Dynamic Roles of microRNAs in Neurogenesis

MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression at the post-transcriptional level by mediating mRNA degradation or translational inhibition. MiRNAs are implicated in many biological functions, including neurogenesis. It has been shown that miRNAs regulate multiple steps of neurogenesis, from neural stem cell proliferation to neuronal differentiation and maturation. MiRNAs execute their functions in a dynamic and context-dependent manner by targeting diverse downstream target genes, from transcriptional factors to epigenetic regulators. Identifying context-specific target genes is instrumental for understanding the roles that miRNAs play in neurogenesis. This review summarizes our current state of knowledge on the dynamic roles that miRNAs play in neural stem cells and neurogenesis

Understanding precipitation recycling over the Tibetan Plateau using tracer analysis with WRF

The precipitation recycling (PR) ratio is an important indicator that quantifies the land-atmosphere interaction strength in the Earth system’s water cycle. To better understand how the heterogeneous land surface in the Tibetan Plateau (TP) contributes to precipitation, we used the water-vapor tracer (WVT) method coupled with the Weather Research and Forecasting (WRF) regional climate model. The goals were to quantify the PR ratio, in terms of annual mean, seasonal variability and diurnal cycle, and to address the relationships of the PR ratio with lake treatments and precipitation amount. Simulations showed that the PR ratio increases from 0.1 in winter to 0.4 in summer when averaged over the TP with the maxima centered at the headwaters of three major rivers (Yangtze, Yellow and Mekong). For the central TP, the highest PR ratio rose to over 0.8 in August, indicating that most of the precipitation was recycled via local evapotranspiration in summer. The larger daily mean and standard deviation of the PR ratio in summer suggested a stronger effect of land-atmosphere interactions on precipitation in summer than in winter. Despite the relatively small spatial extent of inland lakes, the treatment of lakes in WRF significantly impacted the calculation of the PR ratio over the TP, and correcting lake temperature substantially improved both precipitation and PR ratio simulations. There was no clear relationship between PR ratio and precipitation amount; however, a significant positive correlation between PR and convective precipitation was revealed. This study is beneficial for the understanding of land-atmosphere interaction over high mountain regionsThis work is jointly supported by the Strategic Priority Research Program of Chinese Academy of Sciences (XDA2006010202), by the Second Tibetan Plateau Scientific Expedition and Research (STEP) program (2019QZKK010314), by the National Natural Science Foundation of China (91537105 and 91537211), and by the NCAR Water System Program. Support of the Fudan University-Tibet University Joint Laboratory for Biodiversity and Global Change is appreciated. We thank the ECMWF for the free access of the ERA-Interim Reanalysis dataset. The work was carried out at the National Supercomputer Center in TianjinS

A Survey of Geometric Optimization for Deep Learning: From Euclidean Space to Riemannian Manifold

Although Deep Learning (DL) has achieved success in complex Artificial Intelligence (AI) tasks, it suffers from various notorious problems (e.g., feature redundancy, and vanishing or exploding gradients), since updating parameters in Euclidean space cannot fully exploit the geometric structure of the solution space. As a promising alternative solution, Riemannian-based DL uses geometric optimization to update parameters on Riemannian manifolds and can leverage the underlying geometric information. Accordingly, this article presents a comprehensive survey of applying geometric optimization in DL. At first, this article introduces the basic procedure of the geometric optimization, including various geometric optimizers and some concepts of Riemannian manifold. Subsequently, this article investigates the application of geometric optimization in different DL networks in various AI tasks, e.g., convolution neural network, recurrent neural network, transfer learning, and optimal transport. Additionally, typical public toolboxes that implement optimization on manifold are also discussed. Finally, this article makes a performance comparison between different deep geometric optimization methods under image recognition scenarios.Comment: 41 page

Cold atmospheric plasma induces apoptosis in human colon and lung cancer cells through modulating mitochondrial pathway

Cold atmospheric plasma (CAP) is an emerging and promising oncotherapy with considerable potential and advantages that traditional treatment modalities lack. The objective of this study was to investigate the effect and mechanism of plasma-inhibited proliferation and plasma-induced apoptosis on human lung cancer and colon cancer cells in vitro and in vivo. Piezobrush® PZ2, a handheld CAP unit based on the piezoelectric direct discharge technology, was used to generate and deliver non-thermal plasma. Firstly, CAPPZ2 treatment inhibited the proliferation of HT29 colorectal cancer cells and A549 lung cancer cells using CCK8 assay, caused morphological changes at the cellular and subcellular levels using transmission electron microscopy, and suppressed both types of tumor cell migration and invasion using the Transwell migration and Matrigel invasion assay. Secondly, we confirmed plasma-induced apoptosis in the HT29 and A549 cells using the AO/EB staining coupled with flow cytometry, and verified the production of apoptosis-related proteins, such as cytochrome c, PARP, cleaved caspase-3 and caspase-9, Bcl-2 and Bax, using western blotting. Finally, the aforementioned in vitro results were tested in vivo using cell-derived xenograft mouse models, and the anticancer effect was confirmed and attributed to CAP-mediated apoptosis. The immunohistochemical analysis revealed that the expression of cleaved caspase-9, caspase-3, PARP and Bax were upregulated whereas that of Bcl-2 downregulated after CAP treatment. These findings collectively suggest that the activation of the mitochondrial pathway is involved during CAPPZ2-induced apoptosis of human colon and lung cancer cells in vitro and in vivo

Development of a fibroblast activation protein-targeted PET/NIR dual-modality probe and its application in head and neck cancer

Purpose: The combination of near-infrared (NIR) and positron emission tomography (PET) imaging presents an opportunity to utilize the benefits of dual-modality imaging for tumor visualization. Based on the observation that fibroblast activation protein (FAP) is upregulated in cancer-associated fibroblasts (CAFs) infiltrating all solid tumors, including head and neck squamous cell carcinoma (HNSCC), we developed the novel PET/NIR probe [68Ga]Ga-FAP-2286-ICG. Preclinically, the specificity, biodistribution and diagnostic properties were evaluated.Methods: Cell uptake assays were completed with the U87MG cell to evaluate the specificity of the [68Ga]Ga-FAP-2286-ICG. The tumor-targeting efficiency, biodistribution and optimal imaging time window of the [68Ga]Ga-FAP-2286-ICG were studied in mice bearing U87MG xenografts. HNSCC tumor-bearing mice were used to evaluate the feasibility of [68Ga]Ga-FAP-2286-ICG for tumor localization and guided surgical resection of HNSCC tumors.Results: The in vitro experiments confirmed that [68Ga]Ga-FAP-2286-ICG showed good stability, specific targeting of the probe to FAP, and the durable retention effect in high-expressing FAP tumors U87MG cell. Good imaging properties such as good tumor uptake, high tumor-to-background ratios (5.44 ± 0.74) and specificity, and tumor contouring were confirmed in studies with mice bearing the U87MG xenograft. PET/CT imaging of the probe in head and neck cancer-bearing mice demonstrated specific uptake of the probe in the tumor with a clear background. Fluorescence imaging further validated the value of the probe in guiding surgical resection and achieving precise removal of the tumor and residual lesions.Conclusion: In a preclinical model, these attractive [68Ga]Ga-FAP-2286-ICG PET/NIR imaging acquired in head and neck cancer make it a promising FAP-targeted multimodal probe for clinical translation

Who are the preferential targets for intervention programs related to the female condom among sex workers in Southern China?

The authors used a cluster analysis approach to investigate which female sex workers (FSW) are preferential targets for female condom (FC) intervention programs in southern China. Cross-sectional 6-month (N = 316) and 12-month (N = 217) postintervention surveys of FSW were analyzed. Based on FC attitudes and beliefs, initially suggesting FC use to a partner, practicing insertion, total times ever used, and willingness to use in the future, cluster analysis apportioned women into two clusters, with 50.6% and 58.1% of participants in the likely future FC users group at 6 months and 12 months, respectively. Likely future FC users tended to be from boarding houses, older, currently or previously married, experienced with childbirth, with current multiple sex partners, longer history of sex work, and more unprotected sexual encounters. Focusing FC programs on sectors of the community with more FSW who are likely to use FC may be more costeffective for enhancing FC acceptability and usage. © 2013 The Guilford Press

Genome-wide investigation of the AP2/ERF superfamily and their expression under salt stress in Chinese willow (Salix matsudana)

AP2/ERF transcription factors (TFs) play indispensable roles in plant growth, development, and especially in various abiotic stresses responses. The AP2/ERF TF family has been discovered and classified in more than 50 species. However, little is known about the AP2/ERF gene family of Chinese willow (Salix matsudana), which is a tetraploid ornamental tree species that is widely planted and is also considered as a species that can improve the soil salinity of coastal beaches. In this study, 364 AP2/ERF genes of Salix matsudana (SmAP2/ERF) were identified depending on the recently produced whole genome sequencing data of Salix matsudana. These genes were renamed according to the chromosomal location of the SmAP2/ERF genes. The SmAP2/ERF genes included three major subfamilies: AP2 (55 members), ERF (301 members), and RAV (six members) and two Soloist genes. Genes’ structure and conserved motifs were analyzed in SmAP2/ERF family members, and introns were not found in most genes of the ERF subfamily, some unique motifs were found to be important for the function of SmAP2/ERF genes. Syntenic relationships between the SmAP2/ERF genes and AP2/ERF genes from Populus trichocarpa and Salix purpurea showed that Salix matsudana is genetically more closely related to Populus trichocarpa than to Salix purpurea. Evolution analysis on paralog gene pairs suggested that progenitor of S. matsudana originated from hybridization between two different diploid salix germplasms and underwent genome duplication not more than 10 Mya. RNA sequencing results demonstrated the differential expression patterns of some SmAP2/ERF genes under salt stress and this information can help reveal the mechanism of salt tolerance regulation in Salix matsudana

Molecular responses to salinity stress in Salix matsudana (Koidz) females and males

Sexual dimorphism has commonly been found in many species. The phenotypes of Salix matsudana females and males are different under salinity stress. An F1 population was selected to compare the differences between males and females. As a result, males showed stronger roots and heavier dry weights than females. The unique molecular mechanisms of males and females under salinity stress were further analyzed based on the root transcriptome of males and females. Both males and females up-regulated systemic acquired resistance genes, such as ADH and oxygenase-related genes, to resist salt. Moreover, many other abiotic stress response genes were up-regulated in males to adjust to salinity stress, while females showed more down-regulation of nitrogen metabolism-related genes to decrease the harm from salinity stress. The research on salinity tolerance in Salix matsudana males and females would help to further understand sexual dimorphism under selection pressure and provide benefits to the ecological environment

Deviant Dynamics of Resting State Electroencephalogram Microstate in Patients With Subjective Tinnitus

Given the importance of central reorganization and tinnitus, we undertook the current study to investigate changes to electroencephalogram (EEG) microstates and their association with the clinical symptoms in tinnitus. High-density (128 channel) EEG was used to explore changes in microstate features in 15 subjects with subjective tinnitus and 17 age-matched controls. Correlations between microstate parameters and subjective tinnitus symptoms were also analyzed. An increased presence of class A microstate and decreased presence of class D microstate were found in coverage and lifespan of microstate parameters in the tinnitus patients. Syntax analysis also demonstrated an aberrant pattern of activity, with reduced transitions from class D to class B in tinnitus patients. Moreover, a significant positive correlation of tinnitus loudness with increased lifespan of microstate class C was found. Significant differences in temporal characteristics and syntax of the EEG microstate classes were found at rest between tinnitus patients and the healthy subjects. Our study indicates that EEG microstates may provide a possible valuable method to study large-scale brain networks, which may in turn be beneficial to investigation of the neurophysiological mechanisms behind tinnitus

Pan-Genomic Study of Mycobacterium tuberculosis Reflecting the Primary/Secondary Genes, Generality/Individuality, and the Interconversion Through Copy Number Variations

Tuberculosis (TB) has surpassed HIV as the leading infectious disease killer worldwide since 2014. The main pathogen, Mycobacterium tuberculosis (Mtb), contains ~4,000 genes that account for ~90% of the genome. However, it is still unclear which of these genes are primary/secondary, which are responsible for generality/individuality, and which interconvert during evolution. Here we utilized a pan-genomic analysis of 36 Mtb genomes to address these questions. We identified 3,679 Mtb core (i.e., primary) genes, determining their phenotypic generality (e.g., virulence, slow growth, dormancy). We also observed 1,122 dispensable and 964 strain-specific secondary genes, reflecting partially shared and lineage-/strain-specific individualities. Among which, five L2 lineage-specific genes might be related to the increased virulence of the L2 lineage. Notably, we discovered 28 Mtb “Super Core Genes” (SCGs: more than a copy in at least 90% strains), which might be of increased importance, and reflected the “super phenotype generality.” Most SCGs encode PE/PPE, virulence factors, antigens, and transposases, and have been verified as playing crucial roles in Mtb pathogenicity. Further investigation of the 28 SCGs demonstrated the interconversion among SCGs, single-copy core, dispensable, and strain-specific genes through copy number variations (CNVs) during evolution; different mutations on different copies highlight the delicate adaptive-evolution regulation amongst Mtb lineages. This reflects that the importance of genes varied through CNVs, which might be driven by selective pressure from environment/host-adaptation. In addition, compared with Mycobacterium bovis (Mbo), Mtb possesses 48 specific single core genes that partially reflect the differences between Mtb and Mbo individuality