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1.
Transl Stroke Res ; 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39322815

ABSTRACT

Disruption of the blood-brain barrier (BBB) is an important pathological hallmark of ischemic stroke. Blood-brain barrier disruption (BBBD) is a consequence of ischemia and may also exacerbate damage to brain parenchyma. Therefore, maintaining BBB integrity is critical for the central nervous system (CNS) homeostasis. This review offers a concise overview of BBB structure and function, along with the mechanisms underlying its impairment following a stroke. In addition, we review the recent imaging techniques employed to study blood-brain barrier permeability (BBBP) in the context of ischemic brain injury with the goal of providing imaging guidance for stroke diagnosis and treatment from the perspective of the BBBD. This knowledge is vital for developing strategies to safeguard the BBB during cerebral ischemia.

2.
Plant Cell Environ ; 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39257329

ABSTRACT

Apple leaf spot is one of the most devastating diseases in the apple industry, caused by Alternaria alternata f. sp mali (A. alternata). SET-domain group (SDG) proteins function as the histone methyltransferases and participate in plant development and stress responses. However, whether SDG proteins are associated with A. alternata resistance is largely unclear. Here, we describe the pathogen-inducible MdSDG26 gene in apple (Malus × domestica). MdSDG26 has two transcript variants that function similarly in catalyzing histone methylation and A. alternata resistance. Transient overexpression of MdSDG26 increased the global levels of H3K4me3 and H3K36me3, whereas knockdown of MdSDG26 only reduced the H3K36me3 level. Transcriptome analysis revealed that MdSDG26 affected the genome-wide transcriptome changes in response to A. alternata infection. ChIP-qPCR analysis demonstrated that MdSDG26 modulates the levels of H3K36me3 and H3K4me3 at both the promoter and exon regions of MdNTL9. As a negative regulator of A. alternata resistance in apples, MdNTL9 plays a pivotal role in MdSDG26-mediated resistance to A. alternata. Therefore, our findings provide compelling evidence for the regulatory function of MdSDG26 in histone methylation and its molecular role in conferring resistance to A. alternata.

3.
Cell Biochem Biophys ; 2024 Sep 09.
Article in English | MEDLINE | ID: mdl-39249180

ABSTRACT

One of the leading causes of mortality for women is gynecologic cancer (GC). Numerous molecules (tumor suppressor genes or oncogenes) are involved in this form of cancer's invasion, metastasis, tumorigenic process, and therapy resistance. Currently, there is a shortage of efficient methods to eliminate these diseases, hence it is crucial to carry out more extensive studies on GCs. Novel pharmaceuticals are required to surmount this predicament. Highly conserved molecular chaperon, heat shock protein (HSP) 90, is essential for the maturation of recently produced polypeptides and offers a refuge for misfolding or denatured proteins to be turned around. In cancer, the client proteins of HSP90 play a role in the entire process of oncogenesis, which is linked to all the characteristic features of cancer. In this study, we explore the various functions of HSPs in GC progression. We also discuss their potential as promising targets for pharmacological therapy.

4.
Heliyon ; 10(15): e34585, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39144966

ABSTRACT

Objective: Inflammation plays an important role in the transformation of pulmonary nodules (PNs) from benign to malignant. Prediction of benignancy and malignancy of PNs is still lacking efficacy methods. Although Mayo or Brock model have been widely applied in clinical practices, their application conditions are limited. This study aims to construct a diagnostic model of PNs by machine learning using inflammation-related biological markers (IRBMs). Methods: Inflammatory related genes (IRGs) were first extracted from GSE135304 chip data. Then, differentially expressed genes (DEGs) and infiltrating immune cells were screened between malignant pulmonary nodules (MN) and benign pulmonary nodule (BN). Correlation analysis was performed on DEGs and infiltrating immune cells. Molecular modules of IRGs were identified through Consistency cluster analysis. Subsequently, IRBMs in IRGs modules were filtered through Weighted gene co-expression network analysis (WGCNA). An optimal diagnostic model was established using machine learning methods. Finally, external dataset GSE108375 was used to verify this result. Results: 4 hub IRGs and 3 immune cells showed significantly difference between MN and BN, C1 and C2 module, namely PRTN3, ELANE, NFKB1 and CTLA4, T cells CD4 naïve, NK cells activated and Monocytes. IRBMs were screened from black module and yellowgreen module through WGCNA analysis. The Support vector machines (SVM) was identified as the optimal model with the Area Under Curve (AUC) was 0.753. A nomogram was established based on 5 hub IRBMs, namely HS.137078, KLC3, C13ORF15, STOM and KCTD13. Finally, external dataset GSE108375 verified this result, with the AUC was 0.718. Conclusion: SVM model established by 5 hub IRBMs was able to effectively identify MN or BN. Accumulating inflammation and immune dysfunction were important to the transformation from BN to MN.

5.
Article in English | MEDLINE | ID: mdl-39175431

ABSTRACT

The activation of hepatic stellate cells (HSCs) is central to the occurrence and development of liver fibrosis. Our previous studies showed that autophagy promotes HSC activation and ultimately accelerates liver fibrosis. Unc-51-like autophagy activating kinase 1 (ULK1) is an autophagic initiator in mammals, and N 6-methyladenosine (m 6A) modification is closely related to autophagy. In this study, we find that the m 6A demethylase fat mass and obesity-associated protein (FTO), which is the m 6A methylase with the most significant difference in expression, is upregulated during HSC activation and bile duct ligation (BDL)-induced hepatic fibrosis. Importantly, we identify that FTO overexpression aggravates HSC activation and hepatic fibrosis via autophagy. Mechanistically, compared with other autophagy-related genes, ULK1 is a target of FTO because FTO mainly mediates the m 6A demethylation of ULK1 and upregulates its expression, thereby enhancing autophagy and the activation of HSCs. Notably, the m 6A reader YTH domain-containing protein 2 (YTHDC2) decreases ULK1 mRNA level by recognizing the m 6A binding site and ultimately inhibiting autophagy and HSC activation. Taken together, our findings highlight m6A-dependent ULK1 as an essential regulator of HSC autophagy and reveal that ULK1 is a novel potential therapeutic target for hepatic fibrosis treatment.

6.
Genes (Basel) ; 15(8)2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39202427

ABSTRACT

DNA methylation plays an important role in the development and tissue differentiation of eukaryotes. In this study, bisulfite sequencing (BS-seq) technology was used to analyze the DNA methylation profiles of liver tissues taken from Rongchang pigs at three postnatal feeding stages, including newborn, suckling, and adult. The DNA methylation pattern across the genomes or genic region showed little difference between the three stages. We observed 419 differentially methylated regions (DMRs) in promoters, corresponding to 323 genes between newborn and suckling stages, in addition to 288 DMRs, corresponding to 134 genes, between suckling and adult stages and 351 DMRs, corresponding to 293 genes, between newborn and adult stages. These genes with DMRs were mainly enriched in metabolic, immune-related functional processes. Correlation analysis showed that the methylation level of gene promoters was significantly negatively correlated with gene expression. Further, we found that genes related to nutritional metabolism, e.g., carbohydrate metabolism (FAHD1 and GUSB) or fatty acid metabolism (LPIN1 and ACOX2), lost DNA methylation in their promoter, with mRNA expression increased in newborn pigs compared with those in the suckling stage. A few fatty acid metabolism-related genes (SLC27A5, ACOX2) were hypomethylated and highly expressed in the newborn stage, which might satisfy the nutritional requirements of Rongchang pigs with high neonatal birth rates. In the adult stage, HMGCS2-which is related to fatty acid ß-oxidation-was hypomethylated and highly expressed, which explains that the characteristics of high energy utilization in adult Rongchang pigs and their immune-related genes (CD68, STAT2) may be related to the establishment of liver immunity. This study provides a comprehensive analysis of genome-wide DNA methylation patterns in pig liver postnatal development and growth. Our findings will serve as a valuable resource in hepatic metabolic studies and the agricultural food industry.


Subject(s)
DNA Methylation , Liver , Promoter Regions, Genetic , Animals , Liver/metabolism , Liver/growth & development , Swine/growth & development , Swine/genetics , Animals, Newborn/growth & development , Gene Expression Regulation, Developmental , Epigenesis, Genetic
7.
Cells ; 13(14)2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39056780

ABSTRACT

Background: Angiogenesis is essential for various physiological and pathological processes, such as embryonic development and cancer cell proliferation, migration, and invasion. Long noncoding RNAs (lncRNAs) play pivotal roles in normal homeostasis and disease processes by regulating gene expression through various mechanisms, including competing endogenous RNAs (ceRNAs) of target microRNAs (miRNAs). The lncRNA MYU is known to promote prostate cancer proliferation via the miR-184/c-Myc regulatory axis and to be upregulated in vascular endothelial cells under hypoxic conditions, which often occurs in solid tumors. In the present study, we investigated whether MYU might affect cancer growth by regulating angiogenesis in vascular endothelial cells under hypoxia. Methods: The expression of MYU-regulated miR-23a-3p and interleukin-8 (IL-8) in HUVEC cell lines was examined using qRT-PCR. The CCK-8 assay, EdU assay, wound-healing assay, and tube-formation assay were used to assess the effects of MYU on cell proliferation, migration, and tube formation of HUVEC cells in vitro. The dual-luciferase reporter assay was performed to examine the effects of miR-23a-3p on MYU and IL-8 expression. Results: We found that the overexpression of MYU and knockdown of miR-23a-3p in human umbilical vein endothelial cells (HUVECs) under hypoxia promoted cell proliferation, migration, and tube formation. Mechanistically, MYU was shown to bind competitively to miR-23a-3p, thereby preventing miR-23a-3p binding to the 3' untranslated region of IL-8 mRNA. In turn, increased production of pro-angiogenic IL-8 promoted HUVEC proliferation, migration, and tube formation under hypoxia. Conclusion: This study identified a new role for lncRNA MYU as a ceRNA for miR-23a-3p and uncovered a novel MYU-miR-23a-3p-IL-8 regulatory axis for angiogenesis. MYU and/or miR-23a-3p may thus represent new targets for the treatment of hypoxia-related diseases by promoting angiogenesis.


Subject(s)
Cell Hypoxia , Cell Movement , Cell Proliferation , Human Umbilical Vein Endothelial Cells , Interleukin-8 , MicroRNAs , RNA, Long Noncoding , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Human Umbilical Vein Endothelial Cells/metabolism , Cell Proliferation/genetics , Cell Hypoxia/genetics , Cell Movement/genetics , Interleukin-8/metabolism , Interleukin-8/genetics , Neovascularization, Pathologic/genetics , Neovascularization, Pathologic/metabolism , Endothelial Cells/metabolism , Angiogenesis
8.
PLoS One ; 19(7): e0307478, 2024.
Article in English | MEDLINE | ID: mdl-39042660

ABSTRACT

This study investigated the application of artificial intelligence in real-time prediction of professional basketball games, identifying the variations within performance indicators that are critical in determining the outcomes of the games. Utilizing games data from the NBA seasons 2021 to 2023 as the sample, the study constructed a real-time predictive model for NBA game outcomes, integrating the machine learning XGBoost and SHAP algorithms. The model simulated the prediction of game outcomes at different time of games and effectively quantified the analysis of key factors that influenced game outcomes. The study's results demonstrated that the XGBoost algorithm was highly effective in predicting NBA game outcomes. Key performance indicators such as field goal percentage, defensive rebounds, and turnovers were consistently related to the outcomes at all times during the game. In the first half of the game, assists were a key indicator affecting the outcome of the game. In the second half of the games, offensive rebounds and three-point shooting percentage were key indicators affecting the outcome of the games. The performance of the real-time prediction model for NBA game outcomes, which integrates machine learning XGBoost and SHAP algorithms, is found to be excellent and highly interpretable. By quantifying the factors that determine victory, it is able to provide significant decision support for coaches in arranging tactical strategies on the court. Moreover, the study provides reliable data references for sports bettors, athletes, club managers, and sponsors.


Subject(s)
Algorithms , Athletic Performance , Basketball , Machine Learning , Humans
9.
Front Genet ; 15: 1396875, 2024.
Article in English | MEDLINE | ID: mdl-38881796

ABSTRACT

The flower coloration of Brassica crops possesses significant application and economic value, making it a research hotspot in the field of genetics and breeding. In recent years, great progress has been made in the research on color variation and creation of Brassica crops. However, the underlying molecular mechanisms and evolutional processes of flower colors are poorly understood. In this paper, we present a comprehensive overview of the mechanism of flower color formation in plants, emphasizing the molecular basis and regulation mechanism of flavonoids and carotenoids. By summarizing the recent advances on the genetic mechanism of flower color formation and regulation in Brassica crops, it is clearly found that carotenoids and anthocyanins are major pigments for flower color diversity of Brassica crops. Meantime, we also explore the relationship between the emergence of white flowers and the genetic evolution of Brassica chromosomes, and analyze the innovation and multiple utilization of Brassica crops with colorful flowers. This review aims to provide theoretical support for genetic improvements in flower color, enhancing the economic value and aesthetic appeal of Brassica crops.

10.
Front Microbiol ; 15: 1398631, 2024.
Article in English | MEDLINE | ID: mdl-38933022

ABSTRACT

Commensal microbial-host interaction is crucial for host metabolism, growth, development, and immunity. However, research on microbial-host immunity in large animal models has been limited. This study was conducted to investigate the effects of the commensal microbiota on immune function in two model groups: germ-free (GF) and specific-pathogen-free (SPF) piglets. The weight and organ index of the spleen of the GF piglet were larger than those in the SPF piglet (P < 0.05). The histological structure of the red pulp area and mean area of germinal centers were larger in the SPF piglet than in the GF piglet (P < 0.05), whereas the areas of staining of B cells and T cells in the spleen and mesenteric lymph nodes (MLNs) were lower in the GF piglet (P < 0.05). We identified immune-related genes in the spleen and MLNs using RNA sequencing, and used real-time quantitative PCR to analyze the expression of core genes identified in gene set enrichment analysis. The expression levels of genes in the transforming growth factor-ß/SMAD3 signaling pathway, Toll-like receptor 2/MyD88/nuclear factor-κB signaling pathway, and pro-inflammatory factor genes IL-6 and TNF-α in the spleen and MLNs were higher in the SPF piglet and in splenic lymphocytes compared with those in the GF and control group, respectively, under treatment with acetic acid, propionic acid, butyric acid, lipopolysaccharide (LPS), or concanavalin A (ConA). The abundances of plasma cells, CD8++ T cells, follicular helper T cells, and resting natural killer cells in the spleen and MLNs were significantly greater in the SPF piglet than in the GF piglet (P < 0.05). In conclusion, the commensal microbiota influenced the immune tissue structure, abundances of immune cells, and expression of immune-related pathways, indicating the importance of the commensal microbiota for spleen and MLNs development and function. In our study, GF piglet was used as the research model, eliminating the interference of microbiota in the experiment, and providing a suitable and efficient large animal research model for exploring the mechanism of "microbial-host" interactions.

11.
Neuroimage ; 295: 120664, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38825217

ABSTRACT

BACKGROUND: Stroke often damages the basal ganglia, leading to atypical and transient aphasia, indicating that post-stroke basal ganglia aphasia (PSBGA) may be related to different anatomical structural damage and functional remodeling rehabilitation mechanisms. The basal ganglia contain dense white matter tracts (WMTs). Hence, damage to the functional tract may be an essential anatomical structural basis for the development of PSBGA. METHODS: We first analyzed the clinical characteristics of PSBGA in 28 patients and 15 healthy controls (HCs) using the Western Aphasia Battery and neuropsychological test batteries. Moreover, we investigated white matter injury during the acute stage using diffusion magnetic resonance imaging scans for differential tractography. Finally, we used multiple regression models in correlation tractography to analyze the relationship between various language functions and quantitative anisotropy (QA) of WMTs. RESULTS: Compared with HCs, patients with PSBGA showed lower scores for fluency, comprehension (auditory word recognition and sequential commands), naming (object naming and word fluency), reading comprehension of sentences, Mini-Mental State Examination, and Montreal Cognitive Assessment, along with increased scores in Hamilton Anxiety Scale-17 and Hamilton Depression Scale-17 within 7 days after stroke onset (P < 0.05). Differential tractography revealed that patients with PSBGA had damaged fibers, including in the body fibers of the corpus callosum, left cingulum bundles, left parietal aslant tracts, bilateral superior longitudinal fasciculus II, bilateral thalamic radiation tracts, left fornix, corpus callosum tapetum, and forceps major, compared with HCs (FDR < 0.02). Correlation tractography highlighted that better comprehension was correlated with a higher QA of the left inferior fronto-occipital fasciculus (IFOF), corpus callosum forceps minor, and left extreme capsule (FDR < 0.0083). Naming was positively associated with the QA of the left IFOF, forceps minor, left arcuate fasciculus, and uncinate fasciculus (UF) (FDR < 0.0083). Word fluency of naming was also positively associated with the QA of the forceps minor, left IFOF, and thalamic radiation tracts (FDR < 0.0083). Furthermore, reading was positively correlated with the QA of the forceps minor, left IFOF, and UF (FDR < 0.0083). CONCLUSION: PSBGA is primarily characterized by significantly impaired word fluency of naming and preserved repetition abilities, as well as emotional and cognitive dysfunction. Damaged limbic pathways, dorsally located tracts in the left hemisphere, and left basal ganglia pathways are involved in PSBGA pathogenesis. The results of connectometry analysis further refine the current functional localization model of higher-order neural networks associated with language functions.


Subject(s)
Aphasia , Basal Ganglia , Diffusion Tensor Imaging , Stroke , White Matter , Humans , Male , Female , White Matter/diagnostic imaging , White Matter/pathology , Middle Aged , Aged , Diffusion Tensor Imaging/methods , Basal Ganglia/diagnostic imaging , Basal Ganglia/pathology , Stroke/complications , Stroke/diagnostic imaging , Stroke/pathology , Aphasia/diagnostic imaging , Aphasia/etiology , Aphasia/physiopathology , Aphasia/pathology , Language , Adult , Diffusion Magnetic Resonance Imaging
12.
Plant Physiol Biochem ; 213: 108833, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38879984

ABSTRACT

Root plays an important role in plant drought tolerance, especially in horticultural crops like apples. However, the crucial regulator and molecular mechanism in root development of apple trees under drought are not well unknown. Cys2/His2-type Zinc-finger proteins are essential for plant response to drought, while the members of C2H2 Zinc-finger proteins in apple are largely unknown. In this study, we identified the members of the C1-2i subclass family of C2H2 Zinc-finger proteins in apple (Malus × domestica). Among them, MdZAT5 is significantly induced in apple roots under drought conditions and positively regulates apple root development under drought. Further investigation revealed that MdZAT5 positively regulates root development and root hydraulic conductivity by mediating the transcription level of MdMYB88 under drought stress. Taken together, our results demonstrate the importance of MdZAT5 in root development under drought in apple trees. This finding provides a new candidate direction for apple breeding for drought resistance.


Subject(s)
Droughts , Gene Expression Regulation, Plant , Malus , Plant Proteins , Plant Roots , Malus/genetics , Malus/growth & development , Malus/metabolism , Malus/physiology , Plant Roots/growth & development , Plant Roots/genetics , Plant Roots/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Stress, Physiological/genetics
13.
Biosens Bioelectron ; 258: 116357, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38729049

ABSTRACT

The label probe plays a crucial role in enhancing the sensitivity of lateral flow immunoassays. However, conventional fluorescent microspheres (FMs) have limitations due to their short fluorescence lifetime, susceptibility to background fluorescence interference, and inability to facilitate multi-component detection. In this study, carboxylate-modified Eu(III)-chelate-doped polystyrene nanobeads were employed as label probes to construct a multiple time-resolved fluorescent microsphere-based immunochromatographic test strip (TRFM-ICTS). This novel TRFM-ICTS facilitated rapid on-site quantitative detection of three mycotoxins in grains: Aflatoxin B1 (AFB1), Zearalenone (ZEN), and Deoxynivalenol (DON). The limit of detection (LOD) for AFB1, ZEN, and DON were found to be 0.03 ng/g, 0.11 ng/g, and 0.81 ng/g, respectively. Furthermore, the TRFM-ICTS demonstrated a wide detection range for AFB1 (0.05-8.1 ng/g), ZEN (0.125-25 ng/g), and DON (1.0-234 ng/g), while maintaining excellent selectivity. Notably, the test strip exhibited remarkable stability, retaining its detection capability even after storage at 4 °C for over one year. Importantly, the detection of these mycotoxins relied solely on simple manual operations, and with a portable reader, on-site detection could be accomplished within 20 min. This TRFM-ICTS presents a promising solution for sensitive on-site mycotoxin detection, suitable for practical application in various settings due to its sensitivity, accuracy, simplicity, and portability.


Subject(s)
Biosensing Techniques , Edible Grain , Food Contamination , Limit of Detection , Microspheres , Mycotoxins , Zearalenone , Mycotoxins/analysis , Edible Grain/chemistry , Edible Grain/microbiology , Biosensing Techniques/methods , Food Contamination/analysis , Zearalenone/analysis , Chromatography, Affinity/methods , Chromatography, Affinity/instrumentation , Aflatoxin B1/analysis , Aflatoxin B1/isolation & purification , Trichothecenes/analysis , Reagent Strips/analysis , Immunoassay/methods , Immunoassay/instrumentation , Fluorescent Dyes/chemistry
14.
Front Microbiol ; 15: 1402807, 2024.
Article in English | MEDLINE | ID: mdl-38800748

ABSTRACT

Pigs are widely used as animal models in various studies related to humans. The interaction between the gut microbiota and the host has significant effects on the host's health and disease status. However, although there have been many studies investigating the pig gut microbiota, the findings have been inconsistent due to variations in rearing conditions. Interactions between the gut microbiota and host have not been fully explored in pigs. Specific pathogen-free (SPF) pigs are ideal non-primate large animals to study the interactions between the gut microbiota and the host. In this study, we performed high-throughput sequencing analysis of the gut microbiota and the gut tissue transcriptome of six SPF pigs to provide a systematic understanding of the composition, function, and spatial distribution of gut microbiota in SPF pigs. We identified significant differences in microbial diversity and functionality among different gastrointestinal tract sites. Metagenomics data analysis revealed significant differences in alpha diversity and beta diversity of microbiota in different gastrointestinal sites of SPF pigs. Additionally, transcriptomic data indicated significant differences in gene expression as well as KEGG and GO functional enrichment between the small intestine and large intestine. Furthermore, by combining microbial metagenomics and host transcriptomics analyses, specific correlations were found between gut microbiota and host genes. These included a negative correlation between the TCN1 gene and Prevotella dentalis, possibly related to bacterial metabolic pathways involving vitamin B12, and a positive correlation between the BDH1 gene and Roseburia hominis, possibly because both are involved in fatty acid metabolism. These findings lay the groundwork for further exploration of the co-evolution between the microbiota and the host, specifically in relation to nutrition, metabolism, and immunity. In conclusion, we have elucidated the diversity of the gut microbiota in SPF pigs and conducted a detailed investigation into the interactions between the gut microbiota and host gene expression. These results contribute to our understanding of the intricate dynamics between the gut microbiota and the host, offering important references for advancements in life science research, bioproduct production, and sustainable development in animal husbandry.

15.
Front Neurol ; 15: 1349369, 2024.
Article in English | MEDLINE | ID: mdl-38756220

ABSTRACT

Background and purpose: Early blood-brain barrier (BBB) disruption in patients with acute ischemic stroke (AIS) can be detected on perfusion computed tomography (PCT) images before undergoing reperfusion therapy. In this study, we aimed to determine whether early disruption of the BBB predicts intracranial hemorrhage transformation (HT) in patients with AIS undergoing endovascular therapy and further identify factors influencing BBB disruption. Methods: We retrospectively analyzed general clinical and imaging data derived from 159 consecutive patients with acute anterior circulation stroke who were admitted to the Department of Neurology of the First Hospital of Jilin University, and who underwent endovascular treatment between January 1, 2021, and March 31, 2023. We evaluated the relationship between BBB destruction and intracranial HT before endovascular reperfusion therapy and examined the risk factors for early BBB destruction. Results: A total of 159 patients with assessable BBB leakage were included. The median (interquartile range, IQR) age was 63 (54-70) years, 108 (67.9%) patients were male, and the median baseline National Institutes of Health Stroke Scale (NHISS) score was 12 (10-15). Follow-up non-contrast computed tomography (NCCT) detected HT in 63 patients. After logistic regression modeling adjustment, we found that BBB leakage in the true leakage area was slightly more than 2-fold risk of HT (odds ratio [OR], 2.01; 95% confidence interval [CI] 1.02-3.92). Heart rate was also associated with HT (OR, 1.03, 95% CI, 1.00-1.05). High Blood-brain barrier permeability (BBBP) in the true leakage area was positively correlated with infarct core volume (OR, 1.03; 95% CI, 1.01-1.05). Conclusion: Early BBB destruction before endovascular reperfusion therapy was associated with HT, whereas high BBBP correlated positively with infarct core volume.

16.
FASEB J ; 38(10): e23655, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38767449

ABSTRACT

The disruption of mitochondria homeostasis can impair the contractile function of cardiomyocytes, leading to cardiac dysfunction and an increased risk of heart failure. This study introduces a pioneering therapeutic strategy employing mitochondria derived from human umbilical cord mesenchymal stem cells (hu-MSC) (MSC-Mito) for heart failure treatment. Initially, we isolated MSC-Mito, confirming their functionality. Subsequently, we monitored the process of single mitochondria transplantation into recipient cells and observed a time-dependent uptake of mitochondria in vivo. Evidence of human-specific mitochondrial DNA (mtDNA) in murine cardiomyocytes was observed after MSC-Mito transplantation. Employing a doxorubicin (DOX)-induced heart failure model, we demonstrated that MSC-Mito transplantation could safeguard cardiac function and avert cardiomyocyte apoptosis, indicating metabolic compatibility between hu-MSC-derived mitochondria and recipient mitochondria. Finally, through RNA sequencing and validation experiments, we discovered that MSC-Mito transplantation potentially exerted cardioprotection by reinstating ATP production and curtailing AMPKα-mTOR-mediated excessive autophagy.


Subject(s)
AMP-Activated Protein Kinases , Apoptosis , Autophagy , Mesenchymal Stem Cells , Mitochondria , Myocytes, Cardiac , TOR Serine-Threonine Kinases , Animals , Humans , Male , Mice , AMP-Activated Protein Kinases/metabolism , Doxorubicin/pharmacology , Heart Failure/metabolism , Mesenchymal Stem Cells/metabolism , Mice, Inbred C57BL , Mitochondria/metabolism , Mitochondria/transplantation , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , TOR Serine-Threonine Kinases/metabolism
17.
Int J Mol Sci ; 25(10)2024 May 08.
Article in English | MEDLINE | ID: mdl-38791168

ABSTRACT

The normal growth and development of skeletal muscle is essential for the health of the body. The regulation of skeletal muscle by intestinal microorganisms and their metabolites has been continuously demonstrated. Acetate is the predominant short-chain fatty acids synthesized by gut microbiota through the fermentation of dietary fiber; however, the underlying molecular mechanisms governing the interaction between acetate and skeletal muscle during the rapid growth stage remains to be further elucidated. Herein, specific pathogen-free (SPF) mice, germ-free (GF) mice, and germ-free mice supplemented with sodium acetate (GS) were used to evaluate the effects of acetate on the skeletal muscle growth and development of young mice with gut microbiota deficiency. We found that the concentration of serum acetate, body mass gain, succinate dehydrogenase activity, and expression of the myogenesis maker gene of skeletal muscle in the GS group were higher than those in the GF group, following sodium acetate supplementation. Furthermore, the transcriptome analysis revealed that acetate activated the biological processes that regulate skeletal muscle growth and development in the GF group, which are otherwise inhibited due to a gut microbiota deficiency. The in vitro experiment showed that acetate up-regulated Gm16062 to promote skeletal muscle cell differentiation. Overall, our findings proved that acetate promotes skeletal muscle growth and development in young mice via increasing Gm16062 expression.


Subject(s)
Gastrointestinal Microbiome , Muscle Development , Muscle, Skeletal , Animals , Gastrointestinal Microbiome/drug effects , Mice , Muscle, Skeletal/metabolism , Muscle, Skeletal/drug effects , Muscle Development/drug effects , Acetates/pharmacology , Acetates/metabolism , Male , Sodium Acetate/pharmacology , Cell Differentiation/drug effects , Mice, Inbred C57BL
18.
Int J Biol Macromol ; 270(Pt 1): 131796, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38677688

ABSTRACT

As a country with abundant genetic resources of pigs, the domestication history of pigs in China and the adaptive evolution of Chinese pig breeds at different latitudes have rarely been elucidated at the genome-wide level. To fill this gap, we first assembled a high-quality chromosome-level genome of the Chenghua pig and used it as a benchmark to analyse the genomes of 272 samples from three genera of three continents. The divergence of the three species belonging to three genera, Phacochoerus africanus, Potamochoerus porcus, and Sus scrofa, was assessed. The introgression of pig breeds redefined that the migration routes were basically from southern China to central and southwestern China, then spread to eastern China, arrived in northern China, and finally reached Europe. The domestication of pigs in China occurred ∼12,000 years ago, earlier than the available Chinese archaeological domestication evidence. In addition, FBN1 and NR6A1 were identified in our study as candidate genes related to extreme skin thickness differences in Eurasian pig breeds and adaptive evolution at different latitudes in Chinese pig breeds, respectively. Our study provides a new resource for the pig genomic pool and refines our understanding of pig genetic diversity, domestication, migration, and adaptive evolution at different latitudes.


Subject(s)
Domestication , Genome , Animals , Swine/genetics , Genome/genetics , China , Adaptation, Physiological/genetics , Sus scrofa/genetics , Phylogeny , Breeding , Genetic Variation , Evolution, Molecular
19.
Article in English | MEDLINE | ID: mdl-38587950

ABSTRACT

As a challenging computer vision task, Scene Graph Generation (SGG) finds the latent semantic relationships among objects from a given image, which may be limited by the datasets and real-world scenarios. In this paper, we consider a novel incremental learning task called Relationship-Incremental Scene Graph Generation (RISGG) that learns the semantic relationships among objects in an incremental way. Compared with classic Class-Incremental Learning (CIL) problem, RISGG suffers from its special issues: (1) Old class shift - the relationship-labeled object pair may have different labels during different learning sessions. (2) Background shift - the relationship-unlabeled object pair may not be a real unlabeled one. In this work, we address the above issues from the following aspects. First, we present a Divide-and-Conquer (DaC) pipeline to deal with the old class shift via decoupling the recognition of relationship classes and recognizing relationships individually. In this way, label confusion and interaction among different relationships are eliminated during training. Second, we propose a Feature Adapter (FA) to bridge the feature space gap between the current session and the previous one and use our extra supervision to mine old relationship information in the current session. Our proposed network combined DaC and FA, abbreviated DaCFA-Net, for RISGG. Experimental results on the benchmark dataset demonstrate the significant performance gain of DaCFA-Net in RISGG. It gains about 20% improvement against the SGG baselines on the popular VG dataset.

20.
Genome Res ; 34(2): 310-325, 2024 03 20.
Article in English | MEDLINE | ID: mdl-38479837

ABSTRACT

In diploid mammals, allele-specific three-dimensional (3D) genome architecture may lead to imbalanced gene expression. Through ultradeep in situ Hi-C sequencing of three representative somatic tissues (liver, skeletal muscle, and brain) from hybrid pigs generated by reciprocal crosses of phenotypically and physiologically divergent Berkshire and Tibetan pigs, we uncover extensive chromatin reorganization between homologous chromosomes across multiple scales. Haplotype-based interrogation of multi-omic data revealed the tissue dependence of 3D chromatin conformation, suggesting that parent-of-origin-specific conformation may drive gene imprinting. We quantify the effects of genetic variations and histone modifications on allelic differences of long-range promoter-enhancer contacts, which likely contribute to the phenotypic differences between the parental pig breeds. We also observe the fine structure of somatically paired homologous chromosomes in the pig genome, which has a functional implication genome-wide. This work illustrates how allele-specific chromatin architecture facilitates concomitant shifts in allele-biased gene expression, as well as the possible consequential phenotypic changes in mammals.


Subject(s)
Chromatin , Chromosomes , Animals , Swine/genetics , Chromatin/genetics , Haplotypes , Chromosomes/genetics , Genome , Mammals/genetics
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