Deficiency of smooth muscle cell ILF3 alleviates intimal hyperplasia via HMGB1 mRNA degradation-mediated regulation of the STAT3/DUSP16 axis.

Intimal hyperplasia is a complicated pathophysiological phenomenon attributable to in-stent restenosis, and the underlying mechanism remains unclear. Interleukin enhancer-binding factor 3 (ILF3), a double-stranded RNA-binding protein involved in regulating mRNA stability, has been recently demonstrated to assume a crucial role in cardiovascular disease; nevertheless, its impact on intimal hyperplasia remains unknown. In current study, we used samples of human restenotic arteries and rodent models of intimal hyperplasia, we found that vascular smooth muscle cell (VSMC) ILF3 expression was markedly elevated in human restenotic arteries and murine ligated carotid arteries. SMC-specific ILF3 knockout mice significantly suppressed injury induced neointimal formation. In vitro, platelet-derived growth factor type BB (PDGF-BB) treatment elevated the level of VSMC ILF3 in a dose- and time-dependent manner. ILF3 silencing markedly inhibited PDGF-BB-induced phenotype switching, proliferation, and migration in VSMCs. Transcriptome sequencing and RNA immunoprecipitation sequencing depicted that ILF3 maintained its stability upon binding to the mRNA of the high-mobility group box 1 protein (HMGB1), thereby exerting an inhibitory effect on the transcription of dual specificity phosphatase 16 (DUSP16) through enhanced phosphorylation of signal transducer and activator of transcription 3 (STAT3). Therefore, the results both in vitro and in vivo indicated that the loss of ILF3 in VSMC ameliorated neointimal hyperplasia by regulating the STAT3/DUSP16 axis through the degradation of HMGB1 mRNA. Our findings revealed that vascular injury activates VSMC ILF3, which in turn promotes intima formation. Consequently, targeting specific VSMC ILF3 may present a potential therapeutic strategy for ameliorating cardiovascular restenosis.

Common proteins analysis of different mammals' mature milk by 4D-Label-Free.

The milk proteins from samples of 13 different animals were identified utilizing 4D-Label-Free proteomics technology, leading to the identification of a substantial number of proteins. Among the various samples, Chinese people (CHP) milk proteins exhibited the highest count, with 1149 distinct proteins. Simultaneously, we identified common proteins present in these animal milk. It's notable presence in goat milk contributes to enhancing infant infection resistance, showcasing the beneficial role of lactoperoxidase. Galectin-3 binding protein (Gal-3BP) and tetraspanin in human milk are significantly higher than those in other animals, which determine the prominent antiviral effect of human milk and the important processes related to cell transduction. Furthermore, human milk, camel milk, goat milk and sheep milk proved to be rich sources of milk fat globule membrane (MFGM) proteins. The insights obtained from this study can serve as a foundational framework for exploring the role of different animal milk proteins in disease treatment and the composition of infant formula.

A novel magnetic Ti-MOF/chitosan composite for efficient adsorption of Pb(II) from aqueous solutions: Synthesis and investigation.

In this investigation, a composite material comprising Ti-MOF and chitosan, denoted as BD-MOF(Ti)@CS/Fe3O4, was successfully designed for the efficient adsorption of Pb(II) from aqueous solutions. A comprehensive array of characterization techniques, including SEM, XRD, BET, FT-IR, and XPS, were meticulously employed to scrutinize the structural attributes and morphological features of the Pb(II) adsorbent. Notably, the material exhibits adaptability to a broad pH range, with adsorption efficiency reaching 99 % between pH 3 and 6. Kinetic studies reveal that the adsorption process of Pb(II) by BD-MOF(Ti)@CS/Fe3O4 adheres closely to a pseudo-second-order kinetic model. Impressively, within a short duration of 40 min, the adsorption efficiency can reach 85 %. Furthermore, the adsorption isotherm aligns with the Hill isotherm model, signifying cooperative adsorption. This observation underscores the synergistic interplay among the functional groups on the surface of BD-MOF(Ti)@CS/Fe3O4 in capturing Pb(II). As per the Hill model, the theoretical maximum capacity was an impressive 944.9 mg/g. Thermodynamic assessments suggested that the adsorption process was spontaneous, entropy increasing and exothermic. Even in the presence of various interfering ions, BD-MOF(Ti)@CS/Fe3O4 exhibited robust adsorption performance, thereby affirming its utility in complex environments. Moreover, the material demonstrates noteworthy reusability, sustaining effective Pb(II) removal across five consecutive cycles in aqueous solutions.

CircERCC6 Positively Regulates the Induced Activation of SHF Stem Cells in Cashmere Goats via the miR-412-3p/BNC2 Axis in an m6A-Dependent Manner.

The cashmere, a kind of nature protein fiber, is one of the main use of cashmere goats. The induced activation of secondary hair follicle (SHF) stem cells by the dermal papilla cell-derived signals is a key biological process for the morphogenesis and growth of cashmere fiber in cashmere goats. Previously, the circRNA-ERCC6 (circERCC6) was identified from cashmere goat SHFs; however, its biological significance is unclear in the SHF physiology process of cashmere goats. In this study, we found that circERCC6 exhibited significantly higher expression at anagen SHF bulge compared with the counterpart of telogen and harbored three m6A modified sites (named m6A-685, m6A-862, and m6A-995) through methylation immunoprecipitation using a real-time quantitative polymerase chain reaction (Me-RIP-qPCR) technique. The knockdown experiments of circERCC6 in SHF stem cells showed that circERCC6 positively regulates the induced activation of SHF stem cells in cashmere goats. Through a dual-luciferase reporter assay, we demonstrated that m6A-modified circERCC6 (m6A-circERCC6) sponged miR-412-3p to upregulate the expression of BNC2 mRNA in SHFstem cells. Through m6A-deficient mutant assay in circERCC6 knockdown SHF stem cells, we further showed that m6A modification within circERCC6 is required to mediate the miR-412-3p/BNC2 axis to finally promote the proper induced activation of SHF stem cells in cashmere goats.

D-ribose metabolic disorder and diabetes mellitus.

D-ribose, an ubiquitous pentose compound found in all living cells, serves as a vital constituent of numerous essential biomolecules, including RNA, nucleotides, and riboflavin. It plays a crucial role in various fundamental life processes. Within the cellular milieu, exogenously supplied D-ribose can undergo phosphorylation to yield ribose-5-phosphate (R-5-P). This R-5-P compound serves a dual purpose: it not only contributes to adenosine triphosphate (ATP) production through the nonoxidative phase of the pentose phosphate pathway (PPP) but also participates in nucleotide synthesis. Consequently, D-ribose is employed both as a therapeutic agent for enhancing cardiac function in heart failure patients and as a remedy for post-exercise fatigue. Nevertheless, recent clinical studies have suggested a potential link between D-ribose metabolic disturbances and type 2 diabetes mellitus (T2DM) along with its associated complications. Additionally, certain in vitro experiments have indicated that exogenous D-ribose exposure could trigger apoptosis in specific cell lines. This article comprehensively reviews the current advancements in D-ribose's digestion, absorption, transmembrane transport, intracellular metabolic pathways, impact on cellular behaviour, and elevated levels in diabetes mellitus. It also identifies areas requiring further investigation.

Posterior Approximate Clustering-Based Sensitivity Matrix Decomposition for Electrical Impedance Tomography.

This paper introduces a sensitivity matrix decomposition regularization (SMDR) method for electric impedance tomography (EIT). Using k-means clustering, the EIT-reconstructed image can be divided into four clusters, derived based on image features, representing posterior information. The sensitivity matrix is then decomposed into distinct work areas based on these clusters. The elimination of smooth edge effects is achieved through differentiation of the images from the decomposed sensitivity matrix and further post-processing reliant on image features. The algorithm ensures low computational complexity and avoids introducing extra parameters. Numerical simulations and experimental data verification highlight the effectiveness of SMDR. The proposed SMDR algorithm demonstrates higher accuracy and robustness compared to the typical Tikhonov regularization and the iterative penalty term-based regularization method (with an improvement of up to 0.1156 in correlation coefficient). Moreover, SMDR achieves a harmonious balance between image fidelity and sparsity, effectively addressing practical application requirements.

Electrical Properties of Human Lung Nodules in Vitro from 100Hz to 100MHz.

OBJECTIVE: The incidence of pulmonary nodules has been increasing over the past 30 years. Different types of nodules are associated with varying degrees of malignancy, and they engender inconsistent treatment approaches. Therefore, correct distinction is essential for the optimal treatment and recovery of the patients. The commonly-used medical imaging methods have limitations in distinguishing lung nodules to date. A new approach to this problem may be provided by electrical properties of lung nodules. Nevertheless, difference identification is the basis of correct distinction. So, this paper aims to investigate the differences in electrical properties between various lung nodules. METHODS: At variance with existing studies, benign samples were included for analysis. A total of 252 specimens were collected, including 126 normal tissues, 15 benign nodules, 76 adenocarcinomas, and 35 squamous cell carcinomas. The dispersion properties of each tissue were measured over a frequency range of 100Hz to 100MHz. And the relaxation mechanism was analyzed by fitting the Cole-Cole plot. The corresponding equivalent circuit was estimated accordingly. RESULTS: Results validated the significant differences between malignant and normal tissue. Significant differences between benign and malignant lesions were observed in conductivity and relative permittivity. Adenocarcinomas and squamous cell carcinomas are significantly different in conductivity, first-order, second-order differences of conductivity, α-band Cole-Cole plot parameters and capacitance of equivalent circuit. The combination of the different features increased the tissue groups' differences measured by Euclidean distance up to 94.7%. CONCLUSION AND SIGNIFICANCE: In conclusion, the four tissue groups reveal dissimilarity in electrical properties. This characteristic potentially lends itself to future diagnosis of non-invasive lung cancer.

Analysis for lipid nutrient differences in the milk of 13 species from a quantitative non-targeted lipidomics perspective.

Lipids are essential organic components in milk and have been associated with various health benefits for newborns. However, a comprehensive analysis of lipid profiles across multiple species and levels has been lacking. In this study, we employed liquid chromatography-tandem mass spectrometry (LC-MS/MS) to accurately determine the absolute content of lipid molecules. It revealed that ruminants exhibit a higher concentration of short-chain fatty acids compared to non-ruminants. Additionally, we identified ALC (camel), MGH (horse), and DZD (donkey) as species that display similarities to components found in human milk fat. Remarkably, it reveals that porcine milk fat is characterized by long chain lengths, low saturation, and a high proportion of essential fatty acids. PS (22:5_18:2) could potentially serve as a biomarker in porcine milk. These unique characteristics present potential opportunities for the utilization of porcine milk. Overall, our findings provide valuable insights into the lipidomics profiles of milk from different species.

Multi-omics analysis of functional substances and expression verification in cashmere fineness.

BACKGROUND: Numerous factors influence the growth and development of cashmere. Existing research on cashmere has predominantly emphasized a single omics level. Integrating multi-omics analyses can offer a more comprehensive understanding by encompassing the entire spectrum. This study more accurately and comprehensively identified the key factors influencing cashmere fineness using multi-omics analysis. METHODS: This study used skin tissues of coarse cashmere type (CT_LCG) and fine cashmere type Liaoning cashmere goats (FT_LCG) for the analysis. This study employed an integrated approach involving transcriptomics, translatomics, proteomics, and metabolomics to identify substances associated with cashmere fineness. The findings were validated using parallel reaction monitoring (PRM) and multiple reaction monitoring (MRM) techniques. RESULTS: The GO functional enrichment analysis identified three common terms: multicellular organismal process, immune system process, and extracellular region. Furthermore, the KEGG enrichment analysis uncovered the involvement of the arachidonic acid metabolic pathway. Protein expression trends were verified using PRM technology. The expression trends of KRT79, as confirmed by PRM, were consistent with those observed in TMT proteomics and exhibited a positive regulatory effect on cashmere fineness. Metabolite expression trends were confirmed using MRM technology. The expression trends of 9 out of 15 validated metabolites were in agreement with those identified in the non-targeted metabolomics analysis. CONCLUSIONS: This study employed multi-omics analysis to identify key regulators of cashmere fineness, including PLA2G12A, KRT79, and prostaglandin B2. The findings of this study offer valuable data and establish a theoretical foundation for conducting comprehensive investigations into the molecular regulatory mechanisms and functional aspects of cashmere fineness.

Analysis for different flavor compounds in mature milk from human and livestock animals by GC × GC-TOFMS.

Breast milk plays a crucial role in the taste development of infants, which cannot be replicated by other mammalian milk or formulas. This study aimed to identify and characterize the flavor substances in 15 different types of milk and analyze the differences among them. The results showed that human milk contained high levels of esters, particularly fatty acid ethyl esters, which contribute to its unique flavor. The four substances that had the highest flavor contribution in all species were identified as 2,3-butanedione, trimethylamine, isophorone, and acetaldehyde. Furthermore, the analysis of differences revealed that thermal-oxidation of lipids could explain the variation between human milk and other species in terms of flavor compounds. The key differential flavor compounds identified in milk from all species were trimethylamine, propanal, 1-pentanol, pyridine 2-methyl, and 2-butanone. These findings can potentially aid in developing formulas that better meet the taste needs of infants.

Association analysis for SNPs of LIPE and ITGB4 genes with cashmere production performance, body measurement traits and milk production traits in Liaoning cashmere goats.

Liaoning cashmere goat (LCG) is one of the excellent cashmere goat breeds in China. Because of its larger size, better cashmere, and better cashmere production performance, people pay special attention to it. This article mainly studied the relationship between SNP loci of LIPE gene and ITGB4 gene and milk production, cashmere production and body measurement traits of LCGs. We further identified potential SNP loci by PCR-Seq polymorphism detection and gene sequence comparison of LIPE and ITGB4 genes. Further, we use SPSS and SHEsis software to analyze their relationship to production performance. The consequence indicated that CC genotype of LIPE gene T16409C locus was dominant genotype in milk production and cashmere production, while CT genotype of LIPE gene T16409C locus was dominant in body size. The CT genotype of C168T locus of ITGB4 gene is the dominant genotype of body type and cashmere production, while the dominant genotype of milk production is TT genotype. Through joint analysis, in haploid combinations, H1H2:CCCT is the dominant haplotype combination in cashmere fineness. H3H4:TTCT is a dominant haplotype combination of milk production traits and body measurement traits. These dominant genotypes can provide a reliable basis for the study of production performance of LCG.

A deep learning-based fully automatic and clinical-ready framework for regional myocardial segmentation and myocardial ischemia evaluation.

Myocardial ischemia diagnosis with CT perfusion imaging (CTP) is important in coronary artery disease management. Traditional analysis procedure is time-consuming and error-prone due to the semi-manual and operator-dependent nature. To improve the diagnostic performance, a deep learning-based, fully automatic, and clinical-ready framework was developed. Two collaborating deep learning networks including a 3D U-Net for left ventricle segmentation and a CNN for anatomical landmarks detection were trained on 276 subjects. With our processing framework, the 17-segment left ventricular model was automatically generated conformed to the clinical standard. Myocardial blood flow computed by commercial software was extracted within each segment and visualized against the bull's eye plot. The performance was validated on another 45 subjects. Coronary angiography and invasive fractional flow reserve measurements were also performed in these patients to serve as the gold standard for myocardial ischemia diagnosis. As a result, the diagnostic accuracy for our method was 81.08%, much higher than that for commercially available CTP analysis software (56.75%), and our method demonstrated a higher consistency (Kappa coefficient 0.759 vs. 0.585). Besides, the average processing time of our method was much lower (30 ± 10.5 s/subject vs. over 30 min/subject). In conclusion, the proposed deep learning-based framework could be a promising tool for assisting CTP analysis.

Metabonomic analysis of human and 12 kinds of livestock mature milk.

Mature milk, as a nutrient-rich endogenous metabolite, has various beneficial effects on the human body. In order to investigate the specific nutrients provided by different dairy products to humans, we used UHPLC-Q-TOF MS to analyze the highly significantly differentially expressed metabolites in 13 species of mammalian mature milk, which were grouped into 17 major metabolite classes with 1992 metabolites based on chemical classification. KEGG shows that 5 pathways in which differentially significant metabolites are actively involved are ABC transporters, Purine metabolism, Pyrimidine metabolism, Phosphotransferase system, Galactose metabolism. The study found that pig milk and goat milk are closer to human milk and contain more nutrients that are beneficial to human health, followed by camel milk and cow milk. In the context of dairy production, the development of goat milk is more likely to meet human needs and health.

Transcriptomics analysis of cashmere fineness functional genes.

Liaoning cashmere goat (LCG) is a famous cashmere goat breed in China. Cashmere fineness, as an important index to evaluate cashmere quality, is also one of the problems to be improved for Liaoning cashmere goats. Transcriptome studies all mRNA transcribed by a specific tissue or cell in a certain period. It is a key link in the study of gene expression regulation. It plays an important role in the analysis of biological growth and disease. Transcriptome is spatio-temporal specific, that is, gene expression varies in different tissues or at different times. Three coarser and three fine LCG skin samples were sequenced by RNA-seq technology, and a total of 427 differentially expressed genes were obtained, including 291 up-regulated genes and 136 down-regulated genes. In the experiment, we screened out 16 genes that had significant differences in the expression of coarse and fine cashmere of Liaoning cashmere goats, so it was inferred that these 16 genes might have regulatory effects on cashmere fineness. Moreover, GO gene set enrichment analysis revealed that differential genes mainly consist of immune response, MHC protein complex, Heme binding and other pathways. KEGG analysis showed that transplant-versus-host disease and allograft rejection were the main pathways of differential genes.

CircRNA-1967 participates in the differentiation of goat SHF-SCs into hair follicle lineage by sponging miR-93-3p to enhance LEF1 expression.

Circular RNAs (circRNAs), a novel class of non-coding RNAs, can interact with miRNAs through a sequence-driven sponge mechanism, thereby regulating the expression of their downstream target genes. CircRNA-1967 was found in secondary hair follicles (SHFs) of cashmere goats, but its functions are not clear. Here, we showed that both circRNA-1967 and its host gene BNC2 had significantly higher expression in SHF bulge at anagen than those at telogen of cashmere goats. Also, circRNA-1967 participates in the differentiation of SHF stem cells (SHF-SCs) into hair follicle lineage in cashmere goats. RNA pull-down assay verified that circRNA-1967 interacts with miR-93-3p. We also indicated that circRNA-1967 promoted LEF1 expression in SHF-SCs of cashmere goats. By dual-luciferase reporter analysis, we found that circRNA-1967 up-regulated LEF1 expression through the miR-93-3p-mediated pathway. The results from this study demonstrated that circRNA-1967 participated in the differentiation of goat SHF-SCs into hair follicle lineage by sponging miR-93-3p to enhance LEF1 expression. Our founding might constitute a novel pathway for revealing the potential mechanism of the differentiation of SHF-SCs into hair follicle lineage in cashmere goats. Also, these results provided a valuable basis for further enhancing the intrinsic regeneration of cashmere goat SHFs with the formation and growth of cashmere fibers.

Association analysis for SNPs of KRT26 and TCHH genes with cashmere production performance, body measurement traits and milk production traits in Liaoning cashmere goats.

Cashmere fineness is getting thicker, which is one of the key problems in cashmere breeding, however, there have been no systematic studies on the molecular regulation of cashmere fineness. The aim of this study was to investigate the relationship between KRT26 and TCHH gene polymorphism and production performance in Liaoning cashmere goats (LCG). The potential single nucleotide polymorphisms (SNPs) of LCG were detected by sequence alignment and PCR-Seq polymorphism of KRT26 and TCHH genes and analyzed the effect of SNPs on production performance by SPSS software. Two SNPs sites (A559T and A6839G) of two genes were detected. The AA genotype of KRT26 A559T locus was the dominant genotype. AG and GG at TCHH A6839G locus were the dominant genotypes. AAAA was the dominant haplotype combination. The results showed that KRT26 and TCHH genes were associated with cashmere fineness of LCG, and A559T (AA) and A6839G (GG) genotypes were the preferred marker genotypes for cashmere fineness, which provided more theoretical basis for further research on cashmere fineness.

Analysis of m6A methylation in skin tissues of different sex Liaoning cashmere goats.

N6-methyladenosine (m6A) is the most frequent internal modification of mRNA and lncRNA in eukaryotes. We used two high-throughput sequencing method, m6A-seq and RNA-seq to identify pivotal m6A-modified genes in cashmere fineness and fiber growth. 8062 m6A peaks were detected by m6A-seq, including 2157 upregulated and 6445 downregulated. Furthermore, by comparing m6A-modified genes of the male Liaoning Cashmere Goat (M-LCG) and female Liaoning Cashmere Goat (F-LCG) skin tissues, we get 862 differentially expressed m6A-modified genes. To identify differently expressed m6A genes associated with cashmere fineness, 11 genes were selected for validation using real time fluorescent quantitative PCR in M-LCG and F-LCG. This study provides an acadamic basis on the molecular regulation mechanism of m6A modification in cashmere growth process.

Association analysis for SNPs of MSTN and IGFBP-3 genes with body size and other production traits in Liaoning Cashmere Goats.

Liaoning cashmere goat (LCG) have tall bones, high cashmere production and outstanding meat production performance. In recent years, good breeding progress has not been made in terms of body size, meat yield, milk yield and other properties in terms of production. The study focused on the correlation between the SNPs of MSTN and IGFBP-3 genes with the body size performance, cashmere production and milk performance. The MSTN and IGFBP-3 gene sequence alignment and PCR-Seq polymorphism were used to detect the potential SNPs, and the correlation with production performance was analyzed by SPSS and SHEsis software. The results showed that the TT genotype at the T1662G locus of the MSTN gene is dominant and has significant advantages in body measurements such as sacrum height, chest width, and waist height. The C allele at the C4021T locus of IGFBP-3 gene shows an advantage in the body measurement performance. Among the haplotype combinations, H2H2:TGTC is preponderant combination for body size performance, H2H2:TGTC and H1H2:TGCC are preponderant combinations for cashmere production performance, H1H3:GGCC is preponderant combination for milk production performance. It may be a molecular marker for future selection and breeding.

Association analysis between reproduction genes INHA, PGR, RARG with lamb and other traits of Liaoning cashmere goats.

Reproductive traits have a high economic value in goat breeding, and increasing the number of lambs produced by ewes is of great importance to improve the production efficiency of goat farming. Lambing traits in goats are low heritability traits, but their genetic basis is ultimately determined by genes. This study aimed to investigate the relationship between INHA, RARG, and PGR gene polymorphisms and production performance, such as lambing, cashmere production, milk production, and body size in Liaoning cashmere goats. A total of six single nucleotide polymorphisms (SNPs) loci were identified in these three genes, G144A and T504C on the INHA gene, A56G, G144A, G490C on the RARG gene, and G109519T on the PGR gene. For lambing and cashmere production traits, the AA genotype of G144A on the INHA gene, TT on the T504C genotype, GG genotype of G144A on the INHA gene, A56G, G144A, and T504C on RARG and G109519T on PGR gene are dominant genotypes. AATT is a dominant haplotype combination. Allele G can be used as a molecular marker for lambing, cashmere, and milk production traits in Liaoning cashmere goats. Marker-assisted selection can be used for early selection to achieve improvement of genetic traits in Liaoning cashmere goats.

High-throughput analysis of lncRNA in cows with naturally infected Staphylococcus aureus mammary gland.

LncRNA (long non-coding RNA) is an RNA molecule with a length between 200 and 100,000 nt. It does not encode proteins and is involved in a variety of intracellular processes, becoming a research hotspot of genetics. To identify key lncRNAs associated with dairy mastitis, we collected mammary epithelial tissue samples of Normal disease-free Holstein cows (HCN) and unhealthy Holstein cows with Staphylococcus aureus (HCU) and performed RNA sequencing (RNA-seq) on the samples. A total of 270 differentially expressed lncRNAs and 500 differentially expressed mRNAs were identified by high-throughput sequencing and bioinformatics analysis. Furthermore, Hydrolase activity is the most enriched in GO, and ErbB signaling pathway is significantly enriched in KEGG. In addition, through qPCR validation of 5 candidate lncRNAs in HCN and HCU, four differentially expressed lncRNAs MSTRG.498, MSTRG57.1, MSTRG.41.1 and MSTRG 124.1 were confirmed to have significant differentially expressed in cow mastitis. Also, lncRNA MSTRG.498 and its target gene, SMC4, might directly or indirectly play a role in cow mastitis. The regulatory network of lncRNA-miRNA-mRNA has been inferred from a bioinformatics perspective, which may assist understand the underlying molecular mechanism of lncRNAs involved in regulating mastitis in cows. Our findings will provide meaningful resources for further research on the regulatory function of lncRNAs in cow mastitis.