ABSTRACT
Intestinal helminth parasite (IHP) infection induces alterations in the composition of microbial communities across vertebrates, although how gut microbiota may facilitate or hinder parasite infection remains poorly defined. In this work we utilized a zebrafish model to investigate the relationship between gut microbiota, gut metabolites, and IHP infection. We found that extreme disparity in zebrafish parasite infection burden is linked to the composition of the gut microbiome, and that changes in the gut microbiome are associated with variation in a class of endogenously-produced signaling compounds, N-acylethanolamines, that are known to be involved in parasite infection. Using a statistical mediation analysis, we uncovered a set of gut microbes whose relative abundance explains the association between gut metabolites and infection outcomes. Experimental investigation of one of the compounds in this analysis reveals salicylaldehyde, which is putatively produced by the gut microbe Pelomonas, as a potent anthelmintic with activity against Pseudocapillaria tomentosa egg hatching, both in vitro and in vivo. Collectively, our findings underscore the importance of the gut microbiome as a mediating agent in parasitic infection and highlights specific gut metabolites as tools for the advancement of novel therapeutic interventions against IHP infection.
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BACKGROUND: The annual incidence of metabolic-associated fatty liver disease (MAFLD) in China has been increasing and is often overlooked owing to its insidious characteristics. Approximately 50% of the patients have a normal weight or are not obese. They are said to have lean-type MAFLD, and few studies of such patients are available. Because MAFLD is associated with abnormal lipid metabolism, lipid-targeted metabolomics was used in this study to provide experimental evidence for early diagnosis and pathogenesis. AIM: To investigate the serum fatty-acid metabolic characteristics in lean-type MAFLD patients using targeted serum metabolomic technology. METHODS: Between January and June 2022, serum samples were collected from MAFLD patients and healthy individuals who were treated at Shanghai Putuo District Central Hospital for serum metabolomics analysis. Principal component analysis and orthogonal partial least squares-discriminant analysis models were developed, and univariate analysis was used to screen for biomarkers of lean-type MAFLD and analyze metabolic pathways. UPLC-Q-Orbitrap/MS content determination was used to determine serum palmitic acid (PA), oleic acid (OA), linoleic acid (LA), and arachidonic acid (AA) levels in lean-type MAFLD patients. RESULTS: Urea nitrogen and uric acid levels were higher in lean-type MAFLD patients than in healthy individuals (P < 0.05). Alanine transaminase and cholinesterase levels were higher in lean-type MAFLD patients than in healthy individuals (P < 0.01). The expression of high-density lipoprotein and apolipoprotein A-1 were lower in lean-type MAFLD patients than in healthy individuals (P < 0.05) and the expression of triglycerides and fasting blood glucose were increased (P < 0.01). A total of 65 biomarkers that affected the synthesis and metabolism of fatty acids were found with P < 0.05 and variable importance in projection > 1". The levels of PA, OA, LA, and AA were significantly increased compared with healthy individuals. CONCLUSION: The metabolic profiles of lean-type MAFLD patients and healthy participants differed significantly, yielding 65 identified biomarkers. PA, OA, LA, and AA exhibited the most significant changes, offering valuable clinical guidance for prevention and treatment of lean-type MAFLD.
Subject(s)
Biomarkers , Fatty Acids , Metabolomics , Non-alcoholic Fatty Liver Disease , Humans , Metabolomics/methods , Male , Female , Middle Aged , Fatty Acids/blood , Fatty Acids/metabolism , Biomarkers/blood , Adult , Non-alcoholic Fatty Liver Disease/blood , Non-alcoholic Fatty Liver Disease/diagnosis , China/epidemiology , Lipid Metabolism , Case-Control Studies , Thinness/blood , Thinness/diagnosisABSTRACT
Intestinal helminth parasite (IHP) infection induces alterations in the composition of microbial communities across vertebrates, although how gut microbiota may facilitate or hinder parasite infection remains poorly defined. In this work, we utilized a zebrafish model to investigate the relationship between gut microbiota, gut metabolites, and IHP infection. We found that extreme disparity in zebrafish parasite infection burden is linked to the composition of the gut microbiome and that changes in the gut microbiome are associated with variation in a class of endogenously produced signaling compounds, N-acylethanolamines, that are known to be involved in parasite infection. Using a statistical mediation analysis, we uncovered a set of gut microbes whose relative abundance explains the association between gut metabolites and infection outcomes. Experimental investigation of one of the compounds in this analysis reveals salicylaldehyde, which is putatively produced by the gut microbe Pelomonas, as a potent anthelmintic with activity against Pseudocapillaria tomentosa egg hatching, both in vitro and in vivo. Collectively, our findings underscore the importance of the gut microbiome as a mediating agent in parasitic infection and highlight specific gut metabolites as tools for the advancement of novel therapeutic interventions against IHP infection. IMPORTANCE: Intestinal helminth parasites (IHPs) impact human health globally and interfere with animal health and agricultural productivity. While anthelmintics are critical to controlling parasite infections, their efficacy is increasingly compromised by drug resistance. Recent investigations suggest the gut microbiome might mediate helminth infection dynamics. So, identifying how gut microbes interact with parasites could yield new therapeutic targets for infection prevention and management. We conducted a study using a zebrafish model of parasitic infection to identify routes by which gut microbes might impact helminth infection outcomes. Our research linked the gut microbiome to both parasite infection and to metabolites in the gut to understand how microbes could alter parasite infection. We identified a metabolite in the gut, salicylaldehyde, that is putatively produced by a gut microbe and that inhibits parasitic egg growth. Our results also point to a class of compounds, N-acyl-ethanolamines, which are affected by changes in the gut microbiome and are linked to parasite infection. Collectively, our results indicate the gut microbiome may be a source of novel anthelmintics that can be harnessed to control IHPs.
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AIMS: The prognostic significance of N-terminal pro B-type natriuretic peptide (NT-proBNP) in heart failure with preserved ejection fraction (HFpEF) has been well established. HFpEF and atrial fibrillation (AF) commonly coexist, and each contributes to poor outcomes independently. Nevertheless, the ability of NT-proBNP to predict AF in HFpEF patients remains uncertain. METHODS AND RESULTS: A total of 367 HFpEF patients without baseline AF from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial were included. The Cox proportional hazard model was used to assess the association of NT-proBNP with the risk of AF. The C-statistic, categorical net reclassification index (NRI), and integrated discrimination improvement (IDI) were used to evaluate the ability of NT-proBNP in new-onset AF prediction. During a median follow-up of 2.91 years, 17 (4.63%) new-onset AF cases occurred. Every 1000 pg/mL increase in NT-proBNP was associated with a 16% increase in the risk of AF occurrence after adjustments (hazard ratio, 1.16 [95% CI, 1.02-1.32]). NT-proBNP showed a moderate performance for new-onset AF at 3 years (C-statistic, 0.67). Adding NT-proBNP to CHADS2/R2CHADS2/CHA2DS2-VASc/C2HSET scores improved their predictive performance for AF risk (CHADS2: C-statistic, 0.63, CHADS2+NT: C-statistic, 0.69, NRI, 47.46%, IDI, 1.18%; R2CHADS2: C-statistic, 0.65, R2CHADS2+NT: C-statistic, 0.70, NRI, 48.03%, IDI, 0.51%; CHA2DS2-VASc: C-statistic, 0.67, CHA2DS2-VASc+NT: C-statistic, 0.72, NRI, 49.41%, IDI, 0.86%; C2HSET: C-statistic, 0.77, C2HSET+NT: C-statistic, 0.80, NRI, 50.32%, IDI, 1.58%). CONCLUSIONS: Among patients with HFpEF, the NT-proBNP level was positively associated with the incidence of new-onset AF and may be a promising predictor.
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The prognostic value of central pathology review in upper urinary tract cancer (UTUC) remains inadequately addressed in existing literature. In this study, we conducted an extensive central pathology review and presented its influence on multi-center UTUC studies. We conducted a retrospective review of patients who underwent radical nephroureterectomy or segmental resection for UTUC to determine eligibility for central pathology review. In the Taiwan UTUC Collaboration cohort, 377 cases met the criteria for pathology review. We assessed agreement between pathologists using both the total percentage of agreement and simple kappa statistics. The prognostic implications of original and review pathology for various parameters were examined using the Cox regression model. This study included 209 female and 168 male participants. Pathology review revealed substantial interobserver variability in pT staging, with a particularly high rate of pT2 cases being upgraded to pT3 upon central review (17/70 pT2 stage made by local pathologists were finally confirmed as pT3 disease by the review pathologist). The local pathologist cohort identified fewer significant histological predictors in survival models compared to the review pathology cohort. Advanced pT stage, perineural invasion (PNI), and positive surgical margin were independent predictors of poorer overall survival and cancer-specific survival. PNI, lymphatic vascular invasion, and positive surgical margin were independent predictors of disease recurrence. Substantial interobserver variability in histological assessment underscores the importance of centralized pathology review for both multi-center studies and accurate post-operative management of UTUC patients. Advanced stage, perineural invasion, and margin status were significant histological predictors of oncological outcomes.
Subject(s)
Urologic Neoplasms , Humans , Male , Female , Aged , Prognosis , Retrospective Studies , Middle Aged , Urologic Neoplasms/pathology , Urologic Neoplasms/surgery , Urologic Neoplasms/mortality , Neoplasm Staging , Taiwan/epidemiology , Nephroureterectomy , Aged, 80 and overABSTRACT
It is known that asymmetrical maternal transcripts play an important role in the cell fate of the early embryo, but few studies are available in mammal oocytes especially in pig. To investigate the spatial factors in pig oocytes, the oriented bisection was established for collecting karyoplasts (NSOs) and cytoplasts (SSOs) with more than 95% efficiency. Subsequently, RNA-Seq and LC-MS/MS analysis were performed on NSOs and SSOs. Although no differentially expressed genes (DEGs) could be detected between NSOs and SSOs, 89 of the differentially expressed proteins (DEPs) were detected, that 58 proteins higher expressed but 31 proteins lower expressed in NSOs compared with SSOs. These DEPs mainly participated in the 'cell cycle' and 'ribosome' pathway, while the up-regulated DEPs were mainly GO in 'spindle' and 'positive regulation of translation', and the down-regulated DEPs were in 'cytosolic small ribosomal subunit' and 'mRNA binding'. The up-regulated DEP SIRT5 which are related to the regulation of gene expression, epigenetic were further detected and revealed. A spatial asymmetry of maternal factors at the protein level was firstly detected in pig mature oocytes.
Subject(s)
Oocytes , Animals , Oocytes/metabolism , Swine , FemaleABSTRACT
The relationships between the exposure to ambient air pollutants during gestation and the incidence of hypertensive disorders in pregnancy (HDPs) or preeclampsia are contradictory. This prospective cohort study enrolled the participants between January 2020 and December 2021 from the Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology. The exposure to ambient air pollutants and daily temperatures were obtained from the ChinaHighAirPollutants dataset and the Big Earth Data Platform for Three Poles, respectively. Logistic regression models were used as single- and two-pollutant models. Restricted cubic splines were applied to each ambient air pollutant exposure to further evaluate the exposure-response relationships. Quantile G-computation approaches were employed to evaluate the cumulative impact of mixed ambient air pollutants on the incidence risk HDPs and preeclampsia. Among 19,325 participants (median age: 30.2 years), 1669 (8.64%) were diagnosed with HDPs and 180 (0.94%) with preeclampsia. While mostly null risk estimates were observed, exposure to PM1, PM2.5, PM10, and NO2 correlated with a decreased incidence risk for HDPs and preeclampsia during most gestational periods. Additionally, our multi-pollutant model presented that an increase by one quartile in the cumulative effect of ambient air pollutants was associated with a significantly decreased incidence risk for HDPs in the trimester before gestation and in the third trimester during gestation, as well as for preeclampsia in the third trimester during gestation. These findings warrant further investigation into the mechanisms underlying these associations.
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BACKGROUND: While multiple sclerosis (MS) affects less than 1 % of the general population, immune mediated inflammatory diseases (IMIDs) collectively influence 5-10 % of the population. Understanding familial co-aggregation of MS and other IMIDs carries important clinical and public health implications that will enable early detection and personalized treatment. OBJECTIVE: To estimate the familial association between MS and other IMIDs and to quantify their shared genetic basis. DESIGN: Register-based multi-generational nested case-control familial co-aggregation study and genetic correlation study. SETTING: Sweden. PARTICIPANTS: 24,995 individuals with MS matched with 253,870 controls and 1,283,502 first-degree relatives (mothers, fathers, full siblings, and offspring) for familial co-aggregation analysis; population of European ancestry for genetic correlation analysis. MEASUREMENTS: Logistic regressions with adjustment for covariates were used to estimate the odds ratios (ORs) of developing MS in individuals with first-degree relatives diagnosed with IMIDs compared to those without such family history. Pairwise genome-wide genetic correlations were estimated with linkage-disequilibrium score regression. RESULTS: We observed an OR for familial co-aggregation of MS of 1.09 (95 % confidence interval (95%CI) = 1.07-1.11) in families with IMIDs history compared to families without. The association remained broadly consistent after stratification by sex concordance of relative pairs and by kinships. 18 IMID subtypes showed a familial association with MS, 7 of which including other acute widespread myelin destruction, encephalitis or myelitis or encephalomyelitis, inflammatory bowel disease, autoimmune thyroid diseases, systemic lupus erythematosus, other inflammatory system diseases, and sarcoidosis withstood multiple correction. Genetic correlations further revealed a shared genetic basis between 7 IMID subtypes with MS. CONCLUSION: We demonstrated a modest familial co-aggregation of MS with several IMIDs, and such association is likely due to shared genetic factors.
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MicroRNA and mitofusin-2 (Mfn2) play an important role in the myocardial apoptosis induced by acute myocardial infarction (AMI). However, the target relationship and underlying mechanism associated with interorganelle interaction between endoplasmic reticulum (ER) and mitochondria under ischemic condition is not completely clear. MI-induced injury, Mfn2 expression, Mfn2-mediated mitochondrial function and ER stress, and target regulation by miRNA-15b (miR-15b) were evaluated by animal MI and cellular hypoxic models with advanced molecular techniques. The results confirmed that Mfn2 was down-regulated and miR-15b was up-regulated upon the target binding profile under ischemic/hypoxic condition. Our data showed that miR-15b caused cardiac apoptotic injury that was reversed by rAAV9-anti-miR-15b or AMO-15b. The damage effect of miR-15b on Mfn2 expression and mitochondrial function was observed and rescued by rAAV9-anti-miR-15b or AMO-15b. The targeted regulation of miR-15b on Mfn2 was verified by luciferase reporter and microRNA-masking. Importantly, miR-15b-mediated Mfn2 suppression activated PERK/CHOP pathway, by which leads to ER stress and mitochondrial dysfunction, and cardiac apoptosis eventually. In conclusion, our research, for the first time, revealed the missing molecular link in Mfn2 and apoptosis and elucidated that pro-apoptotic miR-15b plays crucial roles during the pathogenesis of AMI through down-regulation of Mfn2 and activation of PERK-mediated ER stress. These findings may provide an opportunity to develop new therapies for prophylaxis and treatment of ischemic heart disease.
Subject(s)
GTP Phosphohydrolases , MicroRNAs , MicroRNAs/genetics , MicroRNAs/metabolism , Animals , GTP Phosphohydrolases/genetics , GTP Phosphohydrolases/metabolism , Male , eIF-2 Kinase/metabolism , eIF-2 Kinase/genetics , eIF-2 Kinase/antagonists & inhibitors , Signal Transduction/physiology , Myocardial Ischemia/metabolism , Myocardial Ischemia/genetics , Myocardial Ischemia/pathology , Mice , Endoplasmic Reticulum Stress/physiology , Endoplasmic Reticulum Stress/genetics , Apoptosis , Mice, Inbred C57BLABSTRACT
Transcription factors play crucial roles in almost all physiological processes including leaf senescence. Cell death is a typical symptom appearing in senescing leaves, which is also classified as developmental programmed cell death (PCD). However, the link between PCD and leaf senescence still remains unclear. Here, we found a WRKY transcription factor WRKY47 positively modulates age-dependent leaf senescence in Arabidopsis (Arabidopsis thaliana). WRKY47 was expressed preferentially in senescing leaves. A subcellular localization assay indicated that WRKY47 was exclusively localized in nuclei. Overexpression of WRKY47 showed precocious leaf senescence, with less chlorophyll content and higher electrolyte leakage, but loss-of-function mutants of WRKY47 delayed this biological process. Through qRT-PCR and dual luciferase reporter assays, we found that WRKY47 could activate the expression of senescence-associated genes (SAGs) and PCD-associated genes to regulate leaf senescence. Furthermore, through electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP)-qPCR, WRKY47 was found to bind to W-box fragments in promoter regions of BFN1 (Bifunctional Nuclease 1) and MC6 (Metacaspase 6) directly. In general, our research revealed that WRKY47 regulates age-dependent leaf senescence by activating the transcription of two PCD-associated genes.
Subject(s)
Arabidopsis Proteins , Arabidopsis , Gene Expression Regulation, Plant , Plant Leaves , Plant Senescence , Transcription Factors , Apoptosis/genetics , Arabidopsis/genetics , Arabidopsis/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Plant Leaves/metabolism , Plant Leaves/genetics , Plant Senescence/genetics , Promoter Regions, Genetic/genetics , Transcription Factors/metabolism , Transcription Factors/geneticsABSTRACT
The influence of tree age on the growth response of Picea likiangensis, a predominant timber species in southwestern China, to climatic factors has been under-researched. In this study, we examined the relationships between tree age and the response of P. likiangensis to climatic factors and extreme drought events using tree-ring samples procured from the southeastern edge of the Tibetan Plateau. The results revealed differential responses of the radial growth of P. likiangensis trees of varying ages to climatic factors and extreme drought events. Specifically, deficient water availability during the early growing season emerged as the principal factor constraining radial growth across all age classes. Young and middle-aged trees (<100 years) demonstrated greater responsiveness to water availability than did mature trees (>100 years). Mature trees, in contrast, demonstrated markedly greater resistance to extreme drought events than young and middle-aged trees. Comparative studies of individual trees across different ages revealed negligible differences in the response of young and middle-aged trees to climatic factors and extreme drought events. Given these responses, future forest management practices should prioritize young and middle-aged trees that are more affected by drought to maximize the ecological value of the species. According to the specific research objectives, sample collection processes should classify mature trees and young and middle-aged trees, to minimize the influence of tree age on the final findings of the study.
Subject(s)
Climate , Droughts , Picea , Picea/growth & development , Picea/physiology , Climate Change , China , Trees/growth & developmentABSTRACT
Exploration of a stably expressed gene as a reference is critical for the accurate evaluation of miRNAs isolated from small extracellular vesicles (sEVs). In this study, we analyzed small RNA sequencing on plasma sEV miRNAs in the training dataset (n = 104) and found that miR-140-3p was the most stably expressed candidate reference for sEV miRNAs. We further demonstrated that miR-140-3p expressed most stably in the validation cohort (n = 46) when compared to two other reference miRNAs, miR-451a and miR-1228-3p, and the commonly-used miRNA reference U6. Finally, we compared the capability of miR-140-3p and U6 as the internal reference for sEV miRNA expression by evaluating key miRNAs expression in lung cancer patients and found that miR-140-3p was more suitable as a sEV miRNA reference gene. Taken together, our data indicated miR-140-3p as a stable internal reference miRNA of plasma sEVs to evaluate miRNA expression profiles in lung cancer patients.
Subject(s)
Extracellular Vesicles , Lung Neoplasms , MicroRNAs , Humans , MicroRNAs/blood , MicroRNAs/genetics , Lung Neoplasms/genetics , Lung Neoplasms/blood , Extracellular Vesicles/genetics , Extracellular Vesicles/metabolism , Female , Male , Reference Standards , Real-Time Polymerase Chain Reaction/standards , Middle Aged , Biomarkers, Tumor/blood , Biomarkers, Tumor/geneticsABSTRACT
The WRKY transcription factor (TF) genes form a large family in higher plants, with 72 members in Arabidopsis (Arabidopsis thaliana). The gaseous phytohormone ethylene (ET) regulates multiple physiological processes in plants. It is known that 1-aminocyclopropane-1-carboxylic acid (ACC) synthases (ACSs, EC 4.4.1.14) limit the enzymatic reaction rate of ethylene synthesis. However, whether WRKY TFs regulate the expression of ACSs and/or ACC oxidases (ACOs, EC 1.14.17.4) remains largely elusive. Here, we demonstrated that Arabidopsis WRKY22 positively regulated the expression of a few ACS and ACO genes, thus promoting ethylene production. Inducible overexpression of WRKY22 caused shorter hypocotyls without ACC treatment. A qRT-PCR screening demonstrated that overexpression of WRKY22 activates the expression of several ACS and ACO genes. The promoter regions of ACS5, ACS11, and ACO5 were also activated by WRKY22, which was revealed by a dual luciferase reporter assay. A follow-up chromatin immunoprecipitation coupled with quantitative PCR (ChIP-qPCR) and electrophoretic mobility shift assay (EMSA) showed that the promoter regions of ACS5 and ACO5 could be bound by WRKY22 directly. Moreover, wrky22 mutants had longer primary roots and more lateral roots than wild type, while WRKY22-overexpressing lines showed the opposite phenotype. In conclusion, this study revealed that WRKY22 acts as a novel TF activating, at least, the expression of ACS5 and ACO5 to increase ethylene synthesis and modulate root development.
Subject(s)
Arabidopsis Proteins , Arabidopsis , Ethylenes , Gene Expression Regulation, Plant , Lyases , Plant Roots , Transcription Factors , Arabidopsis/genetics , Arabidopsis/growth & development , Arabidopsis/metabolism , Ethylenes/metabolism , Ethylenes/biosynthesis , Transcription Factors/metabolism , Transcription Factors/genetics , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Plant Roots/genetics , Plant Roots/growth & development , Plant Roots/metabolism , Lyases/genetics , Lyases/metabolism , Amino Acid Oxidoreductases/genetics , Amino Acid Oxidoreductases/metabolism , Promoter Regions, Genetic/genetics , Carbon-Carbon Lyases/metabolism , Carbon-Carbon Lyases/genetics , Transcriptional Activation/geneticsABSTRACT
BACKGROUND: Dysregulation of enhancer transcription occurs in multiple cancers. Enhancer RNAs (eRNAs) are transcribed products from enhancers that play critical roles in transcriptional control. Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers. METHODS: Initially, a comprehensive analysis of eRNA quantitative trait loci (eRNAQTLs) was performed in The Cancer Genome Atlas (TCGA), and functional features were characterized using multi-omics data. To establish the first eRNAQTL profiles for colorectal cancer (CRC) in China, epigenomic data were used to define active enhancers, which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples. Finally, large-scale case-control studies (34,585 cases and 69,544 controls) were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk. RESULTS: A total of 300,112 eRNAQTLs were identified across 30 different cancer types, which exert their influence on eRNA transcription by modulating chromatin status, binding affinity to transcription factors and RNA-binding proteins. These eRNAQTLs were found to be significantly enriched in cancer risk loci, explaining a substantial proportion of cancer heritability. Additionally, tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer. Moreover, the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer, highlighting their potential as therapeutic targets. Furthermore, multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China (OR = 0.91, 95%CI 0.88-0.95, P = 2.92 × 10-7) and Europe (OR = 0.92, 95%CI 0.88-0.95, P = 4.61 × 10-6). Mechanistically, rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786, which functioned as a transcriptional activator promoting the expression of its target gene SENP7. These two genes synergistically suppressed tumor cell proliferation. Our curated list of variants, genes, and drugs has been made available in CancereRNAQTL ( http://canernaqtl.whu.edu.cn/#/ ) to serve as an informative resource for advancing this field. CONCLUSION: Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability, pinpointing the potential of eRNA-based therapeutic strategies in cancers.
Subject(s)
Enhancer Elements, Genetic , Neoplasms , Quantitative Trait Loci , Humans , Enhancer Elements, Genetic/genetics , Neoplasms/genetics , Genetic Variation/genetics , Genome-Wide Association Study/methods , Colorectal Neoplasms/genetics , Case-Control Studies , RNA/genetics , China , Enhancer RNAsABSTRACT
Molecular techniques that recover unknown sequences next to a known sequence region have been widely applied in various molecular studies, such as chromosome walking, identification of the insertion site of transposon mutagenesis, fusion gene partner, and chromosomal breakpoints, as well as targeted sequencing library preparation. Although various techniques have been introduced for efficiency enhancement, searching for relevant single molecular event present in a large-sized genome remains challenging. Here, the optimized ligation-mediated polymerase chain reaction (PCR) method was developed and successfully identified chromosomal breakpoints far away from the exon of the new exon junction without the need for nested PCR. In addition to recovering unknown sequences next to a known sequence region, the high efficiency of the method could also improve the performance of targeted next-generation sequencing (NGS).
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Objective: This study aimed to explore the needs and constraints to cardiac rehabilitation (CR) among patients diagnosed with coronary heart disease (CHD) in a community-based setting, and thereby facilitating the implementation of effective CR programs for this population. Methods: Focus group interviews were used as the primary research methodology. A total of 11 community-dwelling individuals diagnosed with CHD were selected from a community hospital to participate in in-depth interviews, aiming to discern and analyze their requirements and constraints experienced concerning medical resources and healthcare agency. The textual data underwent examination using Colaizzi's method of descriptive data analysis. Results: Deficits existed in the perceptions of patients with CHD within a community-based setting about their condition and CR, and in the social support for this disease. Patients expressed expectations for professional guidance during CR, gained an understanding about the beneficial effects of emotional stability on cognitive function. Patients expressed their thoughts and feelings regarding the diversity of physical exercise options. Two main themes and seven sub-themes were identified: (a) "Insufficient CR resources for patients": Lack of awareness about CHD; inadequate knowledge about secondary prevention/CR; insufficient support from family and friends. (b) "Patient CR initiative": Patient self-adjustment; expectation of professional rehabilitation guidance; stable emotions improving cognition; diverse attitudes and awareness of exercise. Conclusion: For more effective CR, community-based medical teams should provide more comprehensive and individualized rehabilitation programs. They should focus on individual variations and preferences of patients, as well as enhance the autonomy of patients and improve their self-care ability through effective empowerment measures.
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Host specialization plays a critical role in the ecology and evolution of plant-microbe symbiosis. Theory predicts that host specialization is associated with microbial genome streamlining and is influenced by the abundance of host species, both of which can vary across latitudes, leading to a latitudinal gradient in host specificity. Here, we quantified the host specificity and composition of plant-bacteria symbioses on leaves across 329 tree species spanning a latitudinal gradient. Our analysis revealed a predominance of host-specialized leaf bacteria. The degree of host specificity was negatively correlated with bacterial genome size and the local abundance of host plants. Additionally, we found an increased host specificity at lower latitudes, aligning with the high prevalence of small bacterial genomes and rare host species in the tropics. These findings underscore the importance of genome streamlining and host abundance in the evolution of host specificity in plant-associated bacteria along the latitudinal gradient.
Subject(s)
Genome Size , Host Specificity , Plant Leaves , Symbiosis , Plant Leaves/microbiology , Bacteria/genetics , Bacteria/classification , Genome, Bacterial , Trees/microbiologyABSTRACT
Osteoporosis (OP) is a chronic systemic bone metabolism disease characterized by decreased bone mass, microarchitectural deterioration, and fragility fractures. With the demographic change caused by long lifespans and population aging, OP is a growing health problem. The role of miRNA in the pathogenesis of OP has also attracted widespread attention from scholars in recent years. Type H vessels are unique microvessels of the bone and have become a new focus in the pathogenesis of OP because they play an essential role in osteogenesis-angiogenesis coupling. Previous studies found some miRNAs regulate type H vessel formation through the regulatory factors, including platelet-derived growth factor-BB (PDGF-BB), hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), and so on. These findings help us gain a more in-depth understanding of the relationship among miRNAs, type H vessels, and OP to find a new perspective on treating OP. In the present mini-review, we will introduce the role of type H vessels in the pathogenesis of OP and the regulation of miRNAs on type H vessel formation by affecting regulatory factors to provide some valuable insights for future studies of OP treatment.
Subject(s)
MicroRNAs , Osteoporosis , Animals , Humans , Bone and Bones/blood supply , Bone and Bones/metabolism , Bone and Bones/pathology , MicroRNAs/genetics , MicroRNAs/metabolism , Microvessels/pathology , Microvessels/metabolism , Neovascularization, Pathologic/genetics , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/pathology , Osteogenesis/genetics , Osteogenesis/physiology , Osteoporosis/genetics , Osteoporosis/metabolism , Osteoporosis/pathologyABSTRACT
Climate change has profoundly affected the synchrony of tree growth at multiple scales, thereby altering the structure and function of forest ecosystems. The Asian boreal forests extend southward to the Greater Khingan Range in northeast China. Given the ecological importance and susceptibility to climate change, the impacts of warming on this marginal forest community have been extensively investigated. Nonetheless, how tree growth synchrony changes across this region remains less understood. Focusing on this knowledge gap, we compiled a contiguously-distributed tree-ring network, containing 18 sampling populations and 475 individual larch trees, to explore the changes in multiple-scale growth synchrony across this region. We found increasing growth synchrony at both the individual and population levels over the past decades. The increasing trend of the regional inter-population growth synchrony was well in line with the increasing temperature and PDSI. Furthermore, 11 of the 18 sampling populations showed significant increases in their intra-population growth synchrony. We further associated the sliding intra-population growth synchrony with local climates. Intra-population growth synchrony of 13 and 11 sampling populations were significantly positively correlated with local temperature, and negatively correlated with local PDSI, respectively, demonstrating the driving role of warming-induced drought on growth synchrony. The linear regression model quantifying this relationship suggested that an increase of 1 °C in annual mean temperature would drive the intra-population growth synchrony to increase by 0.047. As warming trends in the study area are projected to continue over this century, our study warns of the further consequences of the increasing growth synchrony may have on the functioning, resilience, and persistence of forests.