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Bone morphogenetic protein 7 (BMP7) belongs to the transforming growth factor β (TGF-β) family, which not only induces cartilage and bone formation, but also regulates eye development and melanoma tumorigenesis in mammals. In teleosts, BMP7 differentiates into two subtypes, bmp7a and bmp7b, which have clearly differentiated structures. To fully understand the functional differentiation of bmp7a and bmp7b in fish species, we successfully constructed bmp7a and bmp7b gene deletion mutants in zebrafish using CRISPR/Cas9-mediated gene editing technology. Our results showed that bmp7a mutation caused abnormal development of the embryo’s dorsal-ventral pattern that led to death; bmp7b mutation induced growth inhibition and increased melanin production in the skin and eye of mutants. Histological analysis revealed that melanin in the retina of the eyes in bmp7b mutants increased, and behavioral observation showed that the vision and sensitivity to food of the mutants were reduced. Transcriptome analysis of the skin and eye tissues showed that the expression changes of wnt7ba and gna14 in bmp7b mutants might promote the increase of melanin. Additionally, the eye transcriptome analysis indicated that changes in the structure of the eyes in bmp7b mutants led to defects in phototransduction, and seven DEGs (rgs9a, rgs9b, rcvrn2, guca1d, grk1b, opn1mw4, and gc2) were identified as key candidate genes that affected the photonic response of the eyes. The study revealed the functional differentiation of bmp7a and bmp7b in teleosts and the first report about the inhibitory effect of bmp7b on melanogenesis may provide useful information for the future research on human melanoma-related diseases.

Intermuscular bone (IB), which occurs only in the myosepta of the lower teleosts, is attracting more attention of researchers due to its particular development and lack of genetic information. MicroRNAs (miRNAs) are emerging as important regulators for biological processes. In the present study, miRNAs from IBs and connective tissue (CT; encircled IBs) from six-month-old Megalobrama amblycephala were characterized and compared. The results revealed the sequences and expression levels of 218 known miRNA genes (belonging to 97 families). Of these miRNAs, 44 known microRNA sequences exhibited significant expression differences between the two libraries, with 24 and 20 differentially-expressed miRNAs exhibiting higher expression in the CT and IBs libraries, respectively. The expressions of 11 miRNAs were selected to validate in nine tissues. Among the high-ranked predicted gene targets, differentiation, cell cycle, metabolism, signal transduction and transcriptional regulation were implicated. The pathway analysis of differentially-expressed miRNAs indicated that they were abundantly involved in regulating the development and differentiation of IBs and CT. This study characterized the miRNA for IBs of teleosts for the first time, which provides an opportunity for further understanding of miRNA function in the regulation of IB development.

Intermuscular bones (IBs) specially exist in lower teleost fish and the molecular mechanism for its development remains to be clarified. In this study, different staining methods and comparative proteomics were conducted to investigate the histological structure and proteome of IB development in Megalobrama amblycephala, including four key IB developmental stages (S1—IBs have not emerged in the tail part; S2—several small IBs started to ossify in the tail part; S3—IBs appeared rapidly; S4—all the IBs appeared with mature morphology). Alcian blue and alizarin red S stained results indicated that IBs were gradually formed from S2 to S4, undergoing intramembranous ossification without a cartilaginous phase. A total of 3368 proteins were identified by using the isobaric tags for relative and absolute quantitation (iTRAQ) approach. Functional annotation showed that proteins which were differentially expressed among stages were involved in calcium, MAPK, Wnt, TGF-β, and osteoclast pathways which played a critical role in bone formation and differentiation. Three proteins (collagen9α1, stat1, tnc) associated with chondrocytes did not exhibit significant changes through S2 to S4; however, proteins (entpd5, casq1a, pvalb, anxa2a, anxa5) which associated with osteoblasts and bone formation and differentiation showed significantly a higher expression level from S1 to S2, as well as to S3 and S4. These further demonstrated that development of IBs did not go through a cartilaginous phase. The inhibitors of TGF-β and Wnt pathways were tested on zebrafish (sp7/eGFP) and the results indicated that both inhibitors significantly delayed IB development. This study provides a comprehensive understanding of the IB ossification pattern, which will help further elucidate the molecular mechanisms for IB development in teleosts.

Hybridization plays an important role in fish breeding. Bream fishes contribute a lot to aquaculture in China due to their economically valuable characteristics and the present study included five bream species, Megalobrama amblycephala, Megalobrama skolkovii, Megalobrama pellegrini, Megalobrama terminalis and Parabramis pekinensis. As maternal inheritance of mitochondrial genome (mitogenome) involves species specific regulation, we aimed to investigate in which way the inheritance of mitogenome is affected by hybridization in these fish species. With complete mitogenomes of 7 hybrid groups of bream species being firstly reported in the present study, a comparative analysis of 17 mitogenomes was conducted, including representatives of these 5 bream species, 6 first generation hybrids and 6 second generation hybrids. The results showed that these 17 mitogenomes shared the same gene arrangement, and had similar gene size and base composition. According to the phylogenetic analyses, all mitogenomes of the hybrids were consistent with a maternal inheritance. However, a certain number of variable sites were detected in all F1 hybrid groups compared to their female parents, especially in the group of M. terminalis (♀) × M. amblycephala (♂) (MT×MA), with a total of 86 variable sites between MT×MA and its female parent. Among the mitogenomes genes, the protein-coding gene nd5 displayed the highest variability. The number of variation sites was found to be related to phylogenetic relationship of the parents: the closer they are, the lower amount of variation sites their hybrids have. The second generation hybrids showed less mitogenome variation than that of first generation hybrids. The non-synonymous and synonymous substitution rates (dN/dS) were calculated between all the hybrids with their own female parents and the results indicated that most PCGs were under negative selection.

The lethal-7 (let-7) miRNA, known as one of the first founding miRNAs, is present in multiple copies in a genome and has diverse functions in animals. In this study, comparative genomic analysis of let-7 miRNAs members in fish species indicated that let-7 miRNA is a sequence conserved family in fish, while different species have the variable gene copy numbers. Among the ten members including let-7a/b/c/d/e/f/g/h/i/j, the let-7a precursor sequence was more similar to ancestral sequences, whereas other let-7 miRNA members were separate from the late differentiation of let-7a. The mostly predicted target genes of let-7 miRNAs are involved in biological process, especially developmental process and growth through Gene Ontology (GO) enrichment analysis. In order to identify the possible different functions of these ten miRNAs in fish growth development, their expression levels were quantified in adult males and females of Megalobrama amblycephala, as well as in 3-, 6-, and 12-months-old individuals with relatively slow- and fast-growth rates. These ten miRNAs had similar tissue expression patterns between males and females, with higher expression levels in the brain and pituitary than that in other tissues (p < 0.05). Among these miRNAs, the relative expression level of let-7a was the highest among almost all the tested tissues, followed by let-7b, let-7d and let-7c/e/f/g/h/i/j. As to the groups with different growth rates, the expression levels of let-7 miRNAs in pituitary and brain from the slow-growth group were always significantly higher than that in the fast-growth group (p < 0.05). These results suggest that let-7 miRNA members could play an important role in the regulation of growth development in M. amblycephala through negatively regulating expression of their target genes.

Coilia nasus, a migratory fish species found in the middle and lower reaches of the Yangtze River and along offshore areas of China, possesses considerable aquacultural and economic potential. However, the species faces challenges due to significant variation in the gonadal development rate among females, resulting in inconsistent ovarian maturation times at the population level, an extended reproductive period, and limitations on fish growth rate due to ovarian prematurity. In the present study, we combined genome-wide association study (GWAS) and comparative transcriptome analysis to investigate the potential single nucleotide polymorphisms (SNPs) and candidate genes associated with population-asynchronous ovarian development in C. nasus. Genotyping of the female population based on whole-genome resequencing yielded 2 120 695 high-quality SNPs, 39 of which were suggestively associated with ovarian development. Of note, a significant SNP peak on LG21 containing 30 suggestively associated SNPs was identified, with cpne5a determined as the causal gene of the peak. Therefore, single-marker and haplotype association analyses were performed on cpne5a, revealing four genetic markers (P<0.05) and seven haplotypes (r2>0.9) significantly associated with the phenotype. Comparative transcriptome analysis of precociously and normally maturing individuals screened out 29 and 426 overlapping differentially expressed genes in the brain and ovary, respectively, between individuals of different body sizes. Integrating the GWAS and transcriptome analysis results, this study identified genes and pathways related to hypothalamic-pituitary-gonadal axis hormone secretion, extracellular matrix, angiogenesis, and gap junctions involved in population-asynchronous ovarian development. The insights gained from this study provide a basis for a deeper understanding of the molecular mechanisms underlying ovarian development in fish and may facilitate the genetic breeding of C. nasus strains exhibiting population-synchronous ovarian development in the future. [ABSTRACT FROM AUTHOR]

The polyoxometalates-based electrochromic energy storage devices (POMs-EESDs) were constructed using P2W17O6111− coated TiO2 as the working electrode and MnO2 film as the counter electrode. The MnO2 films with different thicknesses acted as the charge balancing layer. The device showed bifunctional of enhanced EC and energy storage properties along with high durability and cycle stabilities after the introduction of MnO2 film. The optimistic thickness of MnO2 was found to be 345 nm through balancing the optical modulation and the energy storage properties. For the EC aspect, the optical contrast was enhanced by four times under the potential step of −2.0/1.0 V. The MnO2 film also introduces high capacitance leading to the device can be used as a transparent capacitor. It is the first time to construct high-performance POMs-based EESD only by introducing a simple charge balancing (MnO2) layer in the device. Moreover, the mechanism of the MnO2 layer towards the performance improvement of the POMs-based EESDs was also explained.

Liquefied natural gas (LNG) is a kind of clean energy, and many LNG-powered vessels have been designed and built around the world. However, LNG introduces the potential risk of leakage and explosion accidents; thus, it is necessary to conduct safety assessments on the layout of typical facilities during the initial design stage. In this paper, an on-deck LNG fuel area model is established by employing the computational fluid dynamics (CFD) method according to an LNG-powered Aframax oil tanker. The distribution of potential dangerous areas on the concentration field and temperature field is presented under leakage and diffusion accident conditions with vent masts of different heights. The results show the following: the gas concentration rises rapidly at the initial stage of leakage and tends to stabilize after a certain period; the leakage and diffusion trend of light gas is basically the same as that of heavy gas, and the lowest heavy gas and light gas temperature on the deck between the storage tank and the upper building is -7.9 C and 4.7 °C, respectively, when the venting mast leakage point is at the height of 6 m; and the higher the mast leakage point is, the more safe the ship design. For safety considerations, the height of the venting mast designed in this paper should not be lower than the height of the LNG storage tank, which is 10 m.

Objective: We aimed to explore key immune-related long non-coding RNAs (lncRNAs) and their effect in predicting of prognosis of triple-negative breast cancer (TNBC). Methods: Four datasets of TNBC were downloaded from TCGA and GEO databases. ImmPort database was utilized to acquire immune-related mRNAs. Single sample gene set enrichment analysis (ssGSEA) and correlation analysis were utilized to screen immune-related lncRNAs. Univariate and multivariate Cox regression analyses were utilized to screen independent prognostic lncRNAs to establish prognostic risk model, and the model was evaluated by survival analysis and nomogram. Differential functions and immune cells infiltration in high and low risk group were analyzed by Gene set variation analysis and ssGSEA. Finally, competitive endogenous RNAs was constructed. Results: We revealed 62 immune-related lncRNAs, of which four lncRNAs (RP11-890B15.3, RP11-1024P17.1, MFI2-AS1 and RP11-180N14.1) had independent prognostic value. These four lncRNAs-based prognostic risk model could stratify the TNBC patients into high and low risk groups, and patients with high risk displayed unfavorable outcomes. Nomogram indicated that the prognostic model could indicate TNBC patients survival very well. We further found that high risk group showed significantly enriched immune response to tumor cell, humoral immune response and high infiltrating abundance of regulatory T cell, Type 2 T helper cell, eosinophil, etc. LncRNAs RP11-180N14.1, RP11-1024P17.1 and RP11-890B15.3 regulated more mRNAs by targeting various miRNAs. While MFI2-AS1 regulated three mRNAs by sponging miR-3150a-3p. Conclusion: These four lncRNAs were prognostic biomarkers and could be possible therapeutic targets in TNBC.

ObjectiveTo investigate the effect of BMI in male and/or female partners on embryo development and clinical pregnancy outcome during ART.MethodsData of 11,130 cycles between January 2018 and December 2020 were retrospectively analyzed. They were divided into Group A, B, C, and D based on couples’ BMI values, also were divided into Group I, II, III and IV in IVF cycles and Group i, ii, iii, and iv in ICSI cycles. After grouping, inter-group indicators comparisons and logistic regression analysis were performed.ResultsIn IVF cycles, CPR in Group I and Group III were higher than Group IV. In Group III, it was higher than Group II. The AR in Group IV was higher, but the LBR was lower than Group I, Group II, and Group III. Logistic regression analysis results suggested that AR in Group IV was higher than that in Group I in IVF cycles, whereas LBR was lower.In ICSI cycles, high-quality embryo rate in Group i and Group ii were both higher than that in Group iii and Group iv. The CPR in Group i was higher than Group ii and Group iv, and in Group iii was higher than Group ii and Group iv. The AR in Group i was lower than Group iii and Group iv, and AR in Group ii was lower than Group iv. LBR, in Group I it was higher than Group ii, Group iii, and Group iv. Logistic regression analysis results suggested CPR in Group ii was significantly lower than that in Group i. AR in Group iii was considerably higher than that in Group i. LBR in Group ii and Group iv were significantly lower than that in Group i.ConclusionFemale higher BMI was not conducive to the formation of high-quality embryos in ICSI cycle. Female and/or male BMI affected AR and LBR more than CPR not only in IVF cycles, but also in ICSI cycles.

An elite backcrossed inbred line Z550 with increased grains per panicle was identified from advanced backcrosses between Nipponbare and Xihui 18 by simple sequence repeat (SSR) marker-assisted selection (MAS). Z550 carries 13 substitution segments distributed on chromosomes 1, 6, 7, 8, 9, 10, and 12, with an average substitution length of 1.68 Mb. Compared with the Nipponbare parental line, plant height, panicle length, spikelets per panicle, grains per panicle, and grain weight for Z550 were significantly increased. While the grain width of Z550 was significantly narrower, and the seed setting ratio (81.43%) was significantly lower than that of Nipponbare, it is still sufficient for breeding purposes. Quantitative trait loci (QTLs) mapping for important agronomic traits was conducted with the F2 population derived from Nipponbare crossed with Z550 using the restricted maximum likelihood (REML) method. A total of 16, including 12 previously unreported QTLs were detected, with contribution rates ranging from 1.46 to 10.49%. Grains per panicle was controlled by 8 QTLs, 5 of which increased number of grains whereas 3 decreased it. qGPP-1, with the largest contribution (10.49%), was estimated to increase grains per panicle by 30.67, while qGPP-9, with the minimum contribution rate (2.47%), had an effect of increasing grains per panicle by 15.79. These results will be useful for further development of single segment substitution lines with major QTLs, and for research of their molecular functions via QTL cloning.

In order to analyze the dynamic fracture responses of surrounding rocks in underground space to cyclic impact loads, a series of dynamic compressive tests were conducted using hollow cylindrical and intact sandstone specimens under confining pressures corresponding to 5, 10, and 12 MPa, and the hollow cylindrical sandstone were subject to radial gradient stresses. In the study, the impact loads were applied via a large diameter split Hopkinson pressure bar (SHPB). The results indicated that the hollow cylindrical sandstone exhibited a lower dynamic strength and larger critical strain under radial gradient stress as compared to intact sandstone. The dynamic strength and critical strain of all rock specimens increased significantly with the increase of the number of impact loading, whereas the cumulative absorption energy decreased. Under impact loads with velocity of 11.89 m/s, the cumulative absorption energy increased with the increase of confining pressure. The impact load was a complex process of repeated tension and compression which easily affected the hollow cylindrical sandstone in the radial direction during cyclical impact loading, and the characteristics of zonal disintegration indicated dominant tensile failure and local shear failure. However, a compression-shear failure mode was observed under confining pressure for intact sandstone.

Introduction: Disruption to white matter pathways is an important contributor to the pathogenesis of Parkinson's disease. Fixel-based analysis has recently emerged as a useful fiber-specific tool for examining white matter structure. In this longitudinal study, we used Fixel-based analysis to investigate white matter changes occurring over time in patients with Parkinson's disease. Methods: Fifty patients with idiopathic Parkinson's disease (27 men and 23 women; mean age: 61.8 ± 6.1 years), were enrolled. Diffusion-weighted imaging and clinical examinations were performed at three different time points (baseline, first follow-up [after a mean of 24±2 months], and second follow-up [after a mean of 40 ± 3 months]). Additional 76 healthy control subjects (38 men and 38 women; mean age: 62.3 ± 5.5 years) were examined at baseline. The following fixel-based metrics were obtained: fiber density (FD), fiber bundle cross-section (FC), and a combined measure of both (FDC). Paired comparisons of metrics between three different time points were performed in patients. Linear regression was implemented between longitudinal changes of fixel-based metrics and the corresponding modifications in clinical parameters. A family-wise error corrected p

AIM:To investigate the effect of onset time(T)for macula choroidal thickness(CT)in myopia patient. METHODS:A prospective cohort study was designed.One hundred and twenty-two myopia patients(244 eyes; 67 male and 55 female; aged 30～41 years, mean 35.1±4.6 years old)who received preoperative examinations from March 2014 to April 2015 were recruited in this study. The patients were divided into three groups according to onset time(T):group A(T≤5a), group B(5aF=1.56,P>0.05),age(F=2.13,P>0.05),best corrected visual acuity(BCVA, F=1.41,P>0.05),corneal curvature(F=1.65,P>0.05)and axial length(F=1.89,P>0.05)among the three groups. The choroid in macular region was measured by enhanced depth imaging(EDI)using spectral-domain optical coherence tomography(SD-OCT). This study recorded the CT at subfoveal(SFCT), 1mm at temporal(T1mm), nasal(N1mm), superior(S1mm)and inferior(I1mm)to the fovea and 3mm temporal(T3mm), nasal(N3mm), superior(S3mm)and inferior(I3mm)to the fovea, respectively. The differences of CT at the same position among the three groups were analyzed.RESULTS:The mean SFCT for group A,B,C were 238.32±57.95μm, 230.58±67.21μm, 221.63±62.37μm respectively in this study. The CT was found no significant difference in different locations except N3mm(tA-B=4.34,P3mm(tB-C=7.61,P3mm(t=0.76,P>0.05)between group A and C. Significant difference was found at N3mm(tA-B=4.31,t B-C=7.59,tA-C=12.18; PCONCLUSION:The choroidal thickness decreases as the myopia onset time is earlier, especially at nasal.

MicroRNAs (miRNAs) are important regulators of multiple cellular processes, and the deregulation of miRNA is a common event in diverse human diseases, particularly cancer. However, the mechanisms underlying the relationship between disordered miRNA expression and tumorigenesis have remained largely unknown. In this study, we demonstrated the down-regulation of miR-125b in hepatocellular carcinoma (HCC) tissues and HCC cell lines by Northern blot and quantitative RT-PCR analyses. The ectopic expression of miR-125b reduced the cellular proliferation and cell cycle progression of HCC cells by targeting Mcl-1 and IL6R. Furthermore, the miR-125b-induced inhibition of cell proliferation was rescued by the expression of Mcl-1 or IL6R variants that lacked 3' UTRs. Thus, this study revealed the differential expression of miR-125b in HCC cells and elucidated its potential as a tumor suppressor in HCC development.