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While a definitive understanding of the molecular pathology of posttraumatic stress disorder (PTSD) is far from a current reality, it has become increasingly clear that many of the molecular effects of PTSD are sex specific. Women are twice as likely as men to develop PTSD after a traumatic event, and neurobiological evidence suggests that there are structural differences between the brains of males versus females with PTSD. Recent advances in genomic technologies have begun to shed light on the sex-specific molecular determinants of PTSD, which seem to be governed predominantly by dysfunction of GABAergic (gamma-aminobutyric acidergic) signaling and immune function. We review the current state of the field of PTSD genomics focusing on the effect of sex. We provide an overview of difference in heritability of PTSD based on sex, how difference in gene regulation based on sex impacts the PTSD brain, and what is known about genomic regulation that is dysregulated in specific cell types in PTSD.

MicroRNAs (miRNAs) are small noncoding RNAs that regulate complex gene expression networks in eukaryotic cells. Because of their unique expression patterns, miRNAs are potential molecular markers for specific cell states. Although a system capable of imaging miRNA in living cells is needed to visually detect miRNA expression, very few fluorescence signal-on sensors that respond to expression of target miRNA (miR-ON sensors) are available. Here we report an miR-ON sensor containing a bidirectional promoter-driven Csy4 endoribonuclease and green fluorescent protein, ZsGreen1, for live-cell imaging of miRNAs with post-transcriptional feedback control. Csy4-assisted miR-ON (Csy4-miR-ON) sensors generate negligible background but respond sensitively to target miRNAs, allowing high-contrast fluorescence detection of miRNAs in various human cells. We show that Csy4-miR-ON sensors enabled imaging of various miRNAs, including miR-21, miR-302a, and miR-133, in vitro as well as in vivo. This robust tool can be used to evaluate miRNA expression in diverse biological and medical applications., Graphical abstract, Sano et al. report a fluorescence signal-on sensor for detecting miRNA expression in living cells. This sensor allows imaging of various miRNAs in vitro as well as in vivo. This robust tool can be used to evaluate miRNA expression in diverse biological and medical applications.

This study was designed to assess the occurrence of major insects and rodent pest infestations in stored grain from two districts of Southwestern Ethiopia. Omo Nada and Bako Tibe districts were purposively selected because they are potential maize and sorghum growing regions with high postharvest losses. A total of 160 farmers’ stores from both the districts were randomly selected. The grain samples used in the present study were stored for five different time periods, ranging from 1 to 5 months and from the same farmers’ stores, to identify storage insect pest, determine grain weight loss and insect damage. The results showed that the dominant insect species in maize and sorghum grains were weevils (Sitophilus spp.) followed by the Angoumois gelechiid (Sitotroga cerealella Olivier) and flour beetles (Tribolium spp.). High number of insects were recorded from both plastered and un-plastered gombisa and polypropylene bags. Additionally, the amount of every insect pest in each storage container recorded per 100 g grain increased because the duration of grain storage increased. There have been 0.33-1.29g and 0.44-1g of rodent droppings per 100g sample of maize and sorghum grains, respectively. This showed that faecal dropping per 100 g grain increased along with increase in storage period. Grain damage showed significant (P

The present review has been developed as part of the VIRTUOUS project, funded by the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie-RISE Grant Agreement No 872181 (https://www.virtuoush2020.com/)., Background: The perception of taste is a prime example of complex signal transduction at the subcellular level, involving an intricate network of molecular machinery, which can be investigated to great extent by the tools provided by Computational Molecular Modelling. The present review summarises the current knowledge on the molecular mechanisms at the root of taste transduction, in particular involving taste receptors, highly specialised proteins driving the activation/deactivation of specific cell signalling pathways and ultimately leading to the perception of the five principal tastes: sweet, umami, bitter, salty and sour. The former three are detected by similar G protein-coupled receptors, while the latter two are transduced by ion channels. Scope and approach: The main objective of the present review is to provide a general overview of the molecular structures investigated to date of all taste receptors and the techniques employed for their molecular modelling. In addition, we provide an analysis of the various ligands known to date for the above-listed receptors, including how they are activated in the presence of their target molecule. Key findings and conclusions: In the last years, numerous advances have been made in molecular research and computational investigation of ligand-receptor interaction related to taste receptors. This work aims to outline the progress in scientific knowledge about taste perception and understand the molecular mechanisms involved in the transfer of taste information., European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie-RISE Grant 872181

Across species, adolescence is a period of growing independence that is associated with the maturation of cognitive, social, and affective processing. Reorganization of neural circuits within the frontal cortex is believed to contribute to the emergence of adolescent changes in cognition and behavior. While puberty coincides with adolescence, relatively little is known about which aspects of frontal cortex maturation are driven by pubertal development and gonadal hormones. In this review, we highlight existing work that suggests puberty plays a role in the maturation of specific cell types in the medial prefrontal cortex (mPFC) of rodents, and highlight possible routes by which gonadal hormones influence frontal cortical circuit development.

Regarding synthetic self-healing materials, as healing reactions occur at the molecular level, bond formation occurs when healing chemicals are nanometer distances apart. However, motility of healing chemicals in materials is quite limited, permitting only passive diffusion, which reduces the chance of bond formation. By contrast, biological-tissues exhibit significant high-performance self-healing, and cadherin-mediated cell-cell adhesion is a key mechanism in the healing process. This is because cells are capable of a certain level of motility and actively migrate to damage sites, thereby achieving cell-cell adhesion with high efficacy. Here, we report biological-tissue-inspired, self-healing hydrogels in which azide-modified living cells are covalently cross-linked with alkyne-modified alginate polymers via bioorthogonal reactions. As a proof-of-concept, we demonstrate their unique self-healing capabilities originating from cadherin-mediated adhesion between cells incorporated into the gels as mobile healing mechanism. This study provides an example of self-healing material incorporating living components into a synthetic material to promote self-healing.

Sphaeropsidin A (SphA) is a tetracyclic pimarane diterpene, first isolated as the main phytotoxin produced by Diplodia cupressi the causal agent of a severe canker disease of Italian cypress (Cupressus sempervirens L.). It was also produced, together with several analogues, by different pathogenic Diplodia species and other fungi and showed a broad array of biological activities suggesting its promising application in agriculture and medicine. The anticancer activity of SphA is very potent and cell specific. Recent studies have revealed its unique mode of action. This minireview reports the structures of SphA and its family of natural analogues, their biosynthetic origins, their fungal sources, and biological activities. The preparation of various SphA derivatives is also described as well as the results of structure-activity relationship (SAR) studies and on their potential practical applications.

Since 30 years, bioengineering allowed to reconstruct human tissues using normal human cells. Skin is one of the first organ to be reconstructed thanks to the development of specific cell culture m...

Rationale: Identification of the specific cell types expressing CFTR (cystic fibrosis [CF] transmembrane conductance regulator) is required for precision medicine therapies for CF. However, a full ...

Arg-Gly-Asp (RGD), a classical polypeptide, has been widely used in cell specific recognition. RGDY (Arg-Gly-Asp-Tyr) consists of the RGD sequence and tyrosine. Herein, a functional coating with ce...

Bioinformatics btab370 (2021). doi:10.1093/bioinformatics/btab370, Published by Oxford Univ. Press, Oxford

Basic neuroscience research employs numerous forms of antibodies as key reagents in diverse applications. While the predominant use of antibodies is as immunolabeling reagents, neuroscientists are making increased use of intracellular antibodies or intrabodies. Intrabodies are recombinant antibodies genetically encoded for expression within neurons. These can be used to target various cargo (fluorescent proteins, reporters, enzymes, etc.) to specific molecules and subcellular domains to report on and manipulate neuronal function with high precision. Intrabodies have the advantages inherent in all genetically encoded recombinant antibodies but represent a distinct subclass in that their structure allows for their expression and function within cells. The high precision afforded by the ability to direct their expression to specific cell types, and the selective binding of intrabodies to targets within these allows intrabodies to offer unique advantages for neuroscience research, given the tremendous molecular, cellular and morphological complexity of brain neurons. Intrabodies expressed within neurons have been used for a variety of purposes in basic neuroscience research. Here I provide a general background to intrabodies and their development, and examples of their emerging utility as valuable basic neuroscience research tools.

Respiratory disorders are among the most important medical problems threatening human life. The conventional therapeutics for respiratory disorders are hindered by insufficient drug concentrations at pathological lesions, lack of cell-specific targeting, and various biobarriers in the conducting airways and alveoli. To address these critical issues, various nanoparticle delivery systems have been developed to serve as carriers of specific drugs, DNA expression vectors, and RNAs. The unique properties of nanoparticles, including controlled size and distribution, surface functional groups, high payload capacity, and drug release triggering capabilities, are tailored to specific requirements in drug/gene delivery to overcome major delivery barriers in pulmonary diseases. To avoid off-target effects and improve therapeutic efficacy, nanoparticles with high cell-targeting specificity are essential for successful nanoparticle therapies. Furthermore, low toxicity and high degradability of the nanoparticles are among the most important requirements in the nanoparticle designs. In this review, we provide the most up-to-date research and clinical outcomes in nanoparticle therapies for pulmonary diseases. We also address the current critical issues in key areas of pulmonary cell targeting, biosafety and compatibility, and molecular mechanisms for selective cellular uptake.

Single-cell RNA-Sequencing (scRNA-Seq) has improved our understanding of individual cell types in the human placenta. However, placental scRNA-Seq data is not readily accessible when trying to understand how expression patterns in model systems correspond to those from first trimester human placenta. Therefore, we developed PlacentaCellEnrich, a tool that takes a gene set as input, and then reports if the input set is enriched for genes with placenta cell-specific expression patterns, based on human placenta scRNA-Seq data. The PlacentaCellEnrich tool is freely available at https://placentacellenrich.gdcb.iastate.edu/ for non-profit academic use under the MIT license.

In this review, we describe the photoelectrochemical (PEC) transformation of atmospheric species such as carbon dioxide (CO2) and nitrogen (N2) into useful industrial products on TiO2 and TiO2 composite photoelectrodes. The configuration and classification of PEC cells, and the mechanisms for PEC CO2 and N2 reduction are discussed in detail. Although CO2 and N2 PEC reduction processes are similar to each other with regards to electrode materials, basic working principle and the configuration of the reaction systems, their mechanisms differ significantly. Therefore, various examples of the PEC reduction of CO2 and N2 at TiO2 and titanate-based semiconductor photoelectrodes with different specific cell constructions and reaction mechanisms are introduced and discussed. Despite the significant progress on the PEC reduction of CO2 and N2 at TiO2 based electrodes, some challenges still remain and are outlined. In addition, we propose new approaches to further improve the PEC properties of TiO2 and titanate-based semiconductors for the selective reduction of CO2 and N2 into useful products.

The endogenous H2S-driven theranostic H2S-Gem has been invented. The theranostic prodrug H2S-Gem is selectively activated in cancer cells, releasing active gemcitabine with a simultaneous fluorescence turn-on. H2S-Gem selectively inhibited cancer cell growth compared to the mother chemotherapeutic gemcitabine. Overall, it is a unique protocol for tracking and transporting chemotherapeutic agents to tumor areas without the guidance of tumor-directive ligands.

Extensive interest in the development of α-emitting radionuclides astatine-211 (211At) stems from the potential superiority for the treatment of smaller tumors, disseminated disease, and metastatic disease. VP2, a small molecule fusion peptide, can specifically bind to the VPAC1 receptor which is over-expressed in malignant epithelial tumors. In our recent study, we performed the preparation of 211At labelled VP2 through a one-step method. In this work, we explored the targeted radionuclide therapy with [211At]At-SPC-VP2 in vitro and in vivo. The cytotoxicity and specific cell killing of [211At]At-SPC-VP2 were evaluated using the CCK-8 assay. Compared with the [211At]NaAt, the VPAC1-targeted radionuclide compound [211At]At-SPC-VP2 showed more effective cytotoxicity in vitro. Targeted radioactive therapy trial was carried out in non-small-cell lung cancer (NSCLC) xenograft mice. For the therapy experiment, 4 groups of mice were injected via the tail vein with 370 kBq, 550 kBq, 740 kBq, 3 × ∼246 kBq of [211At]At-SPC-VP2, of which the second and third injections were given 4 and 8 days after the first injection, respectively. As controls, animals were treated with saline or 550 kBq [211At]NaAt. The body weight and tumor size of mice were monitored before the administration and every 2 days thereafter. Cytotoxic radiation of partial tissue samples such as kidneys, liver and stomach of mice were assessed by immunohistochemical examination. The tumor growth was inhibited and significantly improved survival was achieved in mice treated with [211At]At-SPC-VP2, two-fold prolongation of survival compared with the control group, which received normal saline or 550 kBq [211At]NaAt. No renal or hepatic toxicity was observed in the mice receiving [211At]At-SPC-VP2, but gastric pathological sections showed 211At uptake in stomach resulting in later toxicity, highlighting the importance of further enhancing the stability of labelled compounds.

Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), affect the ageing population worldwide and while severely impairing the quality of life of millions, they also cause a massive economic burden to countries with progressively ageing populations. Parallel with the search for biomarkers for early detection and prediction, the pursuit for therapeutic approaches has become growingly intensive in recent years. Various prospective therapeutic approaches have been explored with an emphasis on early prevention and protection, including, but not limited to, gene therapy, stem cell therapy, immunotherapy and radiotherapy. Many pharmacological interventions have proved to be promising novel avenues, but successful applications are often hampered by the poor delivery of the therapeutics across the blood-brain-barrier (BBB). To overcome this challenge, nanoparticle (NP)-mediated drug delivery has been considered as a promising option, as NP-based drug delivery systems can be functionalized to target specific cell surface receptors and to achieve controlled and long-term release of therapeutics to the target tissue. The usefulness of NPs for loading and delivering of drugs has been extensively studied in the context of NDDs, and their biological efficacy has been demonstrated in numerous preclinical animal models. Efforts have also been made towards the development of NPs which can be used for targeting the BBB and various cell types in the brain. The main focus of this review is to briefly discuss the advantages of functionalized NPs as promising theranostic agents for the diagnosis and therapy of NDDs. We also summarize the results of diverse studies that specifically investigated the usage of different NPs for the treatment of NDDs, with a specific emphasis on AD and PD, and the associated pathophysiological changes. Finally, we offer perspectives on the existing challenges of using NPs as theranostic agents and possible futuristic approaches to improve them.

Single-cell multimodal omics (scMulti-omics) technologies have made it possible to trace cellular lineages during differentiation and to identify new cell types in heterogeneous cell populations. The derived information is especially promising for computing cell-type-specific biological networks encoded in complex diseases and improving our understanding of the underlying gene regulatory mechanisms. The integration of these networks could, therefore, give rise to a heterogeneous regulatory landscape (HRL) in support of disease diagnosis and drug therapeutics. In this review, we provide an overview of this field and pay particular attention to how diverse biological networks can be inferred in a specific cell type based on integrative methods. Then, we discuss how HRL can advance our understanding of regulatory mechanisms underlying complex diseases and aid in the prediction of prognosis and therapeutic responses. Finally, we outline challenges and future trends that will be central to bringing the field of HRL in complex diseases forward.

Precise genetic manipulation of specific cell types or tissues to pinpoint gene function requirement is a critical step in studies aimed at unraveling the intricacies of organismal physiology. Drosophila researchers heavily rely on the UAS/Gal4/Gal80 system for tissue-specific manipulations; however, it is often unclear whether the reported Gal4 expression patterns are indeed specific to the tissue of interest such that experimental results are not confounded by secondary sites of Gal4 expression. Here, we surveyed the expression patterns of commonly used Gal4 drivers in adult Drosophila female tissues under optimal conditions and found that multiple drivers have unreported secondary sites of expression beyond their published cell type/tissue expression pattern. These results underscore the importance of thoroughly characterizing Gal4 tools as part of a rigorous experimental design that avoids potential misinterpretation of results as we strive for understanding how the function of a specific gene/pathway in one tissue contributes to whole-body physiology.

Actin is a conserved cytoskeletal protein with essential functions. Here, we review the state-of-the-art reagents, tools and methods used to probe actin biology and functions in zebrafish embryo and larvae. We also discuss specific cell types and tissues where the study of actin in zebrafish has provided new insights into its functions.

Background The Drosophila central nervous system (CNS) is a convenient model system for the study of the molecular mechanisms of conserved neurobiological processes. The manipulation of gene activity in specific cell types and subtypes of the Drosophila CNS is frequently achieved by employing the binary Gal4/UAS system. However, many Gal4 driver lines available from the Bloomington Drosophila Stock Center (BDSC) and commonly used in Drosophila neurobiology are still not well characterized. Among these are three lines with Gal4 driven by the elav promoter (BDSC #8760, #8765, and #458), one line with Gal4 driven by the repo promoter (BDSC #7415), and the 69B-Gal4 line (BDSC #1774). For most of these lines, the exact insertion sites of the transgenes and the detailed expression patterns of Gal4 are not known. This study is aimed at filling these gaps. Results We have mapped the genomic location of the Gal4-bearing P-elements carried by the BDSC lines #8760, #8765, #458, #7415, and #1774. In addition, for each of these lines, we have analyzed the Gal4-driven GFP expression pattern in the third instar larval CNS and eye-antennal imaginal discs. Localizations of the endogenous Elav and Repo proteins were used as markers of neuronal and glial cells, respectively. Conclusions We provide a mini-atlas of the spatial activity of Gal4 drivers that are widely used for the expression of UAS–target genes in the Drosophila CNS. The data will be helpful for planning experiments with these drivers and for the correct interpretation of the results.

Melanins are group of pigments found in almost all organisms. In humans and animals, it is chiefly responsible for the color of skin, hair, and eyes. It is synthesized by specific cell called as melanocyte, which are heterogeneous in distribution. Apart from imparting color, it also executes various functions. This review explains the basics of melanin pigment, its biosynthesis, functions, and related pathological conditions in oral cavity. This article also explains the histopathological identification of melanin in tissues including the immunohistochemical markers.

Advancement in single-cell RNA sequencing leads to exponential accumulation of single-cell expression data. However, there is still lack of tools that could integrate these unlimited accumulation of single-cell expression data. Here, we presented a universal approach iSEEEK for integrating super large-scale single-cell expression via exploring expression rankings of top-expressing genes. We developed iSEEEK with 13.7 million single-cells. We demonstrated the efficiency of iSEEEK with canonical single-cell downstream tasks on five heterogenous datasets encompassing human and mouse samples. iSEEEK achieved good clustering performance benchmarked against well-annotated cell labels. In addition, iSEEEK could transfer its knowledge learned from large-scale expression data on new dataset that was not involved in its development. iSEEEK enables identification of gene-gene interaction networks that are characteristic of specific cell types. Our study presents a simple and yet effective method to integrate super large-scale single-cell transcriptomes and would facilitate translational single-cell research from bench to bedside.

Cells are able to perceive complex mechanical cues across both the micro- and nanoscale which can influence their development. Whilst causative effects between surface topography and cellular function can be demonstrated, the variability in materials used in this screening process makes it difficult to discern whether the observed phenotypic changes are indeed a result of topographical cues alone, or the inherent difference in material properties. A novel approach to directly imprint both micro- and nanoscaled topographical features into the base of conventional cell cultureware is thus developed, facilitating its compatibility with standard biological techniques and methods of analysis. The utility of this technology is demonstrated by performing high-throughput screening across five distinct cell types to interrogate the effects of 12 surface topographies, exemplifying unique cell specific responses to both behavior and cell morphological characteristics. The ability of this technology to underpin new insights into how surface topographies can regulate key image descriptors to drive cell fate determination is further demonstrated. These findings will inform the future development of advanced micro- and nanostructured cell culture substrates that can regulate cell behavior and fate determination across the life sciences, including fundamental cell biology, drug screening, and cell therapy.

Oncolytic viruses (OV) are an attractive prospect due to their two-pronged attack mechanism: direct cell lysis and amplification of an antitumor immune response. Paradoxically this also results in their clearance by the reticuloendothelial system when delivered systemically, which is essential for treating disseminated neoplasms or inaccessible tumors. Nanotechnology is paving the way for new carrier systems designed to overcome the greatest challenges of oncolytic virotherapy namely, systemic administration and specific cell binding and entry into tumors. The use of nanoparticles to protect and deliver OV in circulation is exciting, however their success relies on how they navigate the merry-go-round of often-contradictory phases of nanoparticle delivery including circulatory longevity, tissue permeation and cellular interaction. This chapter discusses these challenges and the strategies endeavoring to overcome them.

PPARγ is a critical transcriptional regulator of adipogenesis and type 2 immune responses, however until recently its role in type 2 innate lymphoid cells had not been characterised. In two papers in this issue of Mucosal Immunology, PPARγ is shown to have a dominant role in ILC2 responses, mediating IL-33-responsiveness and activation.

Our understanding of gut functioning and pathophysiology has grown considerably in the past decades, and advancing technologies enable us to deepen this understanding. Single-cell RNA sequencing (scRNA-seq) has opened a new realm of cellular diversity and transcriptional variation in the human gut at a high, single-cell resolution. ScRNA-seq has pushed the science of the digestive system forward by characterizing the function of distinct cell types within complex intestinal cellular environments, by illuminating the heterogeneity within specific cell populations and by identifying novel cell types in the human gut that could contribute to a variety of intestinal diseases. In this review, we highlight recent discoveries made with scRNA-seq that significantly advance our understanding of the human gut both in health and across the spectrum of gut diseases, including inflammatory bowel disease, colorectal carcinoma and celiac disease.

Bioelectronics aims to design electronic devices which can be fully integrated within tissues to monitor or stimulate specific cell functions. The main challenge is the engineering of the cell–chip interface and diverse materials, and devices have been developed to recapitulate biological architectures and functionalities. In this Prospective article, the authors give an overview on how the bioelectronics community has exploited biomimetic approaches to emulate cell morphologies, interactions, and functions to design optimal electrical platforms to be coupled to living cells.

PD-L1 signaling is important in regulating T cell function and keeping balance of tumor microenvironment, but its role in modifying TCR-T cell cytotoxicity remains unknown. MART-1-specific TCR-T cells (TCR-TMART-1) were stimulated by MEL-526 tumor cells expressing different proportions of PD-L1 and used to perform cytotoxicity assays and single-cell RNA sequencing. Percentage changes of different specific cell clusters were analyzed. The percentage of cluster HLA-DR+CD38+CD8+ was upregulated after antigen stimulation and tumor PD-L1 modified TCR-T cell function through downregulating the percentages of clusters HLA-DR+CD28+CD8+ and HLA-DR+CD38+CD8+ which were higher in TCR-TMART-1 than in Tnull.

Monitoring for cytomegalovirus (CMV)-specific cell-mediated immunity (CMV-CMI) may be useful for individualizing valganciclovir (VGCV) prophylaxis after kidney transplantation (KT). We performed a commercial ELISA-based interferon (IFN)-γ release assay (QTF-CMV) from posttransplant months 2-5 (362 points) in 120 CMV-seropositive KT recipients that received antithymocyte globulin as induction therapy and VGCV prophylaxis (median of 92 days). Forty-seven patients (39.3%) had CMV infection after discontinuation of prophylaxis. The QTF-CMV assay was reactive, nonreactive, and indeterminate in 264 (72.9%), 90 (24.9%), and 8 points (2.2%). The QTF-CMV assay at prophylaxis discontinuation exhibited suboptimal accuracy for predicting protective CMV-CMI (sensitivity: 77.4%; specificity: 34.3%; positive predictive value [PPV]: 64.1%; negative predictive value [NPV]: 50.0%), with no differences in 1-year CMV infection rates between patients with negative (nonreactive or indeterminate) or reactive results (45.8% vs 36.1%; P = .244). Specificity and PPV to predict protective CMV-CMI improved by elevating the IFN-γ cutoff value to 1.13 IU/mL (65.7% and 71.4%) and 7.0 IU/mL (85.7% and 76.2%), although NPVs decreased. The QTF-CMV assay as per manufacturer's interpretative criteria performed poorly to predict protection from CMV infection following discontinuation of VGCV prophylaxis among ATG-treated CMV-seropositive KT recipients. This performance is slightly improved by modifying the IFN-γ positivity threshold.

Scanning electron microscopy (SEM) plays a central role in analyzing structures by imaging a large area of brain tissue at nanometer scales. A vast amount of data in the large area are required to study structural changes of cellular organelles in a specific cell, such as neurons, astrocytes, oligodendrocytes, and microglia among brain tissue, at sufficient resolution. Array tomography is a useful method for large-area imaging, and the osmium-thiocarbohydrazide-osmium (OTO) and ferrocyanide-reduced osmium methods are commonly used to enhance membrane contrast.Because many samples prepared using the conventional technique without en bloc staining are considered inadequate for array tomography, we suggested an alternative technique using post-staining conventional samples and compared the advantages.

Silicon is well known to provide a step change in capacity for lithium-ion battery anodes. We present our thoughts on using porous silicon active materials and the two phase microstructure approach to control silicon volume expansion and capacity during lithiation. With this method silicon can be tailored to the specific cell application desirable by controlling the volume expansion and capacity. The initial results show a negative impact of using controlled capacity activation of porous silicon relative to the control sample which is galvanostatically cycled. We highlight our next steps in exploring this approach.

The extraordinary potential of semiconductor quantum dots (QDs) has resulted in their widespread application in various fields, from engineering technology and the development of laboratory techniques to biomedical imaging and therapeutic strategies. However, the toxicity of QDs remains a concern and has limited their applications in human health. Better understanding of the behavior of QDs as it relates to their composition will enable the exploration of their limitations and development of a strategy to control their toxicity for potential therapeutic applications. Here, we describe approaches to minimize their toxicities according to the specific cell type, organ, or animal species, summarizing recent promising research at the cellular, organ, and whole-organism level.

SUMMARY Human brain organoid systems offer unprecedented opportunities to investigate both neurodevelopmental and neurological disease. Single-cell-based transcriptomics or epigenomics have dissected the cellular and molecular heterogeneity in the brain organoids, revealing a complex organization. Similar but distinct protocols from different labs have been applied to generate brain organoids, providing a large resource to perform a comparative analysis of brain developmental processes. Here, we take a systematic approach to compare the single-cell transcriptomes of various human cortical brain organoids together with fetal brain to define the identity of specific cell types and differentiation routes in each method. Importantly, we identify unique developmental programs in each protocol compared to fetal brain, which will be a critical benchmark for the utility of human brain organoids in the future., In Brief Tanaka et al. report integrative analyses of single-cell RNA-seq for human brain organoids derived from different protocols. They find a unique preference of cell differentiation routes across protocols and provide a benchmark for the use and the improvement of human brain organoids., Graphical Abstract

The past few decades have witnessed the rapid development of responsive probes as tools for sensing and imaging of biomarkers in situ in real-time. Among various responsive probes, “dual-key-and-lock” probes have been recently developed as an emerging approach for the detection of biomolecules in specific cell organelles and/or diseased tissues, such as tumours. In comparison with most commonly used “single-key-and-lock” probes, the new “dual-key-and-lock” probes offer substantial advantages in biosensing and imaging, such as high accuracy and precision, minimal “false positive/negative” results, and high selectivity for biomolecule detection at targeted sites. This focus article presents recent advances in the development of “dual-key-and-lock” responsive probes for biosensing and imaging. Two approaches for the design of these probes, including “dual-key-and-one-lock” and “dual-key-and-two-lock”, are highlighted, along with discussions of the challenges and future research directions at the end.

Nanotechnology is paving the way for new carrier systems designed to overcome the greatest challenges of oncolytic virotherapy; systemic administration and subsequent implications of immune responses and specific cell binding and entry. Systemic administration of oncolytic agents is vital for disseminated neoplasms, however transition of nanoparticles (NP) to virotherapy has yielded modest results. Their success relies on how they navigate the merry-go-round of often-contradictory phases of NP delivery: circulatory longevity, tissue permeation and cellular interaction, with many studies postulating design features optimal for each phase. This review discusses the optimal design of NPs for the transport of oncolytic viruses within these phases, to determine whether improved virotherapeutic efficacy lies in the pharmacokinetic/pharmacodynamics characteristics of the NP–oncolytic viruses complexes rather than manipulation of the virus and targeting ligands.

Precise manipulation of cells within water-in-oil emulsion droplets has the potential to vastly expand the type of cellular assays that can be conducted in droplet-based microfluidics systems. However, achieving such manipulation remains challenging. Here, we present an in-droplet label-free cell separation technology by utilizing different dielectrophoretic responses of two different cell types. Two pairs of angled planar electrodes were utilized to generate positive or negative dielectrophoretic force acting on each cell type, which results in selective in-droplet movement of only one specific cell type at a time. A downstream asymmetric Y-shaped microfluidic junction splits the mother droplet into two daughter droplets, each of which contains only one cell type. The capability of this platform was successfully demonstrated by conducting in-droplet separation from a mixture of Salmonella cells and macrophages, two cell types commonly used as a bacterial pathogenicity analysis model. This technology enable the precise manipulation of cells within droplets, which can be exploited as a critical function in implementing broader ranges of droplet-based microfluidics cellular assays.

Fibrosis occurs in most human organs including the liver, lung, heart and kidney, and is crucial for the progression of most chronic diseases. As an indispensable catabolic process for intracellular quality control and homeostasis, autophagy occurs in most mammalian cells and is implicated in many biological processes including fibrogenesis. Although advances have been made in understanding autophagy process, the potential role of autophagy in fibrotic diseases remains controversial and has recently attracted a great deal of attention. In the current review, we summarize the commonalities of autophagy affecting different types of fibrosis in different organs, including the liver, lung, heart, and kidney as well as in cystic fibrosis, systematically outline the contradictory results and highlight the distinct role of autophagy during the various stages of fibrosis. In summary, the exact role autophagy plays in fibrogenesis depends on specific cell types and different stimuli, and identifying and evaluating the pathogenic contribution of autophagy in fibrogenesis will promote the discovery of novel therapeutic strategies for the clinical management of these fibrotic diseases.

The development of blood-compatible materials represents a grand challenge in biomaterials science. Blood is a complex fluid containing many types of living cells, functional proteins, and other signaling molecules, which work together to protect the circulatory system from injury, pathogens, and foreign materials. Blood-contacting biomaterials include the components of cardiovascular implants (such as stents, shunts, and valves) and extracorporeal circuit components (such as tubing, membranes, and pumps). The engineered materials used in these applications are distinctly unlike the biological tissues that make up the cardiovascular system in their physical, chemical, and biological properties, leading to undesirable—and sometimes catastrophic—blood-material interactions. The pursuit of blood-compatible materials challenges nearly every aspect of materials design, including composition, mechanical properties, structure across multiple length scales, tribology, surface physical-chemistry, and biochemical functionalization. Materials have been designed to bind or reject specific blood proteins, interact favorably with specific cell types, or to interact with particular biochemical pathways in blood. This review summarizes the important blood-material interactions that regulate blood compatibility, organizes recent developments in this field from a materials perspective, and recommends areas for future research.

The specific cell capacitance, equivalent series resistance (ESR) and equivalent distributed resistance (EDR) of porous carbon-based supercapacitors linearly depend on the cationic molecular length of room-temperature ionic liquids.

Background Existing computational methods for studying miRNA regulation are mostly based on bulk miRNA and mRNA expression data. However, bulk data only allows the analysis of miRNA regulation regarding a group of cells, rather than the miRNA regulation unique to individual cells. Recent advance in single-cell miRNA-mRNA co-sequencing technology has opened a way for investigating miRNA regulation at single-cell level. However, as currently single-cell miRNA-mRNA co-sequencing data is just emerging and only available at small-scale, there is a strong need of novel methods to exploit existing single-cell data for the study of cell-specific miRNA regulation. Results In this work, we propose a new method, CSmiR (Cell-Specific miRNA regulation) to combine single-cell miRNA-mRNA co-sequencing data and putative miRNA-mRNA binding information to identify miRNA regulatory networks at the resolution of individual cells. We apply CSmiR to the miRNA-mRNA co-sequencing data in 19 K562 single-cells to identify cell-specific miRNA-mRNA regulatory networks for understanding miRNA regulation in each K562 single-cell. By analyzing the obtained cell-specific miRNA-mRNA regulatory networks, we observe that the miRNA regulation in each K562 single-cell is unique. Moreover, we conduct detailed analysis on the cell-specific miRNA regulation associated with the miR-17/92 family as a case study. The comparison results indicate that CSmiR is effective in predicting cell-specific miRNA targets. Finally, through exploring cell–cell similarity matrix characterized by cell-specific miRNA regulation, CSmiR provides a novel strategy for clustering single-cells and helps to understand cell–cell crosstalk. Conclusions To the best of our knowledge, CSmiR is the first method to explore miRNA regulation at a single-cell resolution level, and we believe that it can be a useful method to enhance the understanding of cell-specific miRNA regulation.

Microvesicles are formed through shedding from the plasma membrane, a process shared by almost all human cells. Microvesicles are highly abundant and have been detected in blood, urine, cerebrospinal fluid, and saliva. They contain a library of cargo derived from their parental cell during formation, including proteases, micro-RNAs and lipids and delivery of this parental cell-derived cargo to other cells can alter target cell function and drive disease. Cell specific molecules on the surface of microvesicles, obtained during microvesicle formation, allows their parental cell to be identified and populations of microvesicles to be investigated for roles in the pathogenesis of various diseases. For instance, recent work by our group has identified a role for neutrophil microvesicles in atherosclerosis. Microvesicle profiles could in future be associated with certain diseases and act as a biomarker to allow for earlier diagnosis. This short review will discuss some of the processes central to all microvesicles before focusing on neutrophil microvesicles, their potential role in cardiovascular disease and the mechanisms that may underpin this.

The neural network in the brain can be viewed as an integrated system assembled from a large number of local neural circuits specialized for particular brain functions. Activities of neurons in local neural circuits are thought to be organized both spatially and temporally under the rules optimized for their roles in information processing. It is well perceived that different areas of the mammalian neocortex have specific cognitive functions and distinct computational properties. However, the organizational principles of the local neural circuits in different cortical regions have not yet been clarified. Therefore, new research principles and related neuro-technologies that enable efficient and precise recording of large-scale neuronal activities and synaptic connections are necessary. Innovative technologies for structural analysis, including tissue clearing and expansion microscopy, have enabled super resolution imaging of the neural circuits containing thousands of neurons at a single synapse resolution. The imaging resolution and volume achieved by new technologies are beyond the limits of conventional light or electron microscopic methods. Progress in genome editing and related technologies has made it possible to label and manipulate specific cell types and discriminate activities of multiple cell types. These technologies will provide a breakthrough for multiscale analysis of the structure and function of local neural circuits. This review summarizes the basic concepts and practical applications of the emerging technologies and new insight into local neural circuits obtained by these technologies.

Background: Vascular homeostasis is maintained by the differentiated phenotype of vascular smooth muscle cells (VSMCs). The landscape of protein coding genes comprising the transcriptome of differentiated VSMCs has been intensively investigated but many gaps remain including the emerging roles of noncoding genes. Methods: We reanalyzed large-scale, publicly available bulk and single-cell RNA sequencing datasets from multiple tissues and cell types to identify VSMC-enriched long noncoding RNAs. The in vivo expression pattern of a novel smooth muscle cell (SMC)–expressed long noncoding RNA, Carmn (cardiac mesoderm enhancer-associated noncoding RNA), was investigated using a novel Carmn green fluorescent protein knock-in reporter mouse model. Bioinformatics and quantitative real-time polymerase chain reaction analysis were used to assess CARMN expression changes during VSMC phenotypic modulation in human and murine vascular disease models. In vitro, functional assays were performed by knocking down CARMN with antisense oligonucleotides and overexpressing Carmn by adenovirus in human coronary artery SMCs. Carotid artery injury was performed in SMC-specific Carmn knockout mice to assess neointima formation and the therapeutic potential of reversing CARMN loss was tested in a rat carotid artery balloon injury model. The molecular mechanisms underlying CARMN function were investigated using RNA pull-down, RNA immunoprecipitation, and luciferase reporter assays. Results: We identified CARMN , which was initially annotated as the host gene of the MIR143/145 cluster and recently reported to play a role in cardiac differentiation, as a highly abundant and conserved, SMC-specific long noncoding RNA. Analysis of the Carmn GFP knock-in mouse model confirmed that Carmn is transiently expressed in embryonic cardiomyocytes and thereafter becomes restricted to SMCs. We also found that Carmn is transcribed independently of Mir143/145 . CARMN expression is dramatically decreased by vascular disease in humans and murine models and regulates the contractile phenotype of VSMCs in vitro. In vivo, SMC-specific deletion of Carmn significantly exacerbated, whereas overexpression of Carmn markedly attenuated, injury-induced neointima formation in mouse and rat, respectively. Mechanistically, we found that Carmn physically binds to the key transcriptional cofactor myocardin, facilitating its activity and thereby maintaining the contractile phenotype of VSMCs. Conclusions: CARMN is an evolutionarily conserved SMC-specific long noncoding RNA with a previously unappreciated role in maintaining the contractile phenotype of VSMCs and is the first noncoding RNA discovered to interact with myocardin.

How a cell changes from one stable phenotype to another one is a fundamental problem in developmental and cell biology. Mathematically, a stable phenotype corresponds to a stable attractor in a generally multi-dimensional state space, which needs to be destabilized so the cell relaxes to a new attractor. Two basic mechanisms for destabilizing a stable fixed point, pitchfork and saddle-node bifurcations, have been extensively studied theoretically; however, direct experimental investigation at the single-cell level remains scarce. Here, we performed live cell imaging studies and analyses in the framework of dynamical systems theories on epithelial-to-mesenchymal transition (EMT). While some mechanistic details remain controversial, EMT is a cell phenotypic transition (CPT) process central to development and pathology. Through time-lapse imaging we recorded single cell trajectories of human A549/Vim-RFP cells undergoing EMT induced by different concentrations of exogenous TGF-β in a multi-dimensional cell feature space. The trajectories clustered into two distinct groups, indicating that the transition dynamics proceeds through parallel paths. We then reconstructed the reaction coordinates and the corresponding quasi-potentials from the trajectories. The potentials revealed a plausible mechanism for the emergence of the two paths where the original stable epithelial attractor collides with two saddle points sequentially with increased TGF-β concentration, and relaxes to a new one. Functionally, the directional saddle-node bifurcation ensures a CPT proceeds towards a specific cell type, as a mechanistic realization of the canalization idea proposed by Waddington.Cells with the same genetic code can take on many different formss, or phenotypes, which have distinct roles and appearances. Sometimes cells switch from one phenotype to another as part of healthy growth or during disease. One such change is the epithelial-to-mesenchymal transition (EMT), which is involved in fetal development, wound healing and the spread of cancer cells. During EMT, closely connected epithelial cells detach from one another and change into mesenchymal cells that are able to migrate. Cells undergo a number of changes during this transition; however, the path they take to reach their new form is not entirely clear. For instance, do all cells follow the same route, or are there multiple ways that cells can shift from one state to the next? To address this question, Wang et al. studied individual lung cancer cells that had been treated with a protein that drives EMT. The cells were then imaged at regular intervals over the course of two to three days to see how they changed in response to different concentrations of protein. Using a mathematical analysis designed to study chemical reactions, Wang et al. showed that the cells transform into the mesenchymal phenotype through two main routes. This result suggests that attempts to prevent EMT, in cancer treatment for instance, would require blocking both paths taken by the cells. This information could be useful for biomedical researchers trying to regulate the EMT process. The quantitative approach of this study could also help physicists and mathematicians study other types of transition that occur in biology.