Prenatal progesterone treatment modulates fetal brain transcriptome and impacts adult offspring behavior in mice.

Maternal exposure to elevated levels of steroid hormones during pregnancy is associated with the development of chronic conditions in offspring that manifest in adulthood. However, the effects of progesterone (P4) administration during early pregnancy on fetal development and subsequent offspring behavior remain poorly understood. In this study, we aimed to investigate the effects of P4 treatment during early pregnancy on the transcript abundance in the fetal brain and assess the behavioral consequences in the offspring during adolescence and adulthood. Using RNA-seq analysis, we examined the impact of P4 treatment on the fetal brain transcriptome in a dosage-dependent manner. Our results revealed differential regulation of genes involved in neurotransmitter transport, synaptic transmission, and transcriptional regulation. Specifically, we observed bidirectional regulation of transcription factors (TFs) by P4 at different doses, highlighting the critical role of these TFs in neurodevelopment. To assess behavioral outcomes, we conducted open field and elevated plus maze tests. Offspring treated with low-dose P4 (LP4) displayed increased exploratory behavior during both adolescence and adulthood. In contrast, the high-dose P4 (HP4) group exhibited impaired exploration and heightened anxiety-like behaviors compared to the control mice. Moreover, in a novel object recognition test, HP4-treated offspring demonstrated impaired object recognition memory during both developmental stages. Additionally, both LP4 and HP4 groups showed reduced social interaction in the three-chamber test. These results suggest that prenatal exposure to P4 exerts a notable influence on the expression of genes associated with neurodevelopment and may induce alterations in behavioral characteristics in progeny, highlighting the need to monitor progesterone levels during pregnancy for long-term impacts on fetal brain development and behavior.

Noncoding RNA Lipotherapeutics: A Promising Breakthrough in Pulmonary Hypertension Treatment.

Pulmonary Hypertension (PH) is a complex cardiovascular disorder characterized by elevated blood pressure in the pulmonary arteries. Current therapeutic approaches for PH have limitations in addressing the underlying molecular mechanisms. This article explores the potential of noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), delivered through Lipid-Based Nanoparticles (LNPs) as a novel treatment strategy. These ncRNAs play critical roles in regulating vascular function and are implicated in PH pathogenesis. LNPs provide a promising method for the efficient and targeted delivery of ncRNAs. Advances in LNP technology, including the incorporation of R8 peptide modification, have shown promise in enhancing the delivery and efficacy of ncRNAs in PH models. Challenges such as biocompatibility, toxicity, and precise targeting must be addressed as these therapies move toward clinical application. The potential of personalized medicine and the integration of artificial intelligence in LNP design are discussed as prospects. In conclusion, ncRNA lipotherapeutics delivered via LNPs offer a transformative approach to treating PH, potentially leading to more effective management and improved patient outcomes in the future. However, continued research and clinical trials are necessary to fully realize their therapeutic potential in the field of PH treatment.

Early statin exposure influences cardiac and skeletal development with implications for ion channel transcriptomes in zebrafish.

Statins, widely prescribed for cholesterol management by inhibiting HMG-CoA reductase in the cholesterol biosynthesis pathway, may also influence vertebrate development. In this study, we investigated the developmental effects of two widely used statins, atorvastatin (ATO) and pravastatin (PRA), on zebrafish offspring. For ATO, we administered doses classified as low (1 µM), medium (5 µM), and high (10 µM), while for PRA, the corresponding concentrations were set at low (18 µM), medium (180 µM), and high (270 µM). Our results showed significant reductions in birth and hatching rates, along with decreased body length in offspring at all ATO concentrations and medium to high PRA concentrations. A notable increase in malformation rates, especially in the spine and heart, was observed across all ATO treatments and in medium and high PRA groups. Additionally, we observed reduced heart contraction rates, decreased heart size, lower bone volumes, and diminished expression of mRNA osteogenic markers. Elevated venous sinus-artery bulb (SV-BA) ratios, increased thoracic area, and abnormal cartilage development were also prominent in all ATO-treated groups. Transcriptome analysis revealed alterations in genes predominantly associated with ion channels. These findings provide insights into the potential impacts of specific concentrations of statins on offspring development and highlight potential gene interactions with statins.

Deficiency of Acetyltransferase nat10 in Zebrafish Causes Developmental Defects in the Visual Function.

Purpose: N4-acetylcytidine (ac4C) is a post-transcriptional RNA modification catalyzed by N-acetyltransferase 10 (NAT10), a critical factor known to influence mRNA stability. However, the role of ac4C in visual development remains unexplored. Methods: Analysis of public datasets and immunohistochemical staining were conducted to assess the expression pattern of nat10 in zebrafish. We used CRISPR/Cas9 and RNAi technologies to knockout (KO) and knockdown (KD) nat10, the zebrafish ortholog of human NAT10, and evaluated its effects on early development. To assess the impact of nat10 knockdown on visual function, we performed comprehensive histological evaluations and behavioral analyses. Transcriptome profiling and real-time (RT)-PCR were utilized to detect alterations in gene expression resulting from the nat10 knockdown. Dot-blot and RNA immunoprecipitation (RIP)-PCR analyses were conducted to verify changes in ac4C levels in both total RNA and opsin mRNA specifically. Additionally, we used the actinomycin D assay to examine the stability of opsin mRNA following the nat10 KD. Results: Our study found that the zebrafish NAT10 protein shares similar structural properties with its human counterpart. We observed that the nat10 gene was prominently expressed in the visual system during early zebrafish development. A deficiency of nat10 in zebrafish embryos resulted in increased mortality and developmental abnormalities. Behavioral and histological assessments indicated significant vision impairment in nat10 KD zebrafish. Transcriptomic analysis and RT-PCR identified substantial downregulation of retinal transcripts related to phototransduction, light response, photoreceptors, and visual perception in the nat10 KD group. Dot-blot and RIP-PCR analyses confirmed a pronounced reduction in ac4C levels in both total RNA and specifically in opsin messenger RNA (mRNA). Additionally, by evaluating mRNA decay in zebrafish treated with actinomycin D, we observed a significant decrease in the stability of opsin mRNA in the nat10 KD group. Conclusions: The ac4C-mediated mRNA modification plays an essential role in maintaining visual development and retinal function. The loss of NAT10-mediated ac4C modification results in significant disruptions to these processes, underlining the importance of this RNA modification in ocular development.

Application of an integrated loach-plant-substrate-microbes non-aerated saturated vertical flow constructed wetlands: Mechanisms of pollutants removal and greenhouse gases reduction.

This study established an integrated loach-plant-substrate-microbes non-aerated saturated vertical flow constructed wetlands (VFCWs) to enhance pollutants removal efficiencies and reduce greenhouse gas emissions simultaneously. The results of the VFCWs experiment indicated that the removal efficiencies of chemical oxygen demand, total phosphorous, and total nitrogen in loach systems were significantly higher than those of non-loach systems, achieving 59.16%, 35.98%, and 40.96%, respectively. The CH4 and N2O emission fluxes were also significantly reduced in the integrated system, resulting in lower global warming potential (GWP) and GWP per unit of pollutants removal. Loaches promoted the transportation of oxygen, facilitated the re-contact and utilization of sediments, reduced CH4 emission, and enhanced nitrogen conversion and phosphorus accumulation. Increased bioavailable carbon and nitrate-nitrogen in the integrated system improved the abundance of denitrifying bacteria, which supported complete denitrification, reducing N2O emissions with high pollutant removal.

Quantitative Evaluation of TOD Performance Based on Multi-Source Data: A Case Study of Shanghai.

Transit-oriented development (TOD) has been widely adopted as a primary urban planning strategy to better integrate transit and land use; further, the pedestrian-oriented perspective has been receiving increasing attention. However, most studies so far have only focused on few features and fail to capture comprehensive perceptions in the transportation (T), pedestrian-oriented accessibility (O), and urban development (D) dimensions. New emerging urban datasets provide a more refined and systematic approach to quantify the characteristics of metro station areas. This study offers a more efficient and convenient process and comprehensive approach to measure TOD performance. With a combination of traditional data collected by an official department, high-resolution open data, and innovative technology, large-scale analyses of 347 metro stations in Shanghai were conducted. Fifteen indicators for T, O, and D were chosen to categorize TOD performance into five clusters. Radar charts, boxplots, and colored maps were used to display numerous quantitative factors for each type. Combining the results with the Shanghai Comprehensive Plan (2017-2035) showed that the majority of Cluster 4 is located at the center of the Five New Towns. The correlation analysis between ridership and TOD performance showed that the transportation dimension indicator has a strong correlation with daily ridership, followed by the O and D indicators. Moreover, ridership per capita was found to be affected by resident density, employment density, O value, and D value, whereas no significant correlation was found between ridership per capita and T value. Population plays a pivotal role in metro passenger traffic, indicating ridership per capita had a high, strong correlation with resident density, with R = 0.658 for weekdays and R = 0.654 for weekends. This study reinterpreted the node-place method and 5Ds framework, resulting in a renewal method with new datasets and analysis tools. It contributes to providing pedestrian-oriented TOD planning methodology for urban planners and policymakers by combining T, O, and D dimensions and visualizing the results with current urban planning.

The role of PhoP/PhoQ two component system in regulating stress adaptation in Cronobacter sakazakii.

Cronobacter sakazakii is an opportunistic foodborne bacterial pathogen that shows resistance to multiple stress conditions. The PhoP/PhoQ two component system is a key regulatory mechanism of stress response and virulence in various bacteria, but its role in C. sakazakii has not been thoroughly studied. In this study, we found the PhoP/PhoQ system in C. sakazakii ATCC BAA-894 enhanced bacterial growth in conditions with low Mg2+, acid pH, and the presence of polymyxin B. Moreover, the ΔphoPQ strain significantly reduced survival following exposure to heat, high osmotic pressure, oxidative or bile salts compared with WT strain. Furthermore, the RNA-seq analysis indicated that 1029 genes were upregulated and 979 genes were downregulated in ΔphoPQ strain. The bacterial secretion system, flagella assembly, beta-Lactam resistance and two-component system pathways were significantly downregulated, while the ABC transporters and microbial metabolism in diverse environments pathways were upregulated. qRT-PCR analysis further confirmed that twelve genes associated with stress tolerance were positively regulated by the PhoP/PhoQ system. Therefore, these findings suggest that the PhoP/PhoQ system is an important regulatory mechanism for C. sakazakii to resist various environmental stress.

A Systematic Measurement of Street Quality through Multi-Sourced Urban Data: A Human-Oriented Analysis.

Many studies have been made on street quality, physical activity and public health. However, most studies so far have focused on only few features, such as street greenery or accessibility. These features fail to capture people's holistic perceptions. The potential of fine grained, multi-sourced urban data creates new research avenues for addressing multi-feature, intangible, human-oriented issues related to the built environment. This study proposes a systematic, multi-factor quantitative approach for measuring street quality with the support of multi-sourced urban data taking Yangpu District in Shanghai as case study. This holistic approach combines typical and new urban data in order to measure street quality with a human-oriented perspective. This composite measure of street quality is based on the well-established 5Ds dimensions: Density, Diversity, Design, Destination accessibility and Distance to transit. They are combined as a collection of new urban data and research techniques, including location-based service (LBS) positioning data, points of interest (PoIs), elements and visual quality of street-view images extraction with supervised machine learning, and accessibility metrics using network science. According to these quantitative measurements from the five aspects, streets were classified into eight feature clusters and three types reflecting the value of street quality using a hierarchical clustering method. The classification was tested with experts. The analytical framework developed through this study contributes to human-oriented urban planning practices to further encourage physical activity and public health.

Molecular characterization of rabies virus isolates in China during 2004.

Human rabies cases have been on the rise during the past few years in China and a total of 2651 cases were reported in 2004. To better understand the current rabies epidemics in China, we isolated rabies viruses from dogs and humans from five provinces and characterized these isolates genetically by sequencing the entire nucleoprotein (N) gene. Comparison of the N genes among these isolates revealed 86.6-99.9% homology and these viruses can be grouped into three lineages. Phylogenetic analysis indicates that all the Chinese isolates have a close relationship with viruses circulating in Asian canine population. When compared with rabies viruses isolated previously, the three lineages were similar to three of the four groups. Thus, our data suggest that rabies viruses currently circulating in China were similar, if not identical, to those reported in the previous epidemics.