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Background: The cell development atlas of transition stage from late Carnegie to fetal development (7–9 weeks) remain unclear. It can be seen that the early period of human embryos (7–9 weeks) is a critical research gap. Therefore, we employed single‑cell RNA sequencing to identify cell types and elucidate differentiation relationships. Results: The single‑cell RNA sequencing analysis determines eighteen cell clusters in human embryos during the 7–9 weeks period. We uncover two distinct pathways of cellular development and differentiation. Initially, mesenchymal progenitor cells differentiated into osteoblast progenitor cells and neural stem cells, respectively. Neural stem cells further differentiated into neurons. Alternatively, multipotential stem cells differentiated into adipocyte, hematopoietic stem cells and neutrophil, respectively. Additionally, COL1A2-(ITGA1 + ITGB1) mediated the cell communication between mesenchymal progenitor cells and osteoblast progenitor cells. NCAM1-FGFR1 facilitated the cell communication between mesenchymal progenitor cells and neural stem cells. Notably, NCAM1-NCAM1 as a major contributor mediated the cell communication between neural stem cells and neurons. Moreover, CGA-FSHR simultaneously mediated the communication between multipotential stem cells, adipocyte, hematopoietic stem cells and neutrophil. Distinct cell clusters activated specific transcription factors such as HIC1, LMX1B, TWIST1, and et al., which were responsible for their specific functions. These coregulators, such as HOXB13, VSX2, PAX5, and et al., may mediate cell development and differentiation in human embryos. Conclusions: We provide the cell development atlas for human embryos (7–9 weeks). Two distinct cell development and differentiation pathways are revealed. [ABSTRACT FROM AUTHOR]

Abstract Background The cell development atlas of transition stage from late Carnegie to fetal development (7–9 weeks) remain unclear. It can be seen that the early period of human embryos (7–9 weeks) is a critical research gap. Therefore, we employed single‑cell RNA sequencing to identify cell types and elucidate differentiation relationships. Results The single‑cell RNA sequencing analysis determines eighteen cell clusters in human embryos during the 7–9 weeks period. We uncover two distinct pathways of cellular development and differentiation. Initially, mesenchymal progenitor cells differentiated into osteoblast progenitor cells and neural stem cells, respectively. Neural stem cells further differentiated into neurons. Alternatively, multipotential stem cells differentiated into adipocyte, hematopoietic stem cells and neutrophil, respectively. Additionally, COL1A2-(ITGA1 + ITGB1) mediated the cell communication between mesenchymal progenitor cells and osteoblast progenitor cells. NCAM1-FGFR1 facilitated the cell communication between mesenchymal progenitor cells and neural stem cells. Notably, NCAM1-NCAM1 as a major contributor mediated the cell communication between neural stem cells and neurons. Moreover, CGA-FSHR simultaneously mediated the communication between multipotential stem cells, adipocyte, hematopoietic stem cells and neutrophil. Distinct cell clusters activated specific transcription factors such as HIC1, LMX1B, TWIST1, and et al., which were responsible for their specific functions. These coregulators, such as HOXB13, VSX2, PAX5, and et al., may mediate cell development and differentiation in human embryos. Conclusions We provide the cell development atlas for human embryos (7–9 weeks). Two distinct cell development and differentiation pathways are revealed.

Abstract Typical differential single-nucleus gene expression (snRNA-seq) analyses in Alzheimer’s disease (AD) provide fixed snapshots of cellular alterations, making the accurate detection of temporal cell changes challenging. To characterize the dynamic cellular and transcriptomic differences in AD neuropathology, we apply the novel concept of RNA velocity to the study of single-nucleus RNA from the cortex of 60 subjects with varied levels of AD pathology. RNA velocity captures the rate of change of gene expression by comparing intronic and exonic sequence counts. We performed differential analyses to find the significant genes driving both cell type-specific RNA velocity and expression differences in AD, extensively compared these two transcriptomic metrics, and clarified their associations with multiple neuropathologic traits. The results were cross-validated in an independent dataset. Comparison of AD pathology-associated RNA velocity with parallel gene expression differences reveals sets of genes and molecular pathways that underlie the dynamic and static regimes of cell type-specific dysregulations underlying the disease. Differential RNA velocity and its linked progressive neuropathology point to significant dysregulations in synaptic organization and cell development across cell types. Notably, most of the genes underlying this synaptic dysregulation showed increased RNA velocity in AD subjects compared to controls. Accelerated cell changes were also observed in the AD subjects, suggesting that the precocious depletion of precursor cell pools might be associated with neurodegeneration. Overall, this study uncovers active molecular drivers of the spatiotemporal alterations in AD and offers novel insights towards gene- and cell-centric therapeutic strategies accounting for dynamic cell perturbations and synaptic disruptions.

Typical differential single-nucleus gene expression (snRNA-seq) analyses in Alzheimer's disease (AD) provide fixed snapshots of cellular alterations, making the accurate detection of temporal cell changes challenging. To characterize the dynamic cellular and transcriptomic differences in AD neuropathology, we apply the novel concept of RNA velocity to the study of single-nucleus RNA from the cortex of 60 subjects with varied levels of AD pathology. RNA velocity captures the rate of change of gene expression by comparing intronic and exonic sequence counts. We performed differential analyses to find the significant genes driving both cell type-specific RNA velocity and expression differences in AD, extensively compared these two transcriptomic metrics, and clarified their associations with multiple neuropathologic traits. The results were cross-validated in an independent dataset. Comparison of AD pathology-associated RNA velocity with parallel gene expression differences reveals sets of genes and molecular pathways that underlie the dynamic and static regimes of cell type-specific dysregulations underlying the disease. Differential RNA velocity and its linked progressive neuropathology point to significant dysregulations in synaptic organization and cell development across cell types. Notably, most of the genes underlying this synaptic dysregulation showed increased RNA velocity in AD subjects compared to controls. Accelerated cell changes were also observed in the AD subjects, suggesting that the precocious depletion of precursor cell pools might be associated with neurodegeneration. Overall, this study uncovers active molecular drivers of the spatiotemporal alterations in AD and offers novel insights towards gene- and cell-centric therapeutic strategies accounting for dynamic cell perturbations and synaptic disruptions. [ABSTRACT FROM AUTHOR]

Alkaline water electrolysis remains one of the most promising technologies for the large‐scale production of green hydrogen. However, further increases in efficiency remain elusive, as new electrode materials that are highly efficient in the laboratory cannot maintain their performance under industrial conditions. Within this work, we present a beaker cell setup, in which the industrial relevance of research materials can already be investigated in the laboratory by applying industrial conditions. Thus, the setup allows for testing at 80 °C in 30 wt. % KOH for more than 300 hours. Electrodes are contacted with an in‐house designed Ni tuck‐in holder and two types of reference electrodes are recommended. In addition, a protocol to unify catalyst research is introduced. [ABSTRACT FROM AUTHOR]

Key message: Overexpression of SlPRE3 is detrimental to the photosynthesis and alters plant morphology and root development. SlPRE3 interacts with SlAIF1/SlAIF2/SlPAR1/SlIBH1 to regulate cell expansion. Basic helix–loop–helix (bHLH) transcription factors play crucial roles as regulators in plant growth and development. In this study, we isolated and characterized SlPRE3, an atypical bHLH transcription factor gene. SlPRE3 exhibited predominant expression in the root and moderate expression in the senescent leaves. Comparative analysis with the wild type revealed significant differences in plant morphology in the 35S:SlPRE3 lines. These differences included increased internode length, rolling leaves with reduced chlorophyll accumulation, and elongated yet fewer adventitious roots. Additionally, 35S:SlPRE3 lines displayed elevated levels of GA3 (gibberellin A3) and reduced starch accumulation. Furthermore, utilizing the Y2H (Yeast two-hybrid) and the BiFC (Bimolecular Fluorescent Complimentary) techniques, we identified physical interactions between SlPRE3 and SlAIF1 (ATBS1-interacting factor 1)/SlAIF2 (ATBS1-interacting factor 2)/SlPAR1 (PHYTOCHROME RAPIDLY REGULATED 1)/SlIBH1 (ILI1-binding bHLH 1). RNA-seq analysis of root tissues revealed significant alterations in transcript levels of genes involved in gibberellin metabolism and signal transduction, cell expansion, and root development. In summary, our study sheds light on the crucial regulatory role of SlPRE3 in determining plant morphology and root development. [ABSTRACT FROM AUTHOR]

Abstract Alkaline water electrolysis remains one of the most promising technologies for the large‐scale production of green hydrogen. However, further increases in efficiency remain elusive, as new electrode materials that are highly efficient in the laboratory cannot maintain their performance under industrial conditions. Within this work, we present a beaker cell setup, in which the industrial relevance of research materials can already be investigated in the laboratory by applying industrial conditions. Thus, the setup allows for testing at 80 °C in 30 wt. % KOH for more than 300 hours. Electrodes are contacted with an in‐house designed Ni tuck‐in holder and two types of reference electrodes are recommended. In addition, a protocol to unify catalyst research is introduced.

Cancer stem cells are the root cause of cancer, which, in essence, is a developmental disorder. All-trans retinoic acid (ATRA) signaling via ligand-activation of the retinoic acid receptors (RARs) plays a crucial role in tissue patterning and development during mammalian embryogenesis. In adults, active RARγ maintains the pool of hematopoietic stem cells, whereas active RARα drives myeloid cell differentiation. Various findings have revealed that ATRA signaling is deregulated in many cancers. The enzymes for ATRA synthesis are downregulated in colorectal, gastric, lung, and oropharyngeal cancers. ATRA levels within breast, ovarian, pancreatic, prostate, and renal cancer cells were lower than within their normal counterpart cells. The importance is that 0.24 nM ATRA activates RARγ (for stem cell stemness), whereas 100 times more is required to activate RARα (for differentiation). Moreover, RARγ is an oncogene regarding overexpression within colorectal, cholangiocarcinoma, hepatocellular, ovarian, pancreatic, and renal cancer cells. The microRNA (miR) 30a-5p downregulates expression of RARγ, and miR-30a/miR-30a-5p is a tumor suppressor for breast, colorectal, gastric, hepatocellular, lung, oropharyngeal, ovarian, pancreatic, prostate, and renal cancer. These complementary findings support the view that perturbations to ATRA signaling play a role in driving the abnormal behavior of cancer stem cells. Targeting ATRA synthesis and RARγ has provided promising approaches to eliminating cancer stem cells because such agents have been shown to drive cell death. [ABSTRACT FROM AUTHOR]

The vascular cambium is an extensive and permanent secondary meristem with wood cells products of periclinal divisions commonly contributed to two directions and arranged in radial files of trees. Cambium activity is the origin of timber production. Taxodium ascendens Brongn is an exotic species in China, and its apical meristem and cambial activity are still elusive, resulting in a lack of understanding about its wood formation and improvement. We thus addressed this knowledge gap by studying Cambium activity. For studying, twigs from five 30-year-old healthy trees were collected between February-2017 and March-2018. Anatomy deciphered its apical meristem with a Cryptomeria–Abies type. The procambium appeared after leaf primordium and initially presented five lobes as observed transversely from a one-year-old shoot. The procambium under the apical differentiated into protophloem first and then protoxylem toward the inside. It means that protoxylem differentiated later than protophloem did. After dormancy, the vascular cambium began to be active, starting in early April 2017, which was later than shoot differentiation. On 25 July 2017, the cambial zone had 9–10 immature xylem cell layers. Both initiation and cessation of the xylem preceded that of the phloem. Until 10 October 2017, few immature elements were found, indicating the translation of cells from activity to dormancy. On 15 November 2017, the cambium contained 3–4 cells in radial rows, which demonstrated the dormancy of the cambium until next spring. Furthermore, immature xylem elements increased as cell layers in the cambium zone and cell fission increased. The growth pattern of T. ascendens revealed that cambial activity is highly seasonal and dependent on changes in abiotic conditions. Thus, the wood formation in the species will be significantly altered in a changing climatic pattern. These enhance our understanding of tree growth science, wood formation, wood structure, wood properties variation and wood improvement in tree breeding. [ABSTRACT FROM AUTHOR]

In this study, we analyzed the energy and reproductive cycles of female and male Gymnodactylus geckoides in the Caatinga area of northeast Brazil. We investigated whether these proxies of body condition, such as reproductive cells maturation and cellular structures changed in response to variation in abiotic and biotic factors (i.e., humidity, temperature, seasonality, body temperature, growing rate and gonad volume), using individuals stored under scientific conditions collected between September 2018 and December 2021. The condition factor showed an isometric growth pattern in the population studied. Meanwhile, the lipid, hepatic, and gonad factors correlated with body growth and showed monthly and seasonal variations, as well as reproductive cell maturation and cellular structure morphology. The cycles displayed constant replacement of energy reserves and mature reproductive cells, indicating constant and acyclic reproduction in G. geckoides. Energy reserves appear to be used for many reproductive activities, including meeting, gestation, and egg laying that occur at different frequencies during different periods in the dry and rainy seasons. Therefore, the reproductive cycle is likely to be strongly controlled by biotic factors, which are modeled using abiotic factors and environmental conditions (environmental patterns which proportionate greater resource availability). Our study is the first to investigate energy cycles and reproductive strategies in G. geckoides. It has shown that this species stores greater amounts of energy during the rainy season and then depletes these reserves during the dry period, since the rainy season correspond to the increase in energy consumption, mainly because of gestation and egg laying. [ABSTRACT FROM AUTHOR]

Comprehensive utilization of cottonseeds is limited by the presence of pigment glands and its inclusion gossypol. The ideal cotton has glandless seeds but a glanded plant, a trait found in only a few Australian wild cotton species, including Gossypium bickii. Introgression of this trait into cultivated species has proved to be difficult. Understanding the biological processes toward pigment gland morphogenesis and the associated underlying molecular mechanisms will facilitate breeding of cultivated cotton varieties with the trait of glandless seeds and glanded plant. In this study, single-cell RNA sequencing (scRNA-seq) was performed on 12 222 protoplasts isolated from cotyledons of germinating G. bickii seeds 48 h after imbibition. Clustered into 14 distinct clusters unsupervisedly, these cells could be grouped into eight cell populations with the assistance of known cell marker genes. The pigment gland cells were well separated from others and could be separated into pigment gland parenchyma cells, secretory cells, and apoptotic cells. By integrating the pigment gland cell developmental trajectory, transcription factor regulatory networks, and core transcription factor functional validation, we established a model for pigment gland formation. In this model, light and gibberellin were verified to promote the formation of pigment glands. In addition, three novel genes, GbiERF114 (ETHYLENE RESPONSE FACTOR 114), GbiZAT11 (ZINC FINGER OF ARABIDOPSIS THALIANA 11), and GbiNTL9 (NAC TRANSCRIPTION FACTOR-LIKE 9), were found to affect pigment gland formation. Collectively, these findings provide new insights into pigment gland morphogenesis and lay the cornerstone for future cotton scRNA-seq investigations. Gossypium bickii possesses the ideal traits of pigment glands, which could contribute to the comprehensive utilization of cottonseeds and resistance to pests and diseases. Using the cotyledon of G. bickii and scRNA-seq technology, this study uncovers the developmental trajectory and transcriptional regulatory networks of cotton pigment glands. [ABSTRACT FROM AUTHOR]

Simple Summary: Gonadal cell lines possess the abilities of self-renewal and differentiation, being used as an efficient tool to analyzing the genes' functions involved in sex differentiation and gametogenesis. Although some significant achievements have been obtained in the gonadal cells' culture or manipulation across multiple phyla including teleost and mammals, there is limited study on gonadal cell manipulation in turtles. In this study, we isolated an ovarian cell line (fGSCs), from the juvenile Asian yellow pond turtle in vitro. The cultured fGSCs were characterized with germline stem cell specific markers' expression using transcriptome sequencing on Illumina platform, reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence (IF). Our study aims to provide a valuable tool to elaborate the molecular mechanisms behind germ cells development, differentiation and oogenesis in the turtle even in reptiles, and also, the established cell line has potential applications to enrich the conservation strategy of aquatic animal germplasm resources. Gonadal cell lines possess the abilities of self-renewal and differentiation, being used as an efficient tool to analyzing the genes' functions involved in sex differentiation and gametogenesis. Although some significant achievements have been obtained in the gonadal cells' culture or manipulation across multiple phyla including teleost and mammals, there is limited study on gonadal cell manipulation in turtles. In this study, we established a new ovarian cell line from the young Asian yellow pond turtle (Mauremys mutica), which exhibited a normal diploid karyotype with high alkaline phosphatase activity. The cell line, designated as YTO2, was then characterized through the analysis of gene expression profiles. The transcriptome analysis and the reverse transcription polymerase chain reaction (RT-PCR) showed that the cells expressed germline genes such as tdrd7, nanos1, klf5, igtb1, hsd17b4 and rad51. Moreover, the immunostaining showed that the germ cell markers, Tdrd7 and Rad51 proteins, were detected predominant in cytoplasm of perinuclear region, while proliferation marker, PCNA, was dominantly observed in the nuclei of cultured cells. Intriguingly, the cells could respond to the retinoic acid induction with significantly increasing the expression level of some meiosis genes, including vasa, dazl, figla, and dmc1. Furthermore, YTO2 cells could be efficiently transfected with the pHBAd-BHG-EGFP adenovirus and properly expressed the exogenous genes. To sum up, an ovarian cell line of the Asian yellow pond turtle had been established and could be stably propagated under in vitro culture condition, as well as being capable of efficiently expressing the exogenous gene tdrd7. This cell line would provide a valuable tool to elaborate the molecular mechanisms behind germ cells development, differentiation and oogenesis in the turtle, even in reptiles. [ABSTRACT FROM AUTHOR]

Cancer stem cells are the root cause of cancer, which, in essence, is a developmental disorder. All-trans retinoic acid (ATRA) signaling via ligand-activation of the retinoic acid receptors (RARs) plays a crucial role in tissue patterning and development during mammalian embryogenesis. In adults, active RARγ maintains the pool of hematopoietic stem cells, whereas active RARα drives myeloid cell differentiation. Various findings have revealed that ATRA signaling is deregulated in many cancers. The enzymes for ATRA synthesis are downregulated in colorectal, gastric, lung, and oropharyngeal cancers. ATRA levels within breast, ovarian, pancreatic, prostate, and renal cancer cells were lower than within their normal counterpart cells. The importance is that 0.24 nM ATRA activates RARγ (for stem cell stemness), whereas 100 times more is required to activate RARα (for differentiation). Moreover, RARγ is an oncogene regarding overexpression within colorectal, cholangiocarcinoma, hepatocellular, ovarian, pancreatic, and renal cancer cells. The microRNA (miR) 30a-5p downregulates expression of RARγ, and miR-30a/miR-30a-5p is a tumor suppressor for breast, colorectal, gastric, hepatocellular, lung, oropharyngeal, ovarian, pancreatic, prostate, and renal cancer. These complementary findings support the view that perturbations to ATRA signaling play a role in driving the abnormal behavior of cancer stem cells. Targeting ATRA synthesis and RARγ has provided promising approaches to eliminating cancer stem cells because such agents have been shown to drive cell death.

Oligodendrocytes are the glial cells responsible for the formation of myelin around axons of the central nervous system (CNS). Myelin is an insulating layer that allows electrical impulses to transmit quickly and efficiently along neurons. If myelin is damaged, as in chronic demyelinating disorders such as multiple sclerosis (MS), these impulses slow down. Remyelination by oligodendrocytes is often ineffective in MS, in part because of the failure of oligodendrocyte precursor cells (OPCs) to differentiate into mature, myelinating oligodendrocytes. The process of oligodendrocyte differentiation is tightly controlled by several regulatory networks involving transcription factors, intracellular signaling pathways, and extrinsic cues. Understanding the factors that regulate oligodendrocyte development is essential for the discovery of new therapeutic strategies capable of enhancing remyelination. Over the past decade, microRNAs (miRNAs) have emerged as key regulators of oligodendrocyte development, exerting effects on cell specification, proliferation, differentiation, and myelination. This article will review the role of miRNAs on oligodendrocyte biology and discuss their potential as promising therapeutic tools for remyelination. [ABSTRACT FROM AUTHOR]

The tongue is a unique muscular organ situated in the oral cavity where it is involved in taste sensation, mastication, and articulation. As a barrier organ, which is constantly exposed to environmental pathogens, the tongue is expected to host an immune cell network ensuring local immune defence. However, the composition and the transcriptional landscape of the tongue immune system are currently not completely defined. Here, we characterised the tissue-resident immune compartment of the murine tongue during development, health and disease, combining single-cell RNA-sequencing with in situ immunophenotyping. We identified distinct local immune cell populations and described two specific subsets of tongue-resident macrophages occupying discrete anatomical niches. Cx3cr1+ macrophages were located specifically in the highly innervated lamina propria beneath the tongue epidermis and at times in close proximity to fungiform papillae. Folr2+ macrophages were detected in deeper muscular tissue. In silico analysis indicated that the two macrophage subsets originate from a common proliferative precursor during early postnatal development and responded differently to systemic LPS in vivo. Our description of the under-investigated tongue immune system sets a starting point to facilitate research on tongue immune-physiology and pathology including cancer and taste disorders.

The vascular cambium is an extensive and permanent secondary meristem with wood cells products of periclinal divisions commonly contributed to two directions and arranged in radial files of trees. Cambium activity is the origin of timber production. Taxodium ascendens Brongn is an exotic species in China, and its apical meristem and cambial activity are still elusive, resulting in a lack of understanding about its wood formation and improvement. We thus addressed this knowledge gap by studying Cambium activity. For studying, twigs from five 30-year-old healthy trees were collected between February-2017 and March-2018. Anatomy deciphered its apical meristem with a Cryptomeria–Abies type. The procambium appeared after leaf primordium and initially presented five lobes as observed transversely from a one-year-old shoot. The procambium under the apical differentiated into protophloem first and then protoxylem toward the inside. It means that protoxylem differentiated later than protophloem did. After dormancy, the vascular cambium began to be active, starting in early April 2017, which was later than shoot differentiation. On 25 July 2017, the cambial zone had 9–10 immature xylem cell layers. Both initiation and cessation of the xylem preceded that of the phloem. Until 10 October 2017, few immature elements were found, indicating the translation of cells from activity to dormancy. On 15 November 2017, the cambium contained 3–4 cells in radial rows, which demonstrated the dormancy of the cambium until next spring. Furthermore, immature xylem elements increased as cell layers in the cambium zone and cell fission increased. The growth pattern of T. ascendens revealed that cambial activity is highly seasonal and dependent on changes in abiotic conditions. Thus, the wood formation in the species will be significantly altered in a changing climatic pattern. These enhance our understanding of tree growth science, wood formation, wood structure, wood properties variation and wood improvement in tree breeding.

Cellular development is orchestrated by evolutionarily conserved signaling pathways, which are often pleiotropic and involve intra- and interpathway epistatic interactions that form intricate, complex regulatory networks. Cryptococcus species are a group of closely related human fungal pathogens that grow as yeasts yet transition to hyphae during sexual reproduction. Additionally, during infection they can form large, polyploid titan cells that evade immunity and develop drug resistance. Multiple known signaling pathways regulate cellular development, yet how these are coordinated and interact with genetic variation is less well understood. Here, we conducted quantitative trait locus (QTL) analyses of a mapping population generated by sexual reproduction of two parents, only one of which is unisexually fertile. We observed transgressive segregation of the unisexual phenotype among progeny, as well as a large-cell phenotype under mating-inducing conditions. These large-cell progeny were found to produce titan cells both in vitro and in infected animals. Two major QTLs and corresponding quantitative trait genes (QTGs) were identified: RIC8 (encoding a guanine-exchange factor) and CNC06490 (encoding a putative Rho-GTPase activator), both involved in G protein signaling. The two QTGs interact epistatically with each other and with the mating-type locus in phenotypic determination. These findings provide insights into the complex genetics of morphogenesis during unisexual reproduction and pathogenic titan cell formation and illustrate how QTL analysis can be applied to identify epistasis between genes. This study shows that phenotypic outcomes are influenced by the genetic background upon which mutations arise, implicating dynamic, complex genotype-to-phenotype landscapes in fungal pathogens and beyond. [ABSTRACT FROM AUTHOR]

Dendritic cells (DC) have a key role in the initiation and progression of inflammatory arthritis (IA). In this study, we identified a DC population that derive from monocytes, characterized as CD209/CD14+ DC, expressing classical DC markers (HLADR, CD11c) and the Mo-DC marker (CD209), while also retaining the monocytic marker CD14. This CD209/CD14+ DC population is present in the circulation of Healthy Control (HC), with increased frequency in Rheumatoid Arthritis (RA) and Psoriatic arthritic (PsA) patients. We demonstrate, for the first time, that circulatory IA CD209/CD14+ DC express more cytokines (IL1β/IL6/IL12/TNFα) and display a unique chemokine receptor expression and co-expression profiles compared to HC. We demonstrated that CD209/CD14+ DC are enriched in the inflamed joint where they display a unique inflammatory and maturation phenotype, with increased CD40 and CD80 and co-expression of specific chemokine receptors, displaying unique patterns between PsA and RA. We developed a new protocol of magnetic isolation and expansion for CD209+ DC from blood and identified transcriptional differences involved in endocytosis/antigen presentation between RA and PsA CD209+ DC. In addition, we observed that culture of healthy CD209+ DC with IA synovial fluid (SF), but not Osteoarthritis (OA) SF, was sufficient to induce the development of CD209/CD14+ DC, leading to a poly-mature DC phenotype. In addition, differential effects were observed in terms of chemokine receptor and chemokine expression, with healthy CD209+ DC displaying increased expression/co-expression of CCR6, CCR7, CXCR3, CXCR4 and CXCR5 when cultured with RA SF, while an increase in the chemokines CCR3, CXCL10 and CXCL11 was observed when cultured with PsA SF. This effect may be mediated in part by the observed differential increase in chemokines expressed in RA vs PsA SF. Finally, we observed that the JAK/STAT pathway, but not the NF-κB pathway (driven by TNFα), regulated CD209/CD14+ DC function in terms of activation, inflammatory state, and migratory capacity. In conclusion, we identified a novel CD209/CD14+ DC population, which is active in the circulation of RA and PsA, an effect potentiated once they enter the joint. Furthermore, we demonstrated that JAK/STAT inhibition can be used as a therapeutic strategy to decrease the inflammatory state of the pathogenic CD209/CD14+ DC. [ABSTRACT FROM AUTHOR]

Abstract Background In epigenetics, the change of the combination of histone modifications at the same genomic location during cell differentiation is of great interest for understanding the function of these modifications and their combinations. Besides analyzing them locally for individual genomic locations or globally using correlations between different cells types, intermediate level analyses of these changes are of interest. More specifically, the different distributions of these combinations for different cell types, respectively, are compared to gain new insights. Results and discussion We propose a new tool called ‘Masakari’ that allows segmenting genomes based on lists of ranges having a certain property, e.g., peaks describing histone modifications. It provides a graphical user interface allowing to select all data sets and setting all parameters needed for the segmentation process. Moreover, the graphical user interface provides statistical graphics allowing to assess the quality and suitability of the segmentation and the selected data. Conclusion Masakari provides statistics based visualizations and thus fosters insights into the combination of histone modification marks on genome ranges, and the differences of the distribution of these combinations between different cell types.

Dendritic cells (DC) have a key role in the initiation and progression of inflammatory arthritis (IA). In this study, we identified a DC population that derive from monocytes, characterized as CD209/CD14+ DC, expressing classical DC markers (HLADR, CD11c) and the Mo-DC marker (CD209), while also retaining the monocytic marker CD14. This CD209/CD14+ DC population is present in the circulation of Healthy Control (HC), with increased frequency in Rheumatoid Arthritis (RA) and Psoriatic arthritic (PsA) patients. We demonstrate, for the first time, that circulatory IA CD209/CD14+ DC express more cytokines (IL1β/IL6/IL12/TNFα) and display a unique chemokine receptor expression and co-expression profiles compared to HC. We demonstrated that CD209/CD14+ DC are enriched in the inflamed joint where they display a unique inflammatory and maturation phenotype, with increased CD40 and CD80 and co-expression of specific chemokine receptors, displaying unique patterns between PsA and RA. We developed a new protocol of magnetic isolation and expansion for CD209+ DC from blood and identified transcriptional differences involved in endocytosis/antigen presentation between RA and PsA CD209+ DC. In addition, we observed that culture of healthy CD209+ DC with IA synovial fluid (SF), but not Osteoarthritis (OA) SF, was sufficient to induce the development of CD209/CD14+ DC, leading to a poly-mature DC phenotype. In addition, differential effects were observed in terms of chemokine receptor and chemokine expression, with healthy CD209+ DC displaying increased expression/co-expression of CCR6, CCR7, CXCR3, CXCR4 and CXCR5 when cultured with RA SF, while an increase in the chemokines CCR3, CXCL10 and CXCL11 was observed when cultured with PsA SF. This effect may be mediated in part by the observed differential increase in chemokines expressed in RA vs PsA SF. Finally, we observed that the JAK/STAT pathway, but not the NF-κB pathway (driven by TNFα), regulated CD209/CD14+ DC function in terms of activation, inflammatory state, and migratory capacity. In conclusion, we identified a novel CD209/CD14+ DC population, which is active in the circulation of RA and PsA, an effect potentiated once they enter the joint. Furthermore, we demonstrated that JAK/STAT inhibition can be used as a therapeutic strategy to decrease the inflammatory state of the pathogenic CD209/CD14+ DC.

Gonadal cell lines possess the abilities of self-renewal and differentiation, being used as an efficient tool to analyzing the genes’ functions involved in sex differentiation and gametogenesis. Although some significant achievements have been obtained in the gonadal cells’ culture or manipulation across multiple phyla including teleost and mammals, there is limited study on gonadal cell manipulation in turtles. In this study, we established a new ovarian cell line from the young Asian yellow pond turtle (Mauremys mutica), which exhibited a normal diploid karyotype with high alkaline phosphatase activity. The cell line, designated as YTO2, was then characterized through the analysis of gene expression profiles. The transcriptome analysis and the reverse transcription polymerase chain reaction (RT-PCR) showed that the cells expressed germline genes such as tdrd7, nanos1, klf5, igtb1, hsd17b4 and rad51. Moreover, the immunostaining showed that the germ cell markers, Tdrd7 and Rad51 proteins, were detected predominant in cytoplasm of perinuclear region, while proliferation marker, PCNA, was dominantly observed in the nuclei of cultured cells. Intriguingly, the cells could respond to the retinoic acid induction with significantly increasing the expression level of some meiosis genes, including vasa, dazl, figla, and dmc1. Furthermore, YTO2 cells could be efficiently transfected with the pHBAd-BHG-EGFP adenovirus and properly expressed the exogenous genes. To sum up, an ovarian cell line of the Asian yellow pond turtle had been established and could be stably propagated under in vitro culture condition, as well as being capable of efficiently expressing the exogenous gene tdrd7. This cell line would provide a valuable tool to elaborate the molecular mechanisms behind germ cells development, differentiation and oogenesis in the turtle, even in reptiles.

Follicular regulatory T (Tfr) cells are recently found to be a special subgroup of regulatory T (Treg) cells. Tfr cells play an important role in regulating the germinal center (GC) response, especially modulating follicular helper T (Tfh) cells and GC‐B cells, thereby affecting the production of antibodies. Tfr cells are involved in the generation and development of many immune‐related and inflammatory diseases. This article summarizes the advances in several aspects of Tfr cell biology, with special focus on definition and phenotype, development and differentiation, regulatory factors, functions, and interactions with T/B cells and molecules involved in performance and regulation of Tfr function. Finally, we highlight the current understanding of Tfr cells involvement in autoimmunity and alloreactivity, and describe some drugs targeting Tfr cells. These latest studies have answered some basic questions in Tfr cell biology and explored the roles of Tfr cells in immune‐mediated diseases. [ABSTRACT FROM AUTHOR]

TET proteins are DNA demethylases that can oxidize 5‐methylcytosine (5mC) to generate 5‐hydroxymethylcytosine (5hmC) and other oxidized mC bases (oxi‐mCs). Importantly, TET proteins govern cell fate decisions during development of various cell types by activating a cell‐specific gene expression program. In this review, we focus on the role of TET proteins in T‐cell lineage specification. We explore the multifaceted roles of TET proteins in regulating gene expression in the contexts of T‐cell development, lineage specification, function, and disease. Finally, we discuss the future directions and experimental strategies required to decipher the precise mechanisms employed by TET proteins to fine‐tune gene expression and safeguard cell identity. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) have been reported to be related to the development of human cancers. However, the function of circ-FOXM1 in non-small cell lung cancer (NSCLC) was largely unknown. Here, we revealed the role and functional mechanism of circ-FOXM1 in NSCLC progression. The relative expression of circ-FOXM1, microRNA-149-5p (miR-149-5p), and autophagy-related 5 (ATG5) was determined by quantitative real-time polymerase chain reaction (RT-qPCR). Cell Counting Kit-8 (CCK-8), flow cytometry, and transwell assay were employed to assess cell viability, apoptosis, and migration, respectively. The relative protein expression was detected by western blot. Furthermore, mouse xenograft was carried out to analyze the effect of circ-FOXM1 on tumor growth in vivo. In addition, the interaction between miR-149-5p and circ-FOXM1 or ATG5 was predicted by Starbase3.0 and confirmed by the dual-luciferase reporter assay and RNA pull-down assay. Circ-FOXM1 and ATG5 levels were upregulated, while the miR-149-5p level was downregulated in NSCLC tissues and cells. Circ-FOXM1 knockdown suppressed NSCLC cell viability, migration, and autophagy, and induced cell apoptosis. Interestingly, circ-FOXM1 targeted miR-149-5p to upregulate the ATG5 level. Moreover, circ-FOXM1 exerted function through repressing miR-149-5p expression, and miR-149-5p exerted function via inhibiting ATG5 expression. Our results suggested that circ-FOXM1 knockdown attenuated the development of NSCLC through modulating the miR-149-5p/ATG5 axis, providing a theoretical basis for the therapy of NSCLC. [ABSTRACT FROM AUTHOR]

Abstract As an essential and fundamental process of life, cell development involves large‐scale reorganization of the 3D genome architecture, which forms the basis of gene regulation. Here, a landscape‐switching model is developed to explore the microscopic chromosomal structural origin of embryonic stem cell (ESC) differentiation and somatic cell reprogramming. It is shown that chromosome structure exhibits significant compartment‐switching in the unit of topologically associating domain. It is found that the chromosome during differentiation undergoes monotonic compaction with spatial repositioning of active and inactive chromosomal loci toward the chromosome surface and interior, respectively. In contrast, an overexpanded chromosome, which exhibits universal localization of loci at the chromosomal surface with erasing the structural characteristics formed in the somatic cells, is observed during reprogramming. An early distinct differentiation pathway from the ESC to the terminally differentiated cell, giving rise to early bifurcation on the Waddington landscape for the ESC differentiation is suggested. The theoretical model herein including the non‐equilibrium effects, draws a picture of the highly irreversible cell differentiation and reprogramming processes, in line with the experiments. The predictions provide a physical understanding of cell differentiation and reprogramming from the chromosomal structural and dynamical perspective and can be tested by future experiments.

Proliferating cells must coordinate central metabolism with the cell cycle. How central energy metabolism regulates bacterial cell cycle functions is not well understood. Our forward genetic selection unearthed the Krebs cycle enzyme citrate synthase (CitA) as a checkpoint regulator controlling the G1→S transition in the polarized alpha-proteobacterium Caulobacter crescentus, a model for cell cycle regulation and asymmetric cell division. We find that loss of CitA promotes the accumulation of active CtrA, an essential cell cycle transcriptional regulator that maintains cells in G1-phase, provided that the (p)ppGpp alarmone is present. The enzymatic activity of CitA is dispensable for CtrA control, and functional citrate synthase paralogs cannot replace CitA in promoting S-phase entry. Our evidence suggests that CitA was appropriated specifically to function as a moonlighting enzyme to link central energy metabolism with S-phase entry. Control of the G1-phase by a central metabolic enzyme may be a common mechanism of cellular regulation.

Abstract Plasmacytoid dendritic cells (pDCs) are a unique subset of dendritic cells specialised in secreting high levels of type I interferons. pDCs play a crucial role in antiviral immunity and have been implicated in the initiation and development of many autoimmune and inflammatory diseases. This review summarises the latest advances in recent years in several aspects of pDC biology, with special focus on pDC heterogeneity, pDC development via the lymphoid pathway, and newly identified proteins/pathways involved in pDC trafficking, nucleic acid sensing and interferon production. Finally, we also highlight the current understanding of pDC involvement in autoimmunity and alloreactivity, and opportunities for pDC‐targeting therapies in these diseases. These new insights have contributed to answers to several fundamental questions remaining in pDC biology and may pave the way to successful pDC‐targeting therapy in the future.

As an essential and fundamental process of life, cell development involves large‐scale reorganization of the 3D genome architecture, which forms the basis of gene regulation. Here, a landscape‐switching model is developed to explore the microscopic chromosomal structural origin of embryonic stem cell (ESC) differentiation and somatic cell reprogramming. It is shown that chromosome structure exhibits significant compartment‐switching in the unit of topologically associating domain. It is found that the chromosome during differentiation undergoes monotonic compaction with spatial repositioning of active and inactive chromosomal loci toward the chromosome surface and interior, respectively. In contrast, an overexpanded chromosome, which exhibits universal localization of loci at the chromosomal surface with erasing the structural characteristics formed in the somatic cells, is observed during reprogramming. An early distinct differentiation pathway from the ESC to the terminally differentiated cell, giving rise to early bifurcation on the Waddington landscape for the ESC differentiation is suggested. The theoretical model herein including the non‐equilibrium effects, draws a picture of the highly irreversible cell differentiation and reprogramming processes, in line with the experiments. The predictions provide a physical understanding of cell differentiation and reprogramming from the chromosomal structural and dynamical perspective and can be tested by future experiments. [ABSTRACT FROM AUTHOR]

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Essential genes are those whose loss of function compromises organism viability or results in profound loss of fitness. Recent gene-editing technologies have provided new opportunities to characterize essential genes. Here, we present an integrated analysis that comprehensively and systematically elucidates the genetic and regulatory characteristics of human essential genes. First, we found that essential genes act as 'hubs' in protein–protein interaction networks, chromatin structure and epigenetic modification. Second, essential genes represent conserved biological processes across species, although gene essentiality changes differently among species. Third, essential genes are important for cell development due to their discriminate transcription activity in embryo development and oncogenesis. In addition, we developed an interactive web server, the Human Essential Genes Interactive Analysis Platform (http://sysomics.com/HEGIAP /), which integrates abundant analytical tools to enable global, multidimensional interpretation of gene essentiality. Our study provides new insights that improve the understanding of human essential genes. [ABSTRACT FROM AUTHOR]

Summary: Plant cell walls constitute the extracellular matrix surrounding plant cells and are composed mainly of polysaccharides. The chemical makeup of the primary plant cell wall, and specifically, the abundance, localization and arrangement of the constituting polysaccharides are intimately linked with growth, morphogenesis and differentiation in plant cells. Visualization of the cell wall components is, therefore, a crucial tool in plant cell developmental studies. In this technical update, we present protocols for fluorescence visualization of cellulose and pectin in selected plant tissues and illustrate examples of some of the available labels that hold promise for live imaging of plant cell wall expansion and morphogenesis. [ABSTRACT FROM AUTHOR]

Plasmacytoid dendritic cells (pDCs) are a unique subset of dendritic cells specialised in secreting high levels of type I interferons. pDCs play a crucial role in antiviral immunity and have been implicated in the initiation and development of many autoimmune and inflammatory diseases. This review summarises the latest advances in recent years in several aspects of pDC biology, with special focus on pDC heterogeneity, pDC development via the lymphoid pathway, and newly identified proteins/pathways involved in pDC trafficking, nucleic acid sensing and interferon production. Finally, we also highlight the current understanding of pDC involvement in autoimmunity and alloreactivity, and opportunities for pDC‐targeting therapies in these diseases. These new insights have contributed to answers to several fundamental questions remaining in pDC biology and may pave the way to successful pDC‐targeting therapy in the future. [ABSTRACT FROM AUTHOR]

Ｉｎ ｏｒｄｅｒ ｔｏ ｕｎｄｅｒｓｔａｎｄ ｗｈｅｔｈｅｒ ｔｈｅｒｅ ａｒｅ ｄｉｆｆｅｒｅｎｃｅｓ ｉｎ ｍｏｒｐｈｏｌｏｇｙ ｏｆ ｍｉｃｒｏｓｔｒｏｂｉｌｕｓ ｏｆ Ｐｉｎｕｓ ｅｌｌｉｏｔｔｉｉ ‘Ｓｏｎｇ- ｔａｉ’ ｄｕｒｉｎｇ ｄｅｖｅｌｏｐｍｅｎｔꎬ ｔｏ ｃｌａｒｉｆｙ ｉｔｓ ａｂｏｒｔｉｏｎ ｐｒｏｃｅｓｓꎬ ａｂｏｒｔｉｏｎ ｍｏｄｅ ａｎｄ ｉｎｆｌｕｅｎｃｉｎｇ ｆａｃｔｏｒｓꎬ ａｎｄ ｔｏ ｐｒｏｖｉｄｅ ｓｃｉｅｎｔｉｆｉｃ ｂａｓｉｓ ｆｏｒ ｕｔｉｌｉｚａｔｉｏｎ ａｎｄ ｌａｔｅｒ ｒｅｓｅａｒｃｈ ｏｆ ｍａｌｅ ｓｔｅｒｉｌｅ ｖａｒｉｅｔｉｅｓ ｏｆ Ｐｉｎｕｓ ｅｌｌｉｏｔｔｉｉꎬ ｔｈｅ ｍｏｒｐｈｏｌｏｇｉｃａｌ ｃｈａｎｇｅｓ ｏｆ ｍｉｃｒｏｓｔｒｏｂｉ- ｌｕｓ ｗｅｒｅ ｏｂｓｅｒｖｅｄ ｂｙ ｕｓｉｎｇ ‘Ｓｏｎｇｔａｉ’ ｓ１０ ａｂｏｒｔｉｖｅ ｌｉｎｅ ａｎｄ ｓ９ ｆｅｒｔｉｌｅ ｌｉｎｅ ａｓ ｍａｔｅｒｉａｌｓꎬ ａｎｄ ｔｈｅ ｍｉｃｒｏｓｔｒｏｂｉｌｕｓ ｗａｓ ｓｌｉｃｅｄ ｉｎ ｐａｒａｆｆｉｎ ａｎｄ ｔｈｅ ｄｅｖｅｌｏｐｍｅｎｔ ｏｆ ｍｉｃｒｏｓｐｏｒｅ ｗａｓ ｏｂｓｅｒｖｅｄ ｕｎｄｅｒ ｏｐｔｉｃａｌ ｍｉｃｒｏｓｃｏｐｅ. Ｔｈｅ ｒｅｓｕｌｔｓ ｗｅｒｅ ａｓ ｆｏｌｌｏｗｓ: Ｔｈｅｒｅ ｗａｓ ｎｏ ｓｉｇｎｉｆｉｃａｎｔ ｄｉｆｆｅｒｅｎｃｅｓ ｂｅｔｗｅｅｎ ｓ１０ ａｂｏｒｔｉｏｎ ｌｉｎｅ ａｎｄ ｓ９ ｆｅｒｔｉｌｅ ｌｉｎｅ ｂｅｆｏｒｅ ｍｅｉｏｔｉｃ ｐｈａｓｅ ｏｆ ｍｉｃｒｏｓｐｏｒｏｃｙ ｄｅｃｅｌｅｒａ- ｔｉｏｎ ａｎｄ ｄｉｖｉｓｉｏｎꎬ ａｎｄ ｔｈｅ ｇｒｏｗｔｈ ｔｒｅｎｄ ｏｆ ｍｉｃｒｏｓｔｒｏｂｉｌｕｓ ｗａｓ ｔｈｅ ｓａｍｅ. Ｉｎ ｔｈｅ ｐｅｒｉｏｄ ｏｆ ｔｅｔｒａｄꎬ ｓ１０ ｍｉｃｒｏｓｐｏｒｅ ｃｅｌｌ ｄｅｖｅｌｏｐｍｅｎｔ ａｎｄ ｍｉｃｒｏｓｔｒｏｂｉｌｕｓ ｍｏｒｐｈｏｌｏｇｉｃａｌ ｄｅｖｅｌｏｐｍｅｎｔ ｗｅｒｅ ａｂｎｏｒｍａｌ. Ｔｈｅ ｔｉｍｅ ｆｒｏｍ ｔｅｔｒａｄ ｔｏ ｍｏｎｏｃｙｔｅ ｍｉｃｒｏｓｐｏｒｅ ｄｅｖｅｌｏｐｍｅｎｔ ｏｆ ｆｅｒｔｉｌｅ ｌｉｎｅｓ ｉｓ ａｂｏｕｔ ５ ｄ. Ｈｏｗｅｖｅｒꎬ ｔｈｅ ａｂｏｒｔｉｏｎ ｌｉｎｅ ｃｏｎｔｉｎｕｅｄ ｔｏ ｄｅｖｅｌｏｐ ｆｏｒ ａｂｏｕｔ ２０ ｄꎬ ａｎｄ ｔｈｅ ｄｕｒａ- ｔｉｏｎ ｗａｓ ｆｏｕｒ ｔｉｍｅｓ ｔｈａｔ ｏｆ ｔｈｅ ｆｅｒｔｉｌｅ ｌｉｎｅ. Ｉｎ ｔｈｅ ｍｅａｎｔｉｍｅꎬ ｔｈｅ ｄｅｖｅｌｏｐｍｅｎｔ ｏｆ ｔａｐｅｔｕｍ ｃｅｌｌｓ ｗａｓ ａｂｎｏｒｍａｌꎬ ｔｈｅ ｄｅｇｒａｄａ- ｔｉｏｎ ｗａｓ ｓｌｏｗꎬ ｔｈｅ ｔｉｓｓｕｅ ａｒｒａｎｇｅｍｅｎｔ ｏｆ ｍｉｃｒｏｓｐｏｒａｎｇｉｕｍ ｗａｌｌ ｗａｓ ｄｉｓｏｒｄｅｒｅｄꎬ ａｎｄ ｔｈｅ ｄｅｇｒａｄａｔｉｏｎ ｗａｓ ｄｅｌａｙｅｄ. Ｆｉｎａｌｌｙꎬ ｓ１０ ｆｏｒｍｓ ａｂｎｏｒｍａｌ ｄｉｎｕｃｌｅａｒ ｐｏｌｌｅｎ ａｎｄ ｎｏ ｐｏｌｌｅｎ ｄｉｓｐｅｒｓｉｏｎ. Ｓｏ ｉｔ ｃａｎ ｂｅ ｒｅａｓｏｎｅｄ ｔｈａｔ ｔｈｅ ａｂｎｏｒｍａｌ ｄｅｖｅｌｏｐｍｅｎｔ ｏｆ ｍｉｃｒｏｓｐｏｒａｎｇｉｕｍ ｗａｌｌ ｃｅｌｌｓꎬ ａｎｄ ｔｈｅ ａｂｎｏｒｍａｌ ｍｏｒｐｈｏｌｏｇｙ ｏｆ ｍｉｃｒｏｓｔｒｏｂｉｌｕｓ.Ｔｈｅ ｔａｐｅｔｕｍ ｄｅｖｅｌｏｐｓ ａｂｎｏｒｍａｌｌｙ ｉｎ ｔｈｅ ｔｅｔ- ｒａｄ ｐｅｒｉｏｄꎬ ａｎｄ ｔｈｅ ｃａｌｌｏｓｅ ｅｎｚｙｍｅ ｃａｎ ｎｏｔ ｂｅ ｓｅｃｒｅｔｅｄ ａｔ ａｐｐｒｏｐｒｉａｔｅ ｔｉｍｅ ｔｏ ｄｅｇｒａｄｅ ｔｈｅ ｃａｌｌｏｓｕｍ ｗａｌｌ ｓｕｒｒｏｕｎｄｉｎｇ ｔｈｅ ｔｅｔｒａｄꎬ ｎｏｒ ｃａｎ ｉｔ ｓｙｎｔｈｅｓｉｚｅ ａｎｄ ｔｒａｎｓｐｏｒｔ ｔｈｅ ｅｎｅｒｇｙ ｓｕｂｓｔａｎｃｅｓ ｎｅｅｄｅｄ ｆｏｒ ｐｏｌｌｅｎ ｆｏｒｍａｔｉｏｎ ｉｎ ａ ｔｉｍｅｌｙ ｍａｎｎｅｒ. Ａｔ ｔｈｅ ｓａｍｅ ｔｉｍｅꎬ ｔｈｅ ｃｙｓｔｉｃ ｗａｌｌ ｃｅｌｌｓ ｓｈｏｗｅｄ ｄｅｌａｙｅｄ ｄｅｇｒａｄａｔｉｏｎ ａｎｄ ｌａｍｉｎａｔｉｏｎ. Ｔｈｉｓ ｓｅｒｉｅｓ ｏｆ ａｂｎｏｒｍａｌ ｃｈａｎｇｅｓ ｌｅａｄｅｄ ｔｏ ｔｈｅ ｎｏｒｍａｌ ｔｅｔｒａｄ ｃｏｕｌｄ ｎｏｔ ｂｅ ｆｏｒｍｅｄꎬ ｗｈｉｃｈ ｍａｄｅ ｔｈｅ ｐｏｌｌｅｎ ａｂｏｒｔｉｏｎ. [ABSTRACT FROM AUTHOR]

OBJECTIVE: In recent years, circular RNAs (circRNAs) and microRNAs (miRNAs) have been shown to be related to the development of esophageal squamous cell carcinoma (ESCC). However, their functional mechanisms remain to be investigated. Herein, we focus our research on the functions and mechanisms of circCNOT6L and miR-384 in ESCC. MATERIALS AND METHODS: The levels of circCNOT6L, miR-384, and fibronectin 1 (FN1) were determined using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). RNase R was used to investigate circCNOT6L stabilization. Cell proliferation and apoptosis were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively. Western blot assay was employed to analyze the protein levels of FN1, proliferation-related genes, and iron metabolism-related genes. In addition, the interaction between miR-384 and circCNOT6L or FN1 was predicted by starBase3.0 and confirmed by the Dual-Luciferase reporter assay. Mouse xenograft was carried out to measure the effect of circCNOT6L on tumor growth in vivo. RESULTS: CircCNOT6L and FN1 levels were upregulated, and miR-384 level was downregulated in ESCC tissues/cells. CircCNOT6L knockdown attenuated ESCC cell proliferation and iron metabolism disorder, as well as accelerated apoptosis. Notably, circCNOT6L targeted miR-384, and miR-384 targeted FN1. MiR-384 depletion and FN1 upregulation weakened the effects of circCNOT6L knockdown and miR-384 overexpression on ESCC cell progression, respectively. Besides, circCNOT6L knockdown inhibited tumor growth in vivo. CONCLUSIONS: Our results demonstrated that circCNOT6L positively regulated the development of ESCC cells via modulating miR-384/ FN1 axis. Our findings provided a theoretical basis for the therapy of ESCC patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Colorectal cancer (CRC) is a common tumor around the world. Circular RNAs (circRNAs) have been reported to be related to the development of CRC. However, the detailed mechanism is complicated. This study aimed to reveal the functional mechanism of circ_0007534 in CRC. PATIENTS AND METHODS: Quantitative real time polymerase chain reation (qRT-PCR) and Western blot assay were performed to analyze gene expression. 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and colony formation assay were carried out to determine cell proliferation ability. Furthermore, cell migratory and invasive abilities were assessed by transwell assay. Glycolytic metabolism was examined via the measurements of extracellular acidification rate (ECAR), glucose consumption, and lactate production. Also, the interaction between circ_0007534 or solute carrier family 25 member 22 (SLC25A22) and miR-613 was predicted and confirmed by starBase v2.0 and the Dual-Luciferase reporter assay, respectively. Mouse xenograft was performed to investigate the effect of circ_0007534 on tumor growth in vivo. RESULTS: Circ_0007534 and SLC25A22 levels were upregulated, and miR-613 level was downregulated in CRC tissues/cells. Circ_0007534 knockdown repressed CRC cell proliferation, colony formation, migration, invasion, and glycolysis. Interestingly, Circ_0007534 targeted miR-613, and miR-613 targeted SLC25A22. Circ_0007534 exerted its function by repressing miR-613 expression, and miR-613 exerted its function via inhibiting SLC25A22 expression. Also, Circ_0007534 repressed miR-613 expression to upregulate SLC25A22 level. Circ_0007534 depletion repressed tumor growth in vivo. CONCLUSIONS: We demonstrated that circ_0007534 knockdown suppressed the growth of CRC cells by regulating miR-613/SLC25A22 axis, providing potential target for the treatment of CRC. [ABSTRACT FROM AUTHOR]

Blood-borne pathogens can cause systemic inflammatory response syndrome (SIRS) followed by protracted, potentially lethal immunosuppression. The mechanisms responsible for impaired immunity post-SIRS remain unclear. We show that SIRS triggered by pathogen mimics or malaria infection leads to functional paralysis of conventional dendritic cells (cDCs). Paralysis affects several generations of cDCs and impairs immunity for 3–4 weeks. Paralyzed cDCs display distinct transcriptomic and phenotypic signatures and show impaired capacity to capture and present antigens in vivo. They also display altered cytokine production patterns upon stimulation. The paralysis program is not initiated in the bone marrow but during final cDC differentiation in peripheral tissues under the influence of local secondary signals that persist after resolution of SIRS. Vaccination with monoclonal antibodies that target cDC receptors or blockade of transforming growth factor β partially overcomes paralysis and immunosuppression. This work provides insights into the mechanisms of paralysis and describes strategies to restore immunocompetence post-SIRS. [Display omitted] • Blood infections cause severe inflammation followed by protracted immunosuppression • Impaired immunity is due to formation of paralyzed conventional dendritic cells (cDCs) • Local secondary signals that persist after resolution of infection induce paralysis • Therapies that overcome or reduce the duration of cDC paralysis restore immunocompetence Ashayeripanah et al. show that severe inflammation triggered by blood infections such as malaria induces formation of functionally impaired (paralyzed) dendritic cells for weeks after resolution of infection. Paralysis causes immune suppression. Transcriptomic, phenotypic, and functional characterization of paralysis leads to designing treatments that restore dendritic cell function and immunocompetence. [ABSTRACT FROM AUTHOR]

In vivo monitoring of rice (Oryza sativa L.) seed germination and seedling growth under general conditions in closed Petri dishes containing agar base medium at room temperature (temperature = 24.5 ± 1 °C, relative humidity = 76 ± 7% (average ± standard deviation)), and induced degenerated callus formation with plant growth regulator, were performed using short-wavelength near-infrared spectroscopy and aquaphotomics over A period of 26 days. The results of spectral analysis suggest changes in water absorbances due to the production of common metabolites, as well as increases in biomass and the sizes of the samples. Quantitative models built to predict the day of the development provided better accuracy for rice seedlings growth compared to callus formation. Eight common water bands were identified as presenting prominent changes in the absorbance pattern. The water matrix of only rice seedlings showed three developmental stages: firstly expressing a predominantly weakly hydrogen-bonded state, then a more strongly hydrogen-bonded state, and then, again, a weakly hydrogen-bonded state at the end. In rice callus induction and proliferation, no similar change in water absorbance pattern was observed. The presented findings indicate the potential of aquaphotomics for the in vivo detection of degeneration in cell development.

Tissue engineering of exogenous skeletal muscle units (SMUs) through isolation of muscle satellite cells from muscle biopsies is a potential treatment method for acute volumetric muscle loss (VML). A current issue with this treatment process is the limited capacity for muscle stem cell (satellite cell) expansion in cell culture, resulting in a decreased ability to obtain enough cells to fabricate SMUs of appropriate size and structural quality and that produce native levels of contractile force. This study determined the impact of human recombinant irisin on the growth and development of three-dimensional (3D) engineered skeletal muscle. Muscle satellite cells were cultured without irisin (control) or with 50, 100, or 250 ng/mL of irisin supplementation. Light microscopy was used to analyze myotube formation with particular focus placed on the diameter and density of the monotubes during growth of the 3D SMU. Following the formation of 3D constructs, SMUs underwent measurement of maximum tetanic force to analyze contractile function, as well as immunohistochemical staining, to characterize muscle structure. The results indicate that irisin supplementation with 250 ng/mL significantly increased the average diameter of myotubes and increased the proliferation and differentiation of myoblasts in culture but did not have a consistent significant impact on force production. In conclusion, supplementation with 250 ng/mL of human recombinant irisin promotes the proliferation and differentiation of myotubes and has the potential for impacting contractile force production in scaffold-free tissue-engineered skeletal muscle.

Abstract Long non-coding RNAs (lncRNAs) have been attracting immense research interests. The relevance of lncRNAs in biological and physiological as well as in pathological processes has increased along with the understanding of their various regulatory mechanisms. Abundant studies have indicated that lncRNAs are involved in the differentiation, proliferation, activation, and initiation of apoptosis in different cell types. However, most studies about the regulating biology of lncRNAs are currently focused on cancer cells. This review is focused on the widely unexplored role of lncRNAs in the cell fate of myeloid cells. In this review, we summarize recent studies that have confirmed lncRNAs to be essential in the development of myeloid cells under normal and pathological conditions.

Recent studies have identified CD49a+Eomes− and CD49a+Eomes+ subsets of tissue-resident NK (trNK) cells in different organs of the mouse. However, the characteristics of CD49a+Eomes−/+ NK cell development and the regulation of Eomes expression in NK cells remain unclear. Here, we established an in vitro cytokine-based feeder-free system in which bone marrow progenitor cells differentiate into CD49a+ NK cells. IL-15 was identified as being the key cytokine in this system that supported the development and maintenance of CD49a+ NK cells. The CD49a+ NK cells generated were Eomes−CD49b− and shared the same phenotype as hepatic trNK cells. IL-4 induced the expression of Eomes in generated NK cells and converted them into CD49a+Eomes+ cells, which were phenotypically and functionally similar to uterine trNK cells. Moreover, the IL-4/STAT6 axis was identified as being important in the generation of CD49a+Eomes+ induced NK cells. Collectively, these studies describe an approach to generate CD49a+Eomes−/+ subsets of NK cells and demonstrate important roles for IL-15 and IL-4 in the differentiation of these cells. These findings have potential for developmental research underlying the generation of different subsets of NK cells and the application of adoptive NK cell transfer therapies.