Search

ObjectiveTo analyze the epidemiological characteristics and etiology of clustered outbreaks of hand， foot， and mouth disease （HFMD） in Pudong New Area， Shanghai from 2017 to 2022， and to provide a scientific basis for the prevention and control of HFMD in the area.MethodsThe data related to HFMD clustered outbreaks from 2017 to 2022 were obtained from the Pudong New Area HFMD outbreak database. Descriptive analysis was conducted to explore the outbreak scope， seasonal characteristics， distribution of occurrence settings， and etiological composition.ResultsFrom 2017 to 2022， Pudong New Area reported a total of 2 547 HFMD clusters， involving 8 884 cases， with an average of 3.49 cases per event. The majority of events （78.52%） had between 2 and 4 cases. The peak reporting periods for clustered HFMD from 2017 to 2019 and in 2021 were during the summer （May‒July） and autumn （September‒November）. The seasonal pattern was less distinct in 2020 and 2022， likely due to the impact of the COVID-19 pandemic. The majority of clustered outbreaks occurred in childcare facilities （44.64%）， followed by households/neighborhood committees （44.21%）， with schools accounting for a smaller proportion （12.39%）. The etiology revealed the coexistence of multiple enterovirus genotypes， with a positive detection rate of 60.46%， and CoxA6 being the dominant strain.ConclusionHFMD clustered outbreaks in Pudong New Area show fluctuating trends， with significant yearly differences in the number of incidents. The predominant seasons for outbreaks are summer and autumn， with CoxA6 identified as the dominant strain. The implementation of prevention and control measures for COVID-19 significantly reduced the occurrence of HFMD outbreaks. Continuous monitoring and focus on large-scale clustered outbreaks in key institutions are essential for the future.

Background: The limited regenerative capacity of damaged neurons in adult mammals severely restricts neural repair. Although stem cell transplantation is promising, its clinical application remains challenging. Direct reprogramming, which utilizes cell plasticity to regenerate neurons, is an emerging alternative approach. Methods: We utilized primary postnatal cortical astrocytes for reprogramming induced neurons (iNs) through the viral-mediated overexpression of the transcription factors Ngn2 and Pax6 (NP). Fluorescence-activated cell sorting (FACS) was used to enrich successfully transfected cells, followed by single-cell RNA sequencing (scRNA-seq) using the 10 × Genomics platform for comprehensive transcriptomic analysis. Results: The scRNA-seq revealed that NP overexpression led to the differentiation of astrocytes into iNs, with percentages of 36% and 39.3% on days 4 and 7 posttransduction, respectively. CytoTRACE predicted the developmental sequence, identifying astrocytes as the reprogramming starting point. Trajectory analysis depicted the dynamic changes in gene expression during the astrocyte-to-iN transition. Conclusions: This study elucidates the molecular dynamics underlying astrocyte reprogramming into iNs, revealing key genes and pathways involved in this process. Our research contributes novel insights into the molecular mechanisms of NP-mediated reprogramming, suggesting avenues for optimizing the efficiency of the reprogramming process. [ABSTRACT FROM AUTHOR]

When studying an outcome Y that is weakly positive but can equal zero (e.g. earnings), researchers frequently estimate an average treatment effect (ATE) for a "log-like" transformation that behaves like log (Y) for large Y but is defined at zero (e.g. log (1 + Y), |$\operatorname{arcsinh}(Y)$|⁠). We argue that ATEs for log-like transformations should not be interpreted as approximating percentage effects, since unlike a percentage, they depend on the units of the outcome. In fact, we show that if the treatment affects the extensive margin, one can obtain a treatment effect of any magnitude simply by rescaling the units of Y before taking the log-like transformation. This arbitrary unit dependence arises because an individual-level percentage effect is not well-defined for individuals whose outcome changes from zero to nonzero when receiving treatment, and the units of the outcome implicitly determine how much weight the ATE for a log-like transformation places on the extensive margin. We further establish a trilemma: when the outcome can equal zero, there is no treatment effect parameter that is an average of individual-level treatment effects, unit invariant, and point identified. We discuss several alternative approaches that may be sensible in settings with an intensive and extensive margin, including (i) expressing the ATE in levels as a percentage (e.g. using Poisson regression), (ii) explicitly calibrating the value placed on the intensive and extensive margins, and (iii) estimating separate effects for the two margins (e.g. using Lee bounds). We illustrate these approaches in three empirical applications. [ABSTRACT FROM AUTHOR]

The enhancement of bioactivity in materials has become an important focus within the field of bone tissue engineering. Four-dimensional intelligent osteogenic module, an innovative fusion of 3D printing with the time axis, shows immense potential in augmenting the bioactivity of these materials, thereby facilitating autologous bone regeneration efficiently. This study focuses on novel bone repair materials, particularly bioactive scaffolds with a developmental osteogenic microenvironment prepared through 3D bioprinting technology. This research mainly creates a developmental osteogenic microenvironment named "DOME". This is primed by the application of a small amount of the small molecule drug SB216763, which activates canonical Wnt signaling in osteocytes, promoting osteogenesis and mineralization nodule formation in bone marrow stromal cells and inhibiting the formation of adipocytes. Moreover, DOME enhances endothelial cell migration and angiogenesis, which is integral to bone repair. More importantly, the DOME-PCI3D system, a 4D intelligent osteogenic module constructed through 3D bioprinting, stably supports cell growth (91.2% survival rate after 7 days) and significantly increases the expression of osteogenic transcription factors in bone marrow stromal cells and induces osteogenic differentiation and mineralization for 28 days. This study presents a novel approach for bone repair, employing 3D bioprinting to create a multifunctional 4D intelligent osteogenic module. This innovative method not only resolves challenges related to shape-matching and biological activity but also demonstrates the vast potential for applications in bone repair. [ABSTRACT FROM AUTHOR]

Summary: Soy protein‐gum Arabic (GA) core‐shell nanoparticles were fabricated as carriers for hydrophobic phytosterol (PS) using an anti‐solvent precipitation (pH 7.0) and then coating GA on the surface of protein‐based PS nanoparticles at pH 4.5. PS nanoparticles stabilised by heat‐treated soy protein isolate (SPI), especially subcritical water‐treated SPI (SW, 120 °C), exhibited higher encapsulation efficiency (EE), loading amount (LA) and colloidal stability than native SPI‐stabilised PS nanoparticles. The highly flexible conformation and more exposed hydrophobic clusters of SW‐treated SPI could result in a quick encapsulation of more PS into the interior of protein molecules during anti‐solvent precipitation. However, for native SPI with rigid globular structure, the loading of PS mainly occurred on the surface hydrophobic sites of protein molecules. After introducing GA (≥5 mg mL−1) to PS nanoparticles fabricated by SW‐treated SPI, submicron‐sized (Dh 250.71~341.76 nm) core‐shell nanoparticles with high acid solubility and thermal stability were formed. The coating of GA decelerated the digestion of SW‐treated SPI, and improved the EE, LA and in vitro bioaccessibility of PS under acidic environment. These results reveal the protein structure dependence of PS encapsulation and provide a simple approach to fabricate biopolymer‐based nanoparticle delivery system for hydrophobic bioactives in acidified functional drinks. [ABSTRACT FROM AUTHOR]

N6-methyladenosine (m6A) is a critical regulator in the fate of RNA, but whether and how m6A executes its functions in different tissues remains largely obscure. Here we report downregulation of a crucial m6A reader, YTHDF2, leading to tissue-specific programmed cell deaths (PCDs) upon fluorene-9-bisphenol (BHPF) exposure. Currently, Bisphenol A (BPA) substitutes are widely used in plastic manufacturing. Interrogating eight common BPA substitutes, we detected BHPF in 14% serum samples of pregnant participants. In a zebrafish model, BHPF caused tissue-specific PCDs triggering cardiac and vascular defects. Mechanistically, BHPF-mediated downregulation of YTHDF2 reduced YTHDF2-facilitated translation of m6A- gch1 for cardiomyocyte ferroptosis, and decreased YTHDF2-mediated m6A- sting1 decay for caudal vein plexus (CVP) apoptosis. The two distinct YTHDF2-mediated m6A regulations and context-dependent co-expression patterns of gch1/ythdf2 and tnfrsf1a/ythdf2 contributed to YTHDF2-mediated tissue-specific PCDs, uncovering a new layer of PCD regulation. Since BHPF/YTHDF2-medaited PCD defects were also observed in mammals, BHPF exposure represents a potential health threat. [ABSTRACT FROM AUTHOR]

Inorganic arsenic (iAs) has been a human health concern and is associated with intestinal malignancies. However, the molecular mechanisms of the iAs‐induced oncogenic process in intestine epithelial cells remain elusive, partly because of the known hormesis effect of arsenic. Here, we established that six‐month exposure to iAs at a concentration similar to those found in contaminated drinking water could promote malignant characteristics, including enhanced proliferation and migration, resistance to apoptosis, and mesenchymal‐like transition in Caco‐2 cells. Transcriptome analysis and mechanism study revealed that key genes and pathways involved in cell adhesion, inflammation and oncogenic regulation were altered during chronic iAs exposure. Specifically, we uncovered that down‐regulation of HTRA1 was essential for the iAs‐induced acquisition of the cancer hallmarks. Further, we evidenced that the loss of HTRA1 during iAs‐exposure could be restored by HDAC6 inhibition. Caco‐2 cells with chronic exposure to iAs exhibited enhanced sensitivity to WT‐161, a specific inhibitor of HDAC6, when used alone than in combination with a chemotherapeutic agent. These findings provide valuable information for understanding the mechanisms of arsenic‐induced carcinogenesis and facilitating the health management of populations in arsenic‐polluted areas. This study explored the molecular mechanism associated with long‐term inorganic arsenic exposure in the colon epithelial Caco‐2 cell model. Our findings revealed that the down‐regulation of HTRA1 was essential for the malignant progression induced by chronic arsenic exposure, which could be restored by HDAC6 inhibition. These findings provide valuable information for understanding the key regulators of arsenic‐induced carcinogenesis. [ABSTRACT FROM AUTHOR]

Photovoltaic (PV) power generation is the most widely adopted renewable energy source. However, its inherent unpredictability poses considerable challenges to the management of power grids. To address the arduous and time-consuming training process of PV prediction models, which has been a major focus of prior research, an improved approach for PV prediction based on neighboring days is proposed in this study. This approach is specifically designed to handle the preprocessing of training datasets by leveraging the results of a similarity analysis of PV power generation. Experimental results demonstrate that this method can significantly reduce the training time of models without sacrificing prediction accuracy, and can be effectively applied in both ensemble and deep learning approaches. [ABSTRACT FROM AUTHOR]

Nervous system diseases present significant challenges to the neuroscience community due to ethical and practical constraints that limit access to appropriate research materials. Somatic cell reprogramming has been proposed as a novel way to obtain neurons. Various emerging techniques have been used to reprogram mature and differentiated cells into neurons. This review provides an overview of somatic cell reprogramming for neurological research and therapy, focusing on neural reprogramming and generating different neural cell types. We examine the mechanisms involved in reprogramming and the challenges that arise. We herein summarize cell reprogramming strategies to generate neurons, including transcription factors, small molecules, and microRNAs, with a focus on different types of cells.. While reprogramming somatic cells into neurons holds the potential for understanding neurological diseases and developing therapeutic applications, its limitations and risks must be carefully considered. Here, we highlight the potential benefits of somatic cell reprogramming for neurological disease research and therapy. This review contributes to the field by providing a comprehensive overview of the various techniques used to generate neurons by cellular reprogramming and discussing their potential applications. [ABSTRACT FROM AUTHOR]

Background: SQSTM1/p62 is a selective autophagy receptor that regulates multiple signaling pathways participating in the initiation and progression of tumors. Metastasis is still the main cause for intrahepatic cholangiocarcinoma (ICC)‐associated mortality. Hence, this study aimed to explore the mechanism of p62 promoting the progression of ICC. Methods: Western blotting and immunohistochemical analyses were conducted to detect the expression level of protein p62 in ICC tissues and its correlation with prognosis. Subsequently, the loss‐of‐function experiments in vitro and in vivo were performed to define the role of p62 in ICC cell proliferation, invasion, and metastasis. Then, the effect of p62 knockdown on mitochondrial function and mitophagy was evaluated by measuring the oxygen consumption rate, and using immunofluorescence and western blotting analyses. Results: The expression of p62 was significantly upregulated in ICC specimens compared with normal tissues. We further illustrated that p62 expression positively correlated with lymph node metastasis and poor prognosis. The loss‐of‐function assays revealed that p62 not only promoted ICC cell proliferation, migration, and invasive capacities in vitro, but also induced lung metastasis in the xenograft mouse model. Mechanistically, high expression of p62‐induced epithelial–mesenchymal transition (EMT) with the upregulation of Snail, vimentin, N‐cadherin, and downregulation of E‐cadherin. Moreover, the autophagy‐dependent function of p62 might play a vital role in maintaining the mitochondrial function of ICC by mitophagy which might further promote EMT. Conclusion: These data provided new evidence for the mechanism by which abundant p62 expression promoted ICC progression, suggesting a promising therapeutic target for antimetastatic strategies in patients with ICC. [ABSTRACT FROM AUTHOR]

Point cloud is a set of three-dimensional points in arbitrary order, which is a popular representation of 3D scene in autonomous navigation and immersive applications in recent years. Compression becomes an inevitable issue due to the huge data volume of point cloud. In order to effectively compress attributes of those points, proper reordering is important. The existing voxel-based point cloud attributes compression scheme uses a naive scan for points reordering. In this paper, we theoretically analyzed 3C properties of point cloud, i.e., Compactness, Clustering and Correlation, of different scan-orders defined by different space filling curves and disclosed that the Hilbert curve can provide the best spatial correlation preservation compared with Z-order and Gray-coded curves. It is also statistically verified that the Hilbert curve always has the best ability of attributes correlation preservation for point clouds with different sparsity. We also proposed a fast and iterative Hilbert address code generation method to implement points reordering. The Hilbert scan-order could be combined with various point cloud attribute coding methods. Experiments show that the correlation preservation feature of the proposed scan-order can bring us 6.1% and 6.5% coding gain for prediction and transform coding, respectively. [ABSTRACT FROM AUTHOR]