An experimental study of acoustic bird repellents for reducing bird encroachment in pear orchards.

Bird invasion will reduce the yield of high-value crops, which threatens the healthy development of agricultural economy. Sonic bird repellent has the advantages of large range, no time and geographical restrictions, and low cost, which has attracted people's attention in the field of agriculture. At present, there are few studies on the application of sonic bird repellents in pear orchards to minimize economic losses and prolong the adaptive capacity of birds. In this paper, a sound wave bird repellent system based on computer vision is designed, which combines deep learning target recognition technology to accurately identify birds and drive them away. The neural network model that can recognize birds is first trained and deployed to the server. Live video is captured by an installed webcam, and the sonic bird repellent is powered by an ESP-8266 relay switch. In a pear orchard, two experimental areas were divided into two experimental areas to test the designed sonic bird repellent device, and the number of bad fruits pecked by birds was used as an indicator to evaluate the bird repelling effect. The results showed that the pear pecked fruit rate was 6.03% in the pear orchard area that used the acoustic bird repeller based on computer recognition, 7.29% in the pear orchard area of the control group that used the acoustic bird repeller with continuous operation, and 13.07% in the pear orchard area that did not use any bird repellent device. While acoustic bird repellers based on computer vision can be more effective at repelling birds, they can be used in combination with methods such as fruit bags to reduce the economic damage caused by birds.

Biocontrol potential of Bacillus velezensis HG-8-2 against postharvest anthracnose on chili pepper caused by Colletotrichum scovillei.

Anthracnose caused by Colletotrichum scovillei is a significant disease of pepper, including in postharvest stage. Bacillus species represent a potential microbial resource for controlling postharvest plant diseases. Here, a strain HG-8-2 was obtained and identified as Bacillus velezensis through morphological, biochemical, physiological, and molecular analyses. The culture filtrate showed highly antifungal activity against C. scovillei both in vitro and on pepper fruit. Crude lipopeptide extracts, which had excellent stability, could effectively inhibit mycelial growth of C. scovillei with an EC50 value of 28.48 ± 1.45 µg mL-1 and inhibited conidial germination. Pretreatment with the extracts reduced the incidence and lesion size of postharvest anthracnose on pepper fruit. Analysis using propidium iodide staining, malondialdehyde content detection and scanning electron microscope observation suggested that the crude lipopeptide extracts harbored antifungal activity by damaging cell membranes and mycelial structures. The RNA-seq analysis conducted on C. scovillei samples treated with the extracts, as compared to untreated samples, revealed significant alterations in the expression of multiple genes involved in protein biosynthesis. Overall, these results demonstrated that B. velezensis HG-8-2 and its crude lipopeptide extracts exhibit highly antagonistic ability against C. scovillei, thereby offering an effective biological agent for the control of anthracnose in pepper fruit.

Concomitant presence of a novel ARPP21 variant and CNVs in Chinese familial amyotrophic lateral sclerosis-frontotemporal dementia patients.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder marked by the degeneration of motor neurons and progressive muscle weakness. Heredity plays an important part in the pathogenesis of ALS. Recently, with the emergence of the oligogenic pathogenic mechanism in ALS and the ongoing discovery of new mutated genes and genomic variants, there is an emerging need for larger-scale and more comprehensive genetic screenings in higher resolution. In this study, we performed whole-genome sequencing (WGS) on 34 familial ALS probands lacking the most common disease-causing mutations to explore the genetic landscape of Chinese ALS patients further. Among them, we identified a novel ARPP21 c.1231G > A (p.Glu411Lys) variant and two copy number variations (CNVs) affecting the PFN1 and RBCK1 genes in a patient with ALS-frontotemporal dementia (FTD). This marks the first report of an ARPP21 variant in Chinese ALS-FTD patients, providing fresh evidence for the association between ARPP21 and ALS. Our findings also underscore the potential role of CNVs in ALS-FTD, suggesting that the cumulative effect of multiple rare variants may contribute to disease onset. Furthermore, compared to the averages in our cohort and the reported Chinese ALS population, this patient displayed a shorter survival time and more rapid disease progression, suggesting the possibility of an oligogenic mechanism in disease pathogenesis. Further research will contribute to a deeper understanding of the rare mutations and their interactions, thus advancing our understanding of the genetic mechanisms underlying ALS and ALS-FTD.

Incidence of medical device-related pressure injuries: a meta-analysis.

BACKGROUND: Medical device-related pressure injures (MDRPIs) are common in critically ill patients and associated with negative clinical outcomes and elevated healthcare expenses. We aim to estimate worldwide incidence of MDRPI and explore associated factors through systemic review and meta-analysis. METHODS: The PubMed, Web of Science, Cochrane Library, and Ovid EMBASE databases were systematically queried to identify relevant studies published from Jan 1, 2010 up until June 30, 2024. Studies were included if they provided data on the incidence or prevalence of MDRPI. Random-effect models were utilized to calculate the overall or domain-specific aggregated estimates of MDRPI. A meta-regression analysis was additionally performed to investigate the heterogeneity among studies. RESULTS: We included 28 observational studies on 117,624 patients in the meta-analysis. The overall incidence of MDRPI was 19.3% (95% confidence interval (CI) 13.5-25.2%). The incidence of MDRPI in Europe, North America, Asia, South America, and Oceania was 17.3% (95% CI 12.7-21.9%), 3.6% (95% CI 0.0-8.5%), 21.9% (95% CI 14.3-29.6%), 48.3% (95% CI 20.8-75.7%), and 13.0% (95% CI 5.0-21.1%), respectively (p < 0.01). Multivariate meta-regressions revealed South America and special inpatient (critically ill patient, etc.) were independently associated with higher MDRPI incidence. CONCLUSIONS: Nearly, 20% of the patients in ICU suffered from MDRPI. The incidence of MDRPI in underdeveloped regions is particularly concerning, highlighting the importance of focusing on measures to prevent it, in order to reduce the medical burden and enhance the quality of life for affected patients.

Superiority of native soil core microbiomes in supporting plant growth.

Native core microbiomes represent a unique opportunity to support food provision and plant-based industries. Yet, these microbiomes are often neglected when developing synthetic communities (SynComs) to support plant health and growth. Here, we study the contribution of native core, native non-core and non-native microorganisms to support plant production. We construct four alternative SynComs based on the excellent growth promoting ability of individual stain and paired non-antagonistic action. One of microbiome based SynCom (SC2) shows a high niche breadth and low average variation degree in-vitro interaction. The promoting-growth effect of SC2 can be transferred to non-sterile environment, attributing to the colonization of native core microorganisms and the improvement of rhizosphere promoting-growth function including nitrogen fixation, IAA production, and dissolved phosphorus. Further, microbial fertilizer based on SC2 and composite carrier (rapeseed cake fertilizer + rice husk carbon) increase the net biomass of plant by 129%. Our results highlight the fundamental importance of native core microorganisms to boost plant production.

Global and regional prevalence and cardiovascular risk of primary aldosteronism: a systematic review and meta-analysis.

BACKGROUND: An updated understanding of global prevalence of primary aldosteronism (PA) is essential for the development of primary prevention and management strategies for PA. We aimed to provide update global and regional prevalence of PA and to evaluate cardiovascular risk of PA compared to essential hypertension (EH). METHODS: We systematically searched PubMed, Web of Science, and Embase for studies on the prevalence of PA or cardiovascular risk of PA published up to July 31, 2022 for this meta-analysis. Global prevalence of PA was calculated using random-effects inverse-variance models and cardiovascular risk of PA was estimated using random-effects models. RESULTS: We identified 39 articles for meta-analysis of PA prevalence, and 13 articles were included in the meta-analysis of cardiovascular risk. Global prevalence of PA was 9.4% (95% CI: 8.3-10.5), with a higher prevalence in males than in females. Prevalence of PA was higher in the South-East Asia than in other regions, and higher in lower middle-income countries than in other economic levels, with greater country-specific differences. Compared with EH, PA had an increased risk of coronary artery disease (OR=1.88, 95% CI: 1.41-2.50), stroke (OR=2.50, 95% CI: 2.08-3.02), heart failure (OR=2.06, 95% CI: 1.33-3.19), and atrial fibrillation (OR=3.17, 95% CI: 2.09-4.80). CONCLUSION: The management of the increasing number of patients with PA and its associated burden of cardiovascular disease is likely to place increasing pressure on health systems. Early detection of PA is essential to reduce the associated burden, especially in areas where the assessment of PA has not received sufficient attention.

Inhibition of SIRT1 relieves hepatocarcinogenesis via alleviating autophagy and inflammation.

Imbalanced Sirtuin 1 (SIRT1) levels may lead to liver diseases through abnormal regulation of autophagy, but the roles of SIRT1-regulated autophagy in hepatocellular carcinoma are still controversial. In this study, we found that SIRT1 mRNA and protein levels were upregulated in hepatocellular carcinoma, and high SIRT1 expression hinted an advanced stage and a poor prognosis. The differentially expressed proteins were significantly elevated in autophagy, cellular response to stress, and immune signaling pathways. In a thioacetamide-induced hepatocellular carcinoma mouse model, we found that SIRT1 expression was highly increased with increased autophagy and excessive macrophage inflammatory response. Next, we established a Hepa 1-6 cells and macrophage co-culture system in vitro to model the alteration of tumor microenvironment, and found that the medium from CCl4-treated or SIRT1-overexpressing Hepa 1-6 cells triggered the polarization of macrophage M1, and the culture medium derived from M1 macrophage promoted Hepa 1-6 cells growth and intracellular oxidative stress. The progression of liver fibrosis in the CCl4-induced liver fibrosis mouse model showed that inhibition of SIRT1 alleviated inflammatory response and ameliorated liver fibrosis. These findings suggest that SIRT1-regulated autophagy and inflammation are oncogenic in hepatocarcinogenesis.

Integrated Methylome and Transcriptome Analysis between Wizened and Normal Flower Buds in Pyrus pyrifolia Cultivar 'Sucui 1'.

Here, cytosine methylation in the whole genome of pear flower buds was mapped at a single-base resolution. There was 19.4% methylation across all sequenced C sites in the Pyrus pyrifolia cultivar 'Sucui 1' flower bud genome. Meantime, the CG, CHG, and CHH sequence contexts (where H = A, T or C) exhibited 47.4%, 33.3%, and 11.9% methylation, respectively. Methylation in different gene regions was revealed through combining methylome and transcriptome analysis, which presented various transcription trends. Genes with methylated promoters exhibited lower expression levels than genes with non-methylated promoters, while body-methylated genes displayed an obvious negative correlation with their transcription levels. The methylation profiles of auxin- and cytokinin-related genes were estimated. And some of them proved to be hypomethylated, with increased transcription levels, in wizened buds. More specifically, the expression of the genes PRXP73, CYP749A22, and CYP82A3 was upregulated as a result of methylation changes in their promoters. Finally, auxin and cytokinin concentrations were higher in wizened flower buds than in normal buds. The exogenous application of paclobutrazol (PP333) in the field influenced the DNA methylation status of some genes and changed their expression level, reducing the proportion of wizened flower buds in a concentration-dependent manner. Overall, our results demonstrated the relationship between DNA methylation and gene expression in wizened flower buds of P. pyrifolia cultivar 'Sucui 1', which was associated with changes in auxin and cytokinin concentrations.

Quercetin inhibits the epithelial-mesenchymal transition and reverses CDK4/6 inhibitor resistance in breast cancer by regulating circHIAT1/miR-19a-3p/CADM2 axis.

Breast cancer (BC) cells have a high risk of metastasis due to epithelial-mesenchymal transition (EMT). Palbociclib (CDK4/6 inhibitor) is an approved drug for BC treatment. However, the drug resistance and metastasis can impair the treatment outcome of Palbociclib. Understanding the mechanisms of EMT and Palbociclib drug resistance in BC is conducive to the formulation of novel therapeutic strategy. Here, we investigated the role of circHIAT1/miR-19a-3p/CADM2 axis in modulating EMT and Palbociclib resistance in BC. circHIAT1 and CADM2 were down-regulated in BC tissues and cell lines, and miR-19a-3p showed an up-regulation. circHIAT1 could interact with miR-19a-3p and suppress its activity, while miR-19a-3p functioned to negatively regulate CADM2. Forced over-expression of circHIAT1 could impaired the EMT status and migratory ability of BC cells, and this effect was inhibited by miR-19a-3p mimic. In addition, we also generated Palbociclib resistant BC cells, and showed that circHIAT1 and CADM2 were down-regulated in the resistant BC cells while miR-19a-3p showed an up-regulation. Forced circHIAT1 over-expression re-sensitized BC cells to Palbociclib treatment. Quercetin, a bioactive flavonoid, could suppressed the migration and invasion of BC cells, and re-sensitized BC cells to Palbociclib. The anti-cancer effect of quercetin could be attributed to its regulatory effect on circHIAT1/miR-19a-3p/CADM2 axis. In vivo tumorigenesis experiment further revealed that quercetin administration enhanced the anti-cancer effect of Palbociclib, an effect was dependent on the up-regulation of circHIAT1 by quercetin. In summary, this study identified quercetin as a potential anti-cancer compound to reverse Palbociclib resistance and impair EMT in BC cells by targeting circHIAT1/miR-19a-3p/CADM2 axis.

Plasma metabolomics signatures of developmental dysplasia of the hip in Tibet plateau.

BACKGROUND: Developmental dysplasia of the hip (DDH) is a common childhood health complaint, whose etiology is multifactorial. The incidence of DDH is variable and higher in Tibet plateau. Here, we collected plasma samples and studied the metabolomics signatures of DDH. METHODS: Fifty babies were enrolled: 25 with DDH and 25 age-matched non-DDH healthy controls (HC group). We collected plasma samples, laboratory parameters and conducted untargeted metabolomics profiling. RESULTS: There are many differential metabolites among patients with DDH, including 4-ß-hydroxymethyl-4-α-methyl-5-α-cholest-7-en-3-beta-ol, ß-cryptoxanthin, α-tocopherol, taurocholic acid, glycocholic acid, 2-(3,4-dihydroxybenzoyloxy)-4,6-dihydroxybenzoate, arabinosylhypoxanthine, leucyl-hydroxyproline, hypoxanthine. The main differential metabolic pathways focused on primary bile acid biosynthesis, arginine and proline metabolism, phenylalanine metabolism, histidine metabolism, purine metabolism. CONCLUSIONS: To our knowledge, this is the first report of metabolomics profile in babies with DHH. By combining the α-tocopherol and taurocholic acid, we could achieve the differential diagnosis of DDH.

SMYD3 Controls Ciliogenesis by Regulating Distinct Centrosomal Proteins and Intraflagellar Transport Trafficking.

The primary cilium is a microtubule-based sensory organelle that plays a critical role in signaling pathways and cell cycle progression. Defects in the structure and/or function of the primary cilium result in developmental diseases collectively known as ciliopathies. However, the constituents and regulatory mechanisms of the primary cilium are not fully understood. In recent years, the activity of the epigenetic modifier SMYD3 has been shown to play a key role in the regulation of cell cycle progression. However, whether SMYD3, a histone/lysine methyltransferase, contributes to the regulation of ciliogenesis remains unknown. Here, we report that SMYD3 drives ciliogenesis via the direct and indirect regulation of cilia-associated components. We show that SMYD3 is a novel component of the distal appendage and is required for centriolar appendage assembly. The loss of SMYD3 decreased the percentage of ciliated cells and resulted in the formation of stumpy cilia. We demonstrated that SMYD3 modulated the recruitment of centrosome proteins (Cep164, Fbf1, Ninein, Ttbk2 and Cp110) and the trafficking of intraflagellar transport proteins (Ift54 and Ift140) important for cilia formation and maintenance, respectively. In addition, we showed that SMYD3 regulated the transcription of cilia genes and bound to the promoter regions of C2cd3, Cep164, Ttbk2, Dync2h1 and Cp110. This study provides insights into the role of SMYD3 in cilia biology and suggests that SMYD3-mediated cilia formation/function may be relevant for cilia-dependent signaling in ciliopathies.

DNA methylation patterns in patients with asthenospermia and oligoasthenospermia.

BACKGROUND: Spermatogenesis is a highly regulated and complex process in which DNA methylation plays a crucial role. This study aimed to explore the differential methylation profiles in sperm DNA between patients with asthenospermia (AS) and healthy controls (HCs), those with oligoasthenospermia (OAS) and HCs, and patients with AS and those with OAS. RESULTS: Semen samples and clinical data were collected from five patients with AS, five patients with OAS, and six age-matched HCs. Reduced representation bisulfite sequencing (RRBS) was performed to identify differentially methylated regions (DMRs) in sperm cells among the different types of patients and HCs. A total of 6520, 28,019, and 16,432 DMRs were detected between AS and HC, OAS and HC, and AS and OAS groups, respectively. These DMRs were predominantly located within gene bodies and mapped to 2868, 9296, and 9090 genes in the respective groups. Of note, 12, 9, and 8 DMRs in each group were closely associated with spermatogenesis and male infertility. Furthermore, BDNF, SMARCB1, PIK3CA, and DDX27; RBMX and SPATA17; ASZ1, CDH1, and CHDH were identified as strong differentially methylated candidate genes in each group, respectively. Meanwhile, the GO analysis of DMR-associated genes in the AS vs. HC groups revealed that protein binding, cytoplasm, and transcription (DNA-templated) were the most enriched terms in the biological process (BP), cellular component (CC), and molecular function (MF), respectively. Likewise, in both the OAS vs. HC and AS vs. OAS groups, GO analysis revealed protein binding, nucleus, and transcription (DNA-templated) as the most enriched terms in BP, CC, and MF, respectively. Finally, the KEGG analysis of DMR-annotated genes and these genes at promoters suggested that metabolic pathways were the most significantly associated across all three groups. CONCLUSIONS: The current study results revealed distinctive sperm DNA methylation patterns in the AS vs. HC and OAS vs. HC groups, particularly between patients with AS and those with OAS. The identification of key genes associated with spermatogenesis and male infertility in addition to the differentially enriched metabolic pathways may contribute to uncovering the potential pathogenesis in different types of abnormal sperm parameters.

Kidney Aging and Chronic Kidney Disease.

The process of aging inevitably leads to an increase in age-related comorbidities, including chronic kidney disease (CKD). In many aspects, CKD can be considered a state of accelerated and premature aging. Aging kidney and CKD have numerous common characteristic features, ranging from pathological presentation and clinical manifestation to underlying mechanisms. The shared mechanisms underlying the process of kidney aging and the development of CKD include the increase in cellular senescence, the decrease in autophagy, mitochondrial dysfunction, and the alterations of epigenetic regulation, suggesting the existence of potential therapeutic targets that are applicable to both conditions. In this review, we provide a comprehensive overview of the common characteristics between aging kidney and CKD, encompassing morphological changes, functional alterations, and recent advancements in understanding the underlying mechanisms. Moreover, we discuss potential therapeutic strategies for targeting senescent cells in both the aging process and CKD.

Advance in Iron Metabolism, Oxidative Stress and Cellular Dysfunction in Experimental and Human Kidney Diseases.

Kidney diseases pose a significant global health issue, frequently resulting in the gradual decline of renal function and eventually leading to end-stage renal failure. Abnormal iron metabolism and oxidative stress-mediated cellular dysfunction facilitates the advancement of kidney diseases. Iron homeostasis is strictly regulated in the body, and disturbance in this regulatory system results in abnormal iron accumulation or deficiency, both of which are associated with the pathogenesis of kidney diseases. Iron overload promotes the production of reactive oxygen species (ROS) through the Fenton reaction, resulting in oxidative damage to cellular molecules and impaired cellular function. Increased oxidative stress can also influence iron metabolism through upregulation of iron regulatory proteins and altering the expression and activity of key iron transport and storage proteins. This creates a harmful cycle in which abnormal iron metabolism and oxidative stress perpetuate each other, ultimately contributing to the advancement of kidney diseases. The crosstalk of iron metabolism and oxidative stress involves multiple signaling pathways, such as hypoxia-inducible factor (HIF) and nuclear factor erythroid 2-related factor 2 (Nrf2) pathways. This review delves into the functions and mechanisms of iron metabolism and oxidative stress, along with the intricate relationship between these two factors in the context of kidney diseases. Understanding the underlying mechanisms should help to identify potential therapeutic targets and develop novel and effective therapeutic strategies to combat the burden of kidney diseases.

The Immune Checkpoint Protein PD-L1 Regulates Ciliogenesis and Hedgehog Signaling.

The primary cilium, an antenna-like sensory organelle that protrudes from the surface of most eukaryotic cell types, has become a signaling hub of growing interest given that defects in its structure and/or function are associated with human diseases and syndromes, known as ciliopathies. With the continuously expanding role of primary cilia in health and diseases, identifying new players in ciliogenesis will lead to a better understanding of the function of this organelle. It has been shown that the primary cilium shares similarities with the immune synapse, a highly organized structure at the interface between an antigen-presenting or target cell and a lymphocyte. Studies have demonstrated a role for known cilia regulators in immune synapse formation. However, whether immune synapse regulators modulate ciliogenesis remains elusive. Here, we find that programmed death ligand 1 (PD-L1), an immune checkpoint protein and regulator of immune synapse formation, plays a role in the regulation of ciliogenesis. We found that PD-L1 is enriched at the centrosome/basal body and Golgi apparatus of ciliated cells and depleting PD-L1 enhanced ciliogenesis and increased the accumulation of ciliary membrane trafficking proteins Rab8a, BBS5, and sensory receptor protein PC-2. Moreover, PD-L1 formed a complex with BBS5 and PC-2. In addition, we found that depletion of PD-L1 resulted in the ciliary accumulation of Gli3 and the downregulation of Gli1. Our results suggest that PD-L1 is a new player in ciliogenesis, contributing to PC-2-mediated sensory signaling and the Hh signaling cascade.

Physiological and transcriptomic analyses provide preliminary insights into the autotoxicity of Lilium brownii.

Lilium brownii F. E. Brown ex Miellez var. viridulum Baker (Longya lily) is a variety of Lilium brownii F.E. Br. ex Miellez. We used HS-SPME and GC-MS to screened the tissues of L. brownii roots, stems, bulbs, and leaves and obtained 2,4-DTBP as an autotoxic substance for subsequent analysis. 2,4-DTBP was highly autotoxic in some treatment groups. Based on changes in physiological indicators, we carried out transcriptomic analysis to investigate the mechanisms of autotoxicity of substances on L. brownii and obtained 188,505 Unigenes. GO and KEGG enrichment analyses showed that L. brownii responded differently to different concentrations and treatment times of 2,4-DTBP. We observed significant changes in genes associated with ROS, phytohormones, and MAPK signaling cascades. 2,4-DTBP affects chloroplasts, the integrity of the respiratory electron transport chain, and ribosomes, causing L. brownii autotoxicity. Our findings provide a practical genomic resource for future research on L. brownii autotoxicity and evidence for the mechanism of action of autotoxic substances.

Limited dependence on soil nitrogen fixation as subtropical forests develop.

Soil nitrogen (N) fixation, driven by microbial reactions, is critical to support the entrance of nitrogen in nutrient poor and pioneer ecosystems. However, how and why N fixation and soil diazotrophs evolve as forests develop remain poorly understood. Here, we used a 60-year forest rewilding chronosequence and found that soil N fixation activity gradually decreased with increasing forest age, experiencing dramatic drops of 64.8% in intermediate stages and 93.0% in the oldest forests. Further analyses revealed loses in diazotrophic diversity and a significant reduction in the abundance of important diazotrophs (e.g., Desulfovibrio and Pseudomonas) as forest develops. This reduction in N fixation, and associated shifts in soil microbes, was driven by acidification and increases in N content during forest succession. Our results provide new insights on the life history of one of the most important groups of soil organisms in terrestrial ecosystems, with consequences for understanding the buildup of nutrients as forest soil develops.

The Function of Termicin from Odontotermes formosanus (Shiraki) in the Defense against Bacillus thuringiensis (Bt) and Beauveria bassiana (Bb) Infection.

Odontotermes formosanus (Shiraki) is a subterranean termite species known for causing severe damage to trees and structures such as dams. During the synergistic evolution of O. formosanus with pathogenic bacteria, the termite has developed a robust innate immunity. Termicin is a crucial antimicrobial peptide in termites, significantly contributing to the defense against external infections. Building upon the successful construction and expression of the dsRNA-HT115 engineering strains of dsOftermicin1 and dsOftermicin2 in our laboratory, this work employs the ultrasonic breaking method to establish an inactivated dsOftermicins-HT115 technological system capable of producing a substantial quantity of dsRNA. This approach also addresses the limitation of transgenic strains which cannot be directly applied. Treatment of O. formosanus with dsOftermicins produced by this method could enhance the virulence of both Bt and Bb to the termites. This study laid the theoretical groundwork for the development of novel termite immunosuppressants and for the advancement and application of termite biological control strategies.

Predicting major adverse cardiovascular events within 3 years by optimization of radiomics model derived from pericoronary adipose tissue on coronary computed tomography angiography: a case-control study.

BACKGROUND: Coronary inflammation induces changes in pericoronary adipose tissue (PCAT) can be detected by coronary computed tomography angiography (CCTA). Our aim was to investigate whether different PCAT radiomics model based on CCTA could improve the prediction of major adverse cardiovascular events (MACE) within 3 years. METHODS: This retrospective study included 141 consecutive patients with MACE and matched to patients with non-MACE (n = 141). Patients were randomly assigned into training and test datasets at a ratio of 8:2. After the robust radiomics features were selected by using the Spearman correlation analysis and the least absolute shrinkage and selection operator, radiomics models were built based on different machine learning algorithms. The clinical model was then calculated according to independent clinical risk factors. Finally, an overall model was established using the radiomics features and the clinical factors. Performance of the models was evaluated for discrimination degree, calibration degree, and clinical usefulness. RESULTS: The diagnostic performance of the PCAT model was superior to that of the RCA-model, LAD-model, and LCX-model alone, with AUCs of 0.723, 0.675, 0.664, and 0.623, respectively. The overall model showed superior diagnostic performance than that of the PCAT-model and Cli-model, with AUCs of 0.797, 0.723, and 0.706, respectively. Calibration curve showed good fitness of the overall model, and decision curve analyze demonstrated that the model provides greater clinical benefit. CONCLUSION: The CCTA-based PCAT radiomics features of three major coronary arteries have the potential to be used as a predictor for MACE. The overall model incorporating the radiomics features and clinical factors offered significantly higher discrimination ability for MACE than using radiomics or clinical factors alone.

DNA methyltransferase 1 (DNMT1) promotes cyst growth and epigenetic age acceleration in autosomal dominant polycystic kidney disease.

Alteration of DNA methylation leads to diverse diseases, and the dynamic changes of DNA methylation (DNAm) on sets of CpG dinucleotides in mammalian genomes are termed "DNAm age" and "epigenetic clocks" that can predict chronological age. However, whether and how dysregulation of DNA methylation promotes cyst progression and epigenetic age acceleration in autosomal dominant polycystic kidney disease (ADPKD) remains elusive. Here, we show that DNA methyltransferase 1 (DNMT1) is upregulated in cystic kidney epithelial cells and tissues and that knockout of Dnmt1 and targeting DNMT1 with hydralazine, a safe demethylating agent, delays cyst growth in Pkd1 mutant kidneys and extends life span of Pkd1 conditional knockout mice. With methyl-CpG binding domain (MBD) protein-enriched genome sequencing (MBD-seq), DNMT1 chromatin immunoprecipitation (ChIP)-sequencing and RNA-sequencing analysis, we identified two novel DNMT1 targets, PTPRM and PTPN22 (members of the protein tyrosine phosphatase family). PTPRM and PTPN22 function as mediators of DNMT1 and the phosphorylation and activation of PKD-associated signaling pathways, including ERK, mTOR and STAT3. With whole-genome bisulfide sequencing in kidneys of patients with ADPKD versus normal individuals, we found that the methylation of epigenetic clock-associated genes was dysregulated, supporting that epigenetic age is accelerated in the kidneys of patients with ADPKD. Furthermore, five epigenetic clock-associated genes, including Hsd17b14, Itpkb, Mbnl1, Rassf5 and Plk2, were identified. Thus, the diverse biological roles of these five genes suggest that their methylation status may not only predict epigenetic age acceleration but also contribute to disease progression in ADPKD.