Genetic diversity of Flaviviridae and Rhabdoviridae EVEs in Aedes aegypti and Aedes albopictus on Hainan Island and the Leizhou Peninsula, China.

BACKGROUND: Hainan Island and the Leizhou Peninsula, the southernmost part of mainland China, are areas where Aedes aegypti and Ae. albopictus are sympatric and are also high-incidence areas of dengue outbreaks in China. Many studies have suggested that Aedes endogenous viral components (EVEs) are enriched in piRNA clusters which can silence incoming viral genomes. Investigation the EVEs present in the piRNA clusters associated with viral infection of Aedes mosquitoes in these regions may provide a theoretical basis for novel transmission-blocking vector control strategies. METHODS: In this study, specific primers for endogenous Flaviviridae elements (EFVEs) and endogenous Rhabdoviridae elements (ERVEs) were used to detect the distribution of Zika virus infection associated EVEs in the genomes of individuals of the two Aedes mosquitoes. Genetic diversity of EVEs with a high detection rate was also analyzed. RESULTS: The results showed that many EVEs associated with Zika virus infection were detected in both Aedes species, with the detection rates were 47.68% to 100% in Ae. aegypti and 36.15% to 92.31% in sympatric Ae. albopictus populations. EVEs detection rates in another 17 Ae. albopictus populations ranged from 29.39% to 89.85%. Genetic diversity analyses of the four EVEs (AaFlavi53, AaRha61, AaRha91 and AaRha100) of Ae. aegypti showed that each had high haplotype diversity and low nucleotide diversity. The number of haplotypes in AaFlavi53 was 8, with the dominant haplotype being Hap_1 and the other 7 haplotypes being further mutated from Hap_1 in a lineage direction. In contrast, the haplotype diversity of the other three ERVEs (AaRha61, AaRha91 and AaRha100) was more diverse and richer, with the haplotype numbers were 9, 15 and 19 respectively. In addition, these EVEs all showed inconsistent patterns of both population differentiation and dispersal compared to neutral evolutionary genes such as the Mitochondrial COI gene. CONCLUSION: The EFVEs and ERVEs tested were present at high frequencies in the field Aedes mosquito populations. The haplotype diversity of the EFVE AaFlavi53 was relatively lower and the three ERVEs (AaRha61, AaRha91, AaRha100) were higher. None of the four EVEs could be indicative of the genetic diversity of the Ae. aegypti population. This study provided theoretical support for the use of EVEs to block arbovirus transmission, but further research is needed into the mechanisms by which these EVEs are antiviral to Aedes mosquitoes.

Impact of Ae-GRD on Ivermectin Resistance and Its Regulation by miR-71-5p in Aedes aegypti.

iGABAR, a member of the Cys-loop ligand-gated ion channel superfamily, is a significant target of the insecticide ivermectin (IVM). GRD is the potential subunit of the insect iGABAR. However, little information about GRD in Ae. aegypti has been reported. In this study, we involved cloning and characterizing the iGABAR subunit GRD of Ae. aegypti (Ae-GRD). Sequence analysis indicated that Ae-GRD, as part of the cysteine-loop ligand-gated ion channel family, is similar to other insect GRD. RNA interference (RNAi) was employed to explore IVM resistance in Ae. aegypti, resulting in a significant reduction in Ae-GRD expression (p < 0.05), and the mortality of Ae. aegypti adults with Ae-GRD knockdown was significantly decreased after exposure to ivermectin. Bioinformatics prediction identified miR-71-5p as a potential regulator of Ae-GRD. In vitro, dual-luciferase reporter assays confirmed that Ae-GRD expression was regulated by miR-71-5p. Microinjection of miR-71-5p mimics upregulated miR-71-5p expression and downregulated Ae-GRD gene expression, reducing mortality by 34.52% following IVM treatment. Conversely, microinjection of a miR-71-5p inhibitor decreased miR-71-5p expression but did not affect the susceptibility to IVM despite increased Ae-GRD expression (p < 0.05). In conclusion, Ae-GRD, as one of the iGABA receptor subunits, is a potential target of ivermectin. It may influence ivermectin resistance by modulating the GABA signaling pathway. The inhibition of Ae-GRD expression by miR-71-5p decreased ivermectin resistance and consequently lowered the mortality rate of Ae. aegypti mosquitoes. This finding provides empirical evidence of the relationship between Ae-GRD and its miRNA in modulating insecticide resistance, offering novel perspectives for mosquito control strategies.

The Link Between Alzheimer's Disease and Stroke: A Detrimental Synergism.

Being age-related disorders, both Alzheimer's disease (AD) and stroke share multiple risk factors, such as hypertension, smoking, diabetes, and apolipoprotein E (APOE) Ɛ4 genotype, and coexist in patients. Accumulation of amyloid-ß plaques and neurofibrillary tangled impair cognitive potential, leading to AD. Blocked blood flow in the neuronal tissues, causes neurodegeneration and cell death in stroke. AD is commonly characterized by cerebral amyloid angiopathy, which significantly elevates the risk of hemorrhagic stroke. Patients with AD and stroke have been both reported to exhibit greater cognitive impairment, followed by multiple pathophysiological mechanisms shared between the two. The manuscript aims to elucidate the relationship between AD and stroke, as well as the common pathways and risk factors while understanding the preventive therapies that might limit the negative impacts of this correlation, with diagnostic modalities and current AD treatments. The authors provide a comprehensive review of the link and aid the healthcare professionals to identify suitable targets and risk factors, that may retard cognitive decline and neurodegeneration in patients. However, more intricate research is required in this regard and an interdisciplinary approach that would target both the vascular and neurodegenerative factors would improve the quality of life in AD patients.

Mother-infant bonding: The role of postpartum depression, violence, and bonding established with one's own mother during childhood.

Mother-infant bonding is influenced by several risk and protective factors, and the literature has investigated the relationships between these factors independently. This study aimed to verify the interrelationships of some of these factors and how they influence mother-infant bonding in Brazil. In this study, 361 mothers participated, and the outcome variable of mother-infant bonding was assessed using the Postpartum Bonding Questionnaire (PBQ). Multivariate regression analysis was performed using a hierarchical model with three blocks structured according to the influence exerted on mother-infant bonding. The PBQ's factor scores were estimated and used in the subsequent analyses to decrease measurement error. The variable "violence experienced by mothers" was statistically significant for explaining the second block model but not significant for the third block. Network analysis was performed after multiple regression, showing that the violence experienced by mothers does not directly influence mother-infant bonding but rather is mediated by postpartum depression. This explains why violence is not significant in the hierarchical multiple regression when maternal depression is added to the model. This study's strengths lie in its utilization of PBQ factor scores and network analysis, enabling the estimation of conditional relationships among variables. This approach provides deeper insights into factors affecting mother-infant bonding.

Varios factores de riesgo y de protección ejercen influencia sobre la unión afectiva madre­infante; la literatura disponible ha investigado las relaciones entre estos factores de una manera independiente. Este estudio se propuso verificar las interrelaciones de algunos de estos factores y cómo ellos influyen en la unión afectiva madre­infante. Se consultó un total de 361 madres y el variable resultado de afectividad madre­infante se evaluó por medio del Cuestionario de Afectividad de Postparto (PBQ). Se llevaron a cabo análisis de regresión multivariados usando un modelo jerárquico con tres estructuras de bloques de acuerdo con la influencia ejercida sobre la unión afectiva madre­infante. Se estimaron y usaron los puntajes de factores del PBQ en los análisis subsecuentes para disminuir el error en la medida. La variable "violencia experimentada por las madres" fue estadísticamente significativa para explicar el segundo modelo de bloque, pero no significativa para el tercer bloque. Se llevó a cabo un análisis de interrelaciones después de la regresión múltiple, demostrando que la violencia experimentada por las madres no influye directamente la afectividad madre­infante, sino que la misma es mediada por la depresión posterior al parto. Esto explica por qué la violencia no es significativa en la jerárquica regresión múltiple cuando la depresión materna se le agrega al modelo. Entre los puntos fuertes de este estudio se incluye el uso de los puntajes de factores del PBQ y el análisis de interrelaciones, lo cual permitió que se estimaran las relaciones condicionales existente dentro del grupo de variables, aportando una mayor comprensión de algunos factores que interfieren en la unión afectiva madre­infante.

Development of a new hazard scoring system in primary neuronal cell cultures for drug-induced acute neuronal toxicity identification in early drug discovery.

We investigated drug-induced acute neuronal electrophysiological changes using Micro-Electrode arrays (MEA) to rat primary neuronal cell cultures. Data based on 6-key MEA parameters were analyzed for plate-to-plate vehicle variability, effects of positive and negative controls, as well as data from over 100 reference drugs, mostly known to have pharmacological phenotypic and clinical outcomes. A Least Absolute Shrinkage and Selection Operator (LASSO) regression, coupled with expert evaluation helped to identify the 6-key parameters from many other MEA parameters to evaluate the drug-induced acute neuronal changes. Calculating the statistical tolerance intervals for negative-positive control effects on those 4-key parameters helped us to develop a new weighted hazard scoring system on drug-induced potential central nervous system (CNS) adverse effects (AEs). The weighted total score, integrating the effects of a drug candidate on the identified six-pivotal parameters, simply determines if the testing compound/concentration induces potential CNS AEs. Hereto, it uses four different categories of hazard scores: non-neuroactive, neuroactive, hazard, or high hazard categories. This new scoring system was successfully applied to differentiate the new compounds with or without CNS AEs, and the results were correlated with the outcome of in vivo studies in mice for one internal program. Furthermore, the Random Forest classification method was used to obtain the probability that the effect of a compound is either inhibitory or excitatory. In conclusion, this new neuronal scoring system on the cell assay is actively applied in the early de-risking of drug development and reduces the use of animals and associated costs.

Identification, spatial distribution, and associated factors of urban protected areas in China.

The increasing proximity between protected areas (PAs) and urban areas, which can lead to urban protected areas (UPAs), is now commonplace. Use of Euclidean distance to measure the distance between PAs and cities has not correctly portrayed the spatial relationship between PAs and cities. We devised an isochronous circle model to accurately measure the distance between 2706 national PAs in 5 categories and 2844 cities in China based on human accessibility to identify urban human activity-influenced protected areas (UHAIPAs) and to quantitatively analyze their distribution patterns and relationships with China's economy, population distribution patterns, and urban development indicators. Most of the PAs in China were established near cities. Of 2746 PAs in China, 18.35% (n = 504) became UPAs, and 58.27% (n = 1600), 16.72% (n = 459), and 3.31% (n = 91) of PAs were within 0-30, 30-60, and 60-90 min, respectively. Both UPAs and UHAIPAs in China in general exhibited obvious spatial aggregation characteristics (e.g., wetland parks and scenic areas), and there was a significant spatial dependence effect among characteristics. The degree of spatial distribution and aggregation of UPAs was correlated with 16 indicators across urban economic development, urban natural substrate, and urban policy support factors. Based on the results of our study, we call for various governments and scholars to focus on areas where wetland parks and PAs overlap with urban boundaries. It is important to emphasize the potential link between the development of agriculture, forestry, livestock and fisheries industries, and UPAs. Overall, we believe that examining the accessibility of PAs can more accurately measure the distance between PAs and cities, and more realistically reflect the possible impacts of urban human activities on PAs, which is helpful for strengthening the conservation and management of PAs.

Identificación, distribución espacial y factores asociados de las áreas urbanas protegidas en China Resumen La creciente proximidad entre las áreas protegidas (AP) y las áreas urbanas, que puede derivar en áreas urbanas protegidas (AUP), es muy común hoy en día. La distancia euclidiana no ha representado correctamente la distancia entre las AP y las ciudades. Por lo anterior, diseñamos un modelo de círculo isócrono para medir con certeza la distancia entre 2706 AP nacionales en cinco categorías y 2844 ciudades de China con base en la accesibilidad humana para identificar las áreas urbanas protegidas con influencia de actividad humana (AUPIAH). También lo usamos para analizar cuantitativamente los patrones de distribución y su relación con la economía china, los patrones de distribución poblacional y los indicadores de desarrollo urbano. La mayoría de las AP en China están establecidas cerca de las ciudades. De las 2746 AP, el 18.35% (n = 504) se convirtieron en AUP y el 58.27% (n = 1600), 16.72% (n = 459) y 3.31% (n = 91) se encontraban de 0­30 minutos, 30­60 y de 60­90 minutos de una ciudad, respectivamente. Tanto las AUP y las AUPIAH exhibieron características obvias de agregación espacial (p. ej.: parques de humedales y áreas escénicas) y hubo un efecto significativo de dependencia espacial entre dichas características. El nivel de distribución y agregación espacial de las AUP tuvo correlación con 16 indicadores de desarrollo económico urbano, sustrato natural urbano y factores de apoyo para las políticas urbanas. Con base en los resultados de nuestro estudio, hacemos un llamado para que diferentes gobiernos y académicos se enfoquen en las áreas en donde se traslapan las AP y los parques de humedales con los límites urbanos. Es importante resaltar la conexión potencial entre el desarrollo de la agricultura, silvicultura, ganadería y pesquería y las AUP. En general, consideramos que analizar la accesibilidad de las AP puede medir de forma más certera la distancia entre las AP y las ciudades, además de que refleja de forma más realista el posible impacto de las actividades humanas sobre las AP, lo cual es útil para fortalecer la conservación y gestión de las AP.