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OBJECTIVE: To investigate the mechanism of Ling-Gui-Zhu-Gan decoction (LGZGD) protects against doxorubicin (DOX)-induced myocardial injury. METHODS: In vivo experiment, rats were divided into six groups: normal group, model group (15 mg/kg, DOX), Dex group(150 mg/kg, Dex), LGZGD-L group (2.1 g/kg), LGZGD-M group (4.2 g/kg), and LGZGD-H group (8.4 g/kg). We used HE and Masson staining to observe the histopathological changes, echocardiography to assess the cardiac function, and western blot and RT-qPCR to detect the expressions of Nrf2, GPX4, Fpn1, and Ptgs2. In vitro experiment, we used immunofluorescence to detect ROS production, and RT-qPCR to detect gene expression of GPX4, Fpn1, and Ptgs2. KEY FINDINGS: In vivo, LGZGD improved cardiac systolic function. LGZGD significantly reduced MDA, LDH, and CK levels, increased SOD activity, enhanced the protein expression of Nrf2, GPX4, and Fpn1, and decreased Ptgs2 levels. In vitro, LGZGD-containing serum significantly reduced ROS, increased the gene expression of GPX4 and Fpn1, and decreased the gene expression of Ptgs2. Furthermore, compared with the LGZGD (si-NC) group, the LGZGD (si-Nrf2) group had decreased gene expression of Nrf2, GPX4, and Fpn1 and increased gene expression of Ptgs2. CONCLUSIONS: LGZGD can ameliorate DOX-cardiotoxicity by activating the Nrf2 signaling pathway and inhibiting ferroptosis in cardiomyocytes.

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Hoarse voice affects the efficiency of communication between people. However, surgical treatment may result in patients with poorer voice quality, and voice repair techniques can only repair vowels. In this paper, we propose a novel multidomain generative adversarial voice conversion method to achieve hoarse-to-normal voice conversion and personalize voices for patients with hoarseness. The proposed method aims to improve the speech quality of hoarse voices through a multidomain generative adversarial network. The proposed method is evaluated on subjective and objective evaluation metrics. According to the findings of the spectrum analysis, the suggested method converts hoarse voice formants more effectively than variational auto-encoder (VAE), Auto-VC (voice conversion), StarGAN-VC (Generative Adversarial Network- Voice Conversion), and CycleVAE. For the word error rate, the suggested method obtains absolute gains of 35.62, 37.97, 45.42, and 50.05 compared to CycleVAE, StarGAN-VC, Auto-VC, and VAE, respectively. The suggested method achieves CycleVAE, VAE, StarGAN-VC, and Auto-VC, respectively, in terms of naturalness by 42.49%, 51.60%, 69.37%, and 77.54%. The suggested method outperforms VAE, CycleVAE, StarGAN-VC, and Auto-VC, respectively, in terms of intelligibility, with absolute gains of 0.87, 0.93, 1.08, and 1.13. In terms of content similarity, the proposed method obtains 43.48%, 75.52%, 76.21%, and 108.62% improvements compared to CycleVAE, StarGAN-VC, Auto-VC, and VAE, respectively. ABX results show that the suggested method can personalize the voice for patients with hoarseness. This study demonstrates the feasibility of voice conversion methods in improving the speech quality of hoarse voices.

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Bovine mastitis is one of the most serious and costly disease affecting dairy cattle production. The present study explored the inflammatory response and autoprotective mechanism of a novel specific high expression BMNCR (bovine mastitis related long non-coding RNA) in S. aureus induced mastitis by miR-145/CBFB axis in dairy cows from the perspective of molecular genetics. In bovine mammary epithelial cells, we preformed loss of function experiments to detect changes in cytokine, proliferation and apoptosis by qRT-PCR, western blot, flow cytometry and EdU staining. The results demonstrated that BMNCR significantly increased cell apoptosis, and inhibited cell proliferation. However, the secretion of IL-1α, IL-2, IL-6, IL-8 and IL-12 were enhanced after knock-down BMNCR. Bioinformatics analysis demonstrated that BMNCR could target 8 miRNAs, in-depth analyses indicated that BMNCR acts as a molecular sponge for bta-miR-145 and CBFB was one of 23 target gene of bta-miR-145 . The results of the present study demonstrated that the role of BMNCR in S. aureus induced mastitis can be mediated by sponge bta-miR-145 activating CBFB expression. BMNCR could be a potential target for mastitis diagnosis and therapy, which may enrich the theoretical research of therapeutic intervention, and further increase milk yield and improve milk quality.

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Long noncoding RNAs have been identified as important regulators of gene expression and animal development. The expression of natural antisense transcripts (NATs) transcribed in the opposite direction to protein-coding genes is usually positively correlated with the expression of homologous sense genes and is the key factor for expression. Here, we identified a conserved noncoding antisense transcript, CFL1-AS1, that plays an important role in muscle growth and development. CFL1-AS1 overexpression and knockout vectors were constructed and transfected into 293T and C2C12 cells. CFL1-AS1 positively regulated CFL1 gene expression, and the expression of CFL2 was also downregulated when CFL1-AS1 was knocked down. CFL1-AS1 promoted cell proliferation, inhibited apoptosis and participated in autophagy. This study expands the research on NATs in cattle and lays a foundation for the study of the biological function of bovine CFL1 and its natural antisense chain transcript CFL1-AS1 in bovine skeletal muscle development. The discovery of this NAT can provide a reference for subsequent genetic breeding and data on the characteristics and functional mechanisms of NATs.

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Cardiovascular diseases (CVDs) are a leading cause of global mortality and have a high incidence rate worldwide. The function of inflammasomes in CVDs has received a lot of attention recently, and the nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome may be a new target for the prevention and treatment of CVDs. Flavonoids, which are found in food and plant extracts, inhibited inflammation in CVDs by regulating the NLRP3 inflammasome. CB-Dock was used to investigate whether 34 flavonoids from natural products acted on NLRP3 inflammasome. In brief, the PDB format of NLRP3 was selected as a protein file, and 34 flavonoids in SDF format were selected as the ligand file, and then input to CB-Dock for molecular docking. The docking results showed that epigallocatechin-3-gallate (EGCG), amentoflavone, baicalin, scutellarin, vitexin, silibinin, and puerarin had good binding affinities to NLRP3, which could be used as NLRP3 inhibitors, and aid in the discovery of lead compounds for the design and development of CVDs.

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Objectives: Inflammation vitally impacts the progression of depression resulting from intracerebral hemorrhage (ICH), while red blood cell distribution width (RDW) marks inflammatory-related diseases. The present study aimed at evaluating how RDW affects depression after ICH. Methods: From prospective analyses of patients admitted to our department between January 2017 and September 2022, ICH patients with complete medical records were evaluated. The 17-item Hamilton Depression (HAMD-17) scale was used for measuring the depressive symptoms at 3 months after ICH. Diagnosis of post-ICH depression was conducted for patients based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria. Results: A total of 438 patients were enrolled in the study, out of which 93 (21.23%) patients had PSD at the 3-month follow-up. Accordingly, patients with depression had higher RDW levels (13.70 [IQR: 13.56-13.89] vs.13.45 [IQR: 12.64-13.75], p < 0.001) at admission compared with those without depression. In multivariate analyses, RDW was used for independently predicting the depression after ICH at 3 months (OR: 2.832 [95% CI: 1.748-4.587], p < 0.001). After adjusting the underlying confounding factors, the odds ratio (OR) of depression after ICH was 4.225 (95% CI: 1.686-10.586, p = 0.002) for the highest tertile of RDW relative to the lowest tertile. With an AUC of 0.703 (95% CI: 0.649-0.757), RDW demonstrated a significantly better discriminatory ability relative to CRP and WBC. RDW as an indicator for predicting depression after ICH had an optimal cutoff value of 13.68, and the sensitivity and specificity were 63.4% and 64.6%, respectively. Conclusions: Elevated RDW level predicted post-ICH depression at 3 months, confirming RDW as an effective inflammatory marker for predicting depression after ICH.

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In recent years, more and more people suffer from voice-related diseases. Given the limitations of current pathological speech conversion methods, that is, a method can only convert a single kind of pathological voice. In this study, we propose a novel Encoder-Decoder Generative Adversarial Network (E-DGAN) to generate personalized speech for pathological to normal voice conversion, which is suitable for multiple kinds of pathological voices. Our proposed method can also solve the problem of improving the intelligibility and personalizing custom speech of pathological voices. Feature extraction is performed using a mel filter bank. The conversion network is an encoder-decoder structure, which is used to convert the mel spectrogram of pathological voices to the mel spectrogram of normal voices. After being converted by the residual conversion network, the personalized normal speech is synthesized by the neural vocoder. In addition, we propose a subjective evaluation metric named "content similarity" to evaluate the consistency between the converted pathological voice content and the reference content. The Saarbrücken Voice Database (SVD) is used to verify the proposed method. The intelligibility and content similarity of pathological voices are increased by 18.67% and 2.60%, respectively. Besides, an intuitive analysis based on a spectrogram was done and a significant improvement was achieved. The results show that our proposed method can improve the intelligibility of pathological voices and personalize the conversion of pathological voices into the normal voices of 20 different speakers. Our proposed method is compared with five other pathological voice conversion methods, and our proposed method has the best evaluation results.

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Cardiovascular diseases (CVDs) are currently the major cause of death and morbidity on a global scale. Thioredoxin-interacting protein (TXNIP) is a marker related to metabolism, oxidation, and inflammation induced in CVDs. The overexpression of TXNIP is closely related to the occurrence and development of CVDs. Hence, TXNIP inhibition is critical for reducing the overactivation of its downstream signaling pathway and, as a result, myocardial cell damage. Due to the chemical variety of dietary phytochemicals, they have garnered increased interest for CVDs prevention and therapy. Phytochemicals are a source of medicinal compounds for a variety of conditions, which aids in the development of effective and safe TXNIP-targeting medications. The objective of this article is to find and virtual screen novel safe, effective, and economically viable TXNIP inhibitors from flavonoids, phenols, and alkaloids derived from foods and plants. The results of the docking study revealed that silibinin, rutin, luteolin, baicalin, procyanidin B2, hesperetin, icariin, and tilianin in flavonoids, polydatin, resveratrol, and salidroside in phenols, and neferine in alkaloids had the highest Vina scores, indicating that these compounds are the active chemicals on TXNIP. In particular, silibinin can be utilized as a lead chemical in the process of structural alteration. These dietary phytochemicals may aid in the discovery of lead compounds for the development of innovative TXNIP agents for the treatment of cardiovascular disease.

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Long non-coding RNAs (LncRNAs) are generally longer than 200 bp in length and play an important regulatory role in the growth and development of skeletal muscle. In the previous work, the non-coding RNAs with abundant expression in bovine tissues were screened out. After quantitative real-time PCR (qPCR), 33 lncRNAs with differential expression in various bovine tissues were identified. Differential expression analysis base on tissue expression profiles of 33 lncRNAs, a long non-coding RNA LncRNA13, which may have effects on bovine muscle development, was found. The expression levels in embryo muscle and adult cattle muscle were significantly different (p < 0.01), so it is speculated that it may have a certain impact on the development of cattle muscle. It was named LncRNA 5.8S rRNA-OT1, and its overexpression vector pcDNA3.1-LncRNA 5.8S rRNA-OT1 was cloned and constructed. The purpose of this study is to further explore its impact on the proliferation and differentiation of bovine muscle cells and accumulate data to lay a foundation for further exploration of the function of LncRNA 5.8S rRNA-OT1 and add basic data for the study of the regulatory mechanism of lncRNA.

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Meat quality and meat composition are not separated from the influences of animal genetic improvement systems; the growth and development of skeletal muscle are the primary factors in agricultural meat production and meat quality. Though the muscle-type cofilin (CFL2) gene has a crucial influence on skeletal muscle fibers and other related functions, the epigenetic modification mechanism of the CFL2 gene regulating meat quality remains elusive. After exploring the spatiotemporal expression data of CFL2 gene in a group of samples from fetal bovine, calf, and adult cattle, we found that the level of CFL2 gene in muscle tissues increased obviously with cattle age, whereas DNA methylation levels of CFL2 gene in muscle tissues decreased significantly along with cattle age by BSP and COBRA, although DNA methylation levels and mRNA expression levels basically showed an opposite trend. In cell experiments, we found that bta-miR-183 could suppress primary bovine myoblast differentiation by negatively regulated CFL2. In addition, we packaged recombinant adenovirus vectors for CFL2 gene knockout and overexpression and found that the CFL2 gene could promote the differentiation of primary bovine myoblasts by regulating marker genes MYOD, MYOG and MYH3. Therefore, CFL2 is an essential mediator for promoting myogenic differentiation by regulating myogenic marker genes in cattle myoblasts.

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Coronary heart disease (CHD) is defined by atherosclerosis, which can result in stenosis or blockage of the arterial cavity, leading to ischemic cardiac diseases such as angina and myocardial infarction. Accumulating evidence indicates that the gut microbiota plays a vital role in the beginning and progression of CHD. The gut microbial metabolite, trimethylamine-N-oxide (TMAO), is intimately linked to the pathophysiology of CHD. TMAO is formed when trimethylamine (TMA) is converted by flavin-containing monooxygenases in the hepatocytes. Therefore, inhibition of TMA production is essential to reduce TMAO levels. Flavonoids may reduce the risk of death from cardiovascular disease. In this article, we reviewed and evaluated twenty-two flavonoids for the therapy of CHD based on their inhibition of TMA-lyase by molecular docking. Docking results revealed that baicalein, fisetin, acacetin, and myricetin in flavonoid aglycones, and baicalin, naringin, and hesperidin in flavonoid glycosides had a good binding effect with TMA-lyase. This indicates that these chemicals were the most active and could be used as lead compounds for structural modification in the future. PRACTICAL APPLICATIONS: Flavonoids are a large class of polyphenolic compounds found in fruits, vegetables, flowers, tea, and herbal medicines, which are inexorably metabolized and transformed into bioactive metabolites by α-rhamnosidase, ß-glucuronidase, ß-glucosidase, and nitroreductase produced by the gut microbiota, which plays a beneficial role in the prevention and treatment of cardiovascular diseases. Because flavonoids protect the cardiovascular system and regulate the gut microbiota, and the gut microbiota is directly connected to TMAO, thus, reducing TMAO levels involves blocking the transition of TMA to TMAO, which may be performed by reducing TMA synthesis. Molecular docking results found that baicalein, fisetin, acacetin, and myricetin in flavonoid aglycones, and baicalin, naringin, and hesperidin in flavonoid glycosides had good binding effects on TMA-lyase, which were the most active and could be used as lead compounds for structural modification.

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As the quality of beef products has received increasing attention, it is essential to explore the underlying transcriptional and epigenetic mechanisms of meat traits. Our project uses Qinchuan cattle as the research subject. First, we examined the spatiotemporal expression pattern of the CFL1 gene in a panel of fetal bovine, calf, and adult cattle samples. Then, we performed DNA methylation experiments of CFL1 on myogenesis and muscle maturation using the BSP amplification and COBRA sequencing techniques and found that high DNA methylation levels showed low expression levels. Next, we performed an assay between bta-miR-182 and the CFL1 gene and demonstrated that miR-182 could promote bovine primary myoblast differentiation by negatively regulated the expression of CFL1. Finally, we constructed an adenovirus overexpression and interference vector and found that CFL1 could suppress the differentiation of bovine primary myoblasts. In summary, our experiment comprehensively analyzes the epigenetic regulation mechanisms of the CFL1 gene in the development and differentiation of bovine primary myoblasts. This has far-reaching significance for improving the meat production and meat quality of Qinchuan cattle. This can provide reliable data support and a theoretical research basis for the rapid and efficient breeding selection of local yellow cattle and the genetic improvement of meat quality.

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Based on our results of genome-wide association analysis, we performed gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis; three candidate genes (ABCG2, CD44, SPP1) were screened in this study for SNPs association analysis with production traits in 999 Holstein cattle. In this research, flight mass spectrometry genotyping was used to detect the polymorphism of SNP seats. It was shown that four, four, and two single nucleotide polymorphisms (SNP) loci were detected for the ABCG2, CD44, and SPP1 genes, respectively, and the different genotypes of these 10 SNPs significantly affected the milk production performance of Chinese Holstein cattle in terms of milk yield, milk fat percentage, milk protein percentage, somatic cell score, and urea nitrogen content. Among them, ABCG2-G.80952G > T locus, ABCG2-G.120017G > A locus and CD44-G.2294G > C locus had significant effects on somatic cell score (p < 0.01). Cows with GG genotypes at ABCG2-G.80952G > T locus, AA and GG genotypes at ABCG2-G.120017G > A locus, and GG genotypes at CD44-G.2294G > C locus had lower somatic cell scores. The present study elucidated that ABCG2, CD44, and SPP1 could be selected for marker-assisted selection and will benefit for future precise molecular breeding.

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Analysing the molecular regulation mechanism of fat deposition in yellow cattle can provide a theoretical basis for the breeding of excellent beef cattle. ANGPTL8 (angiopoietin-like protein 8) promotes the formation of lipid droplets during adipocyte differentiation. To explore the promoter active region of ANGPTL8 and predict potential transcription factors, we further provide a theoretical basis for the functional analysis and regulatory mechanism of ANGPTL8 in adipogenesis. The promoter region of bovine ANGPTL8 was cloned by overlap extension PCR. Online software was used to predict potential transcription factor binding sites, and it identified PPARγ, SREBP1, C/EBPα, and Znf423 transcription factor binding sites in ANGPTL8 promoter region. A luciferase reporter gene vector which contained different deletion fragments of the ANGPTL8 promoter was constructed. Then, the vectors were cotransfected into 293 T cells with the internal control plasmid pRL-TK by cationic liposomes, and the relative fluorescence intensity was detected by a microplate reader. The results of the luciferase activity analysis showed that the core promoter area of ANGPTL8 was in the -885/-227 bp region of the 5' flanking sequence, while just two SREBP1 binding sites occurred in this area. When SREBP1 was knocked down by siRNA, the expression level of ANGPTL8 was reduced, and we speculated that SREBP1 may be an important transcription factor regulating ANGPTL8 transcription.

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We report the near to middle infrared luminescence and energy transfer process of Er(3+)/Yb(3+) co-doped fluorotellurite glasses under 980, 1550 and 800 nm excitations, respectively. Using a 980 nm laser diode pump, enhanced 1.5 and 2.7 µm emissions from Er(3+):I13/2→(4)I15/2 and I11/2→(4)I13/2 transitions are observed, in which Yb(3+) ions can increase pumping efficiency and be used as energy transfer donors. Meanwhile, Yb(3+) can also be used as an acceptor and intensive upconversion luminescence of around 1000 nm is achieved from Er(3+):I11/2→(4)I15/2 and Yb(3+): F5/2→(4)F7/2 transitions using 1550 nm excitation. In addition, the luminescence properties and variation trendency by 800 nm excitation is similar to that using 1550 nm excitation. The optimum Er(3+) and Yb(3+) ion ratio is 1:1.5 and excess Yb(3+) ions decrease energy transfer efficiency under the two pumpings. These results indicate that Er(3+)/Yb(3+) co-doped fluorotellurite glasses are potential middle- infrared laser materials and may be used to increase the efficiency of the silicon solar cells.

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AlF3-based glasses (AlF3-YF3-CaF2-BaF2-SrF2-MgF2) with enhanced thermal and chemical stability were synthesized and compared with the well-known fluorozirconate glass (ZBLAN). The 2.7 µm mid-infrared emission in the AlF3-based glasses was also investigated through the absorption and emission spectra. Both the temperature of glass transition and the characteristic temperatures (ΔT, Hr, k(gl)) of the fluoroaluminate glasses were much larger than those of the ZBLAN glasses. The corrosion phenomenon can be observed by naked-eye, and the transmittance dropped dramatically (0% at 3 µm) when the ZBLAN glass was placed into distilled water. However, the AlF3-based glass was relatively stable. The fluoroaluminate glasses possessed large branching ratio (20%) along with the emission cross section (9.4×10(-21) cm(-2)) of the Er(3+):(4)I(11/2)→(4)I(13/2) transition. Meanwhile, the enhanced 2.7 µm emission in highly Er(3+)-doped AYF glass was obtained. Therefore, these results showed that this kind of fluoride glass has a promising application for solid state lasers at 3 µm.

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The 2.05 µm emission has been obtained using a 980 nm laser excitation in Ho(3+)/Yb(3+)/Er(3+) triply doped fluorotellurite glass. Strong emission near 2.05 µm is demonstrated and the corresponding energy transfer mechanisms are discussed and analyzed according to the photoluminescence performance and absorption measurements. Yb(3+) and Er(3+) ions can absorb the pumping energy and transfer it to Ho(3+) ions efficiently. These results indicate that this Ho(3+)/Yb(3+)/Er(3+) triply doped fluorotellurite glass has potential applications in 2.0 µm laser.

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With a 980 nm laser diode (LD) pumped, the sensitized effect of Yb(3+) ions on 2.7 µm emission properties and energy transfer mechanism in Yb(3+)/Er(3+) co-doped tungsten-tellurite glass were investigated in present paper. Based on absorption spectra, Judd-Ofelt parameters and radiative transition probabilities were calculated and analyzed. The emission spectra were tested and the optimized concentration ratio of Yb(3+) to Er(3+) ions was found to be 3:0.5 with a largest calculated emission cross-section (6.05×10(-21) cm(2)) corresponding to Er(3+):(4)I11/2→(4)I13/2 transition. When the concentration ratio of Yb(3+) to Er(3+) ions was 4:0.5, 1.5 µm and 2.7 µm emission decreased while up-conversion increased. The decreased 1.5 µm and 2.7 µm emission were induced by the saturation of Er(3+):(4)I13/2 level. In brief, the advantageous spectroscopic characteristics indicated that Yb(3+)/Er(3+) co-doped tungsten-tellurite glass may be a promising candidate for application of 2.7 µm emission.

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A new type of fluoride glasses with high erbium-doping concentration (up to 6 mol. % Er(3+)) is investigated. The intensive 2.7 µm fluorescence is demonstrated with minimized concentration quenching. The intensity parameters and radiative properties are determined from the absorption spectrum based on the Judd-Ofelt theory. The prepared Er(3+)-doped ZBYA glass possesses high predicted spontaneous-transition probability (28.92 s(-1)) and large calculated emission cross section (9.8×10(-21) cm(2)). All these results indicate that this Er(3+)-doped ZrF(4)-based fluoride glass has potential applications in 2.7 µm laser materials.