Weak and interfered self-control fails to block problematic mobile phone use: The role of craving and desire thinking.

Problematic mobile phone use (PMPU) has become a worldwide phenomenon with negative impacts on adolescents' daily lives. While self-control has been shown to be related to PMPU, little is known about the underlying mechanisms of this association. Based on the Interaction of Person-Affect-Cognition-Execution model and the strength model of self-control, the current study aims to examine the association between self-control and PMPU, to identify the indirect role of craving, and to determine whether and how the two components of desire thinking exert differential moderating effects. A sample of 1424 adolescents was recruited to complete the scales of self-control, craving, desire thinking, and PMPU. The results suggested that self-control was indirectly associated with PMPU through craving. Furthermore, this indirect association was moderated by verbal perseveration, rather than imaginal prefiguration. Specifically, the indirect association was stronger for adolescents with higher verbal perseveration. The findings deepen our understanding of how self-control is related to PMPU and distinguish the effects of two components of desire thinking among adolescents.

Social addiction or nicotine addiction? The effect of smoking social motivation on inhibitory control under smoking social cues: Evidence from ERPs.

INTRODUCTION: Previous studies and theoretical models suggest that the decreasing effect of smoking-related cues on inhibitory control in individuals who smoke is one of the underlying mechanisms of smoking behavior. However, many studies have overlooked the effects of other types of smoking-related cues, such as social cues. Moreover, previous studies have lacked investigation into whether this decreasing effect is influenced by internal factors. The present study aims to integrate behavioral and electrophysiological indicators to investigate the effect of smoking social cues on inhibitory control in individuals who smoke, as well as the moderating role of social motivations. METHOD: In Experiment 1, a visual Go/NoGo paradigm with four types of backgrounds (neutral, neutral social, smoking object, and smoking social backgrounds) was used to record the error rates and reaction times of 32 participants who smoke. In Experiment 2, the Go/NoGo paradigm with two types of backgrounds (smoking object and smoking social backgrounds) was used to record the error rates, reaction times, and amplitudes of the N2 and P3 event-related potentials among 30 participants who smoke with varying degrees of primed smoking social motivation. RESULTS: (1) Individuals who smoke had higher commission error rates and larger P3 amplitude under smoking social background than under smoking object background; (2) individuals who smoke with primed high smoking social motivation, rather than low motivation had higher commission error rates and larger P3 amplitude under smoking social background than under smoking object background. CONCLUSIONS: Smoking social cues have a greater capacity to decrease inhibitory control in people who smoke than smoking object cues, and this decreasing effect is bolstered by smoking social motivation.

The enhancing effect of social reward on inhibitory control in smokers: Evidence from behaviour and ERP studies.

OBJECTIVE: Prior research has revealed impaired inhibitory control as a pivotal factor contributing to smokers' struggle to control smoking impulses. However, few studies focus on enhancing smokers' inhibitory control. This study investigates the potential of social rewards to bolster inhibitory control among smokers and elucidates the underlying mechanisms. METHODS: In Experiment 1, a reward-based Go/Nogo paradigm assessed error rates and reaction times for 30 smokers exposed to social reward and neutral feedback in distinct contexts (smoking-related and neutral). Experiment 2 used a modified paradigm, incorporating cognitive load manipulation, to investigate error rates, reaction times, N2, and P3 ERPs among 32 smokers facing social reward and neutral feedback under different cognitive loads (high and low). RESULTS: Smokers exhibit lower Nogo error rates with social reward feedback; higher error rates occur with smoking cues and high cognitive load; increased N2, P3 amplitudes under social reward versus neutral feedback; low cognitive load enhances P3 amplitude under social reward. CONCLUSION: Social reward improves smokers' inhibitory control, but this effect weakens with exposure to smoking cues; higher cognitive load further diminishes the enhancement of smokers' inhibitory control by social reward under smoking cues.

Single Nucleus Total RNA Sequencing of Formalin-Fixed Paraffin-Embedded Gliomas.

Gliomas, the predominant form of brain cancer, comprise diverse malignant subtypes with limited curative therapies available. The insufficient understanding of their molecular diversity and evolutionary processes hinders the advancement of new treatments. Technical complexities associated with formalin-fixed paraffin-embedded (FFPE) clinical samples hinder molecular-level analyses of gliomas. Current single-cell RNA sequencing (scRNA-seq) platforms are inadequate for large-scale clinical applications. In this study, automated snRandom-seq is developed, a high-throughput single-nucleus total RNA sequencing platform optimized for archival FFPE samples. This platform integrates automated single-nucleus isolation and droplet barcoding systems with the random primer-based scRNA-seq chemistry, accommodating a broad spectrum of sample types. The automated snRandom-seq is applied to analyze 116 492 single nuclei from 17 FFPE samples of various glioma subtypes, including rare clinical samples and matched primary-recurrent glioblastomas (GBMs). The study provides comprehensive insights into the molecular characteristics of gliomas at the single-cell level. Abundant non-coding RNAs (ncRNAs) with distinct expression profiles across different glioma clusters and uncovered promising recurrence-related targets and pathways in primary-recurrent GBMs are identified. These findings establish automated snRandom-seq as a robust tool for scRNA-seq of FFPE samples, enabling exploration of molecular diversities and tumor evolution. This platform holds significant implications for large-scale integrative and retrospective clinical research.

Fast and flexible profiling of chromatin accessibility and total RNA expression in single nuclei using Microwell-seq3.

Single cell chromatin accessibility profiling and transcriptome sequencing are the most widely used technologies for single-cell genomics. Here, we present Microwell-seq3, a high-throughput and facile platform for high-sensitivity single-nucleus chromatin accessibility or full-length transcriptome profiling. The method combines a preindexing strategy and a penetrable chip-in-a-tube for single nucleus loading and DNA amplification and therefore does not require specialized equipment. We used Microwell-seq3 to profile chromatin accessibility in more than 200,000 single nuclei and the full-length transcriptome in ~50,000 nuclei from multiple adult mouse tissues. Compared with the existing polyadenylated transcript capture methods, integrative analysis of cell type-specific regulatory elements and total RNA expression uncovered comprehensive cell type heterogeneity in the brain. Gene regulatory networks based on chromatin accessibility profiling provided an improved cell type communication model. Finally, we demonstrated that Microwell-seq3 can identify malignant cells and their specific regulons in spontaneous lung tumors of aged mice. We envision a broad application of Microwell-seq3 in many areas of research.

Single-cell RNA sequencing reveals immune cell dysfunction in the peripheral blood of patients with highly aggressive gastric cancer.

Highly aggressive gastric cancer (HAGC) is a gastric cancer characterized by bone marrow metastasis and disseminated intravascular coagulation (DIC). Information about the disease is limited. Here we employed single-cell RNA sequencing to investigate peripheral blood mononuclear cells (PBMCs), aiming to unravel the immune response of patients toward HAGC. PBMCs from seven HAGC patients, six normal advanced gastric cancer (NAGC) patients, and five healthy individuals were analysed by single-cell RNA sequencing. The expression of genes of interest was validated by bulk RNA-sequencing and ELISA. We found a massive expansion of neutrophils in PBMCs of HAGC. These neutrophils are activated, but immature. Besides, mononuclear phagocytes exhibited an M2-like signature and T cells were suppressed and reduced in number. Analysis of cell-cell crosstalk revealed that several signalling pathways involved in neutrophil to T-cell suppression including APP-CD74, MIF-(CD74+CXCR2), and MIF-(CD74+CD44) pathways were increased in HAGC. NETosis-associated genes S100A8 and S100A9 as well as VEGF, PDGF, FGF, and NOTCH signalling that contribute to DIC development were upregulated in HAGC too. This study reveals significant changes in the distribution and interactions of the PBMC subsets and provides valuable insight into the immune response in patients with HAGC. S100A8 and S100A9 are highly expressed in HAGC neutrophils, suggesting their potential to be used as novel diagnostic and therapeutic targets for HAGC.

Dissecting the immune discrepancies in mouse liver allograft tolerance and heart/kidney allograft rejection.

The liver is the most tolerogenic of transplanted organs. However, the mechanisms underlying liver transplant tolerance are not well understood. The comparison between liver transplantation tolerance and heart/kidney transplantation rejection will deepen our understanding of tolerance and rejection in solid organs. Here, we built a mouse model of liver, heart and kidney allograft and performed single-cell RNA sequencing of 66,393 cells to describe the cell composition and immune cell interactions at the early stage of tolerance or rejection. We also performed bulk RNA-seq of mouse liver allografts from Day 7 to Day 60 post-transplantation to map the dynamic transcriptional variation in spontaneous tolerance. The transcriptome of lymphocytes and myeloid cells were characterized and compared in three types of organ allografts. Cell-cell interaction networks reveal the coordinated function of Kupffer cells, macrophages and their associated metabolic processes, including insulin receptor signalling and oxidative phosphorylation in tolerance induction. Cd11b+ dendritic cells (DCs) in liver allografts were found to inhibit cytotoxic T cells by secreting anti-inflammatory cytokines such as Il10. In summary, we profiled single-cell transcriptome analysis of mouse solid organ allografts. We characterized the immune microenvironment of mouse organ allografts in the acute rejection state (heart, kidney) and tolerance state (liver).

Pan-Cancer Single-Nucleus Total RNA Sequencing Using snHH-Seq.

Tumor heterogeneity and its drivers impair tumor progression and cancer therapy. Single-cell RNA sequencing is used to investigate the heterogeneity of tumor ecosystems. However, most methods of scRNA-seq amplify the termini of polyadenylated transcripts, making it challenging to perform total RNA analysis and somatic mutation analysis.Therefore, a high-throughput and high-sensitivity method called snHH-seq is developed, which combines random primers and a preindex strategy in the droplet microfluidic platform. This innovative method allows for the detection of total RNA in single nuclei from clinically frozen samples. A robust pipeline to facilitate the analysis of full-length RNA-seq data is also established. snHH-seq is applied to more than 730 000 single nuclei from 32 patients with various tumor types. The pan-cancer study enables it to comprehensively profile data on the tumor transcriptome, including expression levels, mutations, splicing patterns, clone dynamics, etc. New malignant cell subclusters and exploring their specific function across cancers are identified. Furthermore, the malignant status of epithelial cells is investigated among different cancer types with respect to mutation and splicing patterns. The ability to detect full-length RNA at the single-nucleus level provides a powerful tool for studying complex biological systems and has broad implications for understanding tumor pathology.

Characterization of human pluripotent stem cell differentiation by single-cell dual-omics analyses.

In vivo differentiation of human pluripotent stem cells (hPSCs) has unique advantages, such as multilineage differentiation, angiogenesis, and close cell-cell interactions. To systematically investigate multilineage differentiation mechanisms of hPSCs, we constructed the in vivo hPSC differentiation landscape containing 239,670 cells using teratoma models. We identified 43 cell types, inferred 18 cell differentiation trajectories, and characterized common and specific gene regulation patterns during hPSC differentiation at both transcriptional and epigenetic levels. Additionally, we developed the developmental single-cell Basic Local Alignment Search Tool (dscBLAST), an R-based cell identification tool, to simplify the identification processes of developmental cells. Using dscBLAST, we aligned cells in multiple differentiation models to normally developing cells to further understand their differentiation states. Overall, our study offers new insights into stem cell differentiation and human embryonic development; dscBLAST shows favorable cell identification performance, providing a powerful identification tool for developmental cells.

Effects of Smoking Social Cues on Inhibitory Control in Smokers: An Event-Related Potential Study.

Objective: Reduced inhibitory control is a general characteristic of smokers and becomes increasingly pronounced in smoking-related contexts. However, research has rarely considered differences in the effects of various smoking-related cues. To fill this research gap, this study compared the effects of smoking object-related and smoking social-related cues on inhibitory control in smokers. Methods: We used a visual Go/NoGo paradigm with three types of long-lasting backgrounds (neutral, smoking object, and smoking social background) to record the error rates, reaction times, and amplitudes of the N2 and P3 event-related potentials (ERPs) by 25 smokers and 25 non-smokers. Results: (1) Smokers displayed smaller NoGo-N2 amplitudes than controls under the neutral background; (2) smokers displayed smaller NoGo-N2 amplitudes under the smoking social background and smoking object background than they did under the neutral background; (3) relative to neutral and smoking object backgrounds, smokers displayed higher commission error rates, shorter reaction times, and larger NoGo-P3 amplitudes under smoking social background. Conclusion: Smoking-related stimuli impair inhibitory control in smokers, especially when these stimuli are socially related.

High-throughput single nucleus total RNA sequencing of formalin-fixed paraffin-embedded tissues by snRandom-seq.

Formalin-fixed paraffin-embedded (FFPE) tissues constitute a vast and valuable patient material bank for clinical history and follow-up data. It is still challenging to achieve single cell/nucleus RNA (sc/snRNA) profile in FFPE tissues. Here, we develop a droplet-based snRNA sequencing technology (snRandom-seq) for FFPE tissues by capturing full-length total RNAs with random primers. snRandom-seq shows a minor doublet rate (0.3%), a much higher RNA coverage, and detects more non-coding RNAs and nascent RNAs, compared with state-of-art high-throughput scRNA-seq technologies. snRandom-seq detects a median of >3000 genes per nucleus and identifies 25 typical cell types. Moreover, we apply snRandom-seq on a clinical FFPE human liver cancer specimen and reveal an interesting subpopulation of nuclei with high proliferative activity. Our method provides a powerful snRNA-seq platform for clinical FFPE specimens and promises enormous applications in biomedical research.

Psychometric validation of the Chinese version of the desire thinking questionnaire in adolescent mobile phone users.

BACKGROUND: Desire thinking is a conscious and voluntary cognitive process that is closely linked to levels of craving and addictive behaviors. The Desire Thinking Questionnaire (DTQ) can be used to measure desire thinking in all age groups as well as in addicts. This measurement has also been translated into several languages. This study aimed to test the psychometric properties of the Chinese version of the DTQ (DTQ-C) among adolescent mobile phone users. METHODS: One thousand and ninety-seven adolescents who own a mobile phone and are younger than 18 years old completed the DTQ-C and a battery of questionnaires assessing the big five personality traits, negative affect, brooding, self-control, craving, and problematic mobile phone use (PMPU). The psychometric analyses of the DTQ-C were conducted, including exploratory factor analysis (EFA), confirmatory factor analysis (CFA), reliability, and validity analysis. RESULTS: The EFA revealed a 10-item two-factor structure (i.e., verbal perseveration and imaginal prefiguration) that was confirmed by the CFA. The results of CFA showed fit indexes of χ2/df = 4.83, CFI = 0.967, TLI = 0.954, RMSEA = 0.059, SRMR = 0.032. The total scale had internal consistency reliabilities of 0.93, which demonstrated that DTQ-C presented good reliability. The two dimensions were correlated with PMPU (rverbal perseveration = 0.54; rimaginal prefiguration = 0.45), neuroticism (rverbal perseveration = 0.18; rimaginal prefiguration = 0.14), conscientiousness (rverbal perseveration = -0.19; rimaginal prefiguration = -0.18), depression (rverbal perseveration = 0.22; rimaginal prefiguration = 0.16), anxiety (rverbal perseveration = 0.26; rimaginal prefiguration = 0.22), stress (rverbal perseveration = 0.15; rimaginal prefiguration = 0.10) and self-control (rverbal perseveration = -0.29; rimaginal prefiguration = -0.26), which demonstrated that DTQ-C presented good concurrent validity. The two factors of DTQ-C correlated weakly with brooding (ranging from 0.08 to 0.10). The principal component factor analysis of the two dimensions of desire thinking and craving showed that craving and desire thinking belonged to different dimensions. Both of which showed good divergent validity of desire thinking. Additionally, an examination of incremental validity revealed that two factors were both positively associated with PMPU beyond demographic characteristics, big five personality traits, negative affect, and self-control (Bverbal perseveration = 0.49 and Bimaginal prefiguration = 0.13). CONCLUSIONS: It has been found that the 10-item DTQ-C is a reliable and valid measure of desire thinking in Chinese adolescent mobile phone users.

Construction of a cross-species cell landscape at single-cell level.

Individual cells are basic units of life. Despite extensive efforts to characterize the cellular heterogeneity of different organisms, cross-species comparisons of landscape dynamics have not been achieved. Here, we applied single-cell RNA sequencing (scRNA-seq) to map organism-level cell landscapes at multiple life stages for mice, zebrafish and Drosophila. By integrating the comprehensive dataset of > 2.6 million single cells, we constructed a cross-species cell landscape and identified signatures and common pathways that changed throughout the life span. We identified structural inflammation and mitochondrial dysfunction as the most common hallmarks of organism aging, and found that pharmacological activation of mitochondrial metabolism alleviated aging phenotypes in mice. The cross-species cell landscape with other published datasets were stored in an integrated online portal-Cell Landscape. Our work provides a valuable resource for studying lineage development, maturation and aging.

How many cell types are there in nature? How do they change during the life cycle? These are two fundamental questions that researchers have been trying to understand in the area of biology. In this study, single-cell mRNA sequencing data were used to profile over 2.6 million individual cells from mice, zebrafish and Drosophila at different life stages, 1.3 million of which were newly collected. The comprehensive datasets allow investigators to construct a cross-species cell landscape that helps to reveal the conservation and diversity of cell taxonomies at genetic and regulatory levels. The resources in this study are assembled into a publicly available website at http://bis.zju.edu.cn/cellatlas/.

Socializing with Smoker and Social Smoking Behavior among Chinese Male Smokers with Low Nicotine Dependence: The Mediating Roles of Belief of Smoking Rationalization and Smoker Identity.

BACKGROUND: Previous studies have shown that socializing with other smokers is an essential trigger for social smoking among smokers with a low nicotine dependence. This study further explored the mediating effects of the belief of smoking rationalization and smoker identity on the relationship between socializing with smokers and social smoking behavior. METHODS: A cross-sectional design was conducted. A total of 696 low-nicotine-dependent smokers in China completed questionnaires that assessed socializing with smokers, social smoking behavior, smoker identity, and the belief of smoking rationalization. The mediating roles of the belief of smoking rationalization and smoker identity on the relationship between socializing with smokers and social smoking behavior were assessed by using SPSS 23 and AMOS 23. RESULTS: The belief of smoking rationalization, smoker identity, socializing with smokers, and social smoking behavior were significantly and positively correlated with each other. In addition, this study found an independently mediated role for smoker identity in the relationship with smoker socialization and social smoking behavior, and a sequentially mediated role for smoking rationalization and smoker identity in this relationship. CONCLUSION: Reducing the belief of smoking rationalization and smoker identity may be conducive to reducing social smoking behavior for low-nicotine-dependent smokers when socializing with other smokers.

Deep learning of cross-species single-cell landscapes identifies conserved regulatory programs underlying cell types.

Despite extensive efforts to generate and analyze reference genomes, genetic models to predict gene regulation and cell fate decisions are lacking for most species. Here, we generated whole-body single-cell transcriptomic landscapes of zebrafish, Drosophila and earthworm. We then integrated cell landscapes from eight representative metazoan species to study gene regulation across evolution. Using these uniformly constructed cross-species landscapes, we developed a deep-learning-based strategy, Nvwa, to predict gene expression and identify regulatory sequences at the single-cell level. We systematically compared cell-type-specific transcription factors to reveal conserved genetic regulation in vertebrates and invertebrates. Our work provides a valuable resource and offers a new strategy for studying regulatory grammar in diverse biological systems.

Construction of the axolotl cell landscape using combinatorial hybridization sequencing at single-cell resolution.

The Mexican axolotl (Ambystoma mexicanum) is a well-established tetrapod model for regeneration and developmental studies. Remarkably, neotenic axolotls may undergo metamorphosis, a process that triggers many dramatic changes in diverse organs, accompanied by gradually decline of their regeneration capacity and lifespan. However, the molecular regulation and cellular changes in neotenic and metamorphosed axolotls are still poorly investigated. Here, we develop a single-cell sequencing method based on combinatorial hybridization to generate a tissue-based transcriptomic landscape of the neotenic and metamorphosed axolotls. We perform gene expression profiling of over 1 million single cells across 19 tissues to construct the first adult axolotl cell landscape. Comparison of single-cell transcriptomes between the tissues of neotenic and metamorphosed axolotls reveal the heterogeneity of non-immune parenchymal cells in different tissues and established their regulatory network. Furthermore, we describe dynamic gene expression patterns during limb development in neotenic axolotls. This system-level single-cell analysis of molecular characteristics in neotenic and metamorphosed axolotls, serves as a resource to explore the molecular identity of the axolotl and facilitates better understanding of metamorphosis.

Cell landscape of larval and adult Xenopus laevis at single-cell resolution.

The rapid development of high-throughput single-cell RNA sequencing technology offers a good opportunity to dissect cell heterogeneity of animals. A large number of organism-wide single-cell atlases have been constructed for vertebrates such as Homo sapiens, Macaca fascicularis, Mus musculus and Danio rerio. However, an intermediate taxon that links mammals to vertebrates of more ancient origin is still lacking. Here, we construct the first Xenopus cell landscape to date, including larval and adult organs. Common cell lineage-specific transcription factors have been identified in vertebrates, including fish, amphibians and mammals. The comparison of larval and adult erythrocytes identifies stage-specific hemoglobin subtypes, as well as a common type of cluster containing both larval and adult hemoglobin, mainly at NF59. In addition, cell lineages originating from all three layers exhibits both antigen processing and presentation during metamorphosis, indicating a common regulatory mechanism during metamorphosis. Overall, our study provides a large-scale resource for research on Xenopus metamorphosis and adult organs.

Systematic identification of cell-fate regulatory programs using a single-cell atlas of mouse development.

Waddington's epigenetic landscape is a metaphor frequently used to illustrate cell differentiation. Recent advances in single-cell genomics are altering our understanding of the Waddington landscape, yet the molecular mechanisms of cell-fate decisions remain poorly understood. We constructed a cell landscape of mouse lineage differentiation during development at the single-cell level and described both lineage-common and lineage-specific regulatory programs during cell-type maturation. We also found lineage-common regulatory programs that are broadly active during the development of invertebrates and vertebrates. In particular, we identified Xbp1 as an evolutionarily conserved regulator of cell-fate determinations across different species. We demonstrated that Xbp1 transcriptional regulation is important for the stabilization of the gene-regulatory networks for a wide range of mouse cell types. Our results offer genetic and molecular insights into cellular gene-regulatory programs and will serve as a basis for further advancing the understanding of cell-fate decisions.