Vitamin D3 regulates NSUN2 expression and inhibits melanoma cell proliferation and migration.

The activated form of vitamin D3 [1,25-dihydroxyvitamin D3; 1,25(OH)2D3] is important for various physiological processes, such as bone mineralization and calcium metabolism, and plays an anticancer role in numerous cancers as well. Its role in melanoma cells has yet to be proven. NOP2/Sun RNA methyltransferase 2 (NSUN2) is a typical RNA methyltransferase and is highly expressed in a variety of cancer cells. However, the molecular mechanisms underlying the role of 1,25(OH)2D3 and NSUN2 in melanoma cells remain largely unknown. The current study showed that 1,25(OH)2D3 could significantly and specifically inhibit the proliferation and migration of melanoma B16 cells. 1,25(OH)2D3 enhances vitamin D receptor expression while simultaneously reducing NSUN2 expression in melanoma cells. Subsequently, knockdown of NSUN2 suppressed B16 cell proliferation and migration. RNA-Seq results illuminated that DNA replication, cell proliferation and cell cycle pathways were enriched, and genes promoting these pathways were reduced after knocking down Nsun2. Dual-luciferase reporter assays showed that 1,25(OH)2D3 downregulated reporter gene expression was controlled by the Nsun2 promoter. The results suggest that 1,25(OH)2D3 binds to the vitamin D response element located upstream of the Nsun2 promoter to downregulate Nsun2 transcription activity and then affects the gene expression pattern related to cell proliferation and the cell cycle, thereby restraining B16 cell proliferation and migration.

Transcriptomic analysis of thigh muscle of Lueyang black-bone chicken in free-range and caged feeding.

Lueyang black-bone chicken is free-range in hilly areas and has unique genetic characteristics and excellent muscle quality. However, the molecular mechanisms of breeding mode influence growth and meat quality in Lueyang black-bone chicken are still unclear. Here we analyzed the meat quality and transcriptome data of thigh muscle by comparing free-range and caged modes at the age of 60 and 120 days in Lueyang black-boned chicken. The results demonstrated that the free-range mode could improve the pH value, tenderness, and reducing the hardness of the thigh muscle. Intramuscular fat (IMF) content of the thigh muscle was markedly higher in the caged chickens compared with free-range animals at the age of 60 days. Functional pathway analysis illustrated that tight junction signaling was associated with the formation of slow-twitch fibers in free-range chickens at age of 120 days. All research data proved that the free-range mode could improve muscle quality by promoting the formation of slow-twitch fibers and IMF in thigh muscle in Lueyang black-bone chicken. Based on the animal benefit and healthy, the free-range feeding should be considered during the breeding process of broiler chicken. The results provide good knowledge of the functional molecular mechanisms associated with muscle quality in Lueyang black-bone chicken.

Phosphorylated Adapter RNA Export Protein Is Methylated at Lys 381 by an Methyltransferase-like 21C (METTL21C).

Methyltransferase-like 21C (METTL21C) is a member of the non-histone methyltransferase superfamily, which mainly mediates the methylation of lysine (Lys) residues. The main types of modification are Lys dimethylation and trimethylation. However, at present, most of the studies on METTL21C are focused on humans and mice, and there are few reports on poultry. Therefore, chicken embryo fibroblasts (DF-1) were selected as the object of study. To explore the function of chicken METTL21C (chMETTL21C) in the proliferation of DF-1 cells, flow cytometry and qPCR were used to detect the function of chicken METTL21C in the proliferation of DF-1 cells. The results showed that overexpression of METTL21C blocked the cell cycle in the G1max S phase, thus inhibiting cell proliferation. In addition, based on proteomic analysis, stable overexpression of METTL21C may inhibit the proliferation of DF-1 cells by mediating lysine trimethylation of proliferation-related proteins phosphorylated adapter RNA export protein (PHAX), nucleoside diphosphate kinases (NDPKs), eukaryotic transcription extension factor (eukaryotic translation elongation factor 1A,e EF1A), and inversin (Invs). Through immunoprecipitation (co-IP) and liquid chromatography-mass spectrometry (LC-MS/MS) analysis, METTL21C-mediated PHAX Lys-381 methylation was confirmed to be involved in the regulation of DF-1 cell proliferation. The results of this study provide a reference for analyzing the methylation function of METTL21C and the mechanism of regulating the growth and development of chicken cells.

Effects of Resveratrol on Mouse B16 Melanoma Cell Proliferation through the SHCBP1-ERK1/2 Signaling Pathway.

Melanoma originates from the malignant mutational transformation of melanocytes in the basal layer of the epidermal layer of the skin. It can easily spread and metastasize in the early stage, resulting in a poor prognosis. Therefore, it is particularly important to find effective antitumor adjuvant drugs to inhibit the occurrence and development of melanoma. In this study, we found that resveratrol, a polyphenolic compound from grape plants, can significantly inhibit the proliferation, colony formation and migration of mouse melanoma B16 cells. Notably, resveratrol was also found to inhibit the expression of SHCBP1 in B16 cells. Transcriptional analysis and cellular studies showed that SHCBP1 can activate the MAPK/ERK signaling pathway to regulate cyclin expression and promote the G1/S phase transition of the cell cycle by upregulating ERK1/2 phosphorylation levels. Resveratrol further downregulates the phosphorylation level of ERK1/2 by inhibiting SHCBP1 expression, thus inhibiting tumor cell proliferation. In conclusion, resveratrol inhibits the proliferation of B16 cells by regulating the ERK1/2 signaling pathway through SHCBP1. As an upstream protein of the ERK1/2 signaling pathway, SHCBP1 may be involved in the process of resveratrol-mediated inhibition of tumor cell proliferation.

Human sperm tsRNA as potential biomarker and therapy target for male fertility.

Infertility caused by male factors is routinely diagnosed by assessing traditional semen parameters. Growing evidence has indicated that the tsRNAs carried in sperm act as epigenetic factors and potential biomarkers for the assessment of sperm quality. We recently demonstrated that tRNAGln-TTG derived small RNAs played notable roles in the first cleavage of a porcine embryo. However, the function of human sperm tRNAGln-TTG derived small RNAs as a diagnostic biomarker and its role in early embryo development remains unclear. In this study, we found that human sperm tRNAGln-TTG derived small RNAs were highly associated with sperm quality. By microinjecting the antisense sequence into human tripronuclear (3PN) zygotes followed by single-cell RNA-sequencing, we found that human sperm tRNAGln-TTG derived small RNAs participated in the development of a human embryo. Furthermore, Gln-TTGs might influence embryonic genome activation by modulating noncoding RNA processing. These findings demonstrated that human sperm tRNAGln-TTG derived small RNAs could be potential diagnostic biomarkers and could be used as a clinical target for male infertility.

SNPs analysis of height traits in Ningqiang pony.

Ningqiang pony is one of the five pony breeds in China and is listed as a rare species. It is, therefore, meaningful to conduct stature research on this breed for its efficient reproduction, utilization and protection. This study is based on four SNP variants of adjacent LCORL/NCAPG, HMGA2, ZFAT and LASP1 genes, which have been found to be associated with horse height, and then, the 4 SNP loci in 22 Ningqiang ponies were analyzed. The results showed that there were genetic variations at the four loci in Ningqiang pony, there was a SNP on LCORL/NCAPG, HMGA2 and ZFAT gene all including T allele and C allele and LASP1 including A allele and G allele. Further data analysis revealed that LCORL/NCAPG variant harbor the allele T and LASP1 variant harbor the allele G were significantly related to body height (p < 0.05). These findings suggested that the two SNP mutations within the LCORL/NCAPG and LASP1 genes could be considered as a screening marker for the body height of Ningqiang pony and could provide a new strategy for breeding and protect the rare germplasm resources.

Non-chromatographic purification of thermostable endoglucanase from Thermotoga maritima by fusion with a hydrophobic elastin-like polypeptide.

Endoglucanase EG12B from Thermotoga maritima is a thermophilic cellulase that has great potential for industrial applications. Here, to enable the selective purification of EG12B in a simple and efficient manner, an elastin-like polypeptide (ELP), which acts as a thermally responsive polypeptide, was fused with EG12B to enable its inverse phase transition cycling (ITC). A small gene library comprising ELPs from ELP5 to ELP50 was constructed using recursive directional ligation by plasmid reconstruction. ELP50 was added to the C-terminus of EG12B as a fusion tag to obtain the expression vector pET28-EG12B-ELP50, which was transformed into Escherichia coli BL21 (DE3) to enable the expression of fusion protein via IPTG induction. Gray scanning analysis revealed that the EG12B-ELP50 expression level was up to about 35% of the total cellular proteins. After three rounds of ITC, 8.14 mg of EG12B-ELP50 was obtained from 500-mL lysogeny broth culture medium. The recovery rate and purification fold of EG12B-ELP50 purified by ITC reached 78.1% and 11.8, respectively. The cellulase activity assay showed that EG12B-ELP50 had a better thermostability, higher optimal temperature, and longer half-life than those of free EG12B. Overall, our results suggested that ELP50 could be used as a favorable fusion tag, providing a rapid, simple, and inexpensive strategy for non-chromatographic target-protein purification.

RNA-seq transcriptome analysis of extensor digitorum longus and soleus muscles in large white pigs.

Skeletal muscle fibers are mainly categorized into red and white fiber types, and the ratio of red/white fibers within muscle mass plays a crucial role in meat quality such as tenderness and flavor. To better understand the molecular difference between the two muscle fibers, this study takes advantage of RNA-seq to compare differences in the transcriptome between extensor digitorum longus (EDL; white fiber) and soleus (Sol; red fiber) muscles of large white pigs. In total, 89,658,562 and 46,723,568 raw reads from EDL and Sol were generated, respectively. Comparison between the two transcriptomes revealed 561 differentially expressed genes, with 408 displaying higher and 153 lower levels of expression in Sol. Quantitative real-time polymerase chain reaction validated the differential expression of nine genes. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis discovered several differentially enriched biological functions and processes of the two muscles. Moreover, transcriptome comparison between EDL and Sol identified many muscle-related genes (CSRP3, ACTN2, MYL1, and MYH6) and pathways related to myofiber formation, such as focal adhesion, tight junction formation, extracellular matrix (ECM)-receptor pathway, calcium signaling, and Wnt signaling. In addition, 58,362 and 58,359 single nucleotide polymorphisms were identified in EDL and Sol, respectively, and the sequence of 9069 genes was refined at the 5', 3' or both ends. Numerous novel transcripts and alternatively spliced RNAs were also identified. Our transcriptome analysis constitutes valuable sequence resource for uncovering important genes and pathways involved in muscle fiber type determination, and might help further our understanding of the molecular mechanisms in different types of muscle.

VD3/VDR attenuates bisphenol A-induced impairment in mouse Leydig cells via regulation of autophagy.

Bisphenol A (BPA) is an endocrine disruptor with reproductive toxicity. Further, 1,25-dihydroxyvitamin D3 (VD3) plays an important role in male reproduction by binding vitamin D receptor (VDR) and mediating the pleiotropic biological actions that include spermatogenesis. However, whether VD3/VDR regulates the effect of BPA on Leydig cells (LCs) injury remains unknown. This study aimed to explore the effects of VD on BPA-induced cytotoxicity in mouse LCs. Hereby, LCs treated with BPA, VD3, or both were subjected to the assays of cell apoptosis, proliferation, autophagy, and levels of target proteins. This study unveiled that cell viability was dose-dependently reduced after exposure to BPA. BPA treatment significantly inhibited LC proliferation, induced apoptosis, and also downregulated VDR expression. By jointly analyzing transcriptome data and Comparative Toxicogenomics Database (CTD) data, autophagy signaling pathways related to testicular development and male reproduction were screened out. Therefore, the autophagy phenomenon of cells was further detected. The results showed that BPA treatment could activate cell autophagy, Vdr-/- inhibits cell autophagy, and active VD3 does not have a significant effect on the autophagy of normal LCs. After VD3 and BPA were used in combination, the autophagy of cells was further enhanced, and VD3 could alleviate BPA-induced damage of LCs. In conclusion, this study found that supplementing VD3 could eliminate the inhibition of BPA on VDR expression, further enhance LCs autophagy effect, and alleviate the inhibition of LCs proliferation and induction of apoptosis by BPA, playing a protective role in cells. The research results will provide valuable strategies to alleviate BPA-induced reproductive toxicity.

A single-cell transcriptome atlas of Lueyang black-bone chicken skin.

As the largest organ of the body, the skin participates in various physiological activities, such as barrier function, sensory function, and temperature regulation, thereby maintaining the balance between the body and the natural environment. To date, compositional and transcriptional profiles in chicken skin cells have not been reported. Here, we report detailed transcriptome analyses of cell populations present in the skin of a black-feather chicken and a white-feather chicken using single-cell RNA sequencing (scRNA-seq). By analyzing cluster-specific gene expression profiles, we identified 12 cell clusters, and their corresponding cell types were also characterized. Subsequently, we characterized the subpopulations of keratinocytes, myocytes, mesenchymal cells, fibroblasts, and melanocytes. It is worth noting that we have identified a subpopulation of keratinocytes involved in pigment granule capture and a subpopulation of melanocytes involved in pigment granule deposition, both of which have a higher cell abundance in black-feather chicken compared to white-feather chicken. Meanwhile, we also compared the cellular heterogeneity features of Lueyang black-bone chicken skin with different feather colors. In addition, we also screened out 12 genes those could be potential markers of melanocytes. Finally, we validated the specific expression of SGK1, WNT5A, CTSC, TYR, and LAPTM5 in black-feather chicken, which may be the key candidate genes determining the feather color differentiation of Lueyang black-bone chicken. In summary, this study first revealed the transcriptome characteristics of chicken skin cells via scRNA-seq technology. These datasets provide valuable information for the study of avian skin characteristics and have important implications for future poultry breeding.

Characterization of Genomic, Physiological, and Probiotic Features of Lactiplantibacillus plantarum JS21 Strain Isolated from Traditional Fermented Jiangshui.

This study aimed to understand the genetic and metabolic traits of a Lactiplantibacillus plantarum JS21 strain and its probiotic abilities through laboratory tests and computer analysis. L. plantarum JS21 was isolated from a traditional fermented food known as "Jiangshui" in Hanzhong city. In this research, the complete genetic makeup of JS21 was determined using Illumina and PacBio technologies. The JS21 genome consisted of a 3.423 Mb circular chromosome and five plasmids. It was found to contain 3023 protein-coding genes, 16 tRNA genes, 64 rRNA operons, 40 non-coding RNA genes, 264 pseudogenes, and six CRISPR array regions. The GC content of the genome was 44.53%. Additionally, the genome harbored three complete prophages. The evolutionary relationship and the genome collinearity of JS21 were compared with other L. plantarum strains. The resistance genes identified in JS21 were inherent. Enzyme genes involved in the Embden-Meyerhof-Parnas (EMP) and phosphoketolase (PK) pathways were detected, indicating potential for facultative heterofermentative pathways. JS21 possessed bacteriocins plnE/plnF genes and genes for polyketide and terpenoid assembly, possibly contributing to its antibacterial properties against Escherichia coli (ATCC 25922), Escherichia coli (K88), Staphylococcus aureus (CMCC 26003), and Listeria monocytogenes (CICC 21635). Furthermore, JS21 carried genes for Na+/H+ antiporters, F0F1 ATPase, and other stress resistance genes, which may account for its ability to withstand simulated conditions of the human gastrointestinal tract in vitro. The high hydrophobicity of its cell surface suggested the potential for intestinal colonization. Overall, L. plantarum JS21 exhibited probiotic traits as evidenced by laboratory experiments and computational analysis, suggesting its suitability as a dietary supplement.

Identification of dynamic changes in volatile compounds and metabolites during the smoking process of Zhenba bacon by GC-IMS combined metabolomics.

Zhenba bacon is a traditional cured bacon product with a rich history that originated from Zhenba County, Shaanxi Province. This study aimed to investigate the patterns of volatile compound formation and changes in metabolites during the smoking process in Zhenba bacon. Firstly, the sensory properties and physicochemical properties of Zhenba bacon were analyzed. Gas chromatography-ion mobility spectrometry (GC-IMS) and nontargeted metabolomics technology were used to analyze Zhenba bacon from different smoking stages. The results show a gradual increase in the sensory acceptance and volatile flavor compounds such as aldehydes, ketones, and esters with the prolongation of smoking of Zhenba bacon. LC-MS analysis identified 191 co-expressed differentially metabolites, with amino acid and lipid metabolism being the main metabolic pathways according to KEGG enrichment analysis. Temporal expression analysis of bacon metabolites at each stage revealed a decrease in harmful steroid hormones such as cortisone and an increase in amino acids and lipid metabolites, such as arginine, lysine, acid, and cholesterol, that contribute to the flavor of bacon. In summary, duration of smoking increased, the amount of flavor substances in Zhenba bacon gradually increased, and the safety and quality of bacon reached the optimal level after 32 days of smoking. This study provides valuable insights into the dynamic changes in volatile flavor compounds in Zhenba bacon and establishes a theoretical foundation for quality control during its production.

METTL21C mediates autophagy and formation of slow-twitch muscle fibers in mice after exercise.

Homeostasis is essential for muscle repair and regeneration after skeletal muscle exercise. This study investigated the role of methyltransferase-like 21C (METTL21C) in skeletal muscle of mice after exercise and the potential mechanism. First, muscle samples were collected at 2, 4 and 6 weeks after exercise, and liver glycogen, muscle glycogen, blood lactic acid and triglyceride were assessed. Moreover, the expression levels of autophagy markers and METTL21C in skeletal muscle were analyzed. The results showed that the expression levels of METTL21C and MYH7 in the gastrocnemius muscle of mice in the exercise group were significantly higher after exercise than those in the control group, which suggested that long-term exercise promoted the formation of slow-twitch muscle fibers in mouse skeletal muscle. Likewise, the autophagy capacity was enhanced with the prolongation of exercise in muscles. The findings were confirmed in mouse C2C12 cells. We discovered that knockdown of Mettl21c reduced the expression of MYH7 and the autophagy level in mouse myoblasts. These findings indicate that METTL21C promotes skeletal muscle homeostasis after exercise by enhancing autophagy, and also contributes to myogenic differentiation and the formation of slow muscle fibers.

The potential correlation between the succession of microflora and volatile flavor compounds during the production of Zhenba bacon.

Microbial composition plays an important role in the quality and flavor of bacon. The aims of this study were to detect bacterial community succession using high-throughput sequencing (HTS) and volatile flavor compound changes using gas chromatography-ion mobility spectrometry (GC-IMS) during the production of Zhenba bacon. The results showed that a total of 70 volatile compounds were detected. Among them, ketones, hydrocarbons, aldehydes, esters and alcohols were the main substances in the curing and smoking stages. In addition, the fungal abundance was greater than the bacterial abundance, and there was obvious succession of the microbial community with changes in fermentation time and processing technology. The main functional bacterial genera in the curing and smoking stages were Staphylococcus, Psychrobacter and Latilactobacillus, and the main fungal genera were Fusarium and Debaryomyces. Through correlation analysis, we found that pyrrole, 2-pentanol, methyl isobutyl ketone (MIBK) and ethyl acetate (EA) were significantly correlated with Staphylococcus, Psychrobacter, Pseudomonas and Myroides (p < 0.01), and it is speculated that they contribute significantly to flavor formation. The results of this study are helpful for understanding the microbial dynamics and characteristic volatile flavor compounds in Zhenba bacon, and provide new insights into the relationship between microorganisms and flavor through potential correlations.

MiRNA-199a-3p regulates C2C12 myoblast differentiation through IGF-1/AKT/mTOR signal pathway.

MicroRNAs constitute a class of ~22-nucleotide non-coding RNAs. They modulate gene expression by associating with the 3' untranslated regions (3' UTRs) of messenger RNAs (mRNAs). Although multiple miRNAs are known to be regulated during myoblast differentiation, their individual roles in muscle development are still not fully understood. In this study, we showed that miR-199a-3p was highly expressed in skeletal muscle and was induced during C2C12 myoblasts differentiation. We also identified and confirmed several genes of the IGF-1/AKT/mTOR signal pathway, including IGF-1, mTOR, and RPS6KA6, as important cellular targets of miR-199a-3p in myoblasts. Overexpression of miR-199a-3p partially blocked C2C12 myoblast differentiation and the activation of AKT/mTOR signal pathway, while interference of miR-199a-3p by antisense oligonucleotides promoted C2C12 differentiation and myotube hypertrophy. Thus, our studies have established miR-199a-3p as a potential regulator of myogenesis through the suppression of IGF-1/AKT/mTOR signal pathway.

A simple indanone-based red emission fluorescent probe for the rapid detection of cysteine in vitro and in vivo.

Cysteine is a vital biothiols that plays an important role in numerous physiological and pathological processes. The development of simple molecule tools for detection and analysis Cys in subcellar environment is significant for further exploring their pathophysiological. In this work, a simple but activated fluorescent probe AMIA was constructed with a donor-π-accepter (D- π -A) structure, which using an indanone as the electron-withdrawing unit acting as the fluorophore, dimethylamino group attached to the position 4 of the benzene ring as the electron-donating, two double bonds as the linker group, and the acryloyl ester group as the trigger and response unit. This probe AMIA was exhibited highly selective and sensitive response to Cys over other amino acids and ions under physiological conditions. It was found that AMIA showed a red turn-on fluorescence response at 630 nm towards Cys with a large stroke shift of 170 nm and a very low detection limit of 26.3 nM. HRMS, 1H NMR and TD-DFT calculation further confirmed that the response mechanism is the Cys triggered the addition-cyclization reaction between AMIA' acryloyl group and Cys' sulfhydryl and amino unit, leading to the release of a red fluorescent dye AMIA-OH, which can be identified by naked eyes. Furthermore, AMIA was successfully applied for simultaneous determination of Cys in living cells and zebrafish with lower cytotoxicity and good cell permeability. We hope that this novel indanone-based probe AMIA will provide a new reference for visualized Cys in other complex biological system.

VDR promotes testosterone synthesis in mouse Leydig cells via regulation of cholesterol side chain cleavage cytochrome P450 (Cyp11a1) expression.

BACKGROUND: The vitamin D receptor (VDR) mediates the pleiotropic biological actions that include osteoporosis, immune responses and androgen synthesis.VDR is widely expressed in testis cells such as Leydig cells, Sertoli cells, and sperm. The levels of steroids are critical for sexual development. In the early stage of steroidogenesis, cholesterol is converted to pregnenolone (precursor of most steroid hormones) by cholesterol side-chain lyase (CYP11A1), which eventually synthesizes the male hormone testosterone. OBJECTIVE: This study aims to reveal how VDR regulates CYP11A1 expression and affects testosterone synthesis in murine Leydig cells. METHODS: The levels of VDR, CYP11A1 were determined by quantitative real-time polymerase chain reaction (RT-qPCR) or western blot. Targeted relationship between VDR and Cyp11a1 was evaluated by dual-luciferase reporter assay. The levels of testosterone concentrations in cell culture media serum by enzyme-linked immunosorbent assay (ELISA). RESULTS: Phylogenetic and motif analysis showed that the Cyp11a1 family had sequence loss, which may have special biological functions during evolution. The results of promoter prediction showed that vitamin D response element (VDRE) existed in the upstream promoter region of murine Cyp11a1. Dual-luciferase assay confirmed that VDR could bind candidate VDREs in upstream region of Cyp11a1, and enhance gene expression. Tissue distribution and localizatio analysis showed that Cyp11a1 was mainly expressed in testis, and dominantly existed in murine Leydig cells. Furthermore, over-expression VDR and CYP11A1 significantly increased testosterone synthesis in mice Leydig cells. CONCLUSIONS: Active vitamin D3 (VD3) and Vdr interference treatment showed that VD3/VDR had a positive regulatory effect on Cyp11a1 expression and testosterone secretion. VDR promotes testosterone synthesis in male mice by up-regulating Cyp11a1 expression, which played an important role for male reproduction.

Targeted knockout of Mx in the DF-1 chicken fibroblast cell line impairs immune response against Newcastle disease virus.

Newcastle disease virus (NDV) is an RNA virus taking poultry as the host, and the Newcastle disease (ND) caused by NDV is one of the diseases with serious damage to the health of poultry. Mx encoding by myxovirus resistance gene, induced by type I interferon (IFN), has a wide range of antiviral and GTPase activities in human, mice, and other species via inhibition virus replication. However, the antiviral ability of chicken Mx is still a controversial issue. To explore the effect of chicken Mx post-NDV infection, Mx-knockout DF-1 cells were constructed via CRISPR/Cas9 gene editing system. The number of copies of NDV was detected by RT-qPCR, and the mRNA expression levels of IRF-7, IFN-α, IFN-ß, TNF-α, p21, p27, and Bak in DF-1 cells were analyzed after NDV infection. Compared with control cells, virus titers were much higher in Mx-knockout DF-1 cells post-NDV infection. The deficiency of Mx aggravated the cell pathological features post-NDV infection, and promoted the expression levels of IRF-7, IFN-α, IFN-ß, and pro-inflammatory cytokine TNF-α in host cells. In addition, cells with Mx deficiency could alleviate the harm from virus by enhancing the expression of p21, p27, and Bak, which related to cell proliferation apoptosis. In conclusion, Mx played an important role in antivirus invasion. In the absence of Mx, cells could alleviate the harm from virus infection via retarding cell proliferation and enhancing cell apoptosis.

A genome-wide scan to identify signatures of selection in Lueyang black -bone chicken.

Lueyang black-bone chicken is a domestic breed in China. The genetic mechanism of the formation of important economic traits of this breed has not been studied systematically. Therefore, in this study, whole genome resequencing was used to systematically analyze and evaluate the genetic diversity of the black-feather and white-feather populations, and to screen and identify key genes related to phenotypes. The results of principal component analysis and population structure analysis showed that Lueyang black-feathered chickens and white-feathered chickens could be divided into 2 subgroups, and the genetic diversity of black-feathered chicken was richer than that of white-feathered chickens. Linkage disequilibrium analysis also showed that the selection intensity of black-feathered chickens was lower than for white-feathered chickens, which was mainly due to the small population size of white-feathered chickens and a certain degree of inbreeding. Fixation index (FST) analysis revealed that the candidate genes related to feather color traits were G-gamma, FA, FERM, Kelch, TGFb, Arf, FERM, and melanin synthesis-related gene tyrosinase (TYR). Based on Kyoto Encyclopedia of Genes and Genomes enrichment analysis, Jak-STAT, mTOR, and TGF-ß signaling pathways were mainly related to melanogenesis and plume color. The findings of this study supported important information for the evaluation and protection of chicken genetic resources and help to analyze the unique genetic phenotypes such as melanin deposition and feather color of Lueyang black-bone chicken. Additionally, it could provide basic research data for the improvement and breeding of Lueyang black-bone chicken with characteristic traits.

SHCBP1 Promotes the Proliferation of Breast Cancer Cells by Inhibiting CXCL2.

Breast cancer has the characteristics of high metastasis and recurrence and ranks first in incidence and mortality among female malignant tumors. Shc SH2-domain binding protein 1 (SHCBP1) is an important protein in intracellular signal transduction and cell division, but the role of SHCBP1 in breast cancers remains elusive. Here, we found that SHCBP1 deficiency inhibited the proliferation of breast cancer cells. Mechanistically, SHCPB1 significantly downregulates the mRNA level of CXCL2, which in turn activates the AKT and ERK signaling, while inactivates the p21 and p27 signaling. In addition, overexpression of SHCPB1 downregulates the protein levels of p21 and p27, which could be completely reversed by restoration of CXCL2 expression. Moreover, we analyzed the expression of both SHCPB1 and CXCL2, and found that SHCPB1 is highly expressed in breast cancer cells or tissues from breast cancer patients compared to normal breast cells or adjacent normal tissues, while CXCL2 is lowly expressed in breast cancer cells or tissues. Collectively, our study reveals that SHCBP1 plays an oncogenic role in breast cancer tumorigenesis partially through inhibiting the inflammatory response and ultimately activating the proliferation of breast cancers.