. The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway was activated in RSC96 cells treated with high glucose, which was indicated by increased STAT3 phosphorylation. Blocking STAT3 phosphorylation by chemical inhibitor AG490 induced HDAC1 down-regulation followed by increases in Atg3 and LC3-II/LC3-I. Interestingly, we also found that AG490 treatment enhanced P62 expression in high glucose-stimulated RSC96 cells. Taken together, our findings demonstrate that hyperglycemia inhibits LC3-II/LC3-I in an HDAC1-Atg3-dependent manner and decreases P62 expression in an HDAC-independent manner via the JAK-STAT3 signaling pathway in the Schwann cells of DPN.-Du, W., Wang, N., Li, F. Jia, K., An, J., Liu, Y., Wang, Y., Zhu, L., Zhao, S. Hao, J. STAT3 phosphorylation mediates high glucose-impaired cell autophagy in an HDAC1-dependent and -independent manner in Schwann cells of diabetic peripheral neuropathy.
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Autofagia/efectos de los fármacos , Neuropatías Diabéticas/metabolismo , Glucosa/farmacología , Histona Desacetilasa 1/fisiología , Procesamiento Proteico-Postraduccional , Factor de Transcripción STAT3/metabolismo , Células de Schwann/efectos de los fármacos , Animales , Proteínas Relacionadas con la Autofagia/antagonistas & inhibidores , Proteínas Relacionadas con la Autofagia/biosíntesis , Proteínas Relacionadas con la Autofagia/genética , Biomarcadores , Línea Celular , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Neuropatías Diabéticas/patología , Técnicas de Silenciamiento del Gen , Histona Desacetilasa 1/antagonistas & inhibidores , Histona Desacetilasa 1/genética , Histona Desacetilasas/genética , Histona Desacetilasas/fisiología , Ácidos Hidroxámicos/farmacología , Ratones , Proteínas Asociadas a Microtúbulos/biosíntesis , Proteínas Asociadas a Microtúbulos/genética , Vaina de Mielina/patología , Fibras Nerviosas Mielínicas/patología , Péptido Sintasas/antagonistas & inhibidores , Péptido Sintasas/biosíntesis , Péptido Sintasas/genética , Fosforilación , Interferencia de ARN , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/farmacología , Ratas , Células de Schwann/metabolismo , Nervio Ciático/metabolismo , Nervio Ciático/patología , Tirfostinos/farmacología , Regulación hacia ArribaRESUMEN
Objective: In recent years, faced with a complex economic development environment and the evolving dynamics of the Chinese workplace, talent has become a precious resource that is invaluable yet scarce for every enterprise. As Generation Z employees have gradually entered the labor market, they contribute new perspectives and energies to various enterprises and pose unique challenges. The traditional step-by-step approach no longer meets the needs of today's businesses. Companies require more proactive talents to drive superior performance. Individuals with proactive behavior can effectively plan their career paths and are better equipped to fulfill core organizational tasks. Therefore, it is crucial for organizations to effectively mitigate the perceived negative impacts of proactive behavior, encouraging individuals to exhibit more positive proactive actions. Methods: Based on the proactive motivation model, this study investigates the effects of mentoring, balanced psychological contract, proactive behavior, and agreeableness on the proactive behaviors of new employees. The research surveyed 417 new employees from Guangdong Province, China, who had graduated within the last three years, with a gender distribution of 49.4% male and 50.6% female. Results: Structural Equation Modeling was used for data analysis, and the following results were obtained: First, mentoring positively affected the balanced psychological contract and new employees' proactive behavior. Second, mentoring positively affected the new employees' proactive behavior through the balanced psychological contract. Third, agreeableness played a moderating role in the relationship between mentoring and new employees' proactive behavior, and in the relationship between mentoring and the balanced psychological contracts. Finally, the positive indirect effect of mentoring through the balanced psychological contract on new employees' proactive behavior is positively moderated by agreeableness. Conclusion: The results of this study offer new insights into mentoring research for new employees and provide practical guidance for fostering the balanced psychological contract and proactive behavior among new employees. This research enriches the existing literature on mentoring for new employees by demonstrating the integral roles of agreeableness and a balanced psychological contract in fostering proactive behavior, offering valuable insights for organizational practices aimed at enhancing employee proactivity.
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BACKGROUND: Dihydroartemisinin (DHA) is an artemisinin derivative known for its antimalarial properties. It has also shown potential as an anti-tumor and anti-angiogenic agent. However, its specific role in inhibiting angiogenesis in breast cancer is not well understood. OBJECTIVES: We aimed to investigate the anti-angiogenesis effect of DHA on breast cancer and explore its potential as a therapeutic drug. Our objectives were to assess the impact of DHA on neovascularization induced by MDA-MB-231 cells, evaluate its effects on vessel sprout and tube-formation in vascular endothelial cells, and analyze the expression of key angiogenesis-related proteins. METHODS: Using a chicken chorioallantoic membrane (CAM) model, we cultured MDA-MB-231 cells and treated them with DHA. We assessed neovascularization and cultured vascular endothelial cells with DHA-treated cell media to evaluate vessel sprout and tube-formation. Protein expression levels of VEGF, MMP-2, and MMP-9 were analyzed using Western blotting. RESULTS: DHA significantly attenuated neovascularization induced by MDA-MB-231 cells. It also suppressed vessel sprout and tube-formation of HUVEC cells when exposed to DHA-treated cell media. Furthermore, DHA downregulated the expression of VEGF, MMP-2, and MMP-9 proteins. Mechanistically, DHA inhibited the phosphorylation of PI3K, AKT, ERK, and NF-κB proteins in tumor cells. CONCLUSIONS: Our study provides evidence of the inhibitory effect of DHA on breast cancer angiogenesis. These findings support the potential of DHA as an anti-breast cancer drug and warrant further investigation for its therapeutic applications.
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Artemisininas , Neoplasias , Factor A de Crecimiento Endotelial Vascular , Humanos , Factor A de Crecimiento Endotelial Vascular/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Angiogénesis , Inhibidores de la Angiogénesis/farmacología , Células Endoteliales de la Vena Umbilical Humana , Línea Celular TumoralRESUMEN
Soil organic carbon (SOC) is vital for the global carbon cycle and environmentally sustainable development. Meanwhile, the fast, convenient remote sensing technology has become one of the notable means to monitor SOC content. Nowadays, limitations are found in the inversion of SOC content with high-precision and complex spatial relationships based on scarce ground sample points. It is restrained by the spatial difference in the relationship between SOC content and remote sensing spectra due to the problem of different spectra for the same substance and the influence of topographic and environment (e.g. vegetation and climate). In this regard, the two-point machine learning (TPML) method, which can overcome above problems and deal with complex spatial heterogeneity of relationships between SOC and remote sensing spectra, is used to invert the SOC content in Hailun County, Heilongjiang Province, combined with derived variables from Sentinel-1, Sentinel-2, topography and environment. Based on 10-fold cross-validation and t-test, results indicate that the TPML method boasts the highest inversion accuracy, followed by random forest, gradient boosting regression tree, partial least squares regression and support vector machine. The average r, MAE, RMSE, and RPD of TPML are 0.854, 0.384 %, 0.558 %, and 1.918. Further, the TPML method has been proven to be equal to evaluating the uncertainty of inversion results, by comparing the actual and theoretical error of the inversion result in one subset. The spatial inversion result of SOC content with 10 m resolution by TPML is smoother and has more real details than other models, which are consistent with the distribution of SOC content in different land use types. This study provides both theoretical and technical guidance for using TPML method combined with spectral information of remote sensing to predict soil attributes and offer accurate uncertainty estimation, thereby opening up the opportunity for low-cost, high-precision, and large-scale SOC inversion.
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Lipid metabolism disorders are a major cause of several chronic metabolic diseases which seriously affect public health. Salusinα, a vasoactive peptide, has been shown to attenuate lipid metabolism disorders, although its mechanism of action has not been reported. To investigate the effects and potential mechanisms of Salusinα on lipid metabolism, Salusinα was overexpressed or knocked down using lentiviral vectors. Hepatocyte steatosis was induced by free fatty acid (FFA) after lentiviral transfection into HepG2 cells. The degree of lipid accumulation was assessed using Oil Red O staining and by measuring several biochemical indices. Subsequently, bioinformatics was used to analyze the signaling pathways that may have been involved in lipid metabolism disorders. Finally, semiquantitative PCR and western blotting were used to verify the involvement of the liver kinase B1 (LKB1)/AMPK pathway. Compound C, an inhibitor of AMPK, was used to confirm this mechanism's involvement further. The results showed that Salusinα significantly attenuated lipid accumulation, inflammation and oxidative stress. In addition, Salusinα increased the levels of LKB1 and AMPK, which inhibited the expression of sterol regulatory element binding protein1c, fatty acid synthase and acetylCoA carboxylase. The addition of Compound C abrogated the Salusinαmediated regulation of AMPK on downstream signaling molecules. In summary, overexpression of Salusinα activated the LKB1/AMPK pathway, which in turn inhibited lipid accumulation in HepG2 cells. This provides insights into the potential mechanism underlying the mechanism by which Salusinα ameliorates lipid metabolism disorders while identifying a potential therapeutic target.
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Quinasas de la Proteína-Quinasa Activada por el AMP , Proteínas Quinasas Activadas por AMP , Lipogénesis , Proteínas Serina-Treonina Quinasas , Transducción de Señal , Humanos , Quinasas de la Proteína-Quinasa Activada por el AMP/genética , Proteínas Quinasas Activadas por AMP/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Células Hep G2 , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Péptidos y Proteínas de Señalización Intercelular/genética , Metabolismo de los Lípidos/efectos de los fármacos , Metabolismo de los Lípidos/genética , Trastornos del Metabolismo de los Lípidos/metabolismo , Trastornos del Metabolismo de los Lípidos/genética , Trastornos del Metabolismo de los Lípidos/tratamiento farmacológico , Lipogénesis/genética , Lipogénesis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Transducción de Señal/efectos de los fármacos , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genéticaRESUMEN
Salusinß and adiponectin receptor 1 (adipoR1) serve important roles in the development of certain cardiovascular diseases and lipid metabolism. However, to the best of our knowledge, the relationship between salusinß and adipoR1, and their underlying mechanisms of action, currently remain unclear. In the present study, lentiviral vectors designed to overexpress salusinß or knock down salusinß expression were used in 293T and HepG2 cells. Semiquantitative PCR was performed to investigate the relationship between salusinß and adipoR1 mRNA expression in 293T cells. Western blotting was used to assess the protein expression levels of adipoR1, adenosine monophosphateactivated protein kinase (AMPK), acetylCoA carboxylase (ACC) and carnitine palmitoyl transferase 1A (CPT1A) in transfected HepG2 cells. Simultaneously, HepG2 cells were treated with an adipoR1 inhibitor (thapsigargin) or agonist (AdipoRon) and the resultant changes in the expression levels of the aforementioned proteins were observed. Oil Red O staining and measurements of cellular triglyceride levels were performed to assess the extent of lipid accumulation in HepG2 cells. The results demonstrated that salusinß overexpression downregulated adipoR1 expression and inhibited the phosphorylation of AMPK and ACC, which led to decreased CPT1A protein expression. By contrast, salusinß knockdown increased adipoR1 expression and promoted the phosphorylation of AMPK and ACC, which conversely enhanced CPT1A protein expression. Treatment with adipoR1 agonist, AdipoRon, reversed the effects of salusinß overexpression. In addition, salusinß overexpression enhanced intracellular lipid accumulation in HepG2 cells induced by free fatty acid treatment. These findings highlighted the potential regulatory role of salusinß in adipoR1mediated signaling pathways. To conclude, the present study provided insights into the regulation of fatty acid metabolism by the liver. In particular, salusinß may serve as a potential target for the therapeutic intervention of metabolic disorders of lipids.
Asunto(s)
Proteínas Quinasas Activadas por AMP , Metabolismo de los Lípidos , Receptores de Adiponectina , Humanos , Proteínas Quinasas Activadas por AMP/metabolismo , Ácidos Grasos no Esterificados/metabolismo , Células Hep G2 , Hígado/metabolismo , Receptores de Adiponectina/genética , Receptores de Adiponectina/metabolismoRESUMEN
The superconductivity of cuprates remains a challenging topic in condensed matter physics, and the search for materials that superconduct electricity above liquid nitrogen temperature and even at room temperature is of great significance for future applications. Nowadays, with the advent of artificial intelligence, research approaches based on data science have achieved excellent results in material exploration. We investigated machine learning (ML) models by employing separately the element symbolic descriptor atomic feature set 1 (AFS-1) and a prior physics knowledge descriptor atomic feature set 2 (AFS-2). An analysis of the manifold in the hidden layer of the deep neural network (DNN) showed that cuprates still offer the greatest potential as superconducting candidates. By calculating the SHapley Additive exPlanations (SHAP) value, it is evident that the covalent bond length and hole doping concentration emerge as the crucial factors influencing the superconducting critical temperature (Tc). These findings align with our current understanding of the subject, emphasizing the significance of these specific physical quantities. In order to improve the robustness and practicability of our model, two types of descriptors were used to train the DNN. We also proposed the idea of cost-sensitive learning, predicted the sample in another dataset, and designed a virtual high-throughput search workflow.
RESUMEN
Salusinα and adiponectin, are vasoactive peptides with numerous similar biological effects related to lipid metabolism. Adiponectin has been shown to reduce fatty acid oxidation and to inhibit lipid synthesis of liver cells through its receptor, adiponectin receptor 2 (AdipoR2), but whether salusinα is able to interact with AdipoR2, was not previously reported. To investigate this, in vitro experiments were carried out. The overexpression and interference recombinant plasmids were constructed with salusinα. The lentiviral expression systems of salusinα overexpression and interference were respectively synthesized in 293T cells, and 293T cells were infected with the lentivirus. Finally, the association between salusinα and AdipoR2 was analyzed by semiquantitative PCR. Subsequently, HepG2 cells were also infected with these viruses. The expression levels of AdipoR2, peroxisome proliferatoractivated receptorα (PPARα), apolipoprotein A5 (ApoA5) and sterol regulatory elementbinding transcription factor 1 (SREBP1c) were detected by western blotting, and AdipoR2 inhibitor (thapsigargin) and agonist [4phenyl butyric acid (PBA)] were used to observe the resultant changes in the aforementioned molecules. The results obtained revealed that the overexpression of salusinα increased the level of AdipoR2 in 293T and HepG2 cells, led to an upregulation of the levels of PPARα and ApoA5, and inhibited the expression of SREBP1c, whereas the salusinα interference lentivirus exerted the opposite effects. Notably, thapsigargin inhibited the expression of AdipoR2, PPARα and ApoA5 in HepG2 cells of pHAGESalusinα group, and caused an increase in the level of SREBP1c, whereas the opposite effects were observed in pLKO.1shSalusinα#1 group upon treatment with PBA. Taken together, these data demonstrated that overexpression of salusinα upregulated AdipoR2, which in turn activated the PPARα/ApoA5/SREBP1c signaling pathway to inhibit lipid synthesis in HepG2 cells, thereby providing theoretical data on which to base the clinical application of salusinα as a novel peptide for molecular intervention in fatty liver disease.
Asunto(s)
Adiponectina , PPAR alfa , Humanos , Células Hep G2 , PPAR alfa/genética , PPAR alfa/metabolismo , Apolipoproteína A-V/metabolismo , Adiponectina/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Tapsigargina/farmacología , Metabolismo de los LípidosRESUMEN
Myelocytomatosis (MYC) transcription factors (TFs) in plants are well-known regulators of plant defense against herbivores. However, the role and mechanism of MYC TFs in cotton (Gossypium hirsutum L.) defense against cotton aphids (Aphis gossypii Glover) remain still elusive. Herein, on the basis of aphid-induced cotton transcriptome analysis, GhMYC1374, a cotton MYC2-like TF that was highly induced by cotton aphid attack, has been identified that confers cotton aphid resistance in cotton. GhMYC1374 was an intranuclear transcription factor with three domains: bHLH-MYC_N, RBR and bHLH_AtAIB_like. GhMYC1374 was induced under cotton aphid feeding, exogenous methyl jasmonate (MeJA) and salicylic acid (SA) treatments. GhMYC1374 transient overexpression in cotton plants enhanced cotton aphid-resistance, while GhMYC1374 silence through VIGS (virus induced gene silencing) decreased cotton aphid-resistance. GhMYC1374 transient overexpression of in cotton plants activated the phenylpropane pathway and promoted the synthesis of flavonoids, and resistance to thus enhanced the cotton resistance against aphids. In contrast, GhMYC1374 silence inhibited the biosynthesis of flavonoids. In addition, GhMYC1374 also positively activated the expression of the biosynthetic genes of free gossypol, leading to the high content of free gossypol. Taken together, our results suggest that GhMYC1374 is involved in the cotton defense response against cotton aphids by regulating the biosynthesis of flavonoids and free gossypol.