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Spermatogonial stem cells (SSCs) have vast application prospects in livestock and poultry production, genetic engineering, and medical research. However, the scarcity of SSCs and the complexity of their development limit the elucidation and verification of the mechanism of SSCs in vitro. Although miRNAs have been identified as critical players in germ cell development, upstream regulatory mechanisms by which miRNAs regulate SSCs formation are rarely reported. In this study, miR-1458, which was differentially expressed during SSCs formation, was selected by transcriptomic sequencing. We found that miR-1458, inhibited in an in vitro SSCs induction model,significantly upregulated the expression of germline marker genes (Cvh and integrin β1). Further analysis using Immunofluorescence and Flow Cytometry confirmed that miR-1458 inhibition promotes the formation of spermatogonial stem-like cells (SSCLCs). Immunohistochemical significantly increased the number of SSCs in the testis in vivo. However, significant upregulation of miR-1458 showed opposite results. High-throughput sequencing results showed that miR-1458 interacted with TBX6, one of the target genes of miR-1458, involved in affecting cell differentiation, and dual-luciferase reporter vectors confirmed the targeting relationship between the two. TBX6 overexpression and knockdown in vitro and in vivo have validated its function in SSCs formation. We found that overexpression of TBX6 promoted SSCs formation. Additionally, we identified Vitamin B6, a key metabolite affecting SSCs formation, as an upstream regulator of miR-1458 expression. The results showed that low concentrations of Vitamin B6 led to low expression of miR-1458 by decreasing histone demethylation levels. Overall, our findings suggest that miR-1458 is involved in SSCs formation, which is inhibited by low concentrations of Vitamin B6 and subsequently regulates the formation of SSCs by targeting TBX6, an essential gene involved in embryonic stem cell differentiation. Our study demonstrates the critical role of the Vitamin B6-miR-1458-TBX6 regulatory axis in spermatogonial stem cell formation in Rugao Yellow Chicken, providing new insights into the regulatory mechanisms by which miRNAs affect SSCs formation. It should be noted that most of the germline findings related to miRNAs were obtained by in vitro studies, and in vivo studies are needed to validate our results for clinical applications.

Background: Coronary heart disease (CHD) is the most common cardiovascular disease facing human beings. Cardiac remodelling is an important pathological factor for the progression of heart failure (HF) after CHD. At present, Chinese medicine is widely used in the treatment of HF, but there are still some drugs lack of evidence-based and mechanism evidence. Multi-omics techniques can deep explore candidate pathogenic factors and construct gene regulatory networks.This trial is intended to evaluate the effect on Huoxin pill (HXP) in the treatment of HF after programmable communication interface (PCI). Meantime, multi-omics analysis technique will be used to target the fundamental pathological links of cardiac remodelling, so as to study the mechanism of HXP in the treatment of HF after PCI. Methods: This study is a randomized, double-blind, placebo-controlled trial. Sixty patients with HF undergoing PCI are recruited from the First Affiliated Hospital of Henan University of CM. All selected patients will be randomly attributed to receive conventional treatment + HXP or placebo. The packaging, dosage and smell of placebo and heart activating pill were identical. The primary outcome is NYHA cardiac function grade, while the secondary outcomes included Lee's HF score, exercise tolerance test, and quality of life evaluation. Additional indicators include cardiac ultrasound, electrocardiogram, 24-h dynamic electrocardiogram, myocardial injury indicators, and energy metabolism indicators. Discussion: This study may provide a new treatment option for patients with HF after PCI and provide evidence for the treatment of CHD and HF with HXP. Trial registration: 2023-10-08 registered in China Clinical Trial Registry, registration number ChiCTR2300076402.

There are different stress resistance among different breeds of pigs. Changes in intestinal stem cells (ISCs) are still unclear among various breeds of piglets after early weaning. In the current study, Taoyuan Black and Duroc piglets were slaughtered at 21 days of age (early weaning day) and 24 days of age (3 days after early weaning) for 10 piglets in each group. The results showed that the rate of ISC-driven epithelial renewal in local Taoyuan Black pigs hardly changed after weaning for 3 days. However, weaning stress significantly reduced the weight of the duodenum and jejunum in Duroc piglets. Meanwhile, the jejunal villus height, tight junction-related proteins (ZO-1, Occludin, and Claudin1), as well as the trans-epithelial electrical resistance (TEER) values, were down-regulated after weaning for 3 days in Duroc piglets. Moreover, compared with Unweaned Duroc piglets, the numbers of Olfm4+ ISC cells, PCNA+ mitotic cells, SOX9+ secretory progenitor cells, and Villin+ absorptive cells in the jejunum were reduced significantly 3 days after weaning. And ex vivo jejunal crypt-derived organoids exhibited growth disadvantages in weaned Duroc piglets. Notably, the Keap1/Nrf2 signaling activities and the expression of HO-1 were significantly depressed in weaned Duroc piglets compared to Unweaned Duroc piglets. Thus, we can conclude that ISCs of Duroc piglets were more sensitive to weaning stress injury than Taoyuan Black piglets, and Keap1/Nrf2 signaling is involved in this process.

Abstract Background and purpose: There is increasing evidence to support a role for human herpes viruses in the development of neurodegenerative disorders; however, the association between varicella‐zoster virus (VZV) infection and dementia, and the effect of antiviral therapy on the risk for dementia remain unclear. Methods We searched PubMed, Embase, and the Cochrane Library databases from their dates of inception to May 2023. Odds ratios (ORs) with 95% confidence intervals (CIs) served as indicators of effect sizes in evaluations of the effect of VZV infection and antiviral treatment on dementia risk. Subgroup analyses based on study design, study location, diagnostic criteria of dementia, and VZV subtype classification were also performed. Results A total of 10 studies with 316,846 dementia cases were included in the meta‐analysis. We found that any VZV infection (OR: 1.04, 95% CI: .97–1.12; p = .22), herpes zoster (HZ) (OR: 1.05, 95% CI: .96–1.13; p = .28), or HZ involving the cranial nerves (OR: 1.36, 95% CI: .76–2.43; p = .304) was not associated with an increased risk of dementia. The results of subgroup analyses were consistent with these findings. However, patients infected with VZV who received antiviral treatment had a lower OR than untreated patients infected with VZV. Compared to individuals not infected with VZV, antiviral therapy in those infected with VZV was associated with reduced risk for dementia. Conclusion The association between VZV infection and dementia may be masked by antiviral treatment. Further studies with longer follow‐up times that consider the severity of VZV infection and antiviral treatment are needed to clarify the contribution of VZV infection to the risk for dementia.

ObjectivesTo construct a prognostic nomogram to predict the ablation zone disappearance for patients with papillary thyroid microcarcinoma (PTMC) after microwave ablation (MWA).Materials and methodsFrom April 2020 to April 2022, patients with PTMC who underwent MWA treatment were collected retrospectively. Ultrasound (US) or contrast-enhanced ultrasound (CEUS) was performed at 1 day, 1, 3, 6, 12, 18 and 24 months after MWA to observe the curative effect after ablation. The volume, volume reduction rate (VRR) and complete disappearance rate of the ablation zone at each time point were calculated. Univariate and multivariate logistic regression analysis were used to determine the prognostic factors associated with the disappearance of the ablation zone after MWA, and the nomogram was established and validated.Results72 patients with PTMCs underwent MWA were enrolled into this study. After MWA, no tumor progression (residual, recurrence or lymph node metastasis) and major postoperative complications occurred. The ablation zone in 28 (38.89%) patients did not completely disappear after MWA in the follow-up period. Three variables, including age (odds ratio [OR]: 1.216), calcification type (OR: 12.283), initial maximum diameter (OR: 2.051) were found to be independent prognostic factors predicting ablation zone status after MWA by multivariate analysis. The above variables and outcomes were visualized by nomogram (C-index=0.847).ConclusionsMWA was a safe and effective treatment for PTMC. Older patients with macrocalcification and larger size PTMCs were more unlikely to obtain complete disappearance of ablation zones. Incomplete disappearance of ablation zone was not related to recurrence.

The one-time application of blended urea (BU), combining controlled-release urea (CRU) and uncoated urea, has proven to be a promising nitrogen (N) management strategy. However, the long-term sustainability of blending urea remains largely unexplored. To assess whether a single application of blended urea could effectively replace split uncoated urea applications, a long-term field experiment was conducted in the North China Plain (NCP). The results indicated that, when compared to common urea (CU) at the optimal N rate (180 kg N ha−1), BU achieved comparable grain yields, N uptake and NUE (61% vs. 62). BU exhibited a 12% higher 0–20 cm soil organic nitrogen stock and a 9% higher soil organic carbon (C) stock. Additionally, BU reduced life–cycle reactive N (Nr) losses and the N footprint by 10%, and lowered greenhouse gas (GHG) emissions and the C footprint by 7%. From an economic analysis perspective, BU demonstrated comparable private profitability and a 3% greater ecosystem economic benefit. Therefore, BU under the optimal N rate has the potential to substitute split applications of common urea in the long–term and can be regarded as a sustainable N management strategy for wheat and maize production in the NCP.

BackgroundSex differentiation is a complex and precisely regulated process by multiple genes in chicken. However, it is still unclear on the key genes of sex differentiation.ObjectiveTo explore the function of Tle4z1 screened by RNA-seq sequencing on sex differentiation during the development of chicken embryos.MethodsTle4z1 was differentially expressed from the RNA-seq of ESCs and PGCs in male and female chickens. Then, we established an effective method to overexpression or knocking down the expression of Tle4z1 in ovo and in vitro, respectively. Histomorphological observation, qRT-PCR and ELISA were applied to detect the function of Tle4z1 in the process of male sex differentiation by injecting vectors into embryos at day 0.ResultsIt showed that Tle4z1 has significant male preference in embryonic day 4.5, such phenomenon persisted during the growth period of chicken embryos. Morphological observation results showed that the gonads on both sides of genetic male (ZZ) embryos with Tle4z1 knocking down developed asymmetrically, the gonadal cortex became thicker showing the typical characteristics of genetic female (ZW) gonads. Furthermore, the expression of Cyp19a1, which dominates female differentiation, was significantly increased, while the expression of male marker genes Dmrt1, Sox9, WT1 and AR was significantly downregulated. In addition, the concentration of testosterone also significantly decreased, which was positively correlated with the expression of Tle4z1 (P < 0.01). Conversely, the ZW embryo showed defeminized development when Tle4z1 was overexpressed.ConclusionWe prove that the Tle4z1 is a novel gene through the male sexual differentiation via gene regulation process and synthesis of testosterone, which construct the basis for understanding the molecular mechanism of sex differentiation in chickens.

Lin28A and Lin28B are homologous RNA-binding proteins that participate in the development of primordial germ cells. The mechanisms underlying expression and regulation of Lin28A have been well documented, but such information for Lin28B is limited. In this study, a fragment of the Lin28B promoter was cloned, the pEGFP-pLin28B vector was constructed. DF-1 chicken fibroblasts were transfected and the expression of green fluorescent protein (GFP) was measured. Furtherly, Lin28B promoter of different lengths fragments was cloned using the chromosome-walking method and the fragments were ligated into the PGL3-Basic vector, and transfected into DF-1 cells. Results of dual-luciferase reporter assay showed that the core of the Lin28B promoter was included in the sequence from –1 431 to –1 034 bp. The binding sites of the transcription factor TCF7L2 was showed within this sequence by bioinformatics analysis. The promoter activity of Lin28B was downregulated (P

Although nitrogen (N) fertilizer application plays an essential role in improving crop productivity, an inappropriate management can result in negative impacts on environment and human health. To break this dilemma, a 12-year field experiment (2008–2019) with five N application rates was conducted on the North China Plain (NCP) to evaluate the integrated impacts of optimizing N management (Opt. N, 160 kg N ha−1 on average) on agronomic, environmental, health, and economic performances of summer maize production. Over the 12-year study, the Opt. N treatment achieved the maximal average grain yield (10.6 Mg ha−1) and grain protein yield (793 kg ha−1) among five N treatments. The life cycle assessment methodology was applied to determine the negative impacts on environmental and human health, and both of them increased with the N rate. Compared with the farmers’ conventional N rate (250 kg N ha−1), the Opt. N treatment reduced acidification, eutrophication, global warming, and energy depletion potentials by 29%, 42%, 35%, and 18%, respectively, and reduced the health impact by 32% per Mg of grain yield or grain protein yield produced. Both the Opt. N and Opt. N*50–70% treatments resulted in high private profitability (2038 USD ha−1), ecosystem economic benefit (1811 USD ha−1), and integrated compensation benefit (17,548 USD ha−1). This study demonstrates the potential benefits of long-term optimizing of N management to maintain high maize yields and grain quality, to reduce various environmental impacts and health impacts, and to enhance economic benefits. These benefits can be further enhanced when Opt. N was combined with advanced agronomic management practices. The results also suggest that reducing the optimal N rate from 160 to 145 kg N ha−1 is achievable to further reduce the negative impacts while maintaining high crop productivity. In conclusion, optimizing the N management is essential to promote sustainable summer maize production on the NCP.

Aroma is an essential quality indicator of oolong tea, a tea derived from the Camellia sinensis L. plant. Carboxylic 6 (C6) acids and their derivative esters are important components of fatty acid (FA)-derived volatiles in oolong tea. However, the formation and regulation mechanism of C6 acid during postharvest processing of oolong tea remains unclear. To gain better insight into the molecular and biochemical mechanisms of C6 compounds in oolong tea, a combined analysis of alcohol dehydrogenase (ADH) activity, CsADH2 key gene expression, and the FA-derived metabolome during postharvest processing of oolong tea was performed for the first time, complemented by CsHIP (hypoxia-induced protein conserved region) gene expression analysis. Volatile fatty acid derivative (VFAD)-targeted metabolomics analysis using headspace solid-phase microextraction–gas chromatography time-of-flight mass spectrometry (HS-SPEM-GC-TOF-MS) showed that the (Z)-3-hexen-1-ol content increased after each turnover, while the hexanoic acid content showed the opposite trend. The results further showed that both the ADH activity and CsADH gene expression level in oxygen-deficit-turnover tea leaves (ODT) were higher than those of oxygen-turnover tea leaves (OT). The C6-alcohol-derived ester content of OT was significantly higher than that of ODT, while C6-acid-derived ester content showed the opposite trend. Furthermore, the HIP gene family was screened and analyzed, showing that ODT treatment significantly promoted the upregulation of CsHIG4 and CsHIG6 gene expression. These results showed that the formation mechanism of oolong tea aroma quality is mediated by airflow in the lipoxygenase–hydroperoxide lyase (LOX-HPL) pathway, which provided a theoretical reference for future quality control in the postharvest processing of oolong tea.

In this paper, the properties of wide-angle and ultra-wideband (UWB) absorption of one-dimensional (1-D) superconductor photonic crystals (SPCs) in the terahertz (THz) region are theoretically analyzed by transfer matrix method (TMM). We principally study the absorption features in SPCs with different arrangements by contrast where their external factors and dielectric types are consistent. The arrangements of SPCs adopt two construction rules of generous Fibonacci sequence (GFS) and Cantor-like sequence (CLS). In addition, the influences of the recursive numbers, external factors and polarization-depend properties on the proposed structures are also considered. We introduce multifractal theory to describe the absorption trends and self-similarity of quasi-periodic structural system subtly specific to the variation of recursive numbers. Moreover, the reason for angle-insensitive absorption is also investigated via the interference field theory. The calculated results demonstrate that the UWB absorption can sustain over 80 degrees within THz region for transverse magnetic (TM) wave at high temperature in the proposed SPCs, which provides theoretical guidance for the design of the high-performance THz absorber.

As important factors to oolong tea quality, the accumulation and dynamic change in aroma substances attracts great attention. The volatile composition of oolong tea is closely related to the precursor contents. Fatty acids (FAs) and their derivatives are basic components of oolong tea fragrance during the postharvest process. However, information about the precursors of FAs during the postharvest process of oolong tea production is rare. To investigate the transformation of fatty acids during the process of oolong tea production, gas chromatograph–flame ionization detection (GC-FID) was conducted to analyze the composition of FAs. The results show that the content of total polyunsaturated FAs initially increased and then decreased. Specifically, the contents of α-linolenic acid, linoleic acid and other representative substances decreased after the turn-over process of oolong tea production. The results of partial least squares discrimination analysis (PLS-DA) showed that five types of FAs were obviously impacted by the processing methods of oolong tea (VIP > 1.0). LOX (Lipoxygenase, EC 1.13.11.12) is considered one of the key rate-limiting enzymes of long-chain unsaturated FAs in the LOX-HPL (hydroperoxide lyase) pathway, and the mechanical wounding occurring during the postharvest process of oolong tea production greatly elevated the activity of LOX.

MicroRNAs (miRNAs) are essential factors in the reproductive process of poultry. Here, we found miR-302d is a potential differentiation and negative factor of chicken embryonic stem cells (ESCs) into spermatogonia stem cells (SSCs). The competition mechanism was carried out for the preliminary exploration to determine the relationship among miR-302d, lncRNA-341(interacting with miR-302d), and target gene TLE4. The results showed that lncRNA-341 can competitively bind to miR-302d to decrease the targeted binding of miR-302d and TLE4 which promotes the differentiation of chicken SSCs. Moreover, it is suggested that miR-302d may participate in the Wnt signaling pathway through TLE4.

Objectives To investigate the relationship between coronary artery calcification and calcium deposition in cardiomyocytes. Methods Patients who underwent valve replacement plus surgical ablation for atrial fibrillation, together with left atrial appendage resection, were included. Coronary artery calcification (CAC) score was evaluated prior to surgery using dual-source computed tomography. Samples of left atrial appendage tissue were collected to analyse the following indicators: calcium deposition, alkaline phosphatase activity, calcium content, protein levels of runt-related transcription factor 2 (Runx2), osteopontin and β-catenin, and mRNA levels of osteopontin, endothelin and ghrelin. Relationships between CAC score and various indicators were analysed by univariate logistic or linear regression. Results Out of tissue from eight patients, CAC score was not correlated with cardiomyocyte calcification (odds ratio [OR] 0.984 and OR 0.983; von Kossa or alizarin red staining, respectively). CAC score showed an inverse linear correlation with Runx2 protein (β = –0.75), but was not correlated with osteopontin (β = –0.52) or β-catenin protein (β = –0.56), mRNA levels of osteopontin, endothelin and ghrelin (β = 0.13, 0.02, and 0.02, respectively), alkaline phosphatase activity (β = 0.56), or calcium content (β = –0.22). Conclusions Coronary artery calcification was not correlated with calcium deposition in cardiomyocytes.

Primordial germ cells are the ancestors of female and male cells. Current research has shown that long non-coding RNA (lncRNA) and Histone methylation are the pivotal epigenetic factors in the PGC formation. However, there are few studies on the regulatory mechanism of lncRNA in the formation of PGC. Here, we define the lncRNA highly expressed in chicken PGC, lncCPSET1 (chicken-PGC-specifically-expressed transcript 1) This study found that compared with the interference of lncCPSET1/histone methylase Mll2 alone, the PGC formation was severely inhibited with the interference of lncCPSET1 and histone methylase Mll2 jointly in vivo and in vitro. Studies on the transcription level of lncCPSET1 found that H3K4me2 and transcription factor Jun have a positive effect on the activation of lncCPSET1; while DNA hypomethylation inhibits the expression of lncCPSET1. In terms of mechanism, compared with DNA methylation, H3K4me2 dominates lncCPSET1 activation. H3K4me2 can be enriched in the lncCPSET1 promoter, change its chromosome conformation, recruit the transcription factor Jun, and activate the expression of lncCPSET1. Taken together, we confirmed the model that H3K4me2 rather than DNA hypomethylation mediates Jun to regulate lncCPSET1 transcription, which broadens the study of lncCPSET1 pre-transcriptional mechanism.

Six new diphenyl ethers (1⁻6) along with eleven known analogs were isolated from the ethyl acetate extract of a marine-derived Aspergillus sydowii guided by LC-UV-MS. Their structures were unambiguously characterized by HRESIMS, NMR, as well as chemical derivatization. Compounds 1 and 2 are rare diphenyl ether glycosides containing d-ribose. The absolute configuration of the sugar moieties in compounds 1⁻3 was determined by a LC-MS method. All the compounds were evaluated for their cytotoxicities against eight cancer cell lines, including 4T1, U937, PC3, HL-60, HT-29, A549, NCI-H460, and K562, and compounds 1, 5, 6, and 8⁻11 were found to exhibit selective cytotoxicity against different cancer cell lines.

A series of pyrazolo[3,4-d]pyrimidine derivatives related to allopurinol has been synthesized and evaluated for its cytotoxicity against a panel of three cancer cell lines as well as its xanthine oxidase (XOD) inhibitory activities. Among them, compound 4 showed potent cytotoxicity with IC50 values of 25.5 and 35.2 μM against human hepatoma carcinoma cell lines, BEL-7402 and SMMC-7221, respectively. The anticancer activity of 4 was comparable to that of Tanespimycin (17-N-allylamino-17-demethoxy geldanamycin, 17-AAG) that inhibited the growth of BEL-7402 and SMMC-7221 cells at IC50 values of 12.4 and 9.85 μM, respectively. However, unlike allopurinol, which is also a strong inhibitor of XOD, compound 4 is a much weaker XOD inhibitor, suggesting that the anticancer activities of the allopurinol derivatives may not be associated with XOD inhibition. Moreover, the cytotoxicity of 4 toward normal cells is significantly lower than that of 17-AAG, making 4 a promising lead compound for further optimization of structure-activity relationships that may lead to anticancer agents of clinical utility.