RESUMEN

The carcinogenic effects of benzidine (BZ) on bladder cancer are well documented, but its potential for promoting upper urinary tract urothelial carcinoma (UTUC) remains unclear. The ability of emodin, a natural pharmaceutical compound, to prevent BZ­associated UTUC has not been previously explored. To the best of our knowledge, the present study is the first to reveal that BZ significantly enhanced the survival and migration of UTUC cell lines in vitro. Furthermore, in vivo experiments demonstrated that BZ promoted an increase in the size of subcutaneous tumors in nude mice. Further investigation revealed that BZ upregulated the expression of protein kinase A (PKA) and cyclooxygenase 2 (COX2), along with downstream matrix metalloproteinase 9 (MMP9) and vascular endothelial growth factor (VEGF), in UTUC cells. Moreover, BZ increased the levels of cyclic adenosine monophosphate (cAMP) and prostaglandin E2 (PGE2) in cell lysates. By contrast, emodin reduced the PKA and COX2 expression levels compared with the BZ­treated group. Similarly, the in vivo experiments demonstrated that emodin significantly inhibited tumor growth in BZ­pretreated nude mice, accompanied by reductions in the cAMP, PGE2, MMP9 and VEGF levels. These findings elucidated the role of BZ in promoting UTUC progression. Additionally, emodin has emerged as a novel inhibitor of BZ­induced UTUC development through PKA/COX2 inhibition, suggesting its potential as a natural therapeutic agent against BZ­associated UTUC.

Asunto(s)

Movimiento Celular , Proteínas Quinasas Dependientes de AMP Cíclico , Ciclooxigenasa 2 , Emodina , Transducción de Señal , Ensayos Antitumor por Modelo de Xenoinjerto , Animales , Humanos , Ciclooxigenasa 2/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Ratones , Movimiento Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Línea Celular Tumoral , Emodina/farmacología , Emodina/uso terapéutico , Ratones Desnudos , Supervivencia Celular/efectos de los fármacos , Metaloproteinasa 9 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Neoplasias Urológicas/tratamiento farmacológico , Neoplasias Urológicas/patología , Neoplasias Urológicas/metabolismo , Dinoprostona/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Proliferación Celular/efectos de los fármacos , AMP Cíclico/metabolismo , Bencidinas

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Lung cancer has the highest incidence and mortality rates of all cancer types in China and therefore represents a serious threat to human health. In the present study, the mechanism of rabdoternin E against the proliferation of the lung cancer cell line A549 was explored. It was found that rabdoternin E caused the accumulation of large amounts of reactive oxygen species (ROS), promoted cell S phase arrest by reducing the expression of CDK2 and cyclin A2, induced apoptosis by increasing the Bax/Bcl­2 ratio and promoted the phosphorylation of proteins in the ROS/p38 MAPK/JNK signaling pathway, which is associated with apoptosis and ferroptosis. In addition, it was also found that Z­VAD­FMK (an apoptosis inhibitor), ferrostatin­1 (ferroptosis inhibitor) and N­acetylcysteine (a ROS inhibitor) could partially or greatly reverse the cytotoxicity of rabdoternin E to A549 cells. Similarly, NAC (N­acetylcysteine) treatment notably inhibited the rabdoternin E­stimulated p38 MAPK and JNK activation. Furthermore, in vivo experiments in mice revealed that Rabdoternin E markedly reduced tumor volume and weight and regulated the expression levels of apoptosis and ferroptosis­related proteins (including Ki67, Bcl­2, Bax, glutathione peroxidase 4, solute carrier family 7 member 11 and transferrin) in the tumor tissues of mice. Histopathological observation confirmed that the number of tumor cells decreased markedly after administration of rabdoternin E. Taken together, rabdoternin E induced apoptosis and ferroptosis of A549 cells by activating the ROS/p38 MAPK/JNK signaling pathway. Therefore, the results of the present study showed that rabdoternin E is not toxic to MCF­7 cells (normal lung cells), had no significant effect on body weight and was effective and therefore may be a novel therapeutic treatment for lung cancer.

Asunto(s)

Apoptosis , Neoplasias Pulmonares , Sistema de Señalización de MAP Quinasas , Especies Reactivas de Oxígeno , Proteínas Quinasas p38 Activadas por Mitógenos , Humanos , Especies Reactivas de Oxígeno/metabolismo , Animales , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones , Células A549 , Apoptosis/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Ferroptosis/efectos de los fármacos , Ratones Desnudos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico

RESUMEN

This review explores the roles of the cholinergic system in the heart, comprising the neuronal and non-neuronal cholinergic systems. Both systems are essential for maintaining cardiac homeostasis by regulating the release of acetylcholine (ACh). A reduction in ACh release is associated with the early onset of cardiovascular diseases (CVDs), and increasing evidence supports the protective roles of ACh against CVD. We address the challenges and limitations of current strategies to elevate ACh levels, including vagus nerve stimulation and pharmacological interventions such as cholinesterase inhibitors. Additionally, we introduce alternative strategies to increase ACh in the heart, such as stem cell therapy, gene therapy, microRNAs, and nanoparticle drug delivery methods. These findings offer new insights into advanced treatments for regenerating the injured human heart.

RESUMEN

The application of silicon-based nanomaterials in fast-charging scenarios is hindered by volume expansion during lithiation and side reactions induced by surface effects. Constructing a robust encapsulation structure with high mechanical strength and conductivity is pivotal for optimizing the electrochemical performance of nanostructured silicon anodes. Herein, we propose a multifaceted hierarchical encapsulation structure featuring excellent mechanical strength and high conductivity by sequentially incorporating SiO x , hard carbon, and closed-pore carbon layers around silicon quantum dots, thereby enabling stable cycling at high current densities. In this structure, the ultra-thin SiO x layer strengthens the Si-C interface, while the outermost carbon matrix with closed pores functions both as a conductive network and a barrier against electrolyte intrusion. Notably, the synthesized material exhibits a specific capacity of 1506 mA h g-1 with 90.17% retention after 300 cycles at 1.0 A g-1. After 500 cycles at 5.0 A g-1, it retains 640.4 mA h g-1, over 70% of its initial capacity.

RESUMEN

Objective: Fibroblast growth factor 21 (FGF21) is a secreted protein that regulates body metabolism. In recent years, many observational studies have found that FGF21 is closely related to bone mineral density and osteoporosis, but the causal relationship between them is still unclear. Therefore, this study used two-sample, mediated Mendelian randomization (MR) analysis to explore the causal relationship between FGF21 and osteoporosis and bone mineral density. Methods: We conducted a two-sample, mediator MR Analysis using genetic data from publicly available genome-wide association studies (GWAS) that included genetic variants in the inflammatory cytokine FGF21, and Total body bone mineral density, Heel bone mineral density, Forearm bone mineral density, Femoral neck bone mineral density, osteoporosis. The main analysis method used was inverse variance weighting (IVW) to investigate the causal relationship between exposure and outcome. In addition, weighted median, simple median method, weighted median method and MR-Egger regression were used to supplement the explanation, and sensitivity analysis was performed to evaluate the reliability of the results. Results: MR Results showed that FGF21 overexpression reduced bone mineral density: Total body bone mineral density (OR=0.920, 95%CI: 0.876-0.966), P=0.001), Heel bone mineral density (OR=0.971, 95%CI (0.949-0.993); P=0.01), Forearm bone mineral density (OR=0.882, 95%CI(0.799-0.973); P=0.012), Femoral neck bone mineral density (OR=0.952, 95%CI(0.908-0.998), P=0.039); In addition, it also increased the risk of osteoporosis (OR=1.003, 95%CI (1.001-1.005), P=0.004). Sensitivity analysis supported the reliability of these results. The effect of FGF21 overexpression on osteoporosis may be mediated by type 2 diabetes mellitus and basal metabolic rate, with mediating effects of 14.96% and 12.21%, respectively. Conclusions: Our study suggests that the overexpression of FGF21 may lead to a decrease in bone mineral density and increase the risk of osteoporosis, and the effect of FGF21 on osteoporosis may be mediated through type 2 diabetes and basal metabolic rate. This study can provide a reference for analyzing the potential mechanism of osteoporosis and is of great significance for the prevention and treatment of osteoporosis.

Asunto(s)

Densidad Ósea , Factores de Crecimiento de Fibroblastos , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Osteoporosis , Humanos , Factores de Crecimiento de Fibroblastos/genética , Densidad Ósea/genética , Osteoporosis/genética , Osteoporosis/metabolismo , Femenino , Polimorfismo de Nucleótido Simple , Masculino

RESUMEN

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease globally. Growing data suggests that smoking plays an important role in the evolution of NAFLD. CDGSH iron sulfur domain 3 (CISD3) regulates critical biological activities. However, its role in nicotine-associated NAFLD and its underlying mechanisms have not been elucidated. Mice were given a high-fat diet for 10 weeks to induce the development of NAFLD. The results revealed that in mice with NAFLD, nicotine treatment resulted in reduced CISD3 expression, leading to mitochondrial dysfunction and impaired ß-oxidation. Notably, exacerbation of hepatic steatosis and inflammatory injury was observed. Furthermore, Cisd3-knockout exacerbated lipid accumulation, aggravating oxidative stress and apoptosis. In conclusion, these results contribute to our knowledge of the function of CISD3 in nicotine-associated NAFLD, revealing the possibility of using CISD3 as a potential molecular target for treating NAFLD.

RESUMEN

The translation of discoveries on extracellular vesicle (EV) based cancer biomarkers to personalised precision oncology requires the development of robust, sensitive and specific assays that are amenable to adoption in the clinical laboratory. Whilst a variety of elegant approaches for EV liquid biopsy have been developed, most of them remain as research prototypes due to the requirement of a high level of microfabrication and/or sophisticated instruments. Hence, this study is set to develop a simple DNA aptamer-enabled and fluorescence polarisation-based homogenous assay that eliminates the need to separate unbound detection ligands from the bound species for EV detection. High specificity is achieved by immobilising EVs with one set of antibodies and subsequently detecting them with a DNA aptamer targeting a distinct EV biomarker. This two-pronged strategy ensures the removal of most, if not all, non-EV substances in the input biofluids, including soluble proteins, protein aggregates or non-vesicular particles, prior to quantifying biomarker-positive EVs. A limit of detection of 5.0 × 106 EVs/mL was achieved with a linear quantification range of 5.0 × 108 to 2.0 × 1010 EVs/mL. Facilitated by a multiple parametric analysis strategy, this aptamer-guided fluorescence polarisation assay was capable of distinguishing EVs from three different types of solid cancer cells based on quantitative differences in the levels of the same sets of biomarkers on EVs. Given the simplicity of the method and its ease of implementation in automated clinical biochemistry analysers, this assay could be exploited for future EV-based continuous and real-time monitoring of the emergence of new macro- or micro-metastasis, cancer progression as well as the response to treatment throughout different stages of cancer management in the clinic.

Asunto(s)

Aptámeros de Nucleótidos , Biomarcadores de Tumor , Vesículas Extracelulares , Humanos , Vesículas Extracelulares/metabolismo , Biopsia Líquida/métodos , Aptámeros de Nucleótidos/metabolismo , Biomarcadores de Tumor/metabolismo , Polarización de Fluorescencia/métodos , Línea Celular Tumoral , Neoplasias/metabolismo

RESUMEN

BACKGROUND: Due to similar symptoms of abdominal pain, acute pancreatitis (AP) is often difficult to differentiate from acute aortic dissection (AAD) in clinical practice. It is unknown whether serum amylase and coagulation function indices can be used to distinguish AP from AAD. METHODS: In this retrospective study, 114 AP patients (AP group) and 48 cases with AAD (AAD group) admitted for acute abdominal pain were enrolled for a final analysis. The levels of serum amylase and coagulation function indices, including prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (FIB), and D-dimer (DD), were tested before or on admission and compared between the two groups. Student's t-test was adopted for comparing the mean. Model discrimination was evaluated by using the area under the receiver operating characteristic curve (AUC). Comparison of AUC was performed by using the Z-test. RESULTS: Compared with the AAD group, amylase and FIB were both significantly increased, while DD was significantly lower in the AP group (all p < 0.01). There were no statistically significant differences of PT, INR, and APTT between AP and AAD (all p > 0.05). The AUCs in distinguishing AP from AAD were 0.913, 0.854, and 0.837 for amylase, FIB, and DD, respectively, but there were no significant differences observed among amylase, FIB, and DD (all p > 0.05). Finally, the cutoff values (specificity, sensitivity, and Youden index) in distinguishing between AP and AAD were 114 µ/L (80.70%, 95.83%, 0.765) for amylase, 2.62 g/L (76.32%, 85.42%, 0.617) for FIB, and 2.74 mg/L (95.61%, 62.50%, 0.581) for DD, respectively. CONCLUSIONS: Amylase, FIB, and DD can demonstrate accurate and reliable diagnostic values, suggesting that they are useful and potential biomarkers in distinguishing AP from AAD.

Asunto(s)

Amilasas , Disección Aórtica , Pancreatitis , Humanos , Disección Aórtica/diagnóstico , Disección Aórtica/sangre , Masculino , Amilasas/sangre , Femenino , Pancreatitis/diagnóstico , Pancreatitis/sangre , Persona de Mediana Edad , Estudios Retrospectivos , Diagnóstico Diferencial , Anciano , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Adulto , Coagulación Sanguínea/fisiología , Enfermedad Aguda , Biomarcadores/sangre , Curva ROC , Fibrinógeno/análisis , Fibrinógeno/metabolismo , Pruebas de Coagulación Sanguínea/métodos , Tiempo de Protrombina , Tiempo de Tromboplastina Parcial

RESUMEN

BACKGROUND: The whitefly Bemisia tabaci is one of the world's foremost agricultural pests. Recently, we found that a wild relative of tobacco (Nicotiana benthamiana) demonstrates remarkable attractiveness and nearly 100% lethality towards whiteflies. Therefore, it can act as a dead-end trap crop for whitefly control in the field. However, the underlying mechanism of the significant attractiveness of N. benthamiana towards whiteflies is unclear. RESULTS: Binary-choice assays and olfactory experiments showed that compared to common tobacco (N. tabacum), the volatile of N. benthamiana has a greater attraction to whiteflies. Then we analyzed and compared volatiles from these two Nicotiana species by thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS). We identified 16 chemical compounds that are more abundant in N. benthamiana than in N. tabacum. Seven compounds were further tested with olfactometer assays and we found that, among them, undecane strongly attracted whiteflies. Further experiments revealed that even 0.005 µg mL-1 undecane is attractive to whiteflies. We also silenced the genes that may influence the biosynthesis of undecane and found the production of undecane decreased after silencing NbCER3, and that N. benthamiana plants with less undecane lost their attraction to whiteflies. In addition, we found that applying 0.005 µg mL-1 undecane on yellow sticky traps can increase the number of stuck insects on the traps by ≈40%. CONCLUSION: Undecane from the volatile of N. benthamiana is a critical chemical signal that attracts whiteflies and NbCER3 involved in the biosynthesis of undecane. Undecane may be used to improve the efficiency of yellow sticky traps for whitefly control. © 2024 Society of Chemical Industry.

RESUMEN

Solar-powered seawater production of clean hydrogen fuel is highly prospective. In this work, Ni3C/Mn0.5Cd0.5S (NCMCS) Schottky junctions with excellent visible-light correspondence and photogenerated carrier separation properties are constructed using electrostatic attraction. The material achieves a hydrogen evolution rate of 6472.9 µmol h-1 g-1 in simulated seawater, which is 11 times higher than that of a single Mn0.5Cd0.5S (MCS). More attractively, the composite exhibits excellent hydrogen evolution rates in natural river water, groundwater and tap water, with significantly enhanced practical applicability. The underlying hydrogen evolution mechanism was extrapolated from a combination of experimental and theoretical calculations. The present work provides a low-cost and efficient hydrogen evolution photocatalyst for practical application, which can help promote the efficient conversion of solar-hydrogen energy.

RESUMEN

In the phase 3 Coronavirus Efficacy (COVE) trial (NCT04470427), post-dose two Ancestral Spike-specific binding (bAb) and neutralizing (nAb) antibodies were shown to be correlates of risk (CoR) and of protection against Ancestral-lineage COVID-19 in SARS-CoV-2 naive participants. In the SARS-CoV-2 Omicron era, Omicron subvariants with varying degrees of immune escape now dominate, seropositivity rates are high, and booster doses are administered, raising questions on whether and how these developments affect the bAb and nAb correlates. To address these questions, we assess post-boost BA.1 Spike-specific bAbs and nAbs as CoRs and as correlates of booster efficacy in COVE. For naive individuals, bAbs and nAbs inversely correlate with Omicron COVID-19: hazard ratios (HR) per 10-fold marker increase (95% confidence interval) are 0.16 (0.03, 0.79) and 0.31 (0.10, 0.96), respectively. In non-naive individuals the analogous results are similar: 0.15 (0.04, 0.63) and 0.28 (0.07, 1.08). For naive individuals, three vs two-dose booster efficacy correlates with predicted nAb titer at exposure, with estimates -8% (-126%, 48%), 50% (25%, 67%), and 74% (49%, 87%), at 56, 251, and 891 Arbitrary Units/ml. These results support the continued use of antibody as a surrogate endpoint.

Asunto(s)

Vacuna nCoV-2019 mRNA-1273 , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19 , Inmunización Secundaria , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Humanos , COVID-19/inmunología , COVID-19/virología , COVID-19/prevención & control , SARS-CoV-2/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Glicoproteína de la Espiga del Coronavirus/inmunología , Vacuna nCoV-2019 mRNA-1273/administración & dosificación , Vacuna nCoV-2019 mRNA-1273/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Femenino , Masculino , Adulto , Eficacia de las Vacunas

RESUMEN

Nicotiana benthamiana, a widely acknowledged laboratory model plant for molecular studies, exhibits lethality to certain insect pests and can serve as a dead-end trap plant for pest control in the field. However, the underlying mechanism of N. benthamiana's resistance against insects remains unknown. Here, we elucidate that the lethal effect of N. benthamiana on the whitefly Bemisia tabaci arises from the toxic glandular trichome exudates. By comparing the metabolite profiles of trichome exudates, we found that 51 metabolites, including five O-acyl sugars (O-AS) with medium-chain acyl moieties, were highly accumulated in N. benthamiana. Silencing of two O-AS biosynthesis genes, branched-chain keto acid dehydrogenase (BCKD) and Isopropyl malate synthase-C (IPMS-C), significantly reduced the O-AS levels in N. benthamiana and its resistance against whiteflies. Additionally, we demonstrated that the higher expression levels of BCKD and IPMS-C in the trichomes of N. benthamiana contribute to O-AS synthesis and consequently enhance whitefly resistance. Furthermore, overexpression of NbBCKD and NbIPMS-C genes in the cultivated tobacco Nicotiana tabacum enhanced its resistance to whiteflies. Our study revealed the metabolic and molecular mechanisms underlying the lethal effect of N. benthamiana on whiteflies and presents a promising avenue for improving whitefly resistance.

RESUMEN

Layered silicon (L-Si) anodes are celebrated for their high theoretical capacity but face significant challenges regarding safety and material purity during preparation. This study addresses these challenges by employing NH4Cl-CaSi2 as the raw material in a gas-solid de-alloying process, which enhances both safety and purity compared to traditional methods. The L-Si anodes produced demonstrate outstanding electrochemical performance, delivering a high reversible lithium storage capacity of 1497.7 mA h g-1 at a current density of 0.5 A g-1, and exhibiting stable performance over 1200 charge-discharge cycles. In situ and ex situ characterizations reveal that electrolyte decomposition products effectively fill the voids within the electrode, while the gradual disintegration of the L-Si structure contributes to the formation of a dense, conductive network. This process enhances lithium ion transport and exploits the capacitive storage benefits of layered silicon.

RESUMEN

Creating high-quality contacts between high-melting-point metals and delicate two-dimensional (2D) semiconductors poses a critical challenge to polarity control due to inevitable chemical disorder and Fermi-level pinning observed in the contact regions. Here, we report a van der Waals (vdW) integration strategy to precisely tailor the WSe2 polarity by meticulously modulating metal contact compositions. Controlling the low-melting-point bismuth (Bi) thickness effectively modulates the Bi/Au dominant contact with WSe2. This facilitates the precise polarity transformation between n-type, ambipolar, and p-type, with exceptional field-effect mobilities of 200 cm2 V-1 s-1 for electrons and 136 cm2 V-1 s-1 for holes. Within this vdW geometry, we further demonstrate the fundamental electrical components such as diodes and complementary inverters with enhanced rectification ratios and voltage gains. Our results showcase an effective and compatible with mass manufacturing method for precise polarity modulation of 2D semiconductors, providing a promising pathway toward large-scale high-performance 2D electronics and integrated circuits.

RESUMEN

In practical engineering applications, factors like dust adhesion and environmental changes can cause photovoltaic arrays to exhibit multiple peaks in output power. An optimization algorithm with global optimization capability is needed to track its maximum power. In this regard, this paper proposes an improved marine predator algorithm (IMPA) to extract the maximum power point of photovoltaic system under complex solar irradiation conditions. To overcome the issues in the traditional marine predator algorithm (MPA), the opposition-based learning(OBL) strategy is introduced in IMPA, and the sine cosine algorithm (SCA) is integrated into the iteration stage to enhance the search ability of the algorithm. Furthermore, the low-order converter in the traditional MPPT control system is replaced by the Zeta converter, which increases the operating voltage range. Ultimately, simulation results demonstrate that the MPPT based on IMPA has higher tracking efficiency and shorter response time.The experimental results also indicate the practical feasibility of this method, as well as its high level of stability and robustness.

RESUMEN

Nitrogen (N) deposition, as one of the global change drivers, can alter terrestrial plant diversity and ecosystem function. However, the response of the plant diversity-ecosystem function relationship to N deposition remains unclear. On one hand, in the previous studies, taxonomic diversity (i.e., species richness, SR) was solely considered the common metric of plant diversity, compared to other diversity metrics such as phylogenetic and functional diversity. On the other hand, most previous studies simulating N deposition only included two levels of control versus N enrichment. How various N deposition rates affect multidimensional plant diversity-ecosystem function relationships is poorly understood. Here, a field manipulative experiment with a N addition gradient (0, 1, 2, 4, 8, 16, 32, and 64 g N m-2 yr-1) was carried out to examine the effects of N addition rates on the relationships between plant diversity metrics (taxonomic, phylogenetic, and functional diversity) and ecosystem production in a temperate steppe. Production initially increased and reached the maximum value at the N addition rate of 47 g m-2 yr-1, then decreased along the N-addition gradient in the steppe. SR, functional diversity calculated using plant height (FDis-Height) and leaf chlorophyll content (FDis-Chlorophyll), and phylogenetic diversity (net relatedness index, NRI) were reduced, whereas community-weighted means of plant height (CWMHeight) and leaf chlorophyll content (CWMChlorophyll) were enhanced by N addition. N addition did not affect the relationships of SR, NRI, and FDis-Height with production but significantly affected the strength of the correlation between FDis-Chlorophyll, CWMHeight, and CWMChlorophyll with biomass production across the eight levels of N addition. The findings indicate the robust relationships of taxonomic and phylogenetic diversity and production and the varying correlations between functional diversity and production under increased N deposition in the temperate steppe, highlighting the importance of a trait-based approach in studying the plant diversity-ecosystem function under global change scenarios.

RESUMEN

Primary vaccination with mRNA-1273 (100-µg) was safe and efficacious at preventing coronavirus disease 2019 (COVID-19) in the previously reported, blinded Part A of the phase 3 Coronavirus Efficacy (COVE; NCT04470427) trial in adults (≥18 years) across 99 U.S. sites. The open-label (Parts B and C) primary objectives were evaluation of long-term safety and effectiveness of primary vaccination plus a 50-µg booster dose; immunogenicity was a secondary objective. Of 29,035 open-label participants, 19,609 received boosters (mRNA-1273 [n = 9647]; placebo-mRNA-1273 [n = 9952]; placebo [n = 10] groups). Booster safety was consistent with that reported for primary vaccination. Incidences of COVID-19 and severe COVID-19 were higher during the Omicron BA.1 than Delta variant waves and boosting versus non-boosting was associated with a significant, 47.0% (95% CI : 39.0-53.9%) reduction of Omicron BA.1 incidence (24.6 [23.4 - 25.8] vs 46.4 [40.6 - 52.7]/1000 person-months). In an exploratory Cox regression model adjusted for time-varying covariates, a longer median interval between primary vaccination and boosting (mRNA-1273 [13 months] vs placebo-mRNA-1273 [8 months]) was associated with significantly lower, COVID-19 risk (24.0% [16.0% - 32.0%]) during Omicron BA.1 predominance. Boosting elicited greater immune responses against SARS-CoV-2 than primary vaccination, irrespective of prior SARS-CoV-2 infection. Primary vaccination and boosting with mRNA-1273 demonstrated acceptable safety, effectiveness and immunogenicity against COVID-19, including emergent variants.

Asunto(s)

Vacuna nCoV-2019 mRNA-1273 , Vacunas contra la COVID-19 , COVID-19 , Inmunización Secundaria , SARS-CoV-2 , Humanos , Vacuna nCoV-2019 mRNA-1273/inmunología , COVID-19/prevención & control , COVID-19/inmunología , Adulto , Masculino , Femenino , SARS-CoV-2/inmunología , Persona de Mediana Edad , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/administración & dosificación , Eficacia de las Vacunas , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Inmunogenicidad Vacunal , Anciano , Adulto Joven , Vacunación , Adolescente

RESUMEN

Utilizing cell membranes from diverse cell types for biointerfacing has demonstrated significant advantages in enhancing colloidal stability and incorporating biological properties, tailored specifically for various biomedical applications. However, the structures of these materials, particularly emulsions interfaced with red blood cell (RBC) or platelet (PLT) membranes, remain an underexplored area. This study systematically employs small- and ultra-small-angle neutron scattering (SANS and USANS) with contrast variation to investigate the structure of emulsions containing perfluorohexane within RBC (RBC/PFH) and PLT membranes (PLT/PFH). The findings reveal that the scattering length density of RBC and PLT membranes is 1.5 × 10-6 Å-2, similar to 30% (w/w) deuterium oxide. Using this solvent as a cell membrane-matching medium, estimated droplet diameters are 770 nm (RBC/PFH) and 1.5 µm (PLT/PFH), based on polydispersed sphere model fitting. Intriguingly, calculated patterns and invariant analysis reveal native droplet architectures featuring entirely liquid PFH cores, differing significantly from the observed bubble-droplet core system in electron microscopy. This highlights the advantage of SANS and USANS in differentiating genuine colloidal structures in complex dispersions. In summary, this work underscores the pivotal role of SANS and USANS in characterizing biointerfaced colloids and in uncovering novel colloidal structures with significant potential for biomedical applications and clinical translation.

RESUMEN

Alzheimer's disease (AD), a prevalent cognitive disorder among the elderly, is frequently linked to the abnormal accumulation of myloid-ß (Aß), which is mainly as a result of neuronal death and inflammation. Diosmin, a flavonoid, is considered a potential drug for the treatment of AD. Our study aimed to uncover the molecular mechanism of diosmin in AD therapy. Here, rats were randomly divided into three groups: control, Aß25-35, and Aß25-35 + diosmin groups. AD model rats were induced by Aß25-35 intraventricular injection, meanwhile 50 mg/kg diosmin was orally administered for 6-week intervention. Morris water maze test assessed learning and memory abilities. Hippocampal neuronal damage was determined by HE, Nissl, and TUNEL staining. These assays indicate that diosmin improves cognitive dysfunction and reduces hippocampal neuronal loss and apoptosis. Western blot showed that diosmin reduced Bax (1.21 ± 0.12) and cleaved caspase-3 (1.27 ± 0.12) expression, and increased Bcl-2 (0.70 ± 0.06), p-PI3K (0.71 ± 0.08), and p-AKT (0.96 ± 0.10) in the hippocampus. ELISA indicated diosmin reduces IL-1ß, IL-6, and TNF-α levels, suggesting anti-inflammation effect. These results suggest that diosmin inhibits neuronal apoptosis and neuroinflammatory responses to improve cognitive dysfunction in AD rats, possibly related to upregulation of the PI3K/AKT pathway, providing a scientific basis for its use in AD treatment.