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1.
BMC Neurol ; 24(1): 155, 2024 May 07.
Article En | MEDLINE | ID: mdl-38714927

BACKGROUND: Chronic lung and heart diseases are more likely to lead an intensive end point after stroke onset. We aimed to investigate characteristics and outcomes of endovascular thrombectomy (EVT) in patients with acute large vessel occlusion stroke (ALVOS) and identify the role of comorbid chronic cardiopulmonary diseases in ALVOS pathogenesis. METHODS: In this single-center retrospective study, 191 consecutive patients who underwent EVT due to large vessel occlusion stroke in neurological intensive care unit were included. The chronic cardiopulmonary comorbidities and several conventional stroke risk factors were assessed. The primary efficacy outcome was functional independence (defined as a mRS of 0 to 2) at day 90. The primary safety outcomes were death within 90 days and the occurrence of symptomatic intracranial hemorrhage(sICH). Univariate analysis was applied to evaluate the relationship between factors and clinical outcomes, and logistic regression model were developed to predict the prognosis of ALVOS. RESULTS: Endovascular therapy in ALVOS patients with chronic cardiopulmonary diseases, as compared with those without comorbidity, was associated with an unfavorable shift in the NHISS 24 h after EVT [8(4,15.25) versus 12(7.5,18.5), P = 0.005] and the lower percentage of patients who were functionally independent at 90 days, defined as a score on the modified Rankin scale of 0 to 2 (51.6% versus 25.4%, P = 0.000). There was no significant between-group difference in the frequency of mortality (12.1% versus 14.9%, P = 0.580) and symptomatic intracranial hemorrhage (13.7% versus 19.4%, P = 0.302) or of serious adverse events. Moreover, a prediction model showed that existence of cardiopulmonary comorbidities (OR = 0.456, 95%CI 0.209 to 0.992, P = 0.048) was independently associated with functional independence at day 90. CONCLUSIONS: EVT was safe in ALVOS patients with chronic cardiopulmonary diseases, whereas the unfavorable outcomes were achieved in such patients. Moreover, cardiopulmonary comorbidity had certain clinical predictive value for worse stroke prognosis.


Comorbidity , Endovascular Procedures , Thrombectomy , Humans , Male , Female , Aged , Retrospective Studies , Middle Aged , Endovascular Procedures/methods , Thrombectomy/methods , Thrombectomy/statistics & numerical data , Thrombectomy/adverse effects , Heart Diseases/epidemiology , Heart Diseases/complications , Heart Diseases/surgery , Aged, 80 and over , Cohort Studies , Lung Diseases/epidemiology , Lung Diseases/surgery , Treatment Outcome , Ischemic Stroke/surgery , Ischemic Stroke/epidemiology , Stroke/surgery , Stroke/epidemiology
2.
Transl Vis Sci Technol ; 13(4): 24, 2024 Apr 02.
Article En | MEDLINE | ID: mdl-38630469

Purpose: To investigate the topographic characters of inter-individual variations of the macular choroidal thickness (CT). Methods: This was a retrospective study. Macular CT data for 900 0.2 × 0.2-mm grids from 410 healthy eyes were collected from swept-source optical coherence tomography. Following the analysis of factors associated with mean CT, the ß-coefficients of the included associated factors in each grid were summarized for choroidal thickness changes analysis. Additionally, the coefficient of variance (CoV), coefficient of determination (CoD), and coefficient of variance unexplained (CoVU) for CT were calculated in each individual grid to investigate the inter-individual choroidal variations pattern. Results: Sex (ß = -17.26, female vs. male), age (ß = -1.61, per 1 year), and axial length (ß = -18.62, per 1 mm) were associated with mean macular CT. Females had a thinner choroid in all 900 grids (0.5-26.9 µm). As age increased, the CT noticeably decreased (8.74-19.87 µm per 10 years) in the temporal regions. With axial length elongation, the thinning (7.94-24.91 µm per 1 mm) was more evident in subfoveal and nasal regions. Both the CoV (34.69%-58.00%) and CoVU (23.05%-40.78%) were lower in the temporal regions, whereas the CoD (18.41%-39.66%) was higher in the temporal regions. Conclusions: Choroidal thinning is more predominant in the subfoveal and nasal regions with axial length elongation, but in the temporal region with aging. The inter-individual variation of CT is higher and less determined by sex, age, or axial length in the nasal regions. Translational Relevance: Topographic variation should be considered when interpreting choroidal thickness.


Choroid , Tomography, Optical Coherence , Female , Male , Humans , Child , Retrospective Studies , Choroid/diagnostic imaging
3.
Heliyon ; 10(8): e29382, 2024 Apr 30.
Article En | MEDLINE | ID: mdl-38660246

CRISPR-based screens have discovered novel functional genes involving in diverse tumor biology and elucidated the mechanisms of the cancer pathological states. Recently, with its randomness and unbiasedness, CRISPR screens have been used to discover effector genes with previously unknown roles for AML. Those novel targets are related to AML survival resembled cellular pathways mediating epigenetics, synthetic lethality, transcriptional regulation, mitochondrial and energy metabolism. Other genes that are crucial for pharmaceutical targeting and drug resistance have also been identified. With the rapid development of novel strategies, such as barcodes and multiplexed mosaic CRISPR perturbation, more potential therapeutic targets and mechanism in AML will be discovered. In this review, we present an overview of recent progresses in the development of CRISPR-based screens for the mechanism and target identification in AML and discuss the challenges and possible solutions in this rapidly growing field.

4.
IEEE Trans Biomed Eng ; PP2024 Apr 25.
Article En | MEDLINE | ID: mdl-38662563

OBJECTIVE: Optical Coherence Tomography (OCT) images can provide non-invasive visualization of fundus lesions; however, scanners from different OCT manufacturers largely vary from each other, which often leads to model deterioration to unseen OCT scanners due to domain shift. METHODS: To produce the T-styles of the potential target domain, an Orthogonal Style Space Reparameterization (OSSR) method is proposed to apply orthogonal constraints in the latent orthogonal style space to the sampled marginal styles. To leverage the high-level features of multi-source domains and potential T-styles in the graph semantic space, a Graph Adversarial Network (GAN) is constructed to align the generated samples with the source domain samples. To align features with the same label based on the semantic feature in the graph semantic space, Graph Semantic Alignment (GSA) is performed to focus on the shape and the morphological differences between the lesions and their surrounding regions. RESULTS: Comprehensive experiments have been performed on two OCT image datasets. Compared to state-of-the-art methods, the proposed method can achieve better segmentation. CONCLUSION: The proposed fundus lesion segmentation method can be trained with labeled OCT images from multiple manufacturers' scanners and be tested on an unseen manufacturer's scanner with better domain generalization. SIGNIFICANCE: The proposed method can be used in routine clinical occasions when an unseen manufacturer's OCT image is available for a patient.

5.
Mol Psychiatry ; 2024 Apr 04.
Article En | MEDLINE | ID: mdl-38575805

The dominant ('general') version of the diathesis-stress theory of depression views stressors and genetic vulnerability as independent risks. In the Australian Genetics of Depression Study (N = 14,146; 75% female), we tested whether polygenic scores (PGS) for major depression, bipolar disorder, schizophrenia, anxiety, ADHD, and neuroticism were associated with reported exposure to 32 childhood, past-year, lifetime, and accumulated stressful life events (SLEs). In false discovery rate-corrected models, the clearest PGS-SLE relationships were for the ADHD- and depression-PGSs, and to a lesser extent, the anxiety- and schizophrenia-PGSs. We describe the associations for childhood and accumulated SLEs, and the 2-3 strongest past-year/lifetime SLE associations. Higher ADHD-PGS was associated with all childhood SLEs (emotional abuse, emotional neglect, physical neglect; ORs = 1.09-1.14; p's < 1.3 × 10-5), more accumulated SLEs, and reported exposure to sudden violent death (OR = 1.23; p = 3.6 × 10-5), legal troubles (OR = 1.15; p = 0.003), and sudden accidental death (OR = 1.14; p = 0.006). Higher depression-PGS was associated with all childhood SLEs (ORs = 1.07-1.12; p's < 0.013), more accumulated SLEs, and severe human suffering (OR = 1.17; p = 0.003), assault with a weapon (OR = 1.12; p = 0.003), and living in unpleasant surroundings (OR = 1.11; p = 0.001). Higher anxiety-PGS was associated with childhood emotional abuse (OR = 1.08; p = 1.6 × 10-4), more accumulated SLEs, and serious accident (OR = 1.23; p = 0.004), physical assault (OR = 1.08; p = 2.2 × 10-4), and transportation accident (OR = 1.07; p = 0.001). Higher schizophrenia-PGS was associated with all childhood SLEs (ORs = 1.12-1.19; p's < 9.3-8), more accumulated SLEs, and severe human suffering (OR = 1.16; p = 0.003). Higher neuroticism-PGS was associated with living in unpleasant surroundings (OR = 1.09; p = 0.007) and major financial troubles (OR = 1.06; p = 0.014). A reversed pattern was seen for the bipolar-PGS, with lower odds of reported physical assault (OR = 0.95; p = 0.014), major financial troubles (OR = 0.93; p = 0.004), and living in unpleasant surroundings (OR = 0.92; p = 0.007). Genetic risk for several mental disorders influences reported exposure to SLEs among adults with moderately severe, recurrent depression. Our findings emphasise that stressors and diatheses are inter-dependent and challenge diagnosis and subtyping (e.g., reactive/endogenous) based on life events.

6.
Nat Genet ; 2024 Apr 30.
Article En | MEDLINE | ID: mdl-38689000

We develop a method, SBayesRC, that integrates genome-wide association study (GWAS) summary statistics with functional genomic annotations to improve polygenic prediction of complex traits. Our method is scalable to whole-genome variant analysis and refines signals from functional annotations by allowing them to affect both causal variant probability and causal effect distribution. We analyze 50 complex traits and diseases using ∼7 million common single-nucleotide polymorphisms (SNPs) and 96 annotations. SBayesRC improves prediction accuracy by 14% in European ancestry and up to 34% in cross-ancestry prediction compared to the baseline method SBayesR, which does not use annotations, and outperforms other methods, including LDpred2, LDpred-funct, MegaPRS, PolyPred-S and PRS-CSx. Investigation of factors affecting prediction accuracy identifies a significant interaction between SNP density and annotation information, suggesting whole-genome sequence variants with annotations may further improve prediction. Functional partitioning analysis highlights a major contribution of evolutionary constrained regions to prediction accuracy and the largest per-SNP contribution from nonsynonymous SNPs.

7.
High Alt Med Biol ; 2024 Mar 21.
Article En | MEDLINE | ID: mdl-38511279

Lin, Tian, Huaping Jia, Yunming Li, Yongxing Xu, Bei Zhao, Dong Zheng, Hongfeng Yan, Meihui Zhao, Yanlei Li, Liping Xia, Fengxia Zhou, Cuiping Liu, Ke Ma, Ma Mi, and Jianwen Gu. Epidemiological survey of congenital heart disease among children aged from 2 to 18 in Suo County, Nagqu, Tibet. High Alt Med Biol. 00:000-000, 2024. Background: Studies have reported the prevalence of congenital heart disease (CHD) in parts of Tibet, but relative epidemiological surveys are rare. We aimed to explore the prevalence of CHD in children and its relationship with family history in Suo County, Nagqu, Tibet, an altitude of 3,980 meters. Methods: We recruited 4,002 children aged 2-18 years. Subjects underwent a family history investigation, cardiac auscultation, and clinical manifestation examination and then received echocardiographic screening. Results: The prevalence of CHD among children in Suo County was 0.97% (39 cases), much higher than the prevalence at sea level. The most common subtype was atrial septal defect, accounting for 53.9% of CHD, followed by patent ductus arteriosus (33.3%) and ventricular septal defect (12.8%). We also found that children whose mothers had previously borne children with CHD had a higher risk of CHD than those without (p = 0.002); other factors related to CHD during pregnancy, such as smoking, drinking, drug use, and viral infection, showed no statistical differences between children with and without CHD. Conclusions: The prevalence of CHD in children in Suo County is much higher than at low altitude, consisting mostly of simple forms with left-to-right shunt, with rare complex CHD. These results support implementing diagnostic and treatment plans to prevent CHD in Suo County.

8.
Cereb Cortex ; 34(3)2024 03 01.
Article En | MEDLINE | ID: mdl-38436464

This study aimed to investigate network-level brain functional changes in breast cancer patients and their relationship with fear of cancer recurrence (FCR). Resting-state functional MRI was collected from 43 patients with breast cancer and 40 healthy controls (HCs). Graph theory analyses, whole-brain voxel-wise functional connectivity strength (FCS) analyses and seed-based functional connectivity (FC) analyses were performed to identify connection alterations in breast cancer patients. Correlations between brain functional connections (i.e. FCS and FC) and FCR level were assessed to further reveal the neural mechanisms of FCR in breast cancer patients. Graph theory analyses indicated a decreased clustering coefficient in breast cancer patients compared to HCs (P = 0.04). Patients with breast cancer exhibited significantly higher FCS in both higher-order function networks (frontoparietal, default mode, and dorsal attention systems) and primary somatomotor networks. Among the hyperconnected regions in breast cancer, the left inferior frontal operculum demonstrated a significant positive correlation with FCR. Our findings suggest that breast cancer patients exhibit less segregation of brain function, and the left inferior frontal operculum is a key region associated with FCR. This study offers insights into the neural mechanisms of FCR in breast cancer patients at the level of brain connectome.


Brain Neoplasms , Breast Neoplasms , Connectome , Humans , Female , Breast Neoplasms/diagnostic imaging , Brain Neoplasms/diagnostic imaging , Brain/diagnostic imaging , Fear
9.
Nat Commun ; 15(1): 2713, 2024 Mar 28.
Article En | MEDLINE | ID: mdl-38548728

DNA methylation is an ideal trait to study the extent of the shared genetic control across ancestries, effectively providing hundreds of thousands of model molecular traits with large QTL effect sizes. We investigate cis DNAm QTLs in three European (n = 3701) and two East Asian (n = 2099) cohorts to quantify the similarities and differences in the genetic architecture across populations. We observe 80,394 associated mQTLs (62.2% of DNAm probes with significant mQTL) to be significant in both ancestries, while 28,925 mQTLs (22.4%) are identified in only a single ancestry. mQTL effect sizes are highly conserved across populations, with differences in mQTL discovery likely due to differences in allele frequency of associated variants and differing linkage disequilibrium between causal variants and assayed SNPs. This study highlights the overall similarity of genetic control across ancestries and the value of ancestral diversity in increasing the power to detect associations and enhancing fine mapping resolution.


DNA Methylation , East Asian People , Humans , DNA Methylation/genetics , Quantitative Trait Loci/genetics , Gene Expression Regulation , Linkage Disequilibrium , Polymorphism, Single Nucleotide , Genome-Wide Association Study
11.
Psychoneuroendocrinology ; 164: 107018, 2024 Jun.
Article En | MEDLINE | ID: mdl-38461634

Aging is associated with changes in face processing, including desensitization to face cues like gaze direction and an attentional preference to faces with positive over negative emotional valence. A parallel line of research has shown that acute administration of oxytocin (OT) increases visual attention to social stimuli such as human faces. The current study examined effects of chronic OT administration among older adults on fixation duration to faces that varied in emotional expression, gaze direction, age, and sex. One hundred and twelve generally healthy older adults (aged 55-95 years) underwent a randomized, placebo-controlled, double-blind, between-subject clinical trial in which they self-administered either OT or placebo (P) intranasally twice a day for 4 weeks. The behavioral task involved rating the trustworthiness of faces (i.e., social stimuli) and natural scenes (i.e., non-social control stimuli) during eye tracking and was conducted before and after the intervention. Fixation duration to both the faces and the natural scenes declined from pre- to post-intervention, however this decline was less pronounced among older adults in the OT compared to the P group for faces but not scenes. Further, face cues (emotional expression, gaze direction, age, sex) did not moderate the treatment effect. This study provides first evidence that chronic intranasal OT maintains salience of social cues over time in older adults, perhaps buffering effects of habituation. These findings enhance understanding of OT effects on social cognition among older adults, and would benefit from follow up with a young adult comparison group to directly speak to specificity of observed effects to older adults and reflection of the aging process.


Emotions , Oxytocin , Aged , Humans , Administration, Intranasal , Aging/psychology , Cues , Double-Blind Method , Oxytocin/pharmacology
12.
Environ Sci Technol ; 58(9): 4392-4403, 2024 Mar 05.
Article En | MEDLINE | ID: mdl-38362876

Unraveling the mysterious pathways of pollutants to the deepest oceanic realms holds critical importance for assessing the integrity of remote marine ecosystems. This study tracks the transport of pollutants into the depths of the oceans, a key step in protecting the sanctity of these least explored ecosystems. By analyzing hadal trench samples from the Mariana, Mussau, and New Britain trenches, we found the widespread distribution of organophosphate ester (OPE) flame retardants but a complex transport pattern for the OPE in these regions. In the Mariana Trench seawater column, OPE concentrations range between 17.4 and 102 ng L-1, with peaks at depths of 500 and 4000 m, which may be linked to Equatorial Undercurrent and topographic Rossby waves, respectively. Sediments, particularly in Mariana (422 ng g-1 dw), showed high OPE affinity, likely due to organic matter serving as a transport medium, influenced by "solvent switching", "solvent depletion", and "filtering processes". Amphipods in the three trenches had consistent OPE levels (29.1-215 ng g-1 lipid weight), independent of the sediment pollution patterns. The OPEs in these amphipods appeared more linked to surface-dwelling organisms, suggesting the influence of "solvent depletion". This study highlights the need for an improved understanding of deep-sea pollutant sources and transport, urging the establishment of protective measures for these remote marine habitats.


Amphipoda , Environmental Pollutants , Flame Retardants , Animals , Ecosystem , Organophosphates , Esters , Solvents
13.
Phys Med Biol ; 69(7)2024 Mar 21.
Article En | MEDLINE | ID: mdl-38394676

Objective.Neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) present many similar clinical features. However, there are significant differences in the progression of nAMD and PCV. and it is crucial to make accurate diagnosis for treatment. In this paper, we propose a structure-radiomic fusion network (DRFNet) to differentiate PCV and nAMD in optical coherence tomography (OCT) images.Approach.The subnetwork (RIMNet) is designed to automatically segment the lesion of nAMD and PCV. Another subnetwork (StrEncoder) is designed to extract deep structural features of the segmented lesion. The subnetwork (RadEncoder) is designed to extract radiomic features from the segmented lesions based on radiomics. 305 eyes (155 with nAMD and 150 with PCV) are included and manually annotated CNV region in this study. The proposed method was trained and evaluated by 4-fold cross validation using the collected data and was compared with the advanced differentiation methods.Main results.The proposed method achieved high classification performace of nAMD/PCV differentiation in OCT images, which was an improvement of 4.68 compared with other best method.Significance. The presented structure-radiomic fusion network (DRFNet) has great performance of diagnosing nAMD and PCV and high clinical value by using OCT instead of indocyanine green angiography.


Choroid , Polypoidal Choroidal Vasculopathy , Humans , Choroid/blood supply , Tomography, Optical Coherence/methods , Radiomics , Fluorescein Angiography/methods , Retrospective Studies
14.
Gastroenterol Rep (Oxf) ; 12: goae001, 2024.
Article En | MEDLINE | ID: mdl-38390578

Background: Systemic chemotherapy for gastric cancer with peritoneal metastasis has limited clinical benefit; for those with intraoperative detection of occult peritoneal metastasis, cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is an alternative treatment. However, the feasibility and effects of this modality and criteria for selecting suitable groups remain unclear. This study aimed to explore the safety and efficacy of laparoscopic cytoreductive surgery (L-CRS) followed by HIPEC in gastric cancer with limited peritoneal metastasis, and this study also aimed to determine the optimized cut-off of the peritoneal cancer index. Methods: Between March 2017 and November 2019, patients diagnosed with gastric cancer peritoneal metastases by using laparoscopy and the Sugarbaker peritoneal cancer index of ≤12 were eligible for inclusion. All patients received L-CRS (including gastrectomy with D2 lymph node dissection) and resection of visible peritoneal metastasis, followed by post-operative HIPEC, and systemic chemotherapy. The primary end points were median progression-free survival and median survival time, and the secondary outcomes were morbidity and mortality within 30 days after surgery. Results: Thirty patients were eligible for analysis, of whom 19 (63.3%) were female, and the overall mean age was 53.0 years. The post-operative morbidity was 20% and the severe complication rate was 10%. The median survival time was 27.0 months with a 2-year overall survival rate of 52.3% and median progression-free survival was 14.0 months with a 2-year progression-free survival of 30.4%. Conclusions: L-CRS followed by HIPEC can be safely performed for gastric cancer with limited peritoneal metastasis and potential survival benefits.

15.
Anal Chem ; 96(6): 2658-2665, 2024 02 13.
Article En | MEDLINE | ID: mdl-38311857

Liquid biopsy is of great significance in tumor early diagnosis and treatment stratification. PD-L1-positive small extracellular vesicles (PD-L1+ sEVs) are closely related to tumor growth and immunotherapy response, which are considered valuable liquid biopsy biomarkers. In contrast to conventional in vitro detection, in vivo detection has the ability to improve the detection efficiency and enable continuous or real-time dynamic monitoring. However, in vivo detection of PD-L1+ sEVs has multiple difficulties, such as high cell background, complex blood environments, and lack of a specific and stable detection method. Herein, the in vivo detection of PD-L1+ sEVs method was constructed, which efficiently separated sEVs based on the microfluidic device and quantitatively analyzed PD-L1+ sEVs by aptamer recognition and hybridization chain reaction. The concentration of PD-L1+ sEVs was continuously monitored, and significant differences at different stages of tumor as well as a correlation with tumor volume were found. Diseased and healthy individuals could also be effectively distinguished based on the concentration of PD-L1+ sEVs. The method with good stability, biocompatibility, and detection performance provided a powerful means for in vivo detection of PD-L1+ sEVs, contributing to the clinical diagnosis and treatment of tumor.


Extracellular Vesicles , Neoplasms , Humans , B7-H1 Antigen , Neoplasms/diagnosis , Liquid Biopsy , Lab-On-A-Chip Devices
16.
Sci Rep ; 14(1): 68, 2024 01 02.
Article En | MEDLINE | ID: mdl-38167997

Facial impressions contribute to evaluations of trustworthiness. Older adults are especially vulnerable to trust violations, incurring risks for deception and exploitation. Using the newly developed social Iowa Gambling Task (S-IGT), we examined age-group differences in the impact of facial trustworthiness on decision-making and learning. In the congruent condition (CS-IGT), advantageous decks were paired with trustworthy faces and disadvantageous decks with untrustworthy faces. In the incongruent condition (IS-IGT), this pairing was reversed. Younger (n = 143) and older (n = 129) participants completed either the standard Iowa Gambling Task (IGT), CS-IGT, or IS-IGT. Both age groups preferred trustworthy faces in their initial choices. Older adults performed worse than younger adults across all tasks over time. Further, compared to younger adults, older adults performed worse on the IS-IGT, suggesting that incongruent facial cues interfered with older adults' performance, which aligns with reduced sensitivity to negative social reputations in aging. Multilevel modeling also indicated that age-group differences were most pronounced across all tasks in the last 40 trials. Together these findings suggest that differences between younger and older adults in experience-dependent decision-making are magnified in social contexts that involve a "wolf in sheep's clothing," which may reflect age-related difficulties in integrating incongruent information.


Decision Making , Gambling , Aged , Humans , Aging , Neuropsychological Tests , Trust , Young Adult
17.
Water Res ; 251: 121126, 2024 Mar 01.
Article En | MEDLINE | ID: mdl-38237461

The "V"-shaped structure of hadal trenches acts as a natural collector of organic pollutants, drawing attention to the need for extensive research in these areas. Our review identifies significant concentrations of organic pollutants, including persistent organic pollutants, black carbon, antibiotic-resistant genes, and plastics, which often match those in industrialized regions. They may trace back to both human activities and natural sources, underscoring the trenches' critical role in ocean biogeochemical cycles. We highlight the complex lateral and vertical transport mechanisms within these zones. Advanced methodologies, including stable isotope analysis, biomarker identification, and chiral analysis within isotope-based mixing models, are crucial for discerning the origins and pathways of these pollutants. In forthcoming studies, we aim to explore advanced methods for precise pollutant tracing, develop predictive models to forecast the future distribution and impacts of pollutants in hadal zones and on the Earth's larger ecological systems.


Environmental Pollutants , Humans , Ecosystem , Plastics , Isotopes
18.
J Mol Cell Cardiol ; 186: 57-70, 2024 01.
Article En | MEDLINE | ID: mdl-37984156

BACKGROUND: Macrophage-derived foam cells are a hallmark of atherosclerosis. Scavenger receptors, including lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (OLR-1), are the principal receptors responsible for the uptake and modification of LDL, facilitating macrophage lipid load and the uptake of oxidized LDL by arterial wall cells. Krüppel-like factor 15 (KLF15) is a transcription factor that regulates the expression of genes by binding to the promoter during transcription. Therefore, this study aimed to investigate the precise role of macrophage KLF15 in atherogenesis. METHODS: We used two murine models of atherosclerosis: mice injected with an adeno-associated virus (AAV) encoding the Asp374-to-Tyr mutant version of human PCSK9, followed by 12 weeks on a high-fat diet (HFD), and ApoE-/-- mice on a HFD. We subsequently injected mice with AAV-KLF15 and AAV-LacZ to assess the role of KLF15 in the development of atherosclerosis in vivo. Oil Red O, H&E, and Masson's trichome staining were used to evaluate atherosclerotic lesions. Western blots and RT-qPCR were used to assess protein and mRNA levels, respectively. RESULTS: We determined that KLF15 expression was downregulated during atherosclerosis formation, and KLF15 overexpression prevented atherosclerosis progression. KLF15 expression levels did not affect body weight or serum lipid levels in mice. However, KLF15 overexpression in macrophages prevented foam cell formation by reducing OLR-1-meditated lipid uptake. KLF15 directly targeted and transcriptionally downregulated OLR-1 levels. Restoration of OLR-1 reversed the beneficial effects of KLF15 in atherosclerosis. CONCLUSION: Macrophage KLF15 transcriptionally downregulated OLR-1 expression to reduce lipid uptake, thereby preventing foam cell formation and atherosclerosis. Thus, our results suggest that KLF15 is a potential therapeutic target for atherosclerosis.


Atherosclerosis , Foam Cells , Humans , Mice , Animals , Foam Cells/metabolism , Proprotein Convertase 9/metabolism , Macrophages/metabolism , Atherosclerosis/pathology , Lipoproteins, LDL/metabolism , Kruppel-Like Transcription Factors/genetics , Kruppel-Like Transcription Factors/metabolism
19.
Sci Total Environ ; 914: 169629, 2024 Mar 01.
Article En | MEDLINE | ID: mdl-38157906

High level dissolved B, which poses risks to human health, has been widely observed in geothermal water. In the Guide Basin, NW China, a series of geothermal water samples along a fault show a wide range of B contents ranging from 3.14 to 8.33 mg/L, which are higher than the WHO Guideline value equaling 2.4 mg/L in drinking water. To identify the sources and fate of B, we conduct a comprehensive analysis of hydrochemistry and stable isotopes (D, 18O and 11B) of three thermal fields representing three stages of hydrogeochemical evolution (stages I, II and III). From stage I to III, there are trends of increasing mineral dissolution, which is supported by increasing mean reservoir temperature and concentrations of conservative elements (Cl, Na, K, Li and Si). Geothermal water in stage I with meteoric origin and the lowest reservoir temperature has the highest B/Na resulting from silicate dissolution and falls on the mixing line between granitoids and cold water on the plot of δ11B versus 1/B, showing the control of silicate dissolution. However, geothermal water in stage III has lower Ca, B Sr and B/Na than that in stage II. Because of the occurrence of other processes, geothermal water in stages II and III deviates from the LMWL. Compared with geothermal water in stage I, the increased Sr/Ca and decreased B/Ca show that B are removed by both coprecipitation and vapor separation. With the aid of B isotopes, we find vapor separation dominates in stage II, whereas carbonate precipitation dominates in stage III. Overall, a combined use of three isotopes (H, O and B) and three element ratios (B/Na, B/Ca and Sr/Ca) leads to a complete understanding of B cycle and hydrogeochemical evolution in hydrothermal systems.

20.
Mar Pollut Bull ; 199: 115920, 2024 Feb.
Article En | MEDLINE | ID: mdl-38113801

To investigate the distribution, sources, influencing factors, and ecological risk of polycyclic aromatic hydrocarbons (PAHs) in East China Marginal Seas (ECMSs) sediments, we measured the concentrations of 16 PAHs in 104 surface sediment samples collected from the ECMSs in 2014 and 2016. Total PAH concentration (∑PAHs) ranged from 4.49 to 163.66 ng/g dry weight (dry w), with 65.98 ± 33.00 (mean ± SD) ng/g dry w. The highest PAH concentrations and total organic carbon were observed in areas with fine-grained sediments in the Bohai Sea (BS), Yellow Sea (YS), and coastal East China Sea (ECS), indicating the prominent influence of regional hydrodynamics and sediment properties. The dominant PAH congener in BS and YS was BbF, whereas coastal ECS was Phe. The heterogeneity of PAH sources implies that terrestrial PAH input and shelf mud deposition have crucial roles in the source-sink processes of PAHs in a strongly human-influenced marginal sea.


Polycyclic Aromatic Hydrocarbons , Water Pollutants, Chemical , Humans , Polycyclic Aromatic Hydrocarbons/analysis , Geologic Sediments , Water Pollutants, Chemical/analysis , Environmental Monitoring , Oceans and Seas , China
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