BackgroundRecurrent headaches in headache disorders adversely impact quality of life and job. Migraines and tension-type headache TTH) are the most common primary headaches and a prominent cause of disability globally. However, few research compare headache illness burden in China, India, the United States (US), and Japan.MethodsGlobal and Chinese, the US, Indian, and Japanese migraine and TTH incidence, prevalence, and disability-adjusted life years were taken from the GBD database for 1990–2021. The data is studied utilizing decomposition analysis, health inequality research, joinpoint regression model, and Bayesian Average Annual Percentage Change (BAPC) model.ResultsThe study found that migraine mostly affects women aged 15–49, while TTH are evenly distributed across gender and age. The worldwide average annual percentage change (AAPC) in disease-adjusted life years (DALYs) for migraine and TTH from 1990 to 2021 was 0.0357, a statistically significant trend (p < 0.001), as determined using joinpoint analysis. China exhibited the quickest rise in migraine and TTH incidence and prevalence, as well as the age-standardized rate (ASR) of DALYs, of the four nations analyzed. The US had the highest value of these indicators. Forecasting models reveal that without policy action, migraine prevalence will grow but TTH prevalence would stay unchanged. Decomposition research showed that population expansion is the major cause of migraines and TTH, which will be slightly alleviated by population aging. Health disparities across economic growth areas lessened between 1990 and 2021, according to the report.ConclusionGlobally and in China, migraine and TTH incidence and burden have increased since 1990. Migraines are becoming more common in young and middle-aged women, so headache treatment professionals should invest more in patient education to raise awareness and improve self-management to reduce disease burden and medical costs.
Rationale: Hyperglycemia-induced endothelial dysfunction is a hallmark of diabetic cardiomyopathy, yet the underlying molecular mechanisms remain incompletely understood. This study aimed to investigate how the DNA damage response (DDR) pathway regulates endothelial cell ferroptosis under hyperglycemic conditions, potentially revealing new therapeutic targets for mitigating cardiac damage in type 2 diabetes mellitus (T2DM). Methods: We performed an integrated analysis of publicly available RNA sequencing datasets (GSE280770, GSE89475, GSE161931, CRA007245) to evaluate the role of DDR in hyperglycemia-induced endothelial dysfunction in vitro and in vivo, including in a T2DM mouse model. Key DDR and ferroptosis markers were validated in cardiac microvascular endothelial cells (CMECs) isolated from mice with streptozotocin (STZ)/high-fat diet (HFD)-induced T2DM, with and without treatment with the DNA-PK inhibitors NU7441 or M9831. Results: Hyperglycemia induced a robust DDR in endothelial cells, characterized by the upregulation of DNA-PK complex genes (PRKDC, XRCC5, XRCC6) and increased markers of DNA damage (γH2AX, 8-oxo-dG). This was accompanied by increased expression of pro-ferroptotic genes (Tfrc, Acsl4, Ptgs2), decreased expression of anti-ferroptotic genes (Gpx4, Slc7a11), and elevated lipid peroxidation (MDA, 4-HNE). Pharmacological inhibition of DNA-PK mitigated these effects, reducing oxidative stress, lipid peroxidation, and endothelial permeability, while improving cardiac contractile and relaxation parameters. Conclusions: Our findings implicate the DNA-PK complex as a key regulator of hyperglycemia-induced endothelial ferroptosis in T2DM cardiomyopathy. Targeting DNA-PK complex may represent a novel therapeutic strategy for mitigating microvascular dysfunction and cardiac decline in T2DM.
The Jiangsu-South Yellow Sea area is located on the East Asian Continental Margin and at the junction of South and North China. It is one of the high seismicity areas in eastern China. To enhance our understanding of the relationship between disastrous earthquakes and the geophysical properties of Earth materials, P- and S-wave travel-time data over the past 20 years are inverted to image the 3D distributions of seismic velocity (VP and Vs) and Poisson’s ratio (σ). The results show that the velocity and Poisson’s ratio demonstrate congruence with the prominent geological formations present within the study area. Specifically, the velocity models for the upper crust at depths of 5, 10, and 15 km. We found that within the total study area, 70
This paper describes a three-dimensional and comprehensive method for completing the northern extension of the Maoshan fracture zone from deep to shallow. Gravity field data interpretation and geomagnetic survey were used to initially locate the rupture, followed by shallow seismic survey for precise positioning, and finally the upper rupture point was captured and its Quaternary activities were investigated according to the method of joint geologic profile exploration with small spaced drill holes across the rupture point. Research has found: ① The Maoshan fracture zone continues to extend northward into the urban area of Zhenjiang, and the northern extension of the Maoshan fracture zone cuts at least to the mid-crustal region. ② The shallow part of the northern extension of the Maoshan fracture zone shows normal faulting characteristics, with an inclination to the east and a strike to the north-east, an apparent dip of about 60°, and an apparent break distance of about 3~5 m. ③ The results of the joint geologic profile of the boreholes show that the bedrock surface on both sides of the fracture point has a small difference, and the overlying Quaternary strata do not have any large undulation and do not have any obvious signs of Quaternary activity, so it is comprehensively judged that the northern extension of the Maoshan fracture zone is a pre-Quaternary fracture. This study preliminarily suggests that the Maoshan fault may be geospatially linked to two significant seismic events in the history of the Jiangsu landmass. This finding provides a new perspective for further research on the seismogenic tectonic features and seismic activity patterns in the region, and may inspire future related studies.
Disruption of the mitochondrial quality surveillance (MQS) system contributes to mitochondrial dysfunction in diabetic cardiomyopathy (DCM). In this study, we observed that cardiac expression of phosphoglycerate mutase 5 (PGAM5), a mitochondrial Ser/Thr protein phosphatase, is upregulated in mice with streptozotocin-induced DCM. Notably, DCM-related cardiac structural and functional deficits were negated in cardiomyocyte-specific Pgam5 knockout (Pgam5CKO) mice. Hyperglycemic stress impaired adenosine triphosphate production, reduced respiratory activity, and prolonged mitochondrial permeability transition pore opening in acutely isolated neonatal cardiomyocytes from control Pgam5f/f mice, and these effects were markedly prevented in cardiomyocytes from Pgam5CKO mice. Likewise, three main MQS-governed processes—namely, mitochondrial fission/fusion cycling, mitophagy, and biogenesis—were disrupted by hyperglycemia in Pgam5f/f, but not in Pgam5CKO, cardiomyocytes. On the basis of bioinformatics prediction of interaction between PGAM5 and prohibitin 2 (PHB2), an inner mitochondrial membrane-associated scaffolding protein, co-immunoprecipitation, and immunoblot assays demonstrated that PGAM5 dephosphorylates PHB2 on Ser91. Transfection of cardiomyocytes with phosphodefective or phosphomimetic Ser91 mutants of PHB2 confirmed a critical role for PGAM5-mediated dephosphorylation of PHB2 in mitochondrial dysfunction associated with hyperglycemic stress. Furthermore, knockin mice expressing phosphomimetic PHB2S91D were resistant to diabetes-induced cardiac dysfunction. Our findings highlight the PGAM-PHB2 axis as a novel and critical regulator of mitochondrial dysfunction in DCM.
Rationale: The DNA -dependent protein kinase catalytic subunit (DNA-PKcs) promotes pathological mitochondrial fission during septic acute kidney injury. The mitochondrial open reading frame of the 12S rRNA type -c (MOTS -c) is a mitochondria -derived peptide that exhibits anti-inflammatory properties during cardiovascular illnesses. We explored whether endotoxemia-induced myocardial microvascular injury involved DNA-PKcs and MOTS -c dysregulation. Methods: To induce endotoxemia in vivo, endothelial cell -specific DNA-PKcs-knockout mice were injected intraperitoneally with a single dose of lipopolysaccharide (10 mg/kg) and evaluated after 72 h. Results: Lipopolysaccharide exposure increased DNA-PKcs activity in cardiac microvascular endothelial cells, while pharmacological inhibition or endothelial cell -specific genetic ablation of DNA-PKcs reduced lipopolysaccharide-induced myocardial microvascular dysfunction. Proteomic analyses showed that endothelial DNA-PKcs ablation primarily altered mitochondrial protein expression. Verification assays confirmed that DNA-PKcs drastically repressed MOTS -c transcription by inducing mtDNA breaks via pathological mitochondrial fission. Inhibiting MOTS -c neutralized the endothelial protective effects of DNA-PKcs ablation, whereas MOTS -c supplementation enhanced endothelial barrier function and myocardial microvascular homeostasis under lipopolysaccharide stress. In molecular studies, MOTS -c downregulation disinhibited c -Jun N -terminal kinase (JNK), allowing JNK to phosphorylate profilin-S173. Inhibiting JNK or transfecting cells with a profilin phosphorylation-defective mutant improved endothelial barrier function by preventing F -actin depolymerization and lamellipodial degradation following lipopolysaccharide treatment. Conclusions: DNA-PKcs inactivation during endotoxemia could be a worthwhile therapeutic strategy to restore MOTS -c expression, prevent JNK-induced profilin phosphorylation, improve F -actin polymerization, and enhance lamellipodial integrity, ultimately ameliorating endothelial barrier function and reducing myocardial microvascular injury.
Mitochondrial aldehyde dehydrogenase (ALDH2) offers proven cardiovascular benefit, although its impact on diabetes remains elusive. This study examined the effects of ALDH2 overexpression and knockout on diabetic cardiomyopathy and the mechanism involved with a focus on mitochondrial integrity. Mice challenged with streptozotocin (STZ, 200 mg/kg, via intraperitoneal injection) exhibited pathological alterations, including reduced respiratory exchange ratio, dampened fractional shortening and ejection fraction, increased left ventricular end-systolic and diastolic diameters, cardiac remodeling, cardiomyocyte contractile anomalies, intracellular Ca2+ defects, myocardial ultrastructural injury, oxidative stress, apoptosis, and mitochondrial damage, which were overtly attenuated or accentuated by ALDH2 overexpression or knockout, respectively. Diabetic patients also exhibited reduced plasma ALDH2 activity, cardiac remodeling, and diastolic dysfunction. In addition, STZ challenge altered expression levels of mitochondrial proteins (PGC-1 alpha and UCP2) and Ca2+ regulatory proteins (SERCA, Na+-Ca2+ exchanger, and phospholamban), dampened autophagy and mitophagy (LC3B ratio, TOM20, Parkin, FUNDC1, and BNIP3), disrupted phosphorylation of Akt, GSK3 beta, and Foxo3a, and elevated PTEN phosphorylation, most of which were reversed or worsened by ALDH2 overexpression or knockout, respectively. Furthermore, the novel ALDH2 activator torezolid, as well as the classical ALDH2 activator Alda-1, protected against STZ- or high glucose-induced in vivo or in vitro cardiac anomalies, which was nullified by inhibition of Akt, GSK3 beta, Parkin, or mitochondrial coupling. Our data discerned a vital role for ALDH2 in diabetic cardiomyopathy possibly through regulation of Akt and GSK3 beta activation, Parkin mitophagy, and mitochondrial function.
Introduction: Many observational studies have identified aortic aneurysm (AA) as a cardiovascular complication of immune-mediated inflammatory diseases (IMIDs). However, due to the effects of various confounders, it is still uncertainty whether this association holds or whether reverse causality is involved. Here we conducted a two-sample bidirectional MR study to infer the causal relationships between the two diseases. Method: We obtained genetic association datasets from public GWAS databases in populations of European ancestry. Abiding by the assumptions of Mendelian randomization (MR), we selected valid instrumental variables from genetic variants. Different statistic methods were performed for MR analysis and sensitivity analysis, and the inverse variance weighted (IVW) method was regarded as the most efficient estimate of the causal effect in this study. Results: The IVW method found evidence that genetically predicted AA had a causal effect on rheumatoid arthritis (RA) (OR = 1.06, 95%CI = 1.01-1.12, p = 0.029), but not of RA or other IMIDs on AA. Besides, no evidence showed that AA may increase the risk of inflammatory bowel disease (IBD), Crohn’s disease (CD), ulcerative colitis (UC), systemic lupus erythematosus (SLE) and psoriasis (PSO). The sensitivity analysis confirmed the absence of heterogeneity or horizontal pleiotropy effect. Conclusion: In summary, our study discovered that genetically predicted AA may increase the risk of RA, while no evidence was found that patients with RA had an increased risk of AA. Furthermore, we confirmed no evidence of association between IBD, CD, UC, SLE, PSO and AA. This is in accordance with other reports that demonstrated the human leukocyte antigen molecule in inflammatory aortic aneurysm was a genetic risk loci. Our study provides directions for future research on genetic susceptibility to inflammatory aortic aneurysm.
Rationale: Endotoxemia, caused by lipopolysaccharides, triggers systemic inflammation and myocardial injury by disrupting mitochondrial homeostasis. This study examines the roles of dual specificity phosphatase 1 (Dusp1) and phosphoglycerate mutase family member 1 (Pgam1) in this process. Methods: This study utilized cardiomyocyte-specific Dusp1 knockout ( Dusp1 Cko ) and transgenic ( Dusp1 Tg ) mice, alongside Pgam1 knockout ( Pgam1 Cko ) mice, subjected to LPS-induced endotoxemia. Echocardiography was performed to assess cardiac function. Mitochondrial integrity was evaluated using molecular techniques, including qPCR and Seahorse assays. Additionally, molecular docking studies and Western blot analyses were conducted to explore the interaction between Pgam1 and Dusp1. Results: Using single-cell sequencing and human sample databases, Dusp1 emerged as a novel biomarker for endotoxemia-induced myocardial dysfunction. Experiments with cardiomyocyte-specific Dusp1 knockout ( Dusp1 (Cko) ) and Dusp1 transgenic ( Dusp1 (Tg) ) mice showed that Dusp1 deficiency worsens, while overexpression improves, heart function during LPS-induced myocardial injury. This effect is mediated by regulating inflammation and cardiomyocyte viability. Molecular analyses revealed that LPS exposure leads to Dusp1 dephosphorylation at Ser364, increasing its degradation. Stabilizing Dusp1 phosphorylation enhances mitochondrial function through mitochondrial quality control (MQC), including dynamics, mitophagy, and biogenesis. Functional studies identified Pgam1 as an upstream phosphatase interacting with Dusp1. Pgam1 ablation reduced LPS-induced cardiomyocyte dysfunction and mitochondrial disorder. Conclusions: Pgam1-mediated dephosphorylation of Dusp1 disrupts mitochondrial quality control, leading to myocardial dysfunction in endotoxemia. Targeting the Pgam1-Dusp1 axis represents a promising therapeutic strategy for improving cardiac outcomes in patients with endotoxemia.
Background and objective Migraine is characterized by recurrent headaches, frequently associated with nausea, photophobia, and phonophobia; it is highly prevalent and linked to a heavy socioeconomic burden. While the prevalence of obesity in the general population has increased in recent years, no prior studies exist regarding the relationship between body fat percentage (BF%) and the incidence of severe headaches or migraine. In light of this, we conducted this study to address this gap in data. Methods We utilized data from the National Health and Nutrition Examination Survey (NHANES) involving 5,060 individuals (1999-2004). After adjusting for gender, poverty-to-income ratio (PIR), educational attainment, smoking status, moderate physical activity, and hypertension, we employed restricted cubic spline (RCS) curves and logistic regression to examine the relationship between BF% and the occurrence of severe headaches or migraine. Results The study included 5,060 participants: 1,289 (25.5%) with severe headache or migraine and 3,771 (74.5%) without. Compared to patients without severe headaches or migraine, those with it were more likely to be female and have lower educational attainment, household income, and physical activity, as well as smoking, alcohol consumption, diabetes, and hypertension. In females in particular and overall, the models showed a significant association between BF% and severe headache or migraine, whereas there was no association between BF% and severe headache or migraine in the male population. Multivariate logistic regression analyses using BF% quartiles yielded similar results. Conclusions We observed a substantial positive correlation between BF% and severe headaches or migraine after controlling for pertinent variables. This correlation was particularly strong in females. These findings underscore the intricate nature of the relationship between obesity and migraine, highlighting the necessity for more investigation to clarify the role that BF% plays in the escalation of migraine.
Within the Tan-Lu Fault Zone, the largest active tectonic belt in eastern China, the Anqiu-Juxian Fault exhibits the most recent activity period, evident surface traces, and highest seismic hazard, making it a Holocene active fault. This study utilized the vertical component continuous data observed by 100 short-period temporary stations from August 1–21, 2023, and extracted 1,944 Rayleigh wave group velocity dispersion curves within the period of 0.2–4 s. Using the direct surface wave tomography method, we calculated a high-resolution 3-D shear-wave velocity structure at depths of 0.2–1.25 km within the study area. Our results are summarized as follows: 1) The development of faults F1, F2, and F5 in the Tan-Lu Fault Zone highly correlated with the shear-wave velocity anomalies at depths >0.8 km. Specifically, fault F5 comprised two boundary faults, F5-1 and F5-2, which together controlled a Cenozoic depression covered by a thick, low-velocity sediment layer. 2) The complex velocity structure characteristics in the Suqian area revealed that the influence of faults on the sedimentary layers in the Suqian area was not expressed as an overall uplift or subsidence of the block but rather as differential subsidence. 3) Near Sankeshu, the F5 fault formed a small pull-apart basin. The latest activity in this pull-apart basin has shifted to the fault in the center of the basin, indicating that the pull-apart basin has entered the extinction stage.
Forest soils are usually highly weathered and abundant in mineral-weathering bacteria, which have not been used to mobilize soil minerals for crop production. Here, we used an acidic forest soil with low available phosphorus (P), potassium (K), and silicon (Si) to isolate bacteria capable of co-solubilizing P, K, and Si (PKSi-solubilizing) and the model rice plant to test their potential to mobilize soil P, K, and Si for crop nutrition. Six PKSi-solubilizing strains representative of common mineral-weathering proteobacteria taxa (genera Burkholderia, Paraburkholderia, Collimonas, Pseudomonas, and Agrobacterium) were screened out. They showed diverse P-, K-, or Si-solubilizing activities and produced diverse organic acids. Their mineral-solubilizing activities were positively correlated with the levels of medium pH reduction and gluconic acid production. They promoted the growth of rice seedlings grown in the forest soil by increasing soil available P and Si, plant P, K, and Si cumulative contents and dry weight, and the corresponding root-to-shoot ratios. The growth of rice seedlings alone and with the inoculated PKSi-solubilizing stains in the acidic forest soil did not reduce the soil pH. The forest soil with low available P, K, and Si is a valuable resource for high-performance PKSi-solubilizing bacteria improving soil fertility and crop nutrition. The PKSi-solubilizing bacteria screened out can promote rice seedling growth by mobilizing P, K, and Si from soil to plant in the acidic soil with low available P, K, and Si. They show potentials to mitigate soil P, K, and Si deficiency and promote crop growth, and to recover soluble P, K, and Si from chemical fertilizers and improve the use efficiency of chemical fertilizers, thus reducing the input of chemical fertilizers. They may retard soil acidification by Si-solubilization and improve soil quality.
To investigate the spatial distribution of crustal deformation and related geodynamic processes associated with the Tan-Lu Fault Zone (TLFZ) in East China, we measured crustal anisotropy based on the sinusoidal moveout of the P -to -S conversions from the Moho observed on receiver functions. Totally 142 well-defined crustal anisotropy measurements were obtained from the China National Seismic Network and other broadband dense seismic stations, including three stations exhibiting the pattern of a double layered anisotropy structure. The fast orientations observed at stations in the vicinity of the TLFZ were dominantly fault-parallel except for the southernmost part of the study area, where the fast orientations were approximately normal to the strike of the fault zone and may primarily be attributed to the NW-SE oriented Dabie Orogenic Belt. In the North China Block, NWSE fast orientations were found to be consistent with the dominant orientation of the secondary faults. The Lower Yangtze Block showed two dominant fast orientations. The fault-parallel measurements in the west of the Jiangshao Fault Zone were controlled by the NE-trending faults in the Lower Yangtze Block, while the fast orientations in the east and south of the Jiangshao Fault Zone were dominantly E -W, which could be mainly influenced by the regional principal compressive stress. The average delay time of the entire study area was 0.27 +/- 0.07 s. In the vicinity of the TLFZ where fault-parallel fast orientations were observed, an approximately 44% increase in delay time was observed, suggesting a well-developed fault zone.
Epicardial adipose tissue, or epicardial fat, is a type of visceral fat located between the heart and the pericardium. Due to its anatomical proximity to the heart, EAT plays a significant role in both cardiac physiology and pathologies, including cardiac remodeling and cardiovascular diseases (CVD). However, our understanding of how EAT pathology is influenced by risk factors such as obesity and type 2 diabetes mellitus and how altered EAT can drive cardiac remodeling and CVD, remains limited. Herein, we aimed to summarize and discuss the latest findings on EAT and its role in cardiac remodeling, highlighting the outcomes of clinical and observational studies, provide mechanistic insights, and finally introduce emerging therapeutic agents and nutritional guidelines aimed at preventing these conditions.
Objective This study aimed to identify the potential subgroups of migraines based on the patterns of migraine associated symptoms, vestibular and auditory symptoms using latent class analysis and to explore their characteristics. Method A total of 555 patients with migraine participated in the study. Symptoms such as nausea, vomiting, photophobia, phonophobia, osmophobia, visual symptoms, vestibular symptoms (dizziness, vertigo), and auditory symptoms (tinnitus, hearing loss, aural fullness) were assessed. Latent class analysis was performed to identify subgroups of migraines. Covariates such as gender, age of migraine onset, frequency of migraine attacks per month, and family history were also considered. Results The analysis revealed four latent classes: the Prominent Vestibular; Prominent Nausea; Presenting Symptoms but not prominent or dominant; and Sensory Hypersensitivity groups. Various covariates, such as gender, age of migraine onset, and frequency of migraine attacks, demonstrated significant differences among the four groups. The Sensory Hypersensitivity group showed the presence of multiple sensory symptoms, earlier age of migraine onset, and higher proportion of females. The Prominent Vestibular group had the highest probability of dizziness or vertigo but lacked the presence of auditory symptoms. The Prominent Nausea group exhibited prominent nausea. The Presenting Symptoms but not prominent or dominant group comprised individuals with the highest migraine attacks per month and proportion of chronic migraine. Conclusion This study identifies four subgroups of migraines based on the patterns of symptoms. The findings suggest potential different but overlapped mechanisms behind the vestibular and auditory symptoms of migraine. Considering the different patterns of migraine-related symptoms may provide deeper insights for patients’ prognosis and clinical decision-making.
Soil microbial food web is crucial for maintaining crop production, while its community structure varies among fertilization regimes. Currently, the mechanistic understanding of the relationships between microbial food web and crop production under various nutrient fertilizations is poor. This knowledge gap limits our capacity to achieve precision agriculture for ensuring yield stability. In this study, we investigated the abiotic (i.e., soil chemical properties) and biotic factors (i.e., microbial food web, including bacteria, fungi, archaea and nematodes) that were closely associated with rice (Oryza sativa L.) production, using soils from seven fertilization regimes in distinct sampling locations (i.e., bulk vs rhizosphere soil) at a long-term experimental site. Organic manure alone fertilization (M) and integrated fertilization (NPKM) combining manure with inorganic fertilizers increased soil pH by 0.21-0.41 units and organic carbon content by 49.1 %-65.2 % relative to the nonfertilization (CK), which was distinct with inorganic fertilization. The principal coordinate analysis (PCoA) revealed that soil microbial and nematode communities were primarily shaped by fertilization rather than sampling locations. Organic fertilization (M, NPKM) increased the relative abundance of both r-strategist bacteria, specific taxa within the fungal (i.e., Pezizales) and nematode communities (i.e., omnivores-predators), whereas inorganic fertilization increased K-strategist bacteria abundances relative to the CK. Correspondingly, network analysis showed that the keystone taxa in the amplicon sequence variants (ASVs) enriched by organic manure and inorganic fertilization were mainly affiliated with r- and K-strategist bacteria, respectively. Structural equation modeling (SEM) analysis found that r- and K-strategist bacteria were positively correlated with rice production under organic and inorganic fertilization, respectively. Our results demonstrate that the response patterns of r/K-strategists to nutrient fertilization largely regulate rice yield, suggesting that the enhanced soil fertility and r-strategists contribute to the highest crop production in NPKM fertilization.
The Huoshan region, located on the northern margin of the Dabie Orogenic Belt at the junction of the North China Plate and the Yangtze Plate, is one of the most seismically active and concentrated areas in the Dabie Orogenic Belt and adjacent regions. Utilizing the travel time data from 4,427 seismic events observed by 202 stations, we investigated the deep medium structure of the Huoshan region using the double-difference tomography method. The results reveal the medium structure and characteristics of mid-strong earthquake preparation in the region. The crustal medium in the study area exhibits significant lateral heterogeneity. The Dabie Orogenic Belt shows notably high velocity, whereas the North China Plate and the Yangtze Plate display relatively lower velocities. The Tan-Lu Fault Zone exhibits segmentation characteristics; with the crustal medium velocity south of Lujiang being relatively high, north of Jiashan being relatively low, and between Lujiang and Jiashan being intermediate. The epicenters of mid-strong earthquakes are located on the gradient zones of velocity and Poisson’s ratio. The source regions of these earthquakes show significant anomalies of high Poisson’s ratio and low S-wave velocity, which may indicate the presence of fluids. These anomalies possibly reflect the intrusion of deep materials along the fault zone, which could be the driving force for the preparation of mid-strong earthquakes.
Objectives Autoimmune diseases (ADs) play a significant and intricate role in the onset of cardiovascular diseases (CVDs). Our study aimed to elucidate the shared genetic etiology between Ads and CVDs. Methods We conducted genome-wide pleiotropy analyses to investigate the genetic foundation comprehensively and shared etiology of six ADs and six CVDs. We analyze the genetic architecture and genetic overlap between these traits. Then, SNP-level functional annotation identified significant genomic risk loci and potential causal variants. Gene-level analyses explored shared pleiotropic genes, followed by pathway enrichment analyses to elucidate underlying biological mechanisms. Finally, we assess potential causal pathways between ADs and CVDs. Results Despite negligible overall genetic connections, our results revealed a significant genetic overlap between ADs and CVDs, indicating a complex shared genetic architecture spread throughout the genome. The shared loci implicated several genes, including ATXN2, BRAP, SH2B3, ALDH2 (all located at 12q24.11-12), RNF123, MST1R, RBM6, and UBA7 (all located at 3p21.31), all of which are protein-coding genes. Top biological pathways enriched with these shared genes were related to the immune system and intracellular signal transduction. Conclusions The extensive genetic overlap with mixed effect directions between ADs and CVDs indicates a complex genetic relationship between these diseases. It suggests overlapping genetic risk may contribute to shared pathophysiological and clinical characteristics and may guide clinical treatment and management. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by the Natural Science Foundation of China Excellent Young Scientists Fund (Overseas) (Grant no. K241141101), National Natural Science Foundation (Grant no. 82470452), Guangdong Basic and Applied Basic Research Foundation for Distinguished Young Scholars (Grant no. 24050000763), Shenzhen Pengcheng Peacock Plan, Shenzhen Basic Research General Projects of Shenzhen Science and Technology Innovation Commission (Grant no. JCYJ20230807093514029) (To Y.F.), Natural Science Foundation of China Excellent Young Scientists Fund (Overseas) (Grant no. K241001101) (To Z.L.), National Natural Science Foundation of China (Grant no. 82300315; 82374240), Guangdong Province Basic and Applied Basic Research Fund Project (Grant no. 2024A1515012174; 2024A1515013184), National Administration of Traditional Chinese Medicine Research Project (Grant no. 0102023703), Project of the State Key Laboratory of Dampness Syndrome of Traditional Chinese Medicine jointly established by the province and the ministry (Grant no. SZ2022KF10), Scientific Research Initiation Project of Guangdong Provincial Hospital of Traditional Chinese Medicine (Grant no. 2021KT1709), Research Project of Guangdong Provincial Bureau of Traditional Chinese Medicine (Grant no. 20241120), Guangdong Provincial Key Laboratory of Research on Emergency in TCM (Grant no. 2023B1212060062; 2023KT15450) (To R.Z.), and Center for Computational Science and Engineering at Southern University of Science and Technology. The funder had no role in the design, implementation, analysis, interpretation of the data, approval of the manuscript, and decision to submit the manuscript for publication. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study used only openly available GWAS summary statistics on six autoimmune diseases and six CVDs that have originally been conducted using human data. GWAS summary statistics on RA, SLE, T1D, CD, UC, and PSC are available at the GWAS Catalog (GCST90132223, GCST003156, GCST90014023, GCST004132, GCST004133, and GCST004030). GWAS summary statistics on AF, HF, and Stroke are available at the GWAS Catalog (GCST90104539, GCST009541, and GCST90104539). GWAS summary statistics on CAD and PAD are publicly available for download at the Cardiovascular Disease Knowledge Portal (CVDKP) website: https://cvd.hugeamp.org/datasets.html. GWAS summary statistics on VTE are obtained from the deCODE genetics website: https://www.decode.com/summary data/. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.
Epicardial adipose tissue (EAT) is a unique visceral fat reservoir that shares an immune microenvironment without a distinct boundary with myocardium. Increasingly, visceral fat has been studied as a secondary immune organ, and EAT is no exception in this regard. Cellular subsets of EAT are associated with disease development. In heart failure (HF) patients, however, the immune characteristics of EAT have rarely been studied, especially those non-immune cells related to the immune microenvironment. Herein, an analysis of seven EAT samples by single-cell RNA sequencing (scRNA-Seq) is presented here, including 1 neonate, 1 infant, 1 child, 2 adults with heart failure (Adults-HF) and 2 adult heart transplant donors as non-heart failure control (Adults-Non HF). Analysis of 51730 high-quality cells revealed eleven major cell types in EAT. For the first time, the pseudo-temporal reconstruction technique was employed to plot the cell trajectories of various major cell types (such as T lymphocytes, fibroblasts, endothelial cells, monocytes, and smooth muscle cells) in EAT across different developmental stages, achieving a single-cell resolution. The dynamic gene expression patterns of major cell types presented the immune characteristics of metabolism disorder of zinc and copper ions, and downregulated immune-related pathways in EAT of adult patients with HF. These data provide insights regarding HF immune dysregulation at the cellular level.
A 55-year-old man was admitted to our hospital with renewed chest pain. He underwent total arch replacement combined with frozen elephant trunk (MicroPort, Shanghai, China) for type A aortic dissection 7 years ago. Computed tomography angiography demonstrated a type II endoleak from the left subclavian artery, giant false lumen and severe pleural effusion, implying a ruptured false lumen (A and B/Cover).