Mechanisms Of Differentiation Research Articles

PKDGAN: Private Knowledge Distillation With Generative Adversarial Networks

The deployment of deep learning applications has to address the increasing privacy concerns when using private and sensitive data for training. A conventional deep learning model is prone to privacy attacks that can recover the sensitive information from either model parameters or accesses to the inference model. Recently, differential privacy (DP) has been proposed to offer provable privacy guarantees by randomizing the training process of neural networks. However, many approaches tend to provide the worst case privacy protection for model publishing, inevitably impairing the accuracy of the trained models. Thus, we present a novel private knowledge transfer strategy, where the private teacher trained on sensitive data is not publicly accessible but the student models can be released with privacy guarantees. In this paper, a three-player (teacher-student-discriminator) learning framework, Private Knowledge Distillation with Generative Adversarial Networks (PKDGAN), is proposed, where the student acquires the distilled knowledge from the teacher and is trained with the discriminator to generate similar outputs as the teacher. Moreover, a cooperative learning strategy is also suggested to support the collective training of multiple students against the discriminator when each student is with insufficient unlabelled training data. To enforce rigorous privacy guarantees, PKDGAN applies a Rényi differential privacy mechanism throughout the training process, and use it with a moment accountant technique to track the privacy cost. PKDGAN allows students to be trained with unlabelled public data and very few epochs, which avoids the exposure of training data while ensuring model performance. In the experiments, PKDGAN is found to have consistently good performance on various datasets (MNIST, SVHN, CIFAR-10, and Market-1501). When compared to prior works [1], [2], PKDGAN exhibits 5-82% accuracy loss improvement without compromising any privacy guarantee.

High-quality sika deer omics data and integrative analysis reveal genic and cellular regulation of antler regeneration.

Antler is the only organ that can fully regenerate annually in mammals. However, the regulatory pattern and mechanism of gene expression and cell differentiation during this process remain largely unknown. Here, we obtain comprehensive assembly and gene annotation of the sika deer (Cervus nippon) genome. Together with large-scale chromatin accessibility and gene expression data, we construct gene regulatory networks involved in antler regeneration, identifying four transcription factors, MYC, KLF4, NFE2L2, and JDP2 with high regulatory activity across whole regeneration process. Comparative studies and luciferase reporter assay suggest the MYC expression driven by a cervid-specific regulatory element might be important for antler regenerative ability. We further develop a model called cTOP which integrates single-cell data with bulk regulatory networks and find PRDM1, FOSL1, BACH1, and NFATC1 as potential pivotal factors in antler stem cell activation and osteogenic differentiation. Additionally, we uncover interactions within and between cell programs and pathways during the regeneration process. These findings provide insights into the gene and cell regulatory mechanisms of antler regeneration, particularly in stem cell activation and differentiation.

Comparative Transcriptome Analysis of Sexual Differentiation in Male and Female Gonads of Nao-Zhou Stock Large Yellow Croaker (Larimichthys crocea)

The Nao-zhou stock large yellow croaker (Larimichthys crocea) is a unique economic seawater fish species in China and exhibits significant dimorphism in both male and female phenotypes. Cultivating all-female seedlings can significantly improve breeding efficiency. To accelerate the cultivation process of all female seedlings of this species, it is necessary to deeply understand the regulatory mechanisms of sexual differentiation and gonadal development. This study used Illumina high-throughput sequencing to sequence the transcriptome of the testes and ovaries of Nao-zhou stock large yellow croaker to identify genes and molecular functions related to sex determination. A total of 10,536 differentially expressed genes were identified between males and females, including 5682 upregulated and 4854 downregulated genes. Functional annotation screened out 70 important candidate genes related to sex, including 34 genes highly expressed in the testis (including dmrt1, foxm1, and amh) and 36 genes highly expressed in the ovary (including gdf9, hsd3b1, and sox19b). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis found that differentially expressed genes were significantly enriched in nine signaling pathways related to sex determination and gonadal development, including steroid hormone biosynthesis, MAPK signaling pathway, and the TGF-beta signaling pathway. By screening sex-related differentially expressed genes and mapping protein–protein interaction networks, hub genes such as dmrt1, amh, and cyp19a1a were found to be highly connected. The expression levels of 15 sex-related genes, including amh, dmrt1, dmrt2a, foxl1, and zp3b, were determined by qRT–PCR and RNA sequencing. This study screened for differentially expressed genes related to sex determination and differentiation of Nao-zhou stock large yellow croaker and revealed the signaling pathways involved in gonad development of male and female individuals. The results provide important data for future research on sex determination and differentiation mechanisms, thereby providing a scientific basis for the cultivation of all-female seedlings.

Single-Nucleus RNA Sequencing Reveals the Transcriptome Profiling of Ovarian Cells in Adolescent Cyprinus carpio

The common carp (Cyprinus carpio) is a crucial freshwater species cultivated worldwide for food consumption. Female carp have better growth performance than males, which fascinates scholars to uncover the mechanism of gonadal differentiation and produce mono-sex populations. However, the mechanism of ovarian development at single-cell resolution is limited. Here, we conducted single-nucleus RNA sequencing in adolescent common carp ovaries. Our study obtained transcriptional profiles of 13,155 nuclei and revealed 13 distinct cell clusters in the ovaries, including three subtypes of germ cells and four subtypes of granulosa cells. We subsequently performed pseudotime trajectory analysis to delineate potential mechanisms underlying the development of germ cells and granulosa cells. We identified 1250 dynamic expression genes in germ cells and 1815 in granulosa cells (q-value < 0.01), including zp3, eif4a2 and aspm in germ cells and fshr and esr1 in granulosa cells. The functional annotation showed that dynamic expression genes in germ cells were involved in sperm–egg recognition and some terms related to meiosis, such as sister chromatid segregation and homologous recombination. Genes expressed dynamically in granulosa cells were related to the TGF-β signaling pathway, response to gonadotropin, and development of primary female sexual characteristics. In addition, the dynamic genes expressed in granulosa cells might relate to the complex communication between different cell types. In summary, our study provided a transcriptome profile of common carp ovaries at single-nucleus resolution, and we further revealed the potential cell type-specific mechanisms underlying oogenesis and the differentiation of granulosa cells, which will facilitate breeding all-female common carp populations.

First Report of Bacterial Leaf Spot Disease on Ginger Caused by Enterobacter quasiroggenkampii in China.

In autumn 2023, an unknown leaf spot disease has occurred on ginger (Zingiber officinale Roscoe) in two fields of approximately 1800 m2 in Yongning District (22°49'N; 108°48'E), Nanning, China, with a incidence of 20-30%. The symptoms began as yellow spots on the leaves, expanding into elliptical to irregular lesions with yellow edges, the middle of the lesion turning grey-white in dry weather. Finally, multiple spots caused necrosis of the whole leaf. Twelve diseased leaves from six plants of two fields were collected, surface disinfected and ground. The ground samples were diluted and plated on nutrient agar (NA) medium at 28 °C for 48-72 h. The purified colonies appeared milky white and round, with smooth edges. Three isolates (GL1, GL2 and GL3) were selected for identification and pathogenic determination. They were gram negative, could utilize sorbitol, mannitol, inositol, raffinose, melibiose, disaccharides, and citrate; negative for methyl red, phenylalanine decarboxylase, hydrogen sulfide, urease; positive for voges-proskauer test and ornithine decarboxylase. These characteristics were consistent with Enterobacter genus (Wu et al., 2020). Genomic DNA was extracted from three isolates. The 16S rDNA region was amplified using 27F/1492R primers (Weisburg et al. 1991) and sequenced (accession no. PP837703-PP837705). Blastn analysis revealed that 16S rDNA sequences for GL1 was 99% identical (1373/1387 nt), GL2 96% (1364/1422 nt) and GL3 95% (1365/1435 nt) to Enterobacter quasiroggenkampii WCHECL1060 (NR_179166). To determine the species, the sequences of gyrB, rpoB and atpD genes were amplified using primers gyrB 01-F/gyrB 02-R, rpoB CM7/rpoB CM31b, and atpD 01-F/atpD 02-R, respectively (Lin et al. 2015; Zhu at al. 2010; Zhang et al. 2013). The GenBank accession numbers for the sequences were PP857680-PP857688. A multilocus phylogenetic tree was constructed with the concatenated sequence of 16S rDNA-gyrB-rpoB-atpD by using the Neighbor-Joining (NJ) method with 1000 bootstrap replicates in MEGA6 software. The three isolates clustered with E. quasiroggenkampii. Fifteen Darou ginger variety plants at the 4-5 leaf stage were tested for pathogenicity. Two to three leaves of each ginger plant were pricked with a syringe needle of 0.36mm in diameter or not and inoculated by spraying the bacterial suspension (108 CFU/mL), sterile water was used as a control. Five plants were inoculated with each isolate and the test was repeated three times. After 3-4 days of inoculation, all wounded leaves and about 10% of the unwounded leaves showed symptoms similar to those observed in the field. Control plants did not develop symptoms. Enterobacter quasiroggenkampii isolates were re-isolated from the inoculated leaves with symptoms, and their identity was confirmed by gyrB sequencing and colony morphology, completing Koch's postulates. Enterobacter quasiroggenkampii is a pathogen of humans that can cause nosocomial infections (Wu et al., 2020). In Guangxi, E. quasiroggenkampii was identified as one of the pathogens causing mulberry wilt (Jiao, 2022). To our knowledge, this is the first report of E. quasiroggenkampii causing bacterial leaf spot disease of ginger. The results of this study not only have practical significance for the control of ginger leaf spot, but also can provide excellent materials for the study of the differentiation and pathogenic mechanism of the genus Enterobacter, which has important academic value.

Delay management for heterogeneous traffic in vehicular sensor networks using packet fragmentation of low priority data

AbstractVehicular sensor networks (VSNs) are expected to revolutionize the transportation systems through automated decision‐making. These networks function on the communication between vehicles, traffic infrastructure, and people. One of the major challenges of VSNs is to deal with heterogeneous traffic due to the diverse nature of information and data generated by different types of sensors and devices within the vehicular environment. To ensure an effective operation of the network, it is crucial to offer a differentiated quality of service to each traffic class. Media access control (MAC) protocols offer an opportunity to provide differentiated channel access to the traffic of different priorities. This work is focused on offering comparison of recent MAC schemes in terms of their performance for heterogeneous traffic generated by VSNs. Two protocols FROG‐MAC and UrgMAC have been selected: FROG‐MAC is developed using a simple concept of packet fragmentation, where the packets of lower priority are fragmented to offer an early transmission opportunity to urgent traffic; on the other hand, urgMAC is designed using advanced cross‐layer techniques of two‐tiered service differentiation mechanism, adaptive data rate adjustment mechanism, urgency‐based contention window size adaptation, traffic type adaptive duty cycle, and multimedia message passing. It has been found that the FROG‐MAC outperforms urgMAC in terms of delay, energy consumption and packet delivery ratio.

IGA Approximations of Elastic Interfaces and their Defects in an Elastic Medium with Couple Stress

AbstractThe objective of this work is to develop and implement a computational algorithm for calculating stress and couple-stress fields induced by bulk and interfacial line defects such as dislocations and generalized disclinations within phase/grain boundaries. The thermodynamic driving forces on line and planar defects, responsible for coupled plasticity and interface motion, fully coupled to stress, couple-stress and applied boundary conditions are also computed. A continuum approach for small deformations is considered following the formulation outlined in Acharya and Fressengeas (Continuum mechanics of the interaction of phase boundaries and dislocations in solids. In: Differential Geometry and Continuum Mechanics, pages 123–165, 2015), extended herein in the thermodynamics to accommodate physically necessary ingredients that arose in the modeling in Zhang and Acharya (J Mech Phys Solids 119:188–223, 2018), Zhang et al. (J Mech Phys Solids 114:258–302, 2018). Constitutive relations are derived from kinematics, balance laws and from the use of the second law of thermodynamics in global form. One of the challenges presented by this approach is the inclusion of couple stresses, Toupin (Arch Rational Mech Anal 17(2):85–112, 1964), and the consequent treatment of 4th order systems arising from the equations of balances of linear and angular momentum. In order to deal with these equations, the classical FEM approach is replaced by iso-geometric analysis (IGA), as proposed by Hughes et al. (Comput Methods Appl Mech Eng 194(39):4135–4195, 2005). Results on stress and couple stress fields of the various defects involved are computed. Further, the coupling of the dislocation density with the eigenwall allows for the capturing of the shear parallel to the grain boundary, which has been observed experimentally and through molecular dynamics.

The source and differential enrichment mechanisms of lithium in Gudui geothermal field: Constraints from enrichment and dilution processes of geothermal-type lithium

As a typical high-temperature geothermal system in the Qinghai-Xizang Plateau, the Gudui geothermal field (GDGF) shows notably high lithium content. Compared with other Li-rich geothermal fields, GDGF exhibits differential enrichment of lithium. Furthermore, few studies have focussed on investigation of the depletion of lithium during the ascent of geothermal fluids. Therefore, this study investigated the source, mechanism of differential enrichment of lithium and depletion mechanism of lithium. The δD and δ18O plot and the two-endmember modeling of Sr isotope indicate that geothermal fluids in GDGF were affected by magmatic water and mixing ratios are range from 0.8 to 12 %. Furthermore, the Li isotope mass balance model shows that the leucogranite distributed near GDGF is the primary source of lithium in geothermal fluids. The correlations between Na, K, Li and Cl concentrations indicate that the geothermal waters in eastern and western region originate from different parent geothermal fluids. The δD-Cl plot and enthalpy-chloride diagram reveals that the geothermal water in WGDGF was mainly formed by mixing with shallow surface water, and multiple boiling processes took place in EGDGF. In addition, Lithium in the geothermal fluids might be absorbed by the clay minerals widely distributed in the EGDGF, which causes the depletion in the rise process. In conclusion, the differential enrichment model of lithium in GDGF was constructed.

Identification of Genes and Long Non-Coding RNAs Putatively Related to Portunus trituberculatus Sex Determination and Differentiation Using Oxford Nanopore Technology Full-Length Transcriptome Sequencing.

The swimming crab (Portunus trituberculatus) is an economically important species in China, and its growth traits show obvious sexual dimorphism. Thus, it is important to study the mechanism of sex determination and differentiation in this species. Herein, we identified 2138 differentially expressed genes and 132 differentially expressed long non-coding RNAs (lncRNAs) using Oxford Nanopore Technology full-length transcriptome sequencing. We predicted 561 target genes of the differentially expressed lncRNAs according to their location and base pair complimentary principles. Furthermore, pathways related to sex determination, differentiation, and reproduction were enriched for lncRNAs according to gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses. This indicated that lncRNAs might play regulatory roles in these pathways. Our results could form the basis for future studies of sex determination and differentiation in P. trituberculatus.

Deciphering Mechanisms of Adipocyte Differentiation in Abdominal Fat of Broilers.

The excessive deposition of abdominal fat tissue (AFT) in broilers has emerged as a major concern in the poultry industry. Despite some progress in recent years, the molecular mechanisms underlying AFT development remain ambiguous. The current study combined RNA-seq with transposase-accessible chromatin sequencing (ATAC-seq) to map the dynamic profiling of chromatin accessibility and transcriptional reprogramming in AFT adipocyte differentiation in broilers at day 3 (D3) and D14. Our results found that the levels of CDK1 and PCNA were down-regulated at D14, D28, and D42 compared to D3, while the levels of C/EBPα and FABP4 were up-regulated at D14 and D42 compared to D3. Meanwhile, PPARγ was significantly up-regulated at D28 and D42. RNA-seq of AFT identified 1705 up-regulated and 1112 down-regulated differential expression genes (DEGs) between D3 and D14. Pathways based on up-regulated DEGs mainly enriched some pathways related to adipocyte differentiation, while down-regulated DEGs pointed to DNA replication, cell cycle, and gap junction. Gene set enrichment analysis (GSEA) revealed that DNA replication and the cell cycle were down-regulated at D14, while the insulin signaling pathway was up-regulated. In the OA-induced immortalized chicken preadipocyte (ICP2) model, protein dynamic changes were consistent with AFT from D3 to D14. Same pathways were enriched in ICP2. In addition, based on overlapped DEGs from AFT and ICP2, enriched pathways related to adipocyte differentiation or proliferation mentioned above were all involved. A total of 1600 gain and 16727 loss differential peaks (DPs) were identified in ICP2 by ATAC-seq. Predicted genes from DPs at the promoter regions were enriched in glycerophospholipid metabolism, TGF-β signaling, FoxO signaling, and ubiquitin-mediated proteolysis. DNA motifs predicted 159 transcription factors (TFs) based on gain and loss peaks from the promoter regions, where 1 and 10 TFs were overlapped with up or down TFs from DEGs. Overall, this study presents a framework for the comprehension of the epigenetic regulatory mechanisms of adipocyte differentiation and identifies candidate genes and potential TFs involved in AFT adipocyte differentiation in broilers.

Preparation and characterization of neural stem cell-loaded conductive hydrogel cochlear implant electrode coatings

Sensorineural deafness is a hearing impairment resulting from damage to the auditory nerve or inner ear hair cells. Currently, cochlear implants (CIs) are widely used as hearing aids for sensorineural deafness patients. A fundamental limitation of cochlear implants (CIs) is that spiral ganglion neurons (SGNs) cannot be replenished. This greatly restricts the rehabilitation of sensorineural deafness. Additionally, the insertion of CIs can cause secondary cochlear damage, worsening the condition of the patients' cochlear. Therefore, a new type of neural stem cells (NSCs) loaded graphene oxide-polyaniline/GelMA (GO-PAni/GelMA) conductive hydrogel electrode for cochlear implant was fabricated via in-situ radical polymerization and cyclic UV curing technique. On the one hand, the hydrogel electrode, as a direct contact layer, helps to avoid the physical hurt for cochlear. On the other hand, NSCs were supplemented via the hydrogel carrier and neuronal differentiation was induced by electrical stimulation, which was validated by the experimental results of immunofluorescence, Phalloidin Staining and RT-qPCR. Furthermore, based on RNA sequencing and transcriptome analysis, we hypothesized that the neuronal differentiation of NSCs was adjusted by the calcium signaling pathway and GABAergic synapse. Overall, our cell loading conductive hydrogel electrode may be an effective solution to sensorineural deafness. The revelation of the mechanism of neuronal differentiation promoted by electrical stimulation provides a basis for further sensorineural deafness treatment using conductive hydrogel CI electrode.

Spatial patterns of hydroecological health in the semi-arid yellow river basin: Revelations from machine learning models

The ecosystem of semi-arid watersheds is influenced by a combination of natural climate factors, rainfall, and habitat destruction, resulting in complex mechanisms of spatial differentiation and evolution of water ecological health. Indicator selection in mainstream water ecological health assessment methods, such as the Index of Biotic Integrity (IBI), often relies on subjective reference point choices. This approach tends to overlook the comprehensive impacts and interactions among various environmental stressors. For watersheds significantly influenced by natural climatic factors, considerable uncertainties arise, leading to a lack of scientific justification for establishing water ecological health protection goals. In this study, the nonlinear capabilities of the random forest (RF) model were applied to reduce subjectivity in traditional water ecological health assessments and to more accurately reveal the emerging spatial differentiation patterns and underlying causes of water ecological health in the Wei River Basin (WRB), the largest typical semi-arid watershed of the Yellow River in China. Our findings indicate: (1) Traditional evaluation indices indicate that the overall water ecological health of the WRB is classified as sub-healthy (60 %). The core indicators include dominant species, total algal density, and the percentage of diatom density, with no significant spatial differentiation observed. (2) An improved water ecological health assessment method for semi-arid watersheds, based on the RF model, has been developed to replace traditional subjective judgment steps. This method establishes a complex multi-input–output response relationship (R2>0.85) between environmental stress indicators and the biological integrity index for the WRB. (3) The model results identify key driving factors affecting changes in water ecological health in semi-arid watersheds, with the sensitivity of the new model increasing nearly 11-fold compared to traditional IBI methods. (4) Following improvements, the water ecological health characteristics of the WRB exhibit significant spatial heterogeneity, with a higher dispersion coefficient (1.21), and demonstrate enhanced nonlinear response trends to climatic factors. The application of machine learning models indicates that traditional methods may underestimate the extent of ecological health degradation in watersheds and tend to oversimplify spatial heterogeneity characteristics.

Systematic identification and prediction of sex-specific MADS-box genes in Zanthoxylum armatum during flower development

Zanthoxylum armatum, as a vital economic tree species serving both as a food source and medicinal plant, it stands as one of the key industries supporting rural revitalization in southwestern China, offered significant economic, ecological, and social benefits. In recent years, there has been a significant increase in the occurrence of male flowers being sterile, which has greatly impeded the industrial development of Z. armatum. In this study, we investigated the MADS-box gene as a pivotal transcription factor (TFs) influencing flower development. To gain a comprehensive understanding of the evolutionary dynamics of MADS-box genes in Z. armatum and establish a solid foundation for future research on this significant gene family, we conducted a genome-wide investigation and analyzed the expression patterns of MADS-box genes. The present study identified a total of 72 MADS-box genes (ZaMADS1–72) from Z. armatum and proposed that the ZaMADS41 gene is pivotal candidate gene influencing the female-to-male transformation. Phylogenetic analysis revealed that these genes can be categorized into two types: Type I (29 genes) and Type II (43 genes), with the latter exhibiting more complex protein domains and motifs compared to the former. Protein-protein interactions were observed among members of the ZaMADS-box gene family, while their promoter regions contained cis-acting elements associated with light response, hormone response, and plant growth and development. Expression profiling during different stages of male and female flower development demonstrated distinct high expression patterns for certain genes specifically in mature male or female flowers. Furthermore, the determination of endogenous hormone content indicated a potential correlation between iP9G and MEJA with sex transformation, while iP9G exhibited a significantly negative association with ZaMADS33 expression. This comprehensive study on MADS-box genes in Z. armatum combined with changes in endogenous hormone levels during male and female flower development, provides a solid theoretical foundation for investigating bud differentiation mechanisms and regulatory techniques in this species.

CRISPR-Mediated SRY Gene Mutation Increases the Expression of Female Lineage-Specific Gene in Pre-Implantation Buffalo Embryo.

In mammals, sex determination is governed by the SRY gene on the Y chromosome, redirecting gonadal development from forming ovaries to testes. Mutations or alterations in the SRY gene can significantly affect phenotypic changes and lineage-specific markers. This study aims to elucidate the role of the SRY gene in buffalo embryos using CRISPR-Cas9 technology. We designed a crRNA targeting the HMG domain of the SRY gene using the CRISPOR algorithm. Nucleofection of sgRNA-Cas9 RNPs into buffalo fibroblasts confirmed efficient cleavage at the targeted site. Using this validated guide, we investigated the role of the SRY gene in sexual determination by electroporating CRISPR-Cas9-RNPs into single-stage zygotes of buffalo. Genetic changes in the SRY gene were confirmed through sequencing, revealing mosaic blastocysts with multiple alleles and non-mosaic mutants. Mutations in SRY gene increased the expression of female lineage-specific gene Wnt4 whereas decreased the expression of male specific gene SOX9 in blastocysts, suggesting reprogramming towards female sex determination pathways. Our findings provide insights into buffalo sex differentiation mechanisms and potential applications in reproductive strategies for breeding programmes.

“A Friend Among Strangers” or the Ambiguous Roles of Runx2

The transcription factor Runx2 plays a crucial role in regulating osteogenic differentiation and skeletal development. This factor not only controls the expression of genes involved in bone formation, but also interacts with signaling pathways such as the Notch pathway, which are essential for body development. However, studies have produced conflicting results regarding the relationship between Runx2 and the Notch pathway. Some studies suggest a synergistic interaction between these molecules, while others suggest an inhibitory one, for example, the interplay between Notch signaling, Runx2, and vitamin D3 in osteogenic differentiation and bone remodeling. The findings suggest a complex relationship between Notch signaling and osteogenic differentiation, with ongoing research needed to clarify the mechanisms involved and resolve existing contradictions regarding role of Notch in this process. Additionally, there is increasing evidence of contradictory roles for Runx2 in various tissues and organs, both under normal conditions and in pathological states. This diversity of roles makes Runx2 a potential therapeutic target, offering new directions for research. In this review, we have discussed the mechanisms of osteogenic differentiation and the important role of Runx2 in this process. We have also examined its relationship with different signaling pathways. However, there are still many uncertainties and inconsistencies in our current understanding of these interactions. Additionally, given that Runx2 is also involved in numerous other events in various tissues, we have tried to comprehensively examine its functions outside the skeletal system.

Differential neural mechanisms underlie cortical gating of visual spatial attention mediated by alpha-band oscillations

Selective attention relies on neural mechanisms that facilitate processing of behaviorally relevant sensory information while suppressing irrelevant information, consistently linked to alpha-band oscillations in human M/EEG studies. We analyzed cortical alpha responses from intracranial electrodes implanted in eight epilepsy patients, who performed a visual spatial attention task. Electrocorticographic data revealed a spatiotemporal dissociation between attention-modulated alpha desynchronization, associated with the enhancement of sensory processing, and alpha synchronization, associated with the suppression of sensory processing, during the cue-target interval. Dorsal intraparietal areas contralateral to the attended hemifield primarily exhibited a delayed and sustained alpha desynchronization, while ventrolateral extrastriatal areas ipsilateral to the attended hemifield primarily exhibited an earlier and sustained alpha synchronization. Analyses of cross-frequency coupling between alpha phase and broadband high-frequency activity (HFA) further revealed cross-frequency interactions along the visual hierarchy contralateral to the attended locations. Directionality analyses indicate that alpha phase in early and extrastriatal visual areas modulated HFA power in downstream visual areas, thus potentially facilitating the feedforward processing of an upcoming, spatially predictable target. In contrast, in areas ipsilateral to the attended locations, HFA power modulated local alpha phase in early and extrastriatal visual areas, with suppressed interareal interactions, potentially attenuating the processing of distractors. Our findings reveal divergent alpha-mediated neural mechanisms underlying target enhancement and distractor suppression during the deployment of spatial attention, reflecting enhanced functional connectivity at attended locations, while suppressed functional connectivity at unattended locations. The collective dynamics of these alpha-mediated neural mechanisms play complementary roles in the efficient gating of sensory information.

Wnt/β-catenin signaling pathway: proteins' roles in osteoporosis and cancer diseases and the regulatory effects of natural compounds on osteoporosis.

Osteoblasts are mainly derived from mesenchymal stem cells in the bone marrow. These stem cells can differentiate into osteoblasts, which have the functions of secreting bone matrix, promoting bone formation, and participating in bone remodeling. The abnormality of osteoblasts can cause a variety of bone-related diseases, including osteoporosis, delayed fracture healing, and skeletal deformities. In recent years, with the side effects caused by the application of PTH drugs, biphosphonate drugs, and calmodulin drugs, people have carried out more in-depth research on the mechanism of osteoblast differentiation, and are actively looking for natural compounds for the treatment of osteoporosis. The Wnt/β-catenin signaling pathway is considered to be one of the important pathways of osteoblast differentiation, and has become an important target for the treatment of osteoporosis. The Wnt/β-catenin signaling pathway, whether its activation is enhanced or its expression is weakened, will cause a variety of diseases including tumors. This review will summarize the effect of Wnt/β-catenin signaling pathway on osteoblast differentiation and the correlation between the related proteins in the pathway and human diseases. At the same time, the latest research progress of natural compounds targeting Wnt/β-catenin signaling pathway against osteoporosis is summarized.

Differential expression and co-expression reveal cell types relevant to genetic disorder phenotypes.

Knowledge of the specific cell types affected by genetic alterations in rare diseases is crucial for advancing diagnostics and treatments. Despite significant progress, the cell types involved in the majority of rare disease manifestations remain largely unknown. In this study, we integrated scRNA-seq data from non-diseased samples with known genetic disorder genes and phenotypic information to predict the specific cell types disrupted by pathogenic mutations for 482 disease phenotypes. We found significant phenotype-cell type associations focusing on differential expression and co-expression mechanisms. Our analysis revealed that 13% of the associations documented in the literature were captured through differential expression, while 42% were elucidated through co-expression analysis, also uncovering potential new associations. These findings underscore the critical role of cellular context in disease manifestation and highlight the potential of single-cell data for the development of cell-aware diagnostics and targeted therapies for rare diseases. All code generated in this work is available at https://github.com/SergioAlias/sc-coex.

Epigenetic modifications in transdifferentiation of adipose tissue-derived stromal cells into spontaneously beating cardiomyocyte-like cells

Abstract Background Adipose tissue-derived stromal vascular fraction (adipose SVF) contains pluripotent mesenchymal stem cells and rarely transdifferentiate into beating cardiomyocytes. We developed a simple culture protocol under which the adult murine inguinal adipose SVF reproductively transdifferentiates into beating cardiomyocyte-like cells (beating CM) without inductions in the primary culture. We also reported that Mef2c is a crucial factor in this conversion. However, the characteristics of beating CM and the factors that regulate the differentiation of adipose SVF toward the cardiac lineage are unknown. Purpose To investigate sequential changes in global gene expression profiles of adipose SVF in primary culture and determine the mechanism of differentiation into beating CM. Methods Adipose SVF cells were isolated from adult mice's inguinal subcutaneous fat pad and cultured using the previously established beating CM induction method (Sci Rep. 2021). At 6 time points (days 0, 3, 7, 14, 21, and 28) in primary culture, total RNA was extracted, and RNA-sequencing was performed (n = 3). The data was analyzed using Subio Platform and MetaCore software. To assess the candidate gene and proteins, adipose SVF cells were transduced with the gene using a lentivirus vector and supplemented with the specific inhibitors. The cardiac differentiation was evaluated by quantitative PCR on day 28. Results The beating CM was confirmed on days 14, 21, and 28 in the primary culture. Among prefiltered 14,574 genes, the expression level of 749 genes were significantly changed (153 genes upregulated vs. 596 genes downregulated) between days 7 and 14 (2-fold, P < 0.05), in which beating CM appeared. The GO molecular functions analysis showed that O-GluNAC transferase and histone deacetylase (HDAC)-associated genes were expressed dominantly before day 7, and KLF4-associated genes were expressed prominently after day 14 in primary culture. The expression of cardiac troponin T (Tnnt2) and myosin light chain ventricular type (Myl2) increased on day 3 and day 14, respectively. The HDAC7, an epigenetic regulator, decreased the expression on day 14 or later. Treatment with the HDAC inhibitor (150 nmol/L) increased the expression of Tnnt2 (5-fold vs. control) on day 28 in adipose SVF. Furthermore, treatment of Mef2c-transduced adipose SVFs with HDAC inhibitors increased expression of cardiac troponin T (29-fold vs. control, P < 0.05). Conclusion The time course analysis demonstrated that a remarkable change occurred in the regulation of transcription on day 14 in adipose SVF primary culture. Alterations in epigenetic modifications increased beating CM in adipose SVFs. Adipose SVF could be applied to new cardiac regeneration therapies by increasing the efficiency of introduction into the beating CM.

Epicardial carbohydrate antigen 125 (CA-125) levels, associated with neutrophils activity in heart failure: No differences regarding sex

Abstract Background Carbohydrate antigen 125 (CA125), is the name of the soluble part of mucin-16, after being cleaved, which is detected and increased into circulation in congestive heart failure (HF) patients. Purpose We aimed to study plasma and epicardial fat markers related to inflammation, fibrosis, adiposity, and its association with plasma and epicardial CA125 for understanding the underlying mechanisms of heart failure and the differences between men and women. Methods We have included women and men undergoing open heart surgery (n=134). Epicardial fat biopsy and blood were obtained before the procedure under signed consent. Immunohistochemistry, ELISA, multiplex-Luminex, and real-time PCR were used for analyzing protein or mRNA expression levels of CA125 and markers. Results Out of 135, 57 patients suffered heart failure (HF). CA125 was expressed on the epicardium. Their levels were positively related to neutrophils, monocytes, and fibroblasts-related markers and negatively to adiposity markers. Both, plasma and epicardial CA125 levels were increased in HF patients. In this group of patients, epicardial CA125 levels were positively associated with circulating and local neutrophil activity, measured by defensin 3 levels. After testing all markers between women and men in HF patients, we observed similar levels in plasma and epicardial CA125. However, higher plasma and epicardial adiposity markers and lower mesothelial marker ITLN-1 were detected in women than in men. Conclusion CA125 is expressed in epicardial cells and its higher levels in HF might explain the higher detected levels in plasma. Its association with local and peripheral neutrophils-related markers with CA125 suggests its common pathophysiological mechanism in women and men. However, high plasma and epicardial adiposity and low mesothelial marker ITNL-1 in epicardium in women might explain the differential mechanism in HF.