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.

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.

Recognition of H3K9 methylation by GLP is required for efficient establishment of H3K9 methylation, rapid target gene repression, and mouse viability.

GLP and G9a are major H3K9 dimethylases and are essential for mouse early embryonic development. GLP and G9a both harbor ankyrin repeat domains that are capable of binding H3K9 methylation. However, the functional significance of their recognition of H3K9 methylation is unknown. Here, we report that the histone methyltransferase activities of GLP and G9a are stimulated by neighboring nucleosomes that are premethylated at H3K9. These stimulation events function in cis and are dependent on the H3K9 methylation binding activities of ankyrin repeat domains of GLP and G9a. Disruption of the H3K9 methylation-binding activity of GLP in mice causes growth retardation of embryos, ossification defects of calvaria, and postnatal lethality due to starvation of the pups. In mouse embryonic stem cells (ESCs) harboring a mutant GLP that lacks H3K9me1-binding activity, critical pluripotent genes, including Oct4 and Nanog, display inefficient establishment of H3K9me2 and delayed gene silencing during differentiation. Collectively, our study reveals a new activation mechanism for GLP and G9a that plays an important role in ESC differentiation and mouse viability.

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.

The reference genome and transcriptome of the limestone langur, Trachypithecus leucocephalus, reveal expansion of genes related to alkali tolerance.

BACKGROUND: Trachypithecus leucocephalus, the white-headed langur, is a critically endangered primate that is endemic to the karst mountains in the southern Guangxi province of China. Studying the genomic and transcriptomic mechanisms underlying its local adaptation could help explain its persistence within a highly specialized ecological niche. RESULTS: In this study, we used PacBio sequencing and optical assembly and Hi-C analysis to create a high-quality de novo assembly of the T. leucocephalus genome. Annotation and functional enrichment revealed many genes involved in metabolism, transport, and homeostasis, and almost all of the positively selected genes were related to mineral ion binding. The transcriptomes of 12 tissues from three T. leucocephalus individuals showed that the great majority of genes involved in mineral absorption and calcium signaling were expressed, and their gene families were significantly expanded. For example, FTH1 primarily functions in iron storage and had 20 expanded copies. CONCLUSIONS: These results increase our understanding of the evolution of alkali tolerance and other traits necessary for the persistence of T. leucocephalus within an ecologically unique limestone karst environment.

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.

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.

Comparison of differential expression genes in ovaries and testes of Pearlscale angelfish Centropyge vrolikii based on RNA-Seq analysis.

Pearlscale angelfish Centropyge vrolikii is a kind of protogynous hermaphrodite fish with a natural sexual reversion. Under appropriate social conditions, a female fish can transform into a male fish spontaneously. It is an important prerequisite for artificial breeding to understand the process of its gonadal development and sexual reversion. Gonadal development is regulated by many sex-related genes. In this study, we used unreferenced RNA-Seq technology to sequence the ovary at the perinucleolus stage (OII), ovary at the yolk vesicle stage (OIV),IV and testis (T), respectively; screened the gonadal differential expression genes (DEGs); and analyzed the expression of these genes in different developmental stages of ovary and different sex gonads. The results showed that a total of 142,589 all-unigene samples were assembled, and gene annotation was performed by COG, GO, KEGG, KOG, Pfam, Swissprot, eggNOG, and NR functional database. Comparative analysis revealed that there were 1919 genes that were up-regulated and 1289 genes were down-regulated in comparison to OIV vs OII, while there were 3653 genes that were up-regulated and 2874 genes were down-regulated in comparison of OIV vs T, there were 3345 genes that were up-regulated and 2995 genes were down-regulated in comparison of the OII vs the T. At the same time, the results verified by RT-qPCR were consistent with the variation trend of transcriptome data. Among the results, amh, sox9b, dmrt1, dmrt2, cyp11a, cyp17a, and cyp19a were significantly expressed in the testes, while sox3, sox4, sox11, sox17, and hsd3b7 were significantly expressed in the ovaries. And, the expression of the amh, sox9b, dmrt2, and dmrt1 were low in the OII and OIV, while significantly increased during the ovotestis in the hermaphroditic period (OT), and finally reached the highest level in pure testis after sex reversal. The expression of sox3, sox4, hsd3b7, sox11, and sox17 was significantly reduced during the hermaphroditic period (OT). These results suggested that these genes may play an important role in the process of sex reversal. This study is helpful to further understand the molecular regulation mechanism of gonadal development and sexual reversion in Pearlscale angelfish and also provide important clues for future studies.

The expression and biological function of chemokine CXCL12 and receptor CXCR4/CXCR7 in placenta accreta spectrum disorders.

OBJECTIVES: Investigation of mechanism related to excessive invasion of trophoblast cells in placenta accreta spectrum disorders (PAS) provides more strategies and ideas for clinical diagnosis and treatment. MATERIALS AND METHODS: Blood and placental samples were collected from included patients. The distribution and expression of CXCL12, CXCR4 and CXCR7 proteins in the paraffin of placental tissue in the included cases were analysed, and we analyse the downstream pathways or key proteins involved in cell invasion. RESULTS: Firstly, our results determined that CXCL12 and CXCR4/CXCR7 were increased in extravillous trophoblastic cell (CXCL12: P < .001; CXCR4: P < .001; CXCR7: P < .001), and the expression levels were closely related to the invasion depth of trophoblastic cells. Secondly, CXCL12 has the potential to become a biochemical indicator of PAS since the high expression of placental trophoblast CXCL12 may be an important source of blood CXCL12. Using lentivirus-mediated RNA interference and overexpression assay, it was found that both chemokine CXCL12 and receptor CXCR4/CXCR7 are associated with regulation of trophoblast cell proliferation, migration and invasion. Further results proved that through the activating the phosphorylation and increasing the expression of MLC and AKT proteins in the Rho/rock, PI3K/AKT signalling pathway, CXCL12, CXCR4 and CXCR7 could up-regulate the expression of RhoA, Rac1 and Cdc42 proteins to promote the migration and invasion of extravillous trophoblastic cell and ultimately formate the placenta accrete compare to the normal placenta. CONCLUSIONS: Our research proved that trophoblasts may contribute to a PAS-associated increase in CXCL12 levels in maternal blood. CXCL12 is not only associated with biological roles of PAS, but may also be potential for prediction of PAS.

The impact of mental fatigue on brain activity: a comparative study both in resting state and task state using EEG.

BACKGROUND: Mental fatigue is usually caused by long-term cognitive activities, mainly manifested as drowsiness, difficulty in concentrating, decreased alertness, disordered thinking, slow reaction, lethargy, reduced work efficiency, error-prone and so on. Mental fatigue has become a widespread sub-health condition, and has a serious impact on the cognitive function of the brain. However, seldom studies investigate the differences of mental fatigue on electrophysiological activity both in resting state and task state at the same time. Here, twenty healthy male participants were recruited to do a consecutive mental arithmetic tasks for mental fatigue induction, and electroencephalogram (EEG) data were collected before and after each tasks. The power and relative power of five EEG rhythms both in resting state and task state were analyzed statistically. RESULTS: The results of brain topographies and statistical analysis indicated that mental arithmetic task can successfully induce mental fatigue in the enrolled subjects. The relative power index was more sensitive than the power index in response to mental fatigue, and the relative power for assessing mental fatigue was better in resting state than in task state. Furthermore, we found that it is of great physiological significance to divide alpha frequency band into alpha1 band and alpha2 band in fatigue related studies, and at the same time improve the statistical differences of sub-bands. CONCLUSIONS: Our current results suggested that the brain activity in mental fatigue state has great differences in resting state and task state, and it is imperative to select the appropriate state in EEG data acquisition and divide alpha band into alpha1 and alpha2 bands in mental fatigue related researches.

Evidence of virus-responsive pathways in response to poly I: C challenge in a muscle cell line derived from large yellow croaker Larimichthys crocea.

In this study, a new continuous muscle cell line, LYCMS (large yellow croaker muscle cell line), derived from the muscle tissue of larva of large yellow croaker (Larimichthys crocea) was developed with modified DMEM/F12 medium at 27 °C. The muscle cell line could be passaged at different ratios for different growth rates. Karyotype analysis showed that a large proportion of LYCMS cells had 48 chromosomes. The proliferation of LYCMS cell line could be affected by mammalian growth factors such as human basic fibroblast growth factor (b-FGF), epidermal growth factor (EGF), and hepatocyte growth factor (HGF). GFP expression experiments indicated that the LYCMS cell line could be used for exogenous genes' expression. Different virus response-related genes tested in this study showed diverse change types in expression before and after (0-24 h) polycytidylic acid (poly I: C) challenge of LYCMS cells. This is the first study of virus response signaling pathways of large yellow croaker based on the muscle cell line. The results showed that compared with the in vivo experiments, the use of the LYCMS cell line for immune research is more convenient, efficient, and rapid. By using this model, we demonstrated that MDA5-IPS1-TRAF6-NFκB-cytokines, MDA5-IPS1-TRAF3-IRF3-interferon or TLR22-TRIF-IRF3-interferon, TLR8-MyD88-NFκB-cytokines, and TLR3-TRIF-IRF3-interferon pathways were able to response to poly I: C challenge in the muscle cell line of large yellow croaker.

Mental Fatigue Has Great Impact on the Fractal Dimension of Brain Functional Network.

Mental fatigue has serious negative impacts on the brain cognitive functions and has been widely explored by the means of brain functional networks with the neuroimaging technique of electroencephalogram (EEG). Recently, several researchers reported that brain functional network constructed from EEG signals has fractal feature, raising an important question: what are the effects of mental fatigue on the fractal dimension of brain functional network? In the present study, the EEG data of alpha1 rhythm (8-10 Hz) at task state obtained by a mental fatigue model were chosen to construct brain functional networks. A modified greedy colouring algorithm was proposed for fractal dimension calculation in both binary and weighted brain functional networks. The results indicate that brain functional networks still maintain fractal structures even when the brain is at fatigue state; fractal dimension presented an increasing trend along with the deepening of mental fatigue fractal dimension of the weighted network was more sensitive to mental fatigue than that of binary network. Our current results suggested that mental fatigue has great regular impacts on the fractal dimension in both binary and weighted brain functional networks.

16S rRNA Gene-Based Analysis Reveals the Effects of Gestational Diabetes on the Gut Microbiota of Mice During Pregnancy.

Hyperglycemia is one of the metabolic characteristics of gestational diabetes mellitus (GDM). Considering that GDM is able to cause changes in the gut bacterial community and function in the mother's intestine compared with healthy pregnant women, we aimed to clarify the correlation between hyperglycemia and gut microbiota in a GDM mouse model. Mice were divided into four groups: CE0, GDME0, CE18, and GDME18. C and GDM represent the control (C) and GDM groups, while E0 and E18 represent early or late trimesters of embryo day 0 or 18, respectively. GDM mouse models were created by injecting streptozocin on embryo day 0. The gut microbiota was characterized using the Illumina MiSeq platform targeting the V3-4 region of the 16S rRNA. Operational taxonomic unit analysis revealed a significant difference between CE18 and CE0, in which Akkermansia and Prevotellaceae were more abundant in the early trimester group, CE0. Moreover, the Clostridiales_vadinBB60 group was more abundant, while Parasutterella was much lower in GDME18 than in CE18. The gut microbiota community structure correlated with the GDM state, and LEfSe and molecular ecological network analysis further confirmed these diversities. Our research shows that changes in the community structure of the gut microbiota from the early to late trimester correlate with the GDM state. Changes in the abundance of the probiotic bacteria Akkermansia, Prevotellaceae, and Parasutterella may be involved in the GDM state.

A phenomics-based approach for the detection and interpretation of shared genetic influences on 29 biochemical indices in southern Chinese men.

BACKGROUND: Phenomics provides new technologies and platforms as a systematic phenome-genome approach. However, few studies have reported on the systematic mining of shared genetics among clinical biochemical indices based on phenomics methods, especially in China. This study aimed to apply phenomics to systematically explore shared genetics among 29 biochemical indices based on the Fangchenggang Area Male Health and Examination Survey cohort. RESULT: A total of 1999 subjects with 29 biochemical indices and 709,211 single nucleotide polymorphisms (SNPs) were subjected to phenomics analysis. Three bioinformatics methods, namely, Pearson's test, Jaccard's index, and linkage disequilibrium score regression, were used. The results showed that 29 biochemical indices were from a network. IgA, IgG, IgE, IgM, HCY, AFP and B12 were in the central community of 29 biochemical indices. Key genes and loci associated with metabolism traits were further identified, and shared genetics analysis showed that 29 SNPs (P < 10- 4) were associated with three or more traits. After integrating the SNPs related to two or more traits with the GWAS catalogue, 31 SNPs were found to be associated with several diseases (P < 10- 8). Using ALDH2 as an example to preliminarily explore its biological function, we also confirmed that the rs671 (ALDH2) polymorphism affected multiple traits of osteogenesis and adipogenesis differentiation in 3 T3-L1 preadipocytes. CONCLUSION: All these findings indicated a network of shared genetics and 29 biochemical indices, which will help fully understand the genetics participating in biochemical metabolism.

eQTL analysis from co-localization of 2739 GWAS loci detects associated genes across 14 human cancers.

Genetic variants can predict other "linked" diseases because alterations in one or more genes in vivo may affect relevant phenotype properties. Our study systematically explored the pan-cancer common gene and cancer type-specific genes based on GWAS loci and TCGA data of multiple cancers. It was found that there were 17 SNPs were significantly associated with the expression of 18 genes. Associations between the 18 cis-regulatory genes and the pathologic stage of each cancer showed that MYL2 and PTGFR in HNSC, 4 genes (F8, SATB2, G6PD and UGT1A6) in KIRP, 3 genes (CHMP4C, MAP3K1 and MECP2) in LUAD were all strongly associated with cancer stage levels. Additionally, the survival association analysis showed that SATB2 was correlated with HNSC survival, and MPP1 was strongly associated with the survival of SARC. This study will shed light on the biological pathways involved in cancer-genetic associations, and has the potential to be applied to the predictions of the risk of cancers developing in healthy individuals.

Chronic prostatitis alters the prostatic microenvironment and accelerates preneoplastic lesions in C57BL/6 mice.

BACKGROUND: Chronic prostatitis has been supposed to be associated with preneoplastic lesions and cancer development. The objective of this study was to examine how chronic inflammation results in a prostatic microenvironment and gene mutation in C57BL/6 mice. METHODS: Immune and bacterial prostatitis mouse models were created through abdominal subcutaneous injection of rat prostate extract protein immunization (EAP group) or transurethral instillation of uropathogenic E. coli 1677 (E. coli group). Prostate histology, serum cytokine level, and genome-wide exome (GWE) sequences were examined 1, 3, and 6 months after immunization or injection. RESULT: In the EAP and E. coli groups, immune cell infiltrations were observed in the first and last months of the entire experiment. After 3 months, obvious proliferative inflammatory atrophy (PIA) and prostatic intraepithelial neoplasia (PIN) were observed accompanied with fibrosis hyperplasia in stroma. The decrease in basal cells (Cytokeratin (CK) 5+/p63+) and the accumulation of luminal epithelial cells (CK8+) in the PIA or PIN area indicated that the basal cells were damaged or transformed into different luminal cells. Hic1, Zfp148, and Mfge8 gene mutations were detected in chronic prostatitis somatic cells. CONCLUSION: Chronic prostatitis induced by prostate extract protein immunization or E. coli infection caused a reactive prostatic inflammation microenvironment and resulted in tissue damage, aberrant atrophy, hyperplasia, and somatic genome mutation.

Effects of Mental Fatigue on Small-World Brain Functional Network Organization.

Brain functional network has been widely applied to investigate brain function changes among different conditions and proved to be a small-world-like network. But seldom researches explore the effects of mental fatigue on the small-world brain functional network organization. In the present study, 20 healthy individuals were included to do a consecutive mental arithmetic task to induce mental fatigue, and scalp electroencephalogram (EEG) signals were recorded before and after the task. Correlations between all pairs of EEG channels were determined by mutual information (MI). The resulting adjacency matrices were converted into brain functional networks by applying a threshold, and then, the clustering coefficient (C), characteristic path length (L), and corresponding small-world feature were calculated. Through performing analysis of variance (ANOVA) on the mean MI for every EEG rhythm, only the data of α1 rhythm during the task state were emerged for the further explorations of mental fatigue. For a wide range of thresholds, C increased and L and small-world feature decreased with the deepening mental fatigue. The pattern of the small-world characteristic still existed when computed with a constant degree. Our present findings indicated that more functional connectivities were activated at the mental fatigue stage for efficient information transmission and processing, and mental fatigue can be characterized by a reduced small-world network characteristic. Our results provide a new perspective to understand the neural mechanisms of mental fatigue based on complex network theories.

Thermal Stability Optimization of the Luojia 1-01 Nighttime Light Remote-Sensing Camera's Principal Distance.

The instability of the principal distance of the nighttime light remote-sensing camera of the Luojia 1-01 satellite directly affects the geometric accuracy of images, consequently affecting the results of analysis of nighttime light remote-sensing data. Based on the theory of optical passive athermal design, a mathematical model of optical-passive athermal design for principal distance stabilization is established. Positive and negative lenses of different materials and the mechanical structures of different materials are matched to optimize the optical system. According to the index requirements of the Luojia 1-01 camera, an image-telecentric optical system was designed under the guidance of the established mathematical model. In the temperature range of -20 °C to +60 °C, the principal distance of the system changes from -0.01 µm to +0.28 µm. After on-orbit testing, the geometric accuracy of the designed nighttime light remote-sensing camera is better than 0.20 pixels and less than index requirement of 0.3 pixels, which indicating that the principal distance maintains good stability on-orbit and meets the application requirements of nighttime light remote sensing.