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Abstract The development of the Internet of Things has led to a significant increase in the number of devices, consequently generating a vast amount of data and resulting in an influx of unlabeled data. Collecting these data enables the training of robust models to support a broader range of applications. However, labeling these data can be costly, and the models dependent on labeled data are often unsuitable for rapidly evolving fields like vehicular networks and mobile Internet of Things, where new data continuously emerge. To address this challenge, Self-Supervised Learning (SSL) offers a way to train models without the need for labels. Nevertheless, the data stored locally in vehicles are considered private, and vehicles are reluctant to share data with others. Federated Learning (FL) is an advanced distributed machine learning approach that protects each vehicle’s privacy by allowing models to be trained locally and the model parameters to be exchanged across multiple devices simultaneously. Additionally, vehicles capture images while driving through cameras mounted on their rooftops. If a vehicle’s velocity is too high, the captured images, donated as local data, may be blurred. Simple aggregation of such data can negatively impact the accuracy of the aggregated model and slow down the convergence speed of FL. This paper proposes a FL algorithm for aggregation based on image blur levels, which is called FLSimCo. This algorithm does not require labels and serves as a pre-training stage for SSL in vehicular networks. Simulation results demonstrate that the proposed algorithm achieves fast and stable convergence.

Abstract Background There is currently a high demand for bereavement support coupled with inconclusive findings as to the efficacy of existing approaches. Acceptance and Commitment Therapy (ACT) aims to improve human functioning and has shown efficacy across a wide range of conditions. ACT may be a promising means of supporting bereaved people, yet evidence on the use of ACT for bereavement support is lacking. The aim of this study is to explore how ACT is currently used for bereavement support and practitioner perspectives of how it helps following bereavement. Methods Semi-structured interviews were conducted online via MS Teams with practitioners experienced in using ACT for bereavement support. Data were analysed thematically guided by a framework approach. Results Nine participants were recruited. Three themes were identified: (i) creating psychological space around grief; (ii) using psychological space for value-directed action in the midst of grieving, and (iii) adapting ACT for bereavement support. Practitioners indicated that ACT improves clients’ relationship with distressing internal experiences. Metaphors and mindfulness techniques were used to encourage acceptance of grief responses, taking perspective on distressing thoughts and images, and contact with the present moment. Better relationships with distressing experiences were regarded as less psychologically taxing, improving coping and well-being, while providing the psychological space to engage in value-directed action. Values exploration, sometimes using metaphors and exercises, was seen as supporting the bereaved person to rediscover a sense of purpose and engage in meaningful activities alongside their grief. Practitioners used ACT flexibly, integrating other interventions, and adapted ACT to the perceived sensitivities of bereaved people, and age-related and developmental factors. Conclusion ACT is used to support people who have been bereaved to live effectively with the difficult thoughts and feelings associated with grieving and to enable them to gradually identify, reconnect with, and act in line with their values after loss.

The editing of primary human islets could provide insight into diabetes pathogenesis. Here the authors use CRISPR-Cas9 to target regulatory elements associated with T2D susceptibility.

In recent years, employment has become a growing problem for Chinese college students, who often face issues of slow employment and lazy employment. Guided by the framework of career construction theory, we explored how proactive personality strengthens career adaptability. A total of 423 Chinese college students effectively completed the online survey. The results showed a positive correlation between proactive personality, future work self salience, future time perspective, and career adaptability. Additionally, proactive personality can directly affect career adaptability through three indirect paths: the separate intermediary effect of future work self salience, future time perspective, and the continuous mediating role of future work self salience and future time perspective. The results indicate that proactive personality increases career adaptability through the mediating role of future work self salience and future time perspective. This study contributes to our understanding of the mechanisms underlying the relationship between proactive personality and career adaptability. Additionally, the findings have implications for the career development of college students.

To assist Chinese high school students in improving their career readiness and tackling career decision-making difficulties, we designed a synchronous online career intervention based on the Cognitive Information Processing (CIP) theory during the Covid-19 pandemic. The online career intervention consisted of a series of career courses to develop high school students’ knowledge and skills in career planning, career assessments for exploring their vocational interests and academic self-concept, and a database providing basic information about university majors. To evaluate the intervention’s effectiveness, 957 10th grade students were recruited in the study, 601 participants (girls = 227, boys = 324) were randomly assigned to the experimental group (online career intervention), and 356 (girls = 159, boys = 197) participants were randomly assigned to the control group (no any career interventions). All participants completed a pre- and post-intervention assessment of their career maturity, vocational identity and career decision-making difficulties. Results indicated that the online intervention significantly increased high school students’ career readiness and reduced their career decision-making difficulties. The practical implications of this research for online career interventions directed at Chinese high school students are also discussed.

With the outbreak of COVID-19, many offline academic activities have been turned online, and virtual academic communities have been further emphasized. Based on this situation, this study took the Eagly and Chaiken’s Heuristic-System Model of Persuasion and the general rules of behavioral decision as a theoretical basis, established a theoretical model of sustainable knowledge sharing willingness in virtual academic communities. Firstly, this study developed the scale of willingness to share sustainable knowledge based on the heuristic system model of persuasion. After analyzing the data of 62 participants, the scale was revised. Secondly, 256 valid data were collected from China, the United States, Singapore, and Indonesia. Finally, the conceptual model and theoretical hypothesis were tested based on the data. The results show that knowledge sharing satisfaction is affected by heuristic factors (knowledge sharing quantity, knowledge source credibility) and system factors (knowledge sharing quality, knowledge sharing usefulness), and has a significant positive correlation with sustainable knowledge sharing willingness.

The function of genes linked to type 2 diabetes is poorly characterized. Here the authors combine Drosophila genetics and physiology with human islet biology to identify new regulators of insulin secretion including BCL11A.

Abstract X-linked intellectual disability (XLID) has been associated with various genes. Diagnosis of XLID, especially for non-syndromic ones (NS-XLID), is often hampered by the heterogeneity of this disease. Here we report the case of a Chinese family in which three males suffer from intellectual disability (ID). The three patients shared the same phenotype: no typical clinical manifestation other than IQ score ≤ 70. For a genetic diagnosis for this family we carried out whole exome sequencing on the proband, and validated 16 variants of interest in the genomic DNA of all the family members. A missense mutation (c.710G > T), which mapped to exon 6 of the Rab GDP-Dissociation Inhibitor 1 (GDI1) gene, was found segregating with the ID phenotype, and this mutation changes the 237th position in the guanosine diphosphate dissociation inhibitor (GDI) protein from glycine to valine (p. Gly237Val). Through molecular dynamics simulations we found that this substitution results in a conformational change of GDI, possibly affecting the Rab-binding capacity of this protein. In conclusion, our study identified a novel GDI1 mutation that is possibly NS-XLID causative, and showed that whole exome sequencing provides advantages for detecting novel ID-associated variants and can greatly facilitate the genetic diagnosis of the disease.

Abstract Three-dimensional tissue-structural relationships are not well captured by typical thin-section histology, posing challenges for the study of tissue physiology and pathology. Moreover, while recent progress has been made with intact methods for clearing, labeling, and imaging whole organs such as the mature brain, these approaches are generally unsuitable for soft, irregular, and heterogeneous tissues that account for the vast majority of clinical samples and biopsies. Here we develop a biphasic hydrogel methodology, which along with automated analysis, provides for high-throughput quantitative volumetric interrogation of spatially-irregular and friable tissue structures. We validate and apply this approach in the examination of a variety of developing and diseased tissues, with specific focus on the dynamics of normal and pathological pancreatic innervation and development, including in clinical samples. Quantitative advantages of the intact-tissue approach were demonstrated compared to conventional thin-section histology, pointing to broad applications in both research and clinical settings.

Models of human pancreatic intraepithelial neoplasia (PanIN) development do not exist. Here, the authors induce oncogenicKRAS and mutations in CDKN2A, SMAD4 and TP53in primary human pancreatic cells to generate a PanIN model that recapitulates molecular and pathologic features of native PanINs.

The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered. Here, we profiled gene expression in 12 purified populations of fetal and adult pancreatic epithelial cells representing crucial progenitor cell subsets, and their endocrine or exocrine progeny. Using probabilistic models to decode the general programs organizing gene expression, we identified co-expressed gene sets in cell subsets that revealed patterns and processes governing progenitor cell development, lineage specification, and endocrine cell maturation. Purification of Neurog3 mutant cells and module network analysis linked established regulators such as Neurog3 to unrecognized gene targets and roles in pancreas development. Iterative module network analysis nominated and prioritized transcriptional regulators, including diabetes risk genes. Functional validation of a subset of candidate regulators with corresponding mutant mice revealed that the transcription factors Etv1, Prdm16, Runx1t1 and Bcl11a are essential for pancreas development. Our integrated approach provides a unique framework for identifying regulatory genes and functional gene sets underlying pancreas development and associated diseases such as diabetes mellitus.

Pancreatic islet β-cell insufficiency underlies pathogenesis of diabetes mellitus; thus, functional β-cell replacement from renewable sources is the focus of intensive worldwide effort. However, in vitro production of progeny that secrete insulin in response to physiological cues from primary human cells has proven elusive. Here we describe fractionation, expansion and conversion of primary adult human pancreatic ductal cells into progeny resembling native β-cells. FACS-sorted adult human ductal cells clonally expanded as spheres in culture, while retaining ductal characteristics. Expression of the cardinal islet developmental regulators Neurog3, MafA, Pdx1 and Pax6 converted exocrine duct cells into endocrine progeny with hallmark β-cell properties, including the ability to synthesize, process and store insulin, and secrete it in response to glucose or other depolarizing stimuli. These studies provide evidence that genetic reprogramming of expandable human pancreatic cells with defined factors may serve as a general strategy for islet replacement in diabetes.

Identification of signaling pathways that maintain and promote adult pancreatic islet functions will accelerate our understanding of organogenesis and improve strategies for treating diseases like diabetes mellitus. Previous work has implicated transforming growth factor-beta (TGF-beta) signaling as an important regulator of pancreatic islet development, but has not established whether this signaling pathway is required for essential islet functions in the adult pancreas. Here we describe a conditional system for expressing Smad7, a potent inhibitor of TGF-beta signaling, to identify distinct roles for this pathway in adult and embryonic beta cells. Smad7 expression in Pdx1+ embryonic pancreas cells resulted in striking embryonic beta cell hypoplasia and neonatal lethality. Conditional expression of Smad7 in adult Pdx1+ cells reduced detectable beta cell expression of MafA, menin, and other factors that regulate beta cell function. Reduced pancreatic insulin content and hypoinsulinemia produced overt diabetes that was fully reversed upon resumption of islet TGF-beta signaling. Thus, our studies reveal that TGF-beta signaling is crucial for establishing and maintaining defining features of mature pancreatic beta cells.

BackgroundSuccess in islet-transplantation-based therapies for type 1 diabetes, coupled with a worldwide shortage of transplant-ready islets, has motivated efforts to develop renewable sources of islet-replacement tissue. Islets and neurons share features, including common developmental programs, and in some species brain neurons are the principal source of systemic insulin.Methods and findingsHere we show that brain-derived human neural progenitor cells, exposed to a series of signals that regulate in vivo pancreatic islet development, form clusters of glucose-responsive insulin-producing cells (IPCs). During in vitro differentiation of neural progenitor cells with this novel method, genes encoding essential known in vivo regulators of pancreatic islet development were expressed. Following transplantation into immunocompromised mice, IPCs released insulin C-peptide upon glucose challenge, remained differentiated, and did not form detectable tumors.ConclusionProduction of IPCs solely through extracellular factor modulation in the absence of genetic manipulations may promote strategies to derive transplantable islet-replacement tissues from human neural progenitor cells and other types of multipotent human stem cells.

Pectin is a major constituent of the plant cell wall. Pectate lyase (PEL, EC 4.2.2.2) uses anti-β-elimination chemistry to cleave the α-1,4 glycosidic linkage in the homogalacturonan region of pectin. However, limited information is available on the comprehensive and evolutionary analysis of PELs in the Malvaceae. In this study, we identified 597 PEL genes from 10 Malvaceae species. Phylogenetic and motif analyses revealed that these PELs are classified into six subfamilies: Clades I, II, III, IV, Va, and Vb. The two largest subfamilies, Clades I and II, contained 237 and 222 PEL members, respectively. The members of Clades Va and Vb only contained four or five motifs, far fewer than the other subfamilies. Gene duplication analysis showed that segmental duplication played a crucial role in the expansion of the PEL gene family in Gossypium species. The PELs from Clades I, IV, Va, and Vb were expressed during the fiber elongation stage, but nearly all PEL genes from Clades II and III showed no expression in any of the investigated fiber developmental stages. We further performed single-gene haplotype association analysis in 2,001 G. hirsutum accessions and 229 G. barbadense accessions. Interestingly, 14 PELs were significantly associated with fiber length and strength traits in G. barbadense with superior fiber quality, while only eight GhPEL genes were found to be significantly associated with fiber quality traits in G. hirsutum. Our findings provide important information for further evolutionary and functional research on the PEL gene family members and their potential use for fiber quality improvement in cotton.

IntroductionIn high-stakes environments such as aviation, monitoring cognitive, and mental health is crucial, with electroencephalogram (EEG) data emerging as a keytool for this purpose. However traditional methods like linear models Long Short-Term Memory (LSTM), and Gated Recurrent Unit (GRU) architectures often struggle to capture the complex, non-linear temporal dependencies in EEG signals. These approaches typically fail to integrate multi-scale features effectively, resulting in suboptimal health intervention decisions, especially in dynamic, high-pressure environments like pilot training.MethodsTo overcome these challenges, this study introduces PilotCareTrans Net, a novel Transformer-based model designed for health intervention decision-making in aviation students. The model incorporates dynamic attention mechanisms, temporal convolutional layers, and multi-scale feature integration, enabling it to capture intricate temporal dynamics in EEG data more effectively. PilotCareTrans Net was evaluated on multiple public EEG datasets, including MODA, STEW, SJTUEmotion EEG, and Sleep-EDF, where it outperformed state-of-the-art models in key metrics.Results and discussionThe experimental results demonstrate the model's ability to not only enhance prediction accuracy but also reduce computational complexity, making it suitable for real-time applications in resource-constrained settings. These findings indicate that PilotCareTrans Net holds significant potential for improving cognitive health monitoring and intervention strategies in aviation, thereby contributing to enhanced safety and performance in critical environments.

Parkinson’s disease (PD) is a chronic, progressive neurological disorder primarily affecting motor control, clinically characterized by resting tremor, bradykinesia, rigidity, and other symptoms that significantly diminish the quality of life. Currently, available treatments only alleviate symptoms without halting or delaying disease progression. There is a significant association between PD and type 2 diabetes mellitus (T2DM), possibly due to shared pathological mechanisms such as insulin resistance, chronic inflammation, and mitochondrial dysfunction. PD is caused by a deficiency of dopamine, a neurotransmitter in the brain that plays a critical role in the control of movement. Glucose metabolism and energy metabolism disorders also play an important role in the pathogenesis of PD. This review investigates the neuroprotective mechanisms of glucagon-like peptide-1 (GLP-1) and its receptor agonists, offering novel insights into potential therapeutic strategies for PD. GLP-1 class drugs, primarily used in diabetes management, show promise in addressing PD’s underlying pathophysiological mechanisms, including energy metabolism and neuroprotection. These drugs can cross the blood–brain barrier, improve insulin resistance, stabilize mitochondrial function, and enhance neuronal survival and function. Additionally, they exhibit significant anti-inflammatory and antioxidative stress effects, which are crucial in neurodegenerative diseases like PD. Research indicates that GLP-1 receptor agonists could improve both motor and cognitive symptoms in PD patients, marking a potential breakthrough in PD treatment and prevention. Further exploration of GLP-1’s molecular mechanisms in PD could provide new preventive and therapeutic approaches, especially for PD patients with concurrent T2DM. By targeting both metabolic and neurodegenerative pathways, GLP-1 receptor agonists represent a multifaceted approach to PD treatment, offering hope for better disease management and improved patient outcomes.

PurposeAlthough the application of heterosis has significantly increased crop yield over the past century, the mechanisms underlying this phenomenon still remain obscure. Here, we applied transcriptome sequencing to unravel the impacts of parental expression differences and transcriptomic reprogramming in cotton heterosis.MethodsA high-quality transcriptomic atlas covering 15 developmental stages and tissues was constructed for XZM2, an elite hybrid of upland cotton (Gossypium hirsutum L.), and its parental lines, CRI12 and J8891. This atlas allowed us to identify gene expression differences between the parents and to characterize the transcriptomic reprogramming that occurs in the hybrid.ResultsOur analysis revealed abundant gene expression differences between the parents, with pronounced tissue specificity; a total of 1,112 genes exhibited single-parent expression in at least one tissue. It also illuminated transcriptomic reprogramming in the hybrid XZM2, which included both additive and non-additive expression patterns. Coexpression networks between parents and hybrid constructed via weighted gene coexpression network analysis identified modules closely associated with fiber development. In particular, key regulatory hub genes involved in fiber development showed high-parent dominant or over dominant patterns in the hybrid, potentially driving the emergence of heterosis. Finally, high-depth resequencing data was generated and allele-specific expression patterns examined in the hybrid, enabling the dissection of cis- and trans-regulation contributions to the observed expression differences.ConclusionParental transcriptional differences and transcriptomic reprogramming in the hybrid, especially the non-additive upregulation of key genes, play an important role in shaping heterosis. Collectively, these findings provide new insights into the molecular basis of heterosis in cotton.

Summary: Selection of fruits with enhanced health benefits and superior flavor is an important aspect of peach breeding. Understanding the genetic interplay between appearance and flavor chemicals remains a major challenge. We identify the most important volatiles contributing to consumer preferences for peach, thus establishing priorities for improving flavor quality. We quantify volatiles of a peach population consisting of 184 accessions and demonstrate major reductions in the important flavor volatiles linalool and Z-3-hexenyl acetate in red-fleshed accessions. We identify 474 functional gene regulatory networks (GRNs), among which GRN05 plays a crucial role in controlling both red flesh and volatile content through the NAM/ATAF1/2/CUC (NAC) transcription factor PpBL. Overexpressing PpBL results in reduced expression of PpNAC1, a positive regulator for Z-3-hexenyl acetate and linalool synthesis. Additionally, we identify haplotypes for three tandem PpAATs that are significantly correlated with reduced gene expression and ester content. We develop genetic resources for improvement of fruit quality.

Introduction: Allotetraploid upland cotton (Gossypium hirsutum L.) is native to the Mesoamerican and Caribbean regions, had been improved in the southern United States by the mid-eighteenth century, was then dispersed worldwide. However, a Hainan Island Native Cotton (HIC) has long been grown extensively on Hainan Island, China. Objectives: Explore HIC’s evolutionary relationship and genomic diversity with other tetraploid cottons, its origin and whether it was used for YAZHOUBU (Yazhou cloth, World Intangible Cultural Heritage) weaving, and the role of structural variations (SVs) in upland cotton domestication. Methods: We assembled a high-quality genome of one HIC plant. We performed phylogenetic analysis, divergence time estimation, principal component analysis and population differentiation estimation using cotton assemblies and/or resequencing data. SVs were detected by whole-genome comparison. A F2 population was used for linkage analysis and to study effects of SVs. Buoyancy and salt water tolerance tests for seeds were conducted. Results: We found that the HIC belongs to G. purpurascens. G. purpurascens is best classified as a primitive race of G. hirsutum. The potential for long range transoceanic dispersal of G. purpurascens seeds was proved. A set of SVs, selective sweep regions between G. hirsutum races and cultivars, and quantitative trait loci (QTLs) of eleven agronomic traits were obtained. SVs, especially large-scale SVs, were found to have important effects on cotton domestication and improvement. Of them, eight large-scale inversions strongly associated with yield and fiber quality have probably undergone artificial selection in domestication. Conclusion: G. purpurascens including HIC is a primitive race of G. hirsutum, probably disperse to Hainan from Central America by floating on ocean currents, may have been partly domesticated, planted and was likely used for YAZHOUBU weaving in Hainan much earlier than the Pre-Columbian period. SV plays an important role in cotton domestication and improvement.

Pepper (Capsicum annuum L.) is an economically important crop containing capsaicinoids in the seed and placenta, which has various culinary, medical, and industrial applications. Late embryogenesis abundant (LEA) proteins are a large group of hydrophilic proteins participating in the plant stress response and seed development. However, to date there have been no genome‐wide analyses of the LEA gene family in pepper. In the present study, 82 LEA genes were identified in the C. annuum genome and classified into nine subfamilies. Most CaLEA genes contain few introns (≤ 2) and are unevenly distributed across 10 chromosomes. Eight pairs of tandem duplication genes and two pairs of segmental duplication genes were identified in the LEA gene family; these duplicated genes were highly conserved and may have performed similar functions during evolution. Expression profile analysis indicated that CaLEA genes exhibited different tissue expression patterns, especially during embryonic development and stress response, particularly in cold stress. Three out of five CaLEA genes showed induced expression upon cold treatment. In summary, we have comprehensively reviewed the LEA gene family in pepper, offering a new perspective on the evolution of this family.