Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 557
Filtrar
Más filtros

Tipo del documento
Intervalo de año de publicación
2.
Sci Adv ; 10(44): eads4724, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39475603

RESUMEN

The reactivity of Bin- clusters (n = 2 to 30) with O2 is found to display even-odd alternations. The open-shell even-sized Bin- clusters are more reactive than the closed-shell odd-sized clusters, except Bi18-, which exhibits no observable reactivity toward O2. We have investigated the structure and bonding of Bi18- to understand its remarkable resistance to oxidation. We find that the most stable structure of Bi18- consists of two Bi8 cages linked by a Bi2 dimer, where each atom is bonded to three neighboring atoms. Chemical bonding analyses reveal that each Bi uses its three 6p electrons to form three covalent bonds with its neighbors, resulting in a Bi18- cluster without any dangling bonds. We find that the robust Bi18 framework along with the totally delocalized unpaired electron is responsible for the surprising inertness of Bi18- toward O2. The Bi18 framework is similar to that in Hittorf's phosphorus, suggesting the possibility to create bismuth nanoclusters with interesting structures and properties.

3.
PLoS One ; 19(10): e0300954, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39423192

RESUMEN

OBJECTIVE: This systematic review and meta-analysis aimed to assess interventions to reduce opioid use for patients with chronic non-cancer pain (CNCP) versus usual care or active controls in primary care settings. METHODS: In this registered study (PROSPERO: CRD42022338458), we searched MEDLINE, Embase PsycInfo, CINAHL, and Cochrane Library from inception to December 28th 2021, and updated on Dec 14th 2023 for randomized controlled trials (RCTs) and cohort studies with no restrictions. Methodological quality was assessed using the Cochrane Risk of Bias tool for RCTs and Newcastle Ottawa Scale for cohort studies. Primary outcomes included mean reduction in morphine equivalent daily dose (reported as mean differences [MDs] mg/day; 95% confidence intervals [95%CIs]) and/or opioid cessation proportion. Secondary outcomes were mean changes in pain severity (reported as standardized mean difference [SMDs]; 95%CIs) and (serious) adverse events. Meta-analyses were performed using random-effects models. RESULTS: We identified 3,826 records, of which five RCTs (953 participants) and five cohort studies (901 participants) were included. Overall, opioid dosage was significantly reduced in intervention groups compared to controls (MD: -28.63 mg/day, 95%CI: -39.77 to -17.49; I2 = 31.25%; eight studies). Subgroup analyses revealed significant opioid dose reductions with mindfulness (MD: -29.36 mg/day 95%CI: -40.55 to -18.17; I2 = 0.00%; two trials) and CBT-based multimodalities (MD: -41.68 mg/day; 95%CI: -58.47 to -24.89; I2 = 0.00%; two cohort studies), respectively, compared to usual care. No significant differences were observed in opioid cessation (Odds ratio: 1.10, 95%CI: -0.48 to 2.67, I2 = 58.59%; two trials) or pain severity (SMD: -0.13, 95%CI: -0.37 to 0.11; I2 = 33.51%; three trials). Adverse events were infrequently examined, with withdrawal symptoms commonly reported. CONCLUSIONS: The studied interventions were effective in reducing opioid dosage for people with CNCP in primary care. They highlighted the importance of multidisciplinary collaboration. Large-scale RCTs measuring the long-term effects and cost of these interventions are needed before their implementation.


Asunto(s)
Analgésicos Opioides , Dolor Crónico , Atención Primaria de Salud , Humanos , Analgésicos Opioides/uso terapéutico , Analgésicos Opioides/administración & dosificación , Dolor Crónico/tratamiento farmacológico , Trastornos Relacionados con Opioides/prevención & control , Manejo del Dolor/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto
4.
J Fam Psychol ; 2024 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-39432338

RESUMEN

This study explores how self-compassion mediates the relations between parents' perceptions of children's behaviors and parenting stress, as well as interactions between parents. We conducted a longitudinal actor-partner interdependence mediation model and assessed parents' perceptions of children's behaviors, self-compassion, and parenting stress. A total of 656 pairs of parents (fathers' Mage = 34.96 years, SDage = 5.62; mothers' Mage = 33.13 years, SDage = 5.77) participated in the study. Results revealed that parents' perceptions of children's problem behavior affected their own parenting stress through their self-compassion. Additionally, parents' perceptions of children's prosocial behavior directly influenced their own parenting stress and also affected it through self-compassion in both parents. Parents' perceptions of children's problem behavior directly influenced their partner's parenting stress and also indirectly through their own self-compassion. Similarly, parents' perceptions of children's prosocial behavior affected their partner's parenting stress via self-compassion in both parents. The findings highlighted the importance of parents recognizing and valuing their children's positive behaviors, thereby fostering a constructive "child effect" that improved the dynamics of the parental subsystem. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

5.
Neuropharmacology ; 261: 110175, 2024 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-39357738

RESUMEN

Methamphetamine (METH) has been implicated in inducing memory impairment, but the precise mechanisms underlying this effect remain unclear. Current research often limits itself to singular models or focuses on individual gene or protein functions, which hampers a comprehensive understanding of the underlying mechanisms. In this study, we established three METH mouse exposure models, extracted hippocampal nuclei, and utilized RNA sequencing to analyze changes in mRNA expression profiles. Our results indicate that METH significantly impairs the learning and memory capabilities of mice. Additionally, we observed that METH-induced inflammatory responses occur in the early phase and do not further exacerbate with repeated injections. However, RNA sequencing revealed the persistent enrichment of inflammatory pathway molecules, which correlated with worsened behaviors. This suggests that although METH-induced neuroinflammation plays a critical role in learning and memory impairment, the continued enrichment of inflammatory pathway molecules is associated with behavioral outcomes. These findings provide crucial evidence for the potential application of immune intervention in METH-related disorders.


Asunto(s)
Estimulantes del Sistema Nervioso Central , Hipocampo , Trastornos de la Memoria , Metanfetamina , Ratones Endogámicos C57BL , Enfermedades Neuroinflamatorias , ARN Mensajero , Animales , Metanfetamina/toxicidad , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Masculino , Ratones , ARN Mensajero/metabolismo , Enfermedades Neuroinflamatorias/inducido químicamente , Trastornos de la Memoria/inducido químicamente , Estimulantes del Sistema Nervioso Central/toxicidad , Factores de Tiempo
6.
Int J Food Microbiol ; 427: 110935, 2024 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-39437683

RESUMEN

This study aimed to optimize a novel green CEO nanoemulsions (CEO NEs) and explore its physicochemical properties and the effect on the shelf-life of strawberries during storage at environmental temperature (20-25 °C). We used CEO as oil phase and tea saponin (TS) as a natural surfactant to formulate the novel green CEO NEs, and its potential as an antimicrobial agent was also investigated. The results showed that CEO NEs had a droplet size about 170 nm with uniform distribution and regularly spherical. These CEO NEs exhibited excellent storage stability, thermal stability, pH stability and centrifugal stability. The antimicrobial test indicated that the minimal inhibitory concentration and the minimal bactericidal (fungicidal) concentration of CEO NEs against Escherichia coli, Botrytis cinerea and Aspergillus flavus were 17.81 µg/mL and 35.62 µg/mL, 35.62 µg/mL and 71.25 µg/mL, 2.23 µg/mL and 4.45 µg/mL, respectively, which were significantly lower than those of pure CEO (333.75 µg/mL and 667.5 µg/mL, 667.5 µg/mL and 1335 µg/mL, 41.72 µg/mL and 83.44 µg/mL). More interestingly, after soaking strawberries in CEO NEs for 2 min, the shelf-life of strawberries can be extended to 7 days at environmental temperature, and a lower rate of weight loss and mildew were showed in the group of CEO NEs than other control groups, especially the strawberries in ultrapure water group went bad first, obviously shranked, and contaminated by molds after 3 days. The above results indicate that CEO NEs prepared in this study has great potential as a new green antimicrobial agent in fruit preservation.

7.
Artículo en Inglés | MEDLINE | ID: mdl-39218345

RESUMEN

BACKGROUND: Obesity, characterized by excessive adiposity, is associated with brain structural abnormalities. Nevertheless, the relationships between altered structural nodes of default mode network (DMN), body mass index (BMI), general cognitive ability remained unclear in young adults. METHODS: In this study, we divided a large sample of young adults into three BMI-based groups. We then conducted one-way analyses of variance and post-hoc tests with Bonferroni corrections to investigate abnormal structural brain regions associated with obesity. Furthermore, mediation effects models were built to explore whether the structural alterations influenced the relationship between BMI and general cognitive ability. RESULTS: Compared to their lean and overweight counterparts, young adults with obesity exhibited significantly lower general cognitive ability, higher impulsivity traits, and worse sleep quality. Furthermore, compared with lean group, young adults with obesity exhibited altered cortical thickness of both the left temporal pole and right superior parietal lobule, and abnormal cortical surface area (CSA) of the left entorhinal cortex (EC), a hub within DMN. Moreover, CSA of the left EC mediated the relationship between BMI and general cognitive ability. CONCLUSION: Obesity was linked to altered structural node of DMN, which mediated general cognitive ability in young adults. These findings indicated the negative effect of obesity on DMN and general cognitive ability in young adults.


Asunto(s)
Índice de Masa Corporal , Cognición , Red en Modo Predeterminado , Imagen por Resonancia Magnética , Obesidad , Humanos , Masculino , Obesidad/fisiopatología , Obesidad/patología , Adulto Joven , Femenino , Cognición/fisiología , Red en Modo Predeterminado/diagnóstico por imagen , Red en Modo Predeterminado/patología , Red en Modo Predeterminado/fisiopatología , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Encéfalo/fisiopatología
8.
Inorg Chem ; 63(37): 17215-17224, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39231309

RESUMEN

We report an investigation on the structures and chemical bonding in a series of di-lanthanum boron clusters, La2Bn- (n = 4-6), using photoelectron spectroscopy and theoretical calculations. Well-resolved photoelectron spectra are obtained and used to verify the global minima of the lanthanide boron clusters. The structures of La2B4- and La2B5- are found to consist of open B4 and B5 rings, respectively, around the La2 dimer equatorially. Theoretical evidence of La-La σ bonding is obtained in La2B4-, whereas the bonding in La2B5- is similar to that of an incomplete inverse sandwich without real La-La bonding. The global minimum of La2B6- is completely different, where one of the La atoms can be viewed as substituting a B atom of the B7 cluster due to the high electronic stability of the B73- borozene. The resulting lanthaborozene [LaB6]3- forms a half-sandwich structure with the second La atom, with evidence of La-La σ bonding. Lanthanide-lanthanide bonds are relatively rare in chemistry. The current work suggests that binary lanthanide boron clusters provide interesting systems to study lanthanide-lanthanide bonding.

9.
Viruses ; 16(9)2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39339941

RESUMEN

African swine fever (ASF) is an acute infectious disease with a high mortality rate in both domestic and wild boars. Commercial vaccines or antiviral drugs for ASF were not available due to the complex diversity of the structure and genome of its pathogen African swine fever virus (ASFV). In recent years, there have been many reports on candidate strains of attenuated vaccines for ASFV. In this study, we obtained a recombinant virus named SY18ΔL60LΔCD2v by simultaneously deleting the L60L gene and CD2v gene from highly virulent strain SY18. In vitro, SY18ΔL60LΔCD2v displayed a decreased growth kinetic compared to that of parental SY18. In vivo, high doses (105 TCID50) of SY18ΔL60LΔCD2v can protect pigs (5/5) from attacks by the parental SY18 strain (102 TCID50). Low doses (102 TCID50) of SY18ΔL60LΔCD2v only protected 20% of pigs (1/5) from attacks by the parental SY18 strain (102 TCID50). The results indicated that the absence of these two genes in SY18 could induce protection against the homologous parental strain, and there were no obvious clinical symptoms or viremia. These results indicate that the SY18ΔL60LΔCD2v strain can serve as a new live attenuated vaccine candidate for the prevention and control of ASFV infection.


Asunto(s)
Virus de la Fiebre Porcina Africana , Fiebre Porcina Africana , Eliminación de Gen , Vacunas Atenuadas , Vacunas Virales , Virus de la Fiebre Porcina Africana/genética , Virus de la Fiebre Porcina Africana/inmunología , Virus de la Fiebre Porcina Africana/patogenicidad , Animales , Porcinos , Fiebre Porcina Africana/prevención & control , Fiebre Porcina Africana/virología , Fiebre Porcina Africana/inmunología , Vacunas Atenuadas/inmunología , Vacunas Atenuadas/genética , Vacunas Atenuadas/administración & dosificación , Vacunas Virales/inmunología , Vacunas Virales/genética , Proteínas Virales/genética , Proteínas Virales/inmunología , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Viremia/prevención & control
10.
Phytomedicine ; 135: 156024, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39341125

RESUMEN

BACKGROUND: The development of cancer is accompanied by metabolic reprogramming, and the liver serves as a central hub for lipid transportation. Apigenin, a plant-derived flavonoid, demonstrates potent anticancer properties across various cancer types and exhibits promising potential as a therapeutic agent for cancer treatment. However, there are limited studies focusing on the downstream targets of apigenin. Moreover, there are few reports on the impact of apigenin in lipid metabolism within liver cancer cells. PURPOSE: The objective is to elucidate the metabolic mechanism underlying the inhibitory effect of apigenin on liver cancer progression, search for downstream targets and provide reliable data support for the clinical trials of apigenin. METHODS: Anticancer effects of apigenin were detected at cellular and molecular levels in vitro, and downstream targets of apigenin, especially metabolic pathway genes, were analyzed by transcriptome. Next, the downstream target of apigenin was verified and the biological function of the downstream target was examined. Finally, the downstream target of apigenin was further verified by restoring target gene expression. RESULTS: Cellular molecular experiments showed that Apigenin inhibited the proliferation, migration, invasion and lipid metabolism of hepatocellular carcinoma (HCC) cells. Transcriptome analysis showed apigenin widely regulates histone demethylase, particularly histone H3K4 lysine demethylase 1A (KDM1A). Apigenin treatment inhibited the expression of KDM1A protein and mRNA levels in liver cancer cells, molecular docking predicted the interaction between apigenin and KDM1A. Furthermore, downregulation KDM1A inhibited the proliferation and lipid metabolism of HCC cells, in the same way, overexpressing KDM1A promoted proliferation of HCC cells. Finally, restoring KDM1A expression partially attenuated the effects of apigenin on lipid metabolism in HCC cells. CONCLUSION: In conclusion, our study provides compelling evidence that apigenin inhibits liver cancer progression and elucidates its mechanism of action in regulating lipid metabolism. Specifically, we find that apigenin suppresses the progression of HCC cells by downregulating genes involved in lipid metabolism. Additionally, our results indicate that KDM1A acts as a downstream target of apigenin in the inhibition of lipid metabolism in HCC. These findings offer experimental support for the potential use of apigenin as a therapeutic agent for liver cancer, highlighting its relevance in future clinical applications.

11.
Zhongguo Zhong Yao Za Zhi ; 49(16): 4313-4320, 2024 Aug.
Artículo en Chino | MEDLINE | ID: mdl-39307768

RESUMEN

This study aims to investigate the mechanism of Xueshuantong Injection(XST) on pulmonary fibrosis induced by bleomycin(BLM) in rats based on the coagulation cascade pathway. Sixty SD rats were randomly divided into sham surgery group,model group, pirfenidone(PFD, 50 mg·kg~(-1)) group, and 27, 54, and 81 mg·kg~(-1) XST groups. The rat model of pulmonary fibrosis was established by intratracheal injection of BLM(5 mg·kg~(-1)). After 24 hours, the administration groups were given corresponding drugs, while the sham surgery group and model group were given equal volumes of saline. On the 28th day, samples were collected,and the imaging and collagen fiber changes in the lungs of rats were observed. Immunofluorescence(IF) method was used to detect the expression level of alpha-smooth muscle actin(α-SMA), collagen Ⅰ(Col-Ⅰ), E-cadherin(E-cad), and vimentin(Vim). Western blot was used to determine the protein expression of α-SMA, Col-Ⅰ, Vim, and E-cad. Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of prothrombin fragment(F1 + 2), thrombin-antithrombin complex(TAT), soluble fibrin monomer complex(SFMC), and rat fibrinogen degradation products(FDP) in rat lung tissue. Finally, the mRNA and protein levels of protease activated receptor 1(PAR-1) were detected by RT-qPCR, western blot, and IF. Compared with the model group, the scanning of the lungs of rats receiving XST treatment also exhibited patchy and non-homogeneous shadows, but these shadows were less dense than those in the model group. At the same time, there was a significant decrease in Col-Ⅰ fibers in the lungs of rats, and XST could inhibit epithelial-mesenchymal transition(EMT) and downregulate α-SMA and Col-Ⅰ protein expression. In the aspect of the coagulation system, administration of 81 mg·kg~(-1) XST significantly reduced the levels of SFMC and FDP. Meanwhile, 81 mg·kg~(-1) XST significantly downregulated the mRNA and protein levels of PAR-1. XST has an anti-pulmonary fibrosis effect in rats, and its mechanism may be related to the downregulation of PAR-1 to rebalance the coagulation cascade pathway.


Asunto(s)
Bleomicina , Medicamentos Herbarios Chinos , Fibrosis Pulmonar , Ratas Sprague-Dawley , Animales , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/genética , Bleomicina/efectos adversos , Ratas , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacología , Masculino , Coagulación Sanguínea/efectos de los fármacos , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Humanos , Actinas/metabolismo , Actinas/genética , Cadherinas/genética , Cadherinas/metabolismo , Colágeno Tipo I/metabolismo , Colágeno Tipo I/genética , Vimentina/metabolismo , Vimentina/genética , Inyecciones
12.
Chemphyschem ; : e202400590, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39190709

RESUMEN

The development and applications of porous materials have been revolutionized over the past decades. To fine-tune their fascinating behaviors such as charge-transport, magnetic, and catalytic properties, one of the most effective strategies is incorporating mixed valency into the structures. This Concept provides recent progress on emerging crystalline porous materials, namely, metal-organic frameworks, metal-organic polyhedra, covalent organic frameworks, and hydrogen-bonded organic frameworks, where their mixed valency is either intrinsic or postsynthetically induced via an external stimulus. We further highlight the investigation of mixed valency and potential applications, which sheds light on the design and exploitation of mixed-valence crystalline porous materials.

13.
Zhonghua Nan Ke Xue ; 30(6): 531-539, 2024 Jun.
Artículo en Chino | MEDLINE | ID: mdl-39212363

RESUMEN

OBJECTIVE: To explore the mechanisms of Qianlie Jindan Tablets (QLJD) acting on chronic nonbacterial prostatitis (CNP) in rats based on non-targeted urine metabolomics. METHODS: According to the body mass index, we equally randomized 30 eight-week-old male SD rats into a blank control, a CNP model control and a QLJD medication group. We established the CNP model in the latter groups and, from the 4th day of modeling, treated the rats in the blank and model control groups intragastrically with normal saline and those in the QLJD medication group with QLJD suspension, qd, for 30 successive days. Then we detected the changes in the metabolites of the rats by ultra-high-performance liquid chromatography-tandem mass spectrometry, and identified the differential metabolites in different groups by multivariate statistical analysis, followed by functional annotation of the differential metabolites. RESULTS: Eight common metabolites were identified by metabolomics analysis, of which 5 were decreased in the CNP model controls and increased in the QLJD medication group, while the other 3 increased in the former and decreased in the latter group. Creatinine and genistein were important differential metabolites, and the arginine and proline metabolic pathways and isoflavone biosynthesis pathways were the main ones for QLJD acting on CNP. Compared with the blank controls, the model controls showed up-regulated arginine and proline metabolic pathways, increased production of creatinine, down-regulated isoflavone biosynthetic pathway and decreased production of genistein. The above changes in the model controls were all reversed in the QLJD medication group. CONCLUSION: QLJD acts effectively on CNP in male rats by regulating L-arginine and proline metabolic pathways, as well as the isoflavone biosynthesis pathway and naringenin metabolism.


Asunto(s)
Medicamentos Herbarios Chinos , Metabolómica , Prostatitis , Ratas Sprague-Dawley , Masculino , Animales , Ratas , Prostatitis/metabolismo , Prostatitis/orina , Prostatitis/tratamiento farmacológico , Metabolómica/métodos , Comprimidos , Cromatografía Líquida de Alta Presión , Arginina/metabolismo , Enfermedad Crónica , Genisteína/orina , Prolina/orina , Prolina/metabolismo , Modelos Animales de Enfermedad , Creatinina/orina , Creatinina/metabolismo , Espectrometría de Masas en Tándem
14.
Front Pharmacol ; 15: 1405521, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39144617

RESUMEN

Introduction: Almonertinib is an important third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) exhibiting high selectivity to EGFR-sensitizing and T790M-resistant mutations. Almonertinib resistance is a major obstacle in clinical use. Baicalein possesses antitumor properties, but its mechanism of antitumor action against almonertinib-resistant non-small cell lung cancer (NSCLC) remains unelucidated. Methods: CCK-8 assay was used to examine the survival rate of H1975/AR and HCC827/AR cells following treatment for 24 h with different concentrations of baicalein, almonertinib or their combination. The changes in colony formation ability, apoptosis, and intracellular reactive oxygen species (ROS) levels of the treated cells were analyzed using colony formation assay and flow cytometry. Western blotting was performed to detect the changes in protein expressions in the cells. The effects of pre-treatment with NAC on proliferation, apoptosis, and PI3K/Akt signaling pathway were observed in baicalein- and/or almonertinib-treated cells. A nude mouse model bearing subcutaneous HCC827/AR cell xenograft were treated with baicalein (20 mg/kg) or almonertinib (15 mg/kg), and the tumor volume and body mass changes was measured. Results: Both baicalein and almonertinib represses the viability of HCC827/AR and H1975/AR cells in a concentration-dependent manner. Compared with baicalein or almonertinib alone, the combined application of the two drugs dramatically attenuates cell proliferation; triggers apoptosis; causes cleavage of Caspase-3, PARP, and Caspase-9; downregulates the protein expressions of p-PI3K and p-Akt; and significantly inhibits tumor growth in nude mice. Furthermore, baicalein combined with almonertinib results in massive accumulation of reactive oxygen species (ROS) and preincubation with N-acetyl-L-cysteine (ROS remover) prevents proliferation as well as inhibits apoptosis induction, with partial recovery of the decline of p-PI3K and p-Akt. Discussion: The combination of baicalein and almonertinib can improve the antitumor activity in almonertinib-resistant NSCLC through the ROS-mediated PI3K/Akt pathway.

15.
PLoS Biol ; 22(8): e3002751, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39137170

RESUMEN

ADP ribosylation factor-like GTPase 2 (Arl2) is crucial for controlling mitochondrial fusion and microtubule assembly in various organisms. Arl2 regulates the asymmetric division of neural stem cells in Drosophila via microtubule growth. However, the function of mammalian Arl2 during cortical development was unknown. Here, we demonstrate that mouse Arl2 plays a new role in corticogenesis via regulating microtubule growth, but not mitochondria functions. Arl2 knockdown (KD) leads to impaired proliferation of neural progenitor cells (NPCs) and neuronal migration. Arl2 KD in mouse NPCs significantly diminishes centrosomal microtubule growth and delocalization of centrosomal proteins Cdk5rap2 and γ-tubulin. Moreover, Arl2 physically associates with Cdk5rap2 by in silico prediction using AlphaFold multimer, which was validated by co-immunoprecipitation and proximity ligation assay. Remarkably, Cdk5rap2 overexpression significantly rescues the neurogenesis defects caused by Arl2 KD. Therefore, Arl2 plays an important role in mouse cortical development through microtubule growth via the centrosomal protein Cdk5rap2.


Asunto(s)
Proteínas de Ciclo Celular , Centrosoma , Microtúbulos , Proteínas del Tejido Nervioso , Células-Madre Neurales , Neurogénesis , Animales , Microtúbulos/metabolismo , Ratones , Proteínas del Tejido Nervioso/metabolismo , Proteínas del Tejido Nervioso/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Neurogénesis/genética , Células-Madre Neurales/metabolismo , Centrosoma/metabolismo , Proliferación Celular , Movimiento Celular , Corteza Cerebral/metabolismo , Corteza Cerebral/embriología , Corteza Cerebral/crecimiento & desarrollo , Tubulina (Proteína)/metabolismo , Proteínas de Unión al GTP/metabolismo , Proteínas de Unión al GTP/genética , Factores de Ribosilacion-ADP/metabolismo , Factores de Ribosilacion-ADP/genética
17.
Am J Cancer Res ; 14(6): 2984-2993, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39005674

RESUMEN

This study aimed to define the role of heterogeneity of liver parenchymal enhancement on computed tomography (CT) in the survival of patients with hepatocellular carcinoma (HCC) after hepatic resection. The medical records of patients with HCCs and who had undergone hepatic resection were retrospectively reviewed. The standard deviation (SD) of three different enhanced CT scan images was used to estimate the heterogeneity of liver parenchymal enhancement: SD of > 5.6, heterogenous enhancement, and SD of ≤ 5.6, homogeneous enhancement. A total of 57 patients had heterogenous enhancement, and 143 patients had homogeneous enhancement. The patients with heterogenous enhancement had longer disease-free and overall survivals than those with other enhancements (log-rank test, P < 0.001 and P = 0.036). The pathologic exam showed that heterogenous enhancement tended to develop septa in the peritumoral liver tissues. The prevalence of CD8+ cells was significantly higher in the peritumor liver tissues with septa than in those without (0.83% vs. 0.26%, P < 0.001). The peritumoral CD8/Foxp3 ratio was higher in the liver tissues with septa than in those without (1.22 vs. 0.47, P = 0.001), and patients with CD8/Foxp3 of > 0.8 had better overall survival than those with CD8/Foxp3 of ≤ 0.8 (log-rank test, P = 0.028). In conclusion, patients who had undergone hepatic resection with a heterogenous liver parenchymal enhancement tended to develop hepatic septa, which was associated with a higher CD8/Foxp3 ratio and longer survival. Therefore, contrast-enhanced CT scans might be a useful tool to predict the outcome of HCC.

18.
BMC Plant Biol ; 24(1): 729, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39080585

RESUMEN

BACKGROUND: Straw incorporation serves as an effective strategy to enhance soil fertility and soil microbial biomass carbon (SMBC), which in turn improves maize yield and agricultural sustainability. However, our understanding of nitrogen (N) fertilization and straw incorporation into soil microenvironment is still evolving. This study explored the impact of six N fertilization rates (N0, N100, N150, N200, N250, and N300) with and without straw incorporation on soil fertility, SMBC, enzyme activities, and maize yield. RESULTS: Results showed that both straw management and N fertilization significantly affected soil organic carbon (SOC), total N, SMBC, soil enzyme activities, and maize yield. Specifically, the N250 treatment combined with straw incorporation significantly increased SOC, total N, and SMBC compared to lower fertilization rates. Additionally, enzyme activities such as urease, cellulase, sucrose, catalase, and acid phosphatase reached their peak during the V6 growth stage in the N200 treatment under for both straw management conditions. Compared to N250 and N300 treatments of traditional planting, the N200 treatment with residue incorporation significantly increased yield by 8.30 and 4.22%, respectively. All measured parameters, except for cellulase activity, were significantly higher in spring than in the autumn across both study years, with notable increases observed in 2021. CONCLUSIONS: These findings suggest that optimal levels of SOC, soil total N (STN), and SMBC, along with increased soil enzyme activities, is crucial for sustaining soil fertility and enhancing maize grain yield under straw incorporation and N200 treatments.


Asunto(s)
Fertilizantes , Nitrógeno , Suelo , Zea mays , Zea mays/crecimiento & desarrollo , Zea mays/metabolismo , Suelo/química , Nitrógeno/metabolismo , Producción de Cultivos/métodos , Carbono/metabolismo , Productos Agrícolas/crecimiento & desarrollo , Productos Agrícolas/metabolismo , Biomasa , Microbiología del Suelo , Agricultura/métodos
19.
Chem Commun (Camb) ; 60(59): 7638-7641, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-38963238

RESUMEN

The versatile reactivity of isothiocyanate intermediates enabled the diversity-oriented synthesis (DOS) of N-heterocycles in a DNA-compatible manner. We first reported a mild in situ conversion of DNA-conjugated amines to isothiocyanates. Subsequently, a set of diverse transformations was successfully developed to construct 2-thioxo-quinazolinones, 1,2,4-thiadiazoles, and 2-imino thiazolines. Finally, the feasibility of these approaches in constructing DELs was further demonstrated through enzymatic ligation and mock pool preparation. This study demonstrated the advantages of combining in situ conversion strategies with DOS, which effectively broadened the chemical and structural diversity of DELs.


Asunto(s)
ADN , Compuestos Heterocíclicos , Isotiocianatos , Isotiocianatos/química , ADN/química , Compuestos Heterocíclicos/química , Compuestos Heterocíclicos/síntesis química , Estructura Molecular , Aminas/química , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/síntesis química
20.
Front Immunol ; 15: 1380229, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38911867

RESUMEN

Background: Vitamin E, which is also known as tocopherol, is a compound with a polyphenol structure. Its esterified derivative, Vitamin E succinate (VES), exhibits unique anticancer and healthcare functions as well as immunomodulatory effects. Natural polysaccharides are proved to be a promising material for nano-drug delivery systems, which show excellent biodegradability and biocompatibility. In this study, we employed a novel bletilla striata polysaccharide-vitamin E succinate polymer (BSP-VES) micelles to enhance the tumor targeting and anti-colon cancer effect of andrographolide (AG). Methods: BSP-VES polymer was synthesized through esterification and its structure was confirmed using 1H NMR. AG@BSP-VES was prepared via the dialysis method and the drug loading, entrapment efficiency, stability, and safety were assessed. Furthermore, the tumor targeting ability of AG@BSP-VES was evaluated through targeted cell uptake and in vivo imaging. The antitumor activity of AG@BSP-VES was measured in vitro using MTT assay, Live&Dead cell staining, and cell scratch test. Results: In this study, we successfully loaded AG into BSP-VES micelles (AG@BSP-VES), which exhibited good stability, biosafety and sustained release effect. In addition, AG@BSP-VES also showed excellent internalization capability into CT26 cells compared with NCM460 cells in vitro. Meanwhile, the specific delivery of AG@BSP-VES micelles into subcutaneous and in-situ colon tumors was observed compared with normal colon tissues in vivo during the whole experiment process (1-24 h). What's more, AG@BSP-VES micelles exhibited significant antitumor activities than BSP-VES micelles and free AG. Conclusion: The study provides a meaningful new idea and method for application in drug delivery system and targeted treatment of colon cancer based on natural polysaccharides.


Asunto(s)
Neoplasias del Colon , Diterpenos , Micelas , Polisacáridos , Animales , Neoplasias del Colon/tratamiento farmacológico , Diterpenos/química , Diterpenos/farmacología , Diterpenos/administración & dosificación , Humanos , Ratones , Línea Celular Tumoral , Polisacáridos/química , Antineoplásicos/farmacología , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Sistemas de Liberación de Medicamentos , Ensayos Antitumor por Modelo de Xenoinjerto , Portadores de Fármacos/química , Nanopartículas/química , Sistema de Administración de Fármacos con Nanopartículas/química , Ratones Desnudos , Ratones Endogámicos BALB C
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA