Advances and Challenges in the Hunting Instability Diagnosis of High-Speed Trains.

With the continuous increase in train running speeds and the rapid complexity of operation environments, running stability of the high-speed train is facing significant challenges. A series of abnormal vibration issues, caused by hunting instability, have emerged, including bogie instability alarm, carbody swaying, and carbody shaking, posing a significant threat to the safe and stable operation of high-speed trains. Therefore, the monitoring and diagnosis of hunting instability have become important research topics in rail transit. This review follows the development of fault diagnosis for bogie hunting instability and carbody hunting instability. It first summarizes the existing evaluation standards and innovative diagnostic methods. Due to the current limitation of hunting instability evaluation standards, which can only detect large-amplitude hunting, this paper addresses the gap in evaluation criteria for early-stage, small amplitude hunting instability diagnosis. A thorough overview of the progress made by researches in this field of research is given, emphasizing three primary facets: diagnostic signal sources, diagnostic features, and diagnostic targets. Furthermore, given that existing methods only classify faults into small and large amplitudes, which does not meet the practical need for quickly and accurately identifying fault types and severity during operation, this review introduces existing works on the detailed assessment and fault tracing of hunting instability, as well as the mechanisms underlying its occurrence, with the aim of achieving a comprehensive diagnosis of hunting instability. Finally, the limitations of current methods and the future development trends in hunting instability diagnostics are discussed and summarized. This paper provides readers with a framework for the research process of hunting instability diagnosis, offering valuable references and innovative perspectives for their future research efforts.

Decoding 11-oxygenated androgen synthesis: insights from enzyme gene expression and LC-MS/MS quantification.

BACKGROUND: Adrenal-origin and peripheral tissue-transformed 11-oxygenated androgens are recognized as significant androgens. However, our current understanding of the synthesis of 11-oxygenated androgens, including the organs and cell types involved, remains limited. METHODS: We performed comprehensive analyses on an extensive dataset of normal human tissues, which included bulk RNA data from 30 tissues, single-cell RNA sequencing (scRNA) data from 16 tissues and proteomics data from 29 tissues, to characterize the expression profiles of enzyme-encoding genes. To validate the findings, immunohistochemical and liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques were employed. RESULTS: Our investigation revealed that the gene expression levels of the enzymes HSD11B2 and AKR1C3 were notably elevated in the kidney and intestines. Intriguingly, within these organs, we observed an increasing trend in enzyme expression with age in women, while a decreasing trend was apparent in men. scRNA analysis revealed that HSD11B2 was predominantly expressed in collecting duct principal cells in the kidney, while AKR1C3 was primarily expressed in the proximal tubules. Intriguingly, nearly all epithelial cells in the intestine expressed these key enzymes. Further analysis using LC-MS/MS revealed that the kidney exhibited the highest levels of 11-ketoandrostenedione (11KA4) and 11-ketotestosterone (11KT) among the seven tissues examined, and substantial synthesis of 11KA4 and 11KT was also observed in the intestine. Finally, we developed the TransMap website (http://gxmujyzmolab.cn:16245/TransMap/) to provide comprehensive visualization of all currently available transcriptome data. CONCLUSION: This study offers an overarching perspective on tracing the synthesis of 11-oxygenated androgens in peripheral tissues, thereby providing valuable insights into the potential role of these androgens in humans.

Induction of Pluripotent Stem Cells from Muscle Cells of Large Yellow Croaker (Larimichthys Crocea) Via Electrotransfection.

Induced pluripotent stem cells (iPSCs) are a new type of pluripotent cells reprogrammed from somatic cells back into an embryonic-like pluripotent state of stem cells to study development, disease and potential gene therapies. The induction and regulation mechanisms of iPSCs in fish are still unclear. By using the transfection technique, we investigated the crucial function of the OSKMNL factor co-expression for somatic reprogramming in the muscle cell line of large yellow croaker (Larimichthys crocea) (LYCMs) and successfully established a stable iPSCs line (Lc-OSNL-iPSCs). Stable culturing of iPSCs with high alkaline phosphatase activity and a stable karyotype was achieved. The qRT-PCR and immunofluorescence labeling results revealed that Lc-OSNL-iPSCs displayed a high expression level of pluripotent marker genes such as Nanog, Oct4, and Sox2. There were significant differences between Lc-OSNL-iPSCs, Lc-OSKMNL-iPSCs, and LYCMs, and the expression of several genes in maintaining cell pluripotency was up-regulated when the pluripotency signal pathway of stem cells was activated. The technical system for inducing iPSCs of Larimichthys crocea was constructed in this study. This system can serve as a basic model to understand germ cell differentiation mechanism, gender control, genetics, and breeding of large yellow croaker and a platform for studying iPSCs in fish. Interestingly, the acquired iPSCs serves as a useful material for the directional induction of muscle stem cells, thereby establishing the groundwork for obtaining "artificial fish" in the future.

Human-like adrenal features in Chinese tree shrews revealed by multi-omics analysis of adrenal cell populations and steroid synthesis.

The Chinese tree shrew ( Tupaia belangeri chinensis) has emerged as a promising model for investigating adrenal steroid synthesis, but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans. Here, we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing, spatial transcriptome analysis, mass spectrometry, and immunohistochemistry. We compared the transcriptomes of various adrenal cell types across tree shrews, humans, macaques, and mice. Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans, including CYP11B2, CYP11B1, CYB5A, and CHGA. Biochemical analysis confirmed the production of aldosterone, cortisol, and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands. Furthermore, genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome, primary aldosteronism, hypertension, and related disorders in humans based on genome-wide association studies. Overall, this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland. Our comprehensive results (publicly available at http://gxmujyzmolab.cn:16245/scAGMap/) should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.

Efficient Fault Detection of Rotor Minor Inter-Turn Short Circuit in Induction Machines Using Wavelet Transform and Empirical Mode Decomposition.

This paper introduces a novel approach for detecting inter-turn short-circuit faults in rotor windings using wavelet transformation and empirical mode decomposition. A MATLAB/Simulink model is developed based on electrical parameters to simulate the inter-turn short circuit by adding a resistor parallel to phase "a" of the rotor. The resulting high current in the new phase indicates the presence of the short circuit. By measuring the rotor and stator three-phase currents, the fault can be detected as the currents exhibit asymmetric behavior. Fluctuations in the electromagnetic torque also occur during the fault. The wavelet transform is applied to the rotor current, revealing an effective analysis of sideband frequency components. Specifically, changes in amplitude and frequency, particularly in d7 and a7, indicate the presence of harmonics generated by the inter-turn short circuit. The simulation results demonstrate the effectiveness of wavelet transformation in analyzing these frequency components. Additionally, this study explores the use of empirical mode decomposition to detect faults in their early stages, observing substantial changes in the instantaneous amplitudes of the first three intrinsic mode functions during fault onset. The proposed technique is straightforward and reliable, making it suitable for application in wind turbines with simple electrical inputs.

Screening and Identification of a Prognostic Model of Ovarian Cancer by Combination of Transcriptomic and Proteomic Data.

The integration of transcriptome and proteome analysis can lead to the discovery of a myriad of biological insights into ovarian cancer. Proteome, clinical, and transcriptome data about ovarian cancer were downloaded from TCGA's database. A LASSO-Cox regression was used to uncover prognostic-related proteins and develop a new protein prognostic signature for patients with ovarian cancer to predict their prognosis. Patients were brought together in subgroups using a consensus clustering analysis of prognostic-related proteins. To further investigate the role of proteins and protein-coding genes in ovarian cancer, additional analyses were performed using multiple online databases (HPA, Sangerbox, TIMER, cBioPortal, TISCH, and CancerSEA). The final resulting prognosis factors consisted of seven protective factors (P38MAPK, RAB11, FOXO3A, AR, BETACATENIN, Sox2, and IGFRb) and two risk factors (AKT_pS473 and ERCC5), which can be used to construct a prognosis-related protein model. A significant difference in overall survival (OS), disease-free interval (DFI), disease-specific survival (DSS), and progression-free interval (PFI) curves were found in the training, testing, and whole sets when analyzing the protein-based risk score (p < 0.05). We also illustrated a wide range of functions, immune checkpoints, and tumor-infiltrating immune cells in prognosis-related protein signatures. Additionally, the protein-coding genes were significantly correlated with each other. EMTAB8107 and GSE154600 single-cell data revealed that the genes were highly expressed. Furthermore, the genes were related to tumor functional states (angiogenesis, invasion, and quiescence). We reported and validated a survivability prediction model for ovarian cancer based on prognostic-related protein signatures. A strong correlation was found between the signatures, tumor-infiltrating immune cells, and immune checkpoints. The protein-coding genes were highly expressed in single-cell RNA and bulk RNA sequencing, correlating with both each other and tumor functional states.

Storability and Linear Regression Models of Pericarp Browning and Decay in Fifty Litchi (Litchi chinensis Sonn.) Cultivars at Room Temperature Storage.

The primary cause for the limited shelf life of litchi fruit is rapid pericarp browning and decay. This study aims to evaluate the storability of 50 litchi varieties and establish a linear regression model for pericarp browning and decay based on 11 postharvest physical and chemical indices after 9 days of storage at room temperature. The results indicated that the average value of the browning index and decay rate significantly increased to 3.29% and 63.84% of 50 litchi varieties at day 9, respectively. Different litchi varieties showed different variations in appearance indicators, quality indicators, and physiological indicators. Furthermore, principal component analysis and cluster analysis revealed that Liu Li 2 Hao exhibited the highest resistance to storage, whereas Dong Long Mi Li, Jiao Pan Li, E Dan Li 2 Hao, and Ren Shan Li were not resistant. Stepwise multiple regression analysis further demonstrated that the factors were highly correlated with the decay index, with a partial correlation coefficient of 0.437 between the effective index and the decay index. Therefore, pericarp thickness, relative conductivity, pericarp laccase activity, and total soluble solids were significant indicators for the comprehensive evaluation of litchi browning and decay, and relative conductivity was the significant determinant causing fruit browning. These findings provide a new perspective on the sustainable development of the litchi industry.

Associations of circulation levels of cytokines with birthweight, preterm birth, spontaneous miscarriages, and stillbirth: A Mendelian randomization analysis.

Background: The association between immune imbalances and adverse pregnancy outcomes has been extensive investigated by observational studies, but remain unclear. Thus, this study aimed to establish the causality of the circulation levels of cytokines on adverse pregnancy outcomes, such as offspring's birthweight (BW), preterm birth (PTB), spontaneous miscarriage (SM), and stillbirth (SB). Methods: Two-sample Mendelian randomization (MR) analysis was employed to investigate potential causal relations between 41 cytokines and pregnancy outcomes on the basis of previously published GWAS datasets. Multivariable MR (MVMR) analysis was implemented to investigate the effect of the composition of cytokine networks on the pregnancy outcomes. Potential risk factors were further estimated to explore the potential mediators. Results: Genetic correlation analysis based on large GWAS data sources revealed that genetically predicted MIP1b (ß = -0.027, S.E. = 0.010, p = 0.009) and MCSF (ß = -0.024, S.E. = 0.011, p = 0.029) were associated with reduced offspring's BW, MCP1 (OR: 0.90, 95% CI: 0.83-0.97, p = 0.007) was associated with reduced SM risk, SCF (ß = -0.014, S.E. = 0.005, p = 0.012) associated with decreased number of SB in MVMR. The univariable MR showed that GROa (OR: 0.92, 95% CI: 0.87-0.97, p = 0.004) was associated with decreased PTB risk. Except for the MCSF-BW association, all above associations surpassed the Bonferroni corrected threshold. The MVMR results revealed that MIF, SDF1a, MIP1b, MCSF and IP10 composed cytokine networks, associated with offspring's BW. Risk factors analysis indicated that the above causal associations might be mediated by smoking behaviors. Conclusion: These findings suggest the causal associations of several cytokines with adverse pregnancy outcomes, which were potentially mediated by smoking and obesity. Some of the results did not been corrected through multiple tests and larger samples verification is required in further studies.

Expression pattern analysis of anti-Mullerian hormone in testis development of pearlscale angelfish (Centropyge vrolikii).

In vertebrates, anti-Mullerian hormone (Amh) secreted by Sertoli cells (SC) performs a pivotal function in male sex differentiation. Compared with that of higher vertebrates, the expression pattern of Amh is more diversified in fish. In this study, the full-length complementary DNA (cDNA) of Amh in Centropyge vrolikii (Cv-Amh) was cloned and analysed, which was 2,470 bp, including a 238 bp 5'UTR, a 1,602 bp ORF and a 633 bp 3'UTR; the similarity of Amh between Cv-Amh and other fish is relatively high. The quantitative real-time PCR (qRT-PCR) results of healthy tissues and gonads at sex reversal stages in C. vrolikii showed that the expression level of Amh in the testis was significantly higher than that in other tissues (P < 0.05). Amh was weakly expressed in the vitellogenic stage ovary and perinucleolus stage ovary, but its expression significantly increased in the gonads at the hermaphroditic stage, and finally reached the highest in the pure testis after sexual reversal. The results of in situ hybridization indicated that the positive signal of Amh was strongly concentrated in SCs of testis. After Amh knockdown in the gonads, the effect on sex-related genes was tested using qRT-PCR. Among these, the expression of Dmrt1, Cyp11a, Hsd11b2, Sox8 and Sox9 significantly decreased, whereas that of Cyp19a, Sox4, Foxl2 and Sox3 increased. These results suggested that Amh could be the pivotal gene in reproductive regulation in C. vrolikii, and the data will contribute to sex-related research of C. vrolikii in the future.

Combined Metabolome and Transcriptome Analyses Unveil the Molecular Mechanisms of Fruit Acidity Variation in Litchi (Litchi chinensis Sonn.).

Fruit acidity determines the organoleptic quality and nutritive value of most fruits. In litchi, although the organic acid composition of pulps is known, the molecular mechanisms and genes underlying variation in fruit acidity remain elusive. Herein, developing pulps of two contrasting litchi varieties, Huaizhi (HZ, low-acidity) and Boye_No.8 (B8, high-acidity), were subjected to metabolomics and transcriptomics, and the dynamic metabolome and transcriptional changes were determined. Measurements revealed that the dominant acidity-related organic acid in litchi pulps is malate, followed in low levels by citrate and tartrate. Variation in litchi pulps' acidity is mainly associated with significant differences in malate and citrate metabolisms during fruit development. Malic acid content decreased by 91.43% and 72.28% during fruit ripening in HZ and B8, respectively. The content of citric acid increased significantly in B8, while in HZ it was reduced considerably. Differentially accumulated metabolites and differentially expressed genes analyses unveiled fumarate, succinate, 2-oxoglutarate, GABA (γ-aminobutyric acid), phosphoenolpyruvate, and citrate metabolisms as the key driving pathways of litchi fruits' acidity variation. The drastic malate and citrate degradation in HZ was linked to higher induction of fumarate and GABA biosynthesis, respectively. Thirty candidate genes, including three key genes (LITCHI026501.m2, fumarase; LITCHI020148.m5, glutamate decarboxylase; and LITCHI003343.m3, glutamate dehydrogenase), were identified for functional studies toward genetic modulation of litchi fruit acidity. Our findings provide insights into the molecular basis of acidity variation in litchi and provide valuable resources for fruit quality improvement.

Establishment and characterization of the ovary cell line derived from two-spot puffer Takifugu bimaculatus and its application for gene editing and marine toxicology.

Takifugu bimaculatus is a marine fish with high nutritional value. Its ovary contains tetrodotoxin (TTX) which is a severe neurotoxin that limits its edible value of it. To understand the mechanism of oogenesis and production of TTX in T. bimaculatus, an ovarian cell line named TBO from an adolescent ovary was established. TBO was composed of fibroblast-like cells that expressed the ovarian follicle cells marker gene Foxl2 and highly expressed TTX binding protein 2 (PSTBP2) but did not express the germ cells marker gene Vasa. Therefore, TBO seems to be mainly composed of follicle cells and possibly a small percentage of oocytes. Electroporation was used to successfully transfect the pEGFP-N1 and pNanog-N1 vectors into the TBO cell line with a high transfection efficiency. The morphological changes and survival rates of the exposed cells proved that this cell line was effective for exposure to conotoxins (CTXs), another group of toxins related to food safety. Furthermore, PSTBP2 was knocked out in TBO using CRISPR/Cas9 technology, showing that sgRNA2 could mutate PSTBP2. The results suggested that TBO will be more convenient, efficient, and rapid for reproduction and toxicology investigation, and gene editing. This study laid the groundwork for future research into the fish gonadal cell culture and food-related marine toxins. In conclusion, a cell line has been generated from T. bimaculatus, which might represent a valuable model for fish studies in the fields of toxicology and gene editing.

dmrtb1 is involved in the testicular development in Larimichthys crocea.

In brief: dmrtb1 performs critical functions in sex determination/differentiation and gonadal development in many organisms, but its role in teleost is rarely studied. Through gene cloning, in situ hybridization, and RNA interference technology, the function of dmrtb1 in testicular development of large yellow croaker (Larimichthys crocea) was studied; our study will be helpful in understanding further the molecular regulation mechanism of Lcdmrtb1/Lcdmrt6 in testicular development in L. crocea, and our results enrich the theory of fish dmrts involved in reproductive regulation and provide a new idea for sex control breeding of L. crocea by manipulating reproductive pathway. Abstract: Doublesex- and mab-3-related transcription factor B1 (dmrtb1/dmrt6) belongs to one of the members of DMRT family, which performs critical functions in sex determination and differentiation, gonadal development, and functional maintenance. However, knowledge of its exact mechanism remains unclear in teleost. Very little is known about the role of dmrtb1 in the gonad development of Larimichthys crocea. In this study, a dmrtb1 homolog in L. crocea named as Lcdmrtb1 with the full-length cDNA was isolated and characterized. Except for the conserved DM domain, the other regions had low homology. Of the tissues sampled, Lcdmrtb1 was only found to be highly expressed in the testis. In situ hybridization of testis revealed Lcdmrtb1 in both spermatogonia and spermatocytes. After Lcdmrtb1 interference in the testis cells (LYCT) of L. crocea, the expression levels of Lcdmrtb1 and Lcdmrt1 were significantly decreased; subsequently, testicular cell morphology changed from fibrous to round and their growth rate slowed. Similarly, the expression levels of Lcdmrtb1, Lcdmrt1, sox9a/b, and amh were significantly decreased after RNAi in the testis. Furthermore, it was discovered that the spermatogonia had disappeared, and the Sertoli cells had been reduced. The results of immunohistochemistry showed that the expression of Sox9 protein in the testis was not detected after dmrtb1 was knocked down. These results indicated that the absence of Lcdmrtb1 not only greatly inhibited cell growth and destroyed the morphology of testis cells but also down-regulated Lcdmrt1 expression in the testis. This study will be helpful in understanding further the molecular regulation mechanism of Lcdmrtb1/Lcdmrt6 in testicular development in L. crocea.

Corrigendum: Single-cell transcriptomics reveals the complexity of the tumor microenvironment of treatment-naive osteosarcoma.

[This corrects the article DOI: 10.3389/fonc.2021.709210.].

A spatiotemporal steroidogenic regulatory network in human fetal adrenal glands and gonads.

Human fetal adrenal glands produce substantial amounts of dehydroepiandrosterone (DHEA), which is one of the most important precursors of sex hormones. However, the underlying biological mechanism remains largely unknown. Herein, we sequenced human fetal adrenal glands and gonads from 7 to 14 gestational weeks (GW) via 10× Genomics single-cell transcriptome techniques, reconstructed their location information by spatial transcriptomics. Relative to gonads, adrenal glands begin to synthesize steroids early. The coordination among steroidogenic cells and multiple non-steroidogenic cells promotes adrenal cortex construction and steroid synthesis. Notably, during the window of sexual differentiation (8-12 GW), key enzyme gene expression shifts to accelerate DHEA synthesis in males and cortisol synthesis in females. Our research highlights the robustness of the action of fetal adrenal glands on gonads to modify the process of sexual differentiation.

The molecular regulation mechanism of dmrt1-based on the establishment of the testis cell line derived from two-spot puffer Takifugu bimaculatus.

The establishment of fish cell lines can provide an important in vitro model for developmental biology, pathology, and genetics and also an effective tool to investigate the interactions and related functions of genes. Two-spot puffer Takifugu bimaculatus is a high economic and nutritional value marine fish in Fujian in recent years. Nevertheless, dmrt1 plays a key role in the male differentiation from invertebrates to vertebrates. To understand the molecular regulatory mechanisms of dmrt1 in T. bimaculatus, a testis cell line called TBTc from a juvenile testis of this organism was established with modified Leibovitz's L-15 medium supplemented with 20% FBS, fish serum, embryo extract, and other growth factors. The TBTc with a stable karyotype can be passaged continuously, which was composed of fibroblast-like cells and expressed the marker genes of male-special cells, dmrt1, and amh, and the absence of vasa expression may rule out the possibility of the presence of germ cells. Therefore, TBTc appeared to consist of the mixture of the Sertoli cell and germ cell of the testis. The dmrt1 was significantly expressed in the testes and slightly expressed in the late embryonic development, illustrating that the dmrt1 may participate in the molecular regulation of gonads development and sex differentiation. With the high transfection efficiency of TBTc by electroporation, the cell lines could be used effectively in the study for the expression of exogenous and endogenous genes. Meanwhile, after the knockdown of dmrt1, the morphological changes and survival rates of cells proved that dmrt1 could affect the growth of testicular cells. Furthermore, with the loss of dmrt1, the expression of male-bias genes amh, sox9, and cyp11a was significantly decreased, and the expression of female-bias genes foxl2, sox3, and cyp19a was increased, which suggested that dmrt1 upregulates amh, sox9, and cyp11a and downregulates foxl2, sox3, and cyp19a to participate in the testis development. As a first fish gonadal cell lines of T. bimaculatus, which can be a more convenient, efficient, and rapid model for the investigation of the expression and function of genes, the results will lay a foundation for the next study of the molecular regulation mechanism in gonadal development and sex determination of fish in the future.

Characterization of the transcription factor Sox3 regulating the gonadal development of pearlscale angelfish (Centropyge vrolikii).

As a member of the Sox gene family, Sox3 plays a vital role in gonadal development and gametogenesis. Nevertheless, the exact expression pattern of this gene in fish is still unknown. Here, we identified the Sox3 gene of Centropyge vrolikii, namely, Cv-Sox3. The Cv-Sox3 mRNA expression in the ovary and testis was detected by reverse transcription-polymerase chain reaction (RT-PCR) analysis, and the mRNA expression level of Cv-Sox3 in the ovary in the resting stage was significantly higher than that in other tissues. The phylogenetic tree and alignment of multiple sequences were constructed to analyze the evolutionary relationships of Cv-Sox3. Cv-Sox3 was relatively conserved in the evolution of teleost fish, indicating the importance and similarity of its function. The in situ hybridization results demonstrate that Cv-Sox3 was present in the follicle cells and cytoplasm of oocytes in the ovary of different stages, and the positive signals occurred in germ cells of the testis. After interfering with Cv-Sox3, the growth rate of ovarian cells in culture became slow, and the expression of ovary-bias-related genes Cyp19a and Foxl2 significantly increased. Meanwhile, the expression of testis-bias-related genes Dmrt1, Sox9, Cyp11a, Amh, and Sox8 significantly decreased. These results suggest that Cv-Sox3 gene might be expressed in the germ cells of male and female gonads during gonadal development. This study provides a precise expression pattern of Cv-Sox3 and demonstrates that Cv-Sox3 might play a significant role in the reproductive regulation of C. vrolikii. In this study, Sox3 of C. vrolikii (Cv-Sox3) was cloned to understand the expression pattern in the gonadal development, which is expressed in germ cells, involved in the process of gonadal development. The results demonstrated that Cv-Sox3 may play a significant role in the reproductive regulation of C. vrolikii.

Single-cell transcriptomics reveals cell type diversity of human prostate.

Extensive studies have been performed to describe the phenotypic changes occurring during malignant transformation of the prostate. However, the cell types and associated changes that contribute to the development of prostate diseases and cancer remain elusive, largely due to the heterogeneous composition of prostatic tissues. Here, we conduct a comprehensive evaluation of four human prostate tissues by single-cell RNA sequencing (scRNA-seq) to analyze their cellular compositions. We identify 18 clusters of cell types, each with distinct gene expression profiles and unique features; of these, one cluster of epithelial cells (Ep) is found to be associated with immune function. In addition, we characterize a special cluster of fibroblasts and aberrant signaling changes associated with prostate cancer (PCa). Moreover, we provide insights into the epithelial changes that occur during the cellular senescence and aging. These results expand our understanding of the unique functional associations between the diverse prostatic cell types and the contributions of specific cell clusters to the malignant transformation of prostate tissues and PCa development.

BMP4 preserves the developmental potential of mESCs through Ube2s- and Chmp4b-mediated chromosomal stability safeguarding.

Chemically defined medium is widely used for culturing mouse embryonic stem cells (mESCs), in which N2B27 works as a substitution for serum, and GSK3ß and MEK inhibitors (2i) help to promote ground-state pluripotency. However, recent studies suggested that MEKi might cause irreversible defects that compromise the developmental potential of mESCs. Here, we demonstrated the deficient bone morphogenetic protein (BMP) signal in the chemically defined condition is one of the main causes for the impaired pluripotency. Mechanistically, activating the BMP signal pathway by BMP4 could safeguard the chromosomal integrity and proliferation capacity of mESCs through regulating downstream targets Ube2s and Chmp4b. More importantly, BMP4 promotes a distinct in vivo developmental potential and a long-term pluripotency preservation. Besides, the pluripotent improvements driven by BMP4 are superior to those by attenuating MEK suppression. Taken together, our study shows appropriate activation of BMP signal is essential for regulating functional pluripotency and reveals that BMP4 should be applied in the serum-free culture system.

Characterization of the Nanog gene involved in the gonadal development in pearlscale angelfish (Centropyge vrolikii).

The homeodomain transcription factor Nanog plays a crucial role in the embryonic and gonadal development and the maintenance of embryonic stem cells (ESCs), interacting with transcription factors such as Oct4 and Sox2 in mammals. Nevertheless, its pathways to molecular mechanisms remain unclear as to teleosts. This study investigates the role of the Nanog gene in gonadal development and sex reversal of pearlscale angelfish (Centropyge vrolikii). To understand the expression pattern of gonadal development, we identified the Nanog gene of C. vrolikii, which we named Cv-Nanog. The full-length cDNA sequence of Cv-Nanog was 2,136 bp in length and encoded a homeodomain protein of 436 amino acid residues. The gene structure and western blot prove results that Cv-Nanog was homologous to the Nanog gene of mammalians. The protein sequence comparison demonstrates that the Cv-Nanog shared a high degree of similarity with orthologs from other vertebrates in the conserved homeodomain. The Cv-Nanog gene was substantially expressed in gonads, and the expression was significantly higher in the ovaries than in the testis, according to quantitative real-time PCR (qRT-PCR) and western blot analyses. In situ hybridization reveals that the transcripts were located in the cytoplasm and membrane of the oocytes in the ovaries and testes. The expression of Cv-Nanog mRNA was weak in Sertoli cells but strong in germ cells. After overexpression of Cv-Nanog, the expression levels of pluripotent factors Sox2 and Oct4 increased significantly with 21.5-fold and 12.2-fold, respectively. Simultaneously, the TGF-beta signaling pathway was activated, and the gonadal cell growth was promoted. The expression of ovary-bias genes Cyp19a and Foxl2 was upregulated, and the expression of testis-bias genes Sox9 and Dmrt1 was downregulated to promote ovarian development. These results imply that the Nanog gene might play a crucial role in the process of gonadal development and sexual reversion in C. vrolikii. This study provides new insight to understand the molecular regulatory mechanism of the Nanog gene further and important clues for the future studies in gonadal development.

A Practical Application for Quantitative Brain Fatigue Evaluation Based on Machine Learning and Ballistocardiogram.

Brain fatigue is often associated with inattention, mental retardation, prolonged reaction time, decreased work efficiency, increased error rate, and other problems. In addition to the accumulation of fatigue, brain fatigue has become one of the important factors that harm our mental health. Therefore, it is of great significance to explore the practical and accurate brain fatigue detection method, especially for quantitative brain fatigue evaluation. In this study, a biomedical signal of ballistocardiogram (BCG), which does not require direct contact with human body, was collected by optical fiber sensor cushion during the whole process of cognitive tasks for 20 subjects. The heart rate variability (HRV) was calculated based on BCG signal. Machine learning classification model was built based on random forest to quantify and recognize brain fatigue. The results showed that: Firstly, the heart rate obtained from BCG signal was consistent with the result displayed by the medical equipment, and the absolute difference was less than 3 beats/min, and the mean error is 1.30 ± 0.81 beats/min; secondly, the random forest classifier for brain fatigue evaluation based on HRV can effectively identify the state of brain fatigue, with an accuracy rate of 96.54%; finally, the correlation between HRV and the accuracy was analyzed, and the correlation coefficient was as high as 0.98, which indicates that the accuracy can be used as an indicator for quantitative brain fatigue evaluation during the whole task. The results suggested that the brain fatigue quantification evaluation method based on the optical fiber sensor cushion and machine learning can carry out real-time brain fatigue detection on the human brain without disturbance, reduce the risk of human accidents in human-machine interaction systems, and improve mental health among the office and driving personnel.