Novel polymorphisms in CYP4A22 associated with susceptibility to coronary heart disease.

BACKGROUND: Coronary heart disease (CHD) has become a worldwide public health problem. Genetic factors are considered important risk factors for CHD. The aim of this study was to explore the correlation between CYP4A22 gene polymorphism and CHD susceptibility in the Chinese Han population. METHODS: We used SNPStats online software to complete the association analysis among 962 volunteers. False-positive report probability analysis was used to confirm whether a positive result is noteworthy. Haploview software and SNPStats were used for haplotype analysis and linkage disequilibrium. Multi-factor dimensionality reduction was applied to evaluate the interaction between candidate SNPs. RESULTS: In overall and some stratified analyses (male, age ≤ 60 years or CHD patients complicated with hypertension), CYP4A22-rs12564525 (overall, OR = 0.83, p-value is 0.042) and CYP4A22-rs2056900 (overall, OR = 1.22, p-value is 0.032) were associated with the risk of CHD. CYP4A22-4926581 was associated with increased CHD risk only in some stratified analyses. FPRP indicated that all positive results in our study are noteworthy findings. In addition, MDR showed that the single-locus model composed of rs2056900 is the best model for predicting susceptibility to CHD. CONCLUSION: There are significant associations between susceptibility to CHD and CYP4A22 rs12564525, and rs2056900.

Anterior cruciate ligament injury should not be considered a contraindication for medial unicompartmental knee arthroplasty: Finite element analysis.

PURPOSE: The research objective of this study is to use finite element analysis to investigate the impact of anterior cruciate ligament (ACL) injury on medial unicompartmental knee arthroplasty (UKA) and explore whether patients with ACL injuries can undergo UKA. METHODS: Based on the morphology of the ACL, models of ACL with diameters ranging from 1 to 10mm are created. Finite element models of UKA include ACL absence and ACLs with different diameters. After creating a complete finite element model and validating it, four different types of loads are applied to the knee joint. Statistical analysis is conducted to assess the stress variations in the knee joint structure. RESULTS: A total of 11 finite element models of UKA were established. Regarding the stress on the ACL, as the diameter of the ACL increased, when a vertical load of 750N was applied to the femur, combined with an anterior tibial load of 105N, the stress on the ACL increased from 2.61 MPa to 4.62 MPa, representing a 77.05% increase. Regarding the equivalent stress on the polyethylene gasket, a notable high stress change was observed. The stress on the gasket remained between 12.68 MPa and 14.33 MPa in all models. the stress on the gasket demonstrated a decreasing trend. The equivalent stress in the lateral meniscus and lateral femoral cartilage decreases, reducing from the maximum stress of 4.71 MPa to 2.61 MPa, with a mean value of 3.73 MPa. This represents a reduction of 44.72%, and the statistical significance is (P < 0.05). However, under the other three loads, there was no significant statistical significance (P > 0.05). CONCLUSION: This study suggests that the integrity of the ACL plays a protective role in performing medial UKA. However, this protective effect is limited when performing medial UKA. When the knee joint only has varying degrees of ACL injury, even ACL rupture, and the remaining structures of the knee joint are intact with anterior-posterior stability in the knee joint, it should not be considered a contraindication for medial UKA.

Gut microbiota and immune mediation: a Mendelian randomization study on granulomatosis with polyangiitis.

Background: The gut microbiota plays a pivotal role in influencing various health outcomes, including immune-mediated conditions. Granulomatosis with Polyangiitis (GPA) is one such condition, and its potential associations with gut microbiota remain underexplored. Method: Using a two-sample Mendelian randomization approach, we investigated the causal links between gut microbiota and GPA. We sourced our data from multiple cohorts and consortiums, including the MiBioGen consortium. Our study design incorporated both direct associations and mediation effects of immune traits on the relationship between gut microbiota and GPA. Results: Our analysis revealed significant associations between 1 phylum, 1 family 9 genus microbiota taxa and GPA. Furthermore, we identified several immune cell traits that mediated the effects of gut microbiota on GPA. For instance, the family Defluviitaleaceae and genus Defluviitaleaceae UCG011 influenced GPA through CD11c in granulocytes. The mediation effect proportions further elucidated the complex dynamics between gut microbiota exposures, immune markers, and their combined influence on GPA. Conclusion: Our findings underscore the intricate relationship between gut microbiota, immune markers, and GPA. The identified associations and mediation effects provide valuable insights into the potential therapeutic avenues targeting gut microbiota to manage GPA.

CYP4V2 rs56413992 C > T was associated with the risk of coronary heart disease in the Chinese Han population: a case-control study.

PURPOSE: The research aimed to detect the association between single nucleotide polymorphisms (SNPs) in CYP4V2 gene and coronary heart disease (CHD) risk. METHODS: This case-control study included 487 CHD subjects and 487 healthy individuals. Logistic regression was performed to analyze the connection between five SNPs in CYP4V2 (rs1398007, rs13146272, rs3736455, rs1053094, and rs56413992) and CHD risk, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the connection. RESULTS: As a result, we found that rs56413992 T allele (OR = 1.36, 95% CI = 1.09-1.70, p = 0.007) and CT genotype (OR = 1.40, 95% CI = 1.06-1.83, p = 0.017) were significantly associated with an increased risk of CHD in the overall analysis. Precisely, rs56413992 was linked to an elevated risk of CHD in people aged > 60, males, smokers and drinkers. The study also indicated that rs1398007 was linked to an increased CHD risk in drinkers. In addition, rs1053094 was correlated with a decreased risk of CHD complicated with diabetes mellitus (DM), and rs1398007 was correlated with a decreased risk of CHD complicated with hypertension (HTN). CONCLUSION: This study was the first to experimentally demonstrate that CYP4V2 rs56413992 was associated with the risk of CHD, which will provide a certain reference for revealing the pathogenesis of CHD.

Pax-8: Molecular biology, pathophysiology, and potential pathogenesis.

Transcription factors, as the convergence points of multiple signaling pathways in eukaryotic cells, are closely involved in disease development. Pax-8, an important transcription factor belonging to the Pax family, exerts a crucial influence on the regulation of gene expression required for both physiological conditions and pathological processes. Pax-8 contributes to the pathogenesis of many human diseases, ranging from cardiovascular disease to many cancers, and therefore, it can be imagined that Pax-8 holds great therapeutic potential. In this review, we summarize the structure, distribution, function, and regulatory mechanisms of Pax-8 to provide a new research direction for Pax-8.

Deriving particulate backscattering coefficient at 400†nm from small-scale optically shallow waters using Landsat-8 data: a case study at Luhuitou Peninsula, Sanya.

The particulate backscattering coefficient (bbp) plays an important role in the growth of coral reefs by influencing the light field conditions. Small-scale optically shallow waters are commonly found in coastal fringing reefs, making it challenging to monitor the spatial and temporal patterns accurately using Aqua satellites with a low spatial resolution. In this study, six existing optimization-based algorithms for deriving bbp at 400 nm (bbp(400)) were evaluated with three simulated Landsat-8 (spatial resolution = 30 m) data sets and in situ data from the Luhuitou Peninsula, Sanya. The comparison results indicated that the HOPE (hyperspectral optimization process exemplar) (Fix-H-error or Fix-H-error-free) algorithm which sets an input value of the water depth alone outperformed other algorithms. However, the estimated bbp(400) from all the algorithms tended to be either overestimated and underestimated due to the improper the spectral shape value of the backscattering coefficient. The HOPE (Fix-H-error) algorithm estimated-bbp(400) from in situ reflectance also had a good correlation with the in situ total suspended particle concentrations data derived-bbp(400), with a correlation coefficient of 0.83. Therefore, the HOPE (Fix-H-error) algorithm was selected to estimate the bbp(400) from satellite-based Landsat-8 data of the Luhuitou Peninsula, Sanya. Time-series (2014-2021) results from these Landsat-8 images reveal the seasonal variation of bbp(400). The bbp(400) was low from May to September every year. From October to December or January, bbp(400) had an increasing trend, and then it decreased until May. Spatial analysis indicated that bbp(400) decreased with increasing water depth. The spatial and temporal patterns of bbp(400) were consistent with in situ observations reported in the literature. This study preliminarily showed the efficiency of an optimization-based algorithm in deriving bbp(400) in small-scale optically shallow water region using Landsat-8 data.

Enhancing impacts of mesoscale eddies on Southern Ocean temperature variability and extremes.

As a major sink of anthropogenic heat and carbon, the Southern Ocean experienced pronounced warming with increasing extreme temperature events over the past decades. Mesoscale eddies that strongly influence the uptake, redistribution, and storage of heat in the ocean are expected to play important roles in these changes, yet observational evidence remains limited. Here, we employ a comprehensive analysis of over 500,000 historical hydrographic profile measurements combined with satellite-based eddy observations to show enhanced thermal eddy imprints in the Southern Ocean. Our observations reveal that anticyclonic (cyclonic) eddies are responsible for nearly half of the subsurface high (low)-temperature extremes detected, although only 10% of the profiles are located in eddy interiors. Over the past decade (2006 to 2019), both mean and extreme temperature anomalies within eddies in the Antarctic Circumpolar Current increased significantly, promoting the rise in subsurface ocean temperature variability. This enhanced role of eddies is likely a result of enhanced eddy pumping due to the increase in eddy intensity and ocean stratification caused by ocean warming. Our analysis underscores the crucial role of eddies in amplifying ocean temperature variability and extremes, with their effects expected to be even more pronounced as global warming persists.

Role of CYP19A1 Loci (rs28757157 and rs3751591) with Ischemic Stroke Risk in the Chinese Han Population.

Introduction: Ischemic stroke (IS) is a multifactorial and polygenic disease, which is affected by genetic factors. In this study, we explored the role of CYP19A1 single nucleotide polymorphisms (SNPs) in IS in the Chinese population. Methods: 1302 subjects (651 controls and 651 cases) were recruited in this case-control study. Four candidate SNPs (rs28757157 C/T, rs3751592 C/T, rs3751591 G/A, rs59429575 C/T) of CYP19A1 were selected by the 1000 genomes project database. The association between CYP19A1 SNPs and IS risk was assessed using logistic regression analysis with odds ratio (OR) and 95% confidence intervals (CIs). False-positive report probability (FPRP) analysis further verified the positive results. The interaction of SNP-SNP was analyzed by multi-factor dimensionality reduction (MDR) to predict is risk. Results: In the research, CYP19A1 loci (rs28757157 and rs3751591) were associated with the occurrence of IS. The two variants conferred an increased susceptibility to IS in the subjects aged over 60 years old, smokers and drinkers. Rs28757157 was related to the risk of IS in females, non-smokers and subjects with BMI less than 24, while rs59429575 was related to the risk of IS in males and subjects with BMI greater than 24. Conclusion: The study revealed that there is a significant association between CYP19A1 loci (rs28757157 and rs3751591) and IS risk in the Chinese Han population, providing a theoretical basis for further exploring its specific role in the pathogenesis of IS.

Genetic Variants of CYP4F2 Associated with Ischemic Stroke Susceptibility in the Han Population from Southern China.

Background: The pathophysiological mechanism of ischemic stroke is complex. Traditional risk factors cannot fully or only partially explain the occurrence and development of IS. Genetic factors are getting more and more attention. Our study aimed to explore the association between CYP4F2 gene polymorphism and susceptibility to IS. Methods: A total of 1322 volunteers were enrolled to perform an association analysis through SNPStats online software. Using FPRP (false-positive report probability) to detect whether the result is a noteworthy finding. The interaction of SNP-SNP in IS risk was assessed by multi-factor dimensionality reduction. Statistical analysis of this study was mainly completed by SPSS 22.0 software. Results: Mutant allele "A" (OR = 1.24) and genotype "AA" (OR = 1.49) or "GA" (OR = 1.26) of CYP4F2-rs2108622 are risk genetic factors for IS. Rs2108622 is significantly associated with an increased risk of IS among subjects who are females, aging >60 years old, with BMI ≥24 kg/m2, and smoking or drinking volunteers. CYP4F2-rs3093106 and -rs3093105 are associated with susceptibility to IS among smoking, drinking subjects, or IS patients complicated with hypertension. Conclusion: CYP4F2-rs2108622, -rs3093106, and -rs3093105 are associated with an increased risk of IS.

Role and therapeutic potential of gelsolin in atherosclerosis.

Atherosclerosis is the major pathophysiological basis of a variety of cardiovascular diseases and has been recognized as a lipid-driven chronic inflammatory disease. Gelsolin (GSN) is a member of the GSN family. The main function of GSN is to cut and seal actin filaments to regulate the cytoskeleton and participate in a variety of biological functions, such as cell movement, morphological changes, metabolism, apoptosis and phagocytosis. Recently, more and more evidences have demonstrated that GSN is Closely related to atherosclerosis, involving lipid metabolism, inflammation, cell proliferation, migration and thrombosis. This article reviews the role of GSN in atherosclerosis from inflammation, apoptosis, angiogenesis and thrombosis.

Acute myocardial infarction followed by radiofrequency therapy for gastroesophageal reflux disease in a man: A case report.

Coronary artery disease (CAD) is a common comorbidity of gastroesophageal reflux disease. Since the distal esophagus and heart share a common afferent vagal supply, the delivery of radiofrequency in the distal esophagus can stimulate the coronary artery and induce acute myocardial infarction in a patient with CAD.

Minimally invasive treatment of cirrhotic secondary hypersplenism with high-intensity focused ultrasound.

High-intensity focused ultrasound (HIFU) has been reported to be a minimally invasive effective method for the treatment of secondary hypersplenism. However, neither the short-term efficacy nor the indications and/or contraindications have been described in patients with cirrhosis. From October 2019 to May 2021, eleven cases of patients with cirrhotic secondary hypersplenism were enrolled. The blood counts, liver function tests and abdominal ultrasound and/or MRI scans of all patients were closely evaluated. Among these 11 patients, eight (72.7%) patients were classified as Child-Pugh A, and the other 3 (27.3%) patients were Child-Pugh B; Five (45%) patients were diagnosed with gallstone, including multiple small stones in 2 patients and single stone in 3 patients. HIFU was performed successfully in all 11 patients. After HIFU, hematologic parameters and liver function were significantly improved in all 11 patients (p < 0.05). The HIFU ablated volume to spleen volume rate was 35-61%. Complications were ecchymosis of the waist in 7 (63.3%) patients, ablated area pain in 3 (27.3%) patients, and choledocholithiasis in 2 (18.2%) patients with multiple small gallstones. All of them recovered smoothly without additional treatment except for 2 patients with choledocholithiasis recovered with risky endoscopic retrograde cholangiopancreatography (ERCP) treatment. This series suggested that HIFU is an effective and safe treatment for cirrhotic secondary hypersplenism in patients classified as Child-Pugh A or B. However, multiple small gallstones could be a relative contraindication for it.

The prevalence of coronary atherosclerosis in patients with refractory gastroesophageal reflux disease ready for antireflux surgery.

Coronary atherosclerosis (CAS) and gastroesophageal reflux disease (GERD) share common risk factors. The existing CAS may not only increase the possibility of GERD to be refractory GERD (RGERD), but also increase the risk of antireflux surgery for these patients. The aim of this study was to estimate the prevalence of CAS and its potential risk factors in patients with RGERD ready for antireflux surgery. The retrospective analysis was performed in the digestive disease center of Suining Central Hospital, a teritary hospital in Sichuan, China. Records of patients with RGERD admitted to the hospital for antireflux surgery between July 2018, and June 2021 were included. The included patients were divided into the RGERD group and RGERD-CAS group based on the coronary computed tomography angiography (CCTA) results, which were defined as no CAS and CAS (<50% mild stenosis or ≥50% significant stenosis). In total, 448 patients with RGERD qualified for the study. The prevalence of CAS in these patients was 45.1%. Specifically, 246 patients (54.9%) were in the RGERD group, and 202 patients (45.1%) were in the RGERD-CAS group. Among these 202 patients with CAS, 120 patients (59.4%) had mild CAS (<50% stenosis), 82 patients (40.6%) had significant CAS (≥50% stenosis). Five independent risk factors, including male sex, high blood pressure (HBP), diabetes mellitus (DM), Barrett's esophagus (BE) and family history of coronary artery disease were identified for the occurrence of CAS in patients with RGERD ready for antireflux surgery after adjusting for other factors. CAS is prevalent in patients with RGERD ready for antireflux surgery. Routing CTTA was suggested to exclude potential coronary artery disease in RGERD patients ready for antireflux surgery with independent risk factors.

Metoprolol Protects Against Arginine Vasopressin-Induced Cellular Senescence in H9C2 Cardiomyocytes by Regulating the Sirt1/p53/p21 Axis.

Cardiomyocyte senescence is involved in the pathological mechanism of cardiac diseases. Metoprolol is a ß1 receptor blocker used for the treatment of hypertension. Recent studies show that Metoprolol can protect cardiomyocytes against ischemia injury. The present study aims to investigate the protective effects of Metoprolol against arginine vasopressin (AVP)-induced cellular senescence in cultured cardiomyocytes. The cell proliferation assay and cytotoxicity lactate dehydrogenase assay showed that the highest tolerated dosage of Metoprolol in H9C2 cardiomyocytes was optimized as 10 µM. The enzyme-linked immunosorbent assay showed that Metoprolol significantly ameliorated the elevated level of the DNA oxidation product 8-hydroxy-2 deoxyguanosine. Metoprolol also decreased the percentage of senescence-associated ß-galactosidase positive cells and improved the telomerase activity under AVP exposure. Moreover, treatment with Metoprolol ameliorated the decreased intracellular nicotinamide phosphoribosyltransferase activity, nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NAD+/NADPH) ratio, and Sirtuin1 activity in cardiomyocytes by AVP. Finally, Metoprolol was able to downregulate the AVP-induced expression of acetylated p53 and p21. Taken together, our data reveal that Metoprolol protected the cardiomyocytes from AVP-induced senescence.

Myristica fragrans promotes ABCA1 expression and cholesterol efflux in THP-1-derived macrophages.

Myristica fragrans is a traditional herbal medicine and has been shown to alleviate the development of atherosclerosis. However, the anti-atherogenic mechanisms of M. fragrans are still to be addressed. In this study, we explored the effect of M. fragrans on lipid metabolism and inflammation and its mechanisms in THP-1-derived macrophages. The quantitative polymerase chain reaction and western blot analysis results showed that M. fragrans promotes cholesterol efflux from THP-1-derived macrophages and reduces intracellular total cholesterol, cholesterol ester, and free cholesterol contents in a dose- and a time-dependent manner. Further study found that liver X receptor alpha (LXRα) antagonist GGPP significantly blocked the upregulation of ABCA1 expression with M. fragrans treatment. In addition, chromatin immunoprecipitation assay confirmed that GATA binding protein 3 (GATA3) can bind to the LXRα promoter, and inhibition of GATA3 led to the downregulation of LXRα and ATP-binding cassette subfamily A member 1 expression. Furthermore, M. fragrans reduced lipid accumulation, followed by decreasing tumor necrosis factor-α, interleukin (IL)-6, and IL-1ß and increasing IL-10 produced by THP-1-derived macrophages. Therefore, M. fragrans is identified as a valuable therapeutic medicine for atherosclerotic cardiovascular disease.

MiR-30d inhibits cardiomyocytes autophagy promoting ferroptosis after myocardial infarction.

BACKGROUND: To investigate the effect of microRNA-30d (miR-30d) on autophagy and reveal the mechanism of autophagy promoting ferroptosis in H9C2 cells. METHODS: First, we detected miR-30d expression of myocardial tissue in the sham and myocardial infarction (MI) group, and then analyzed by biochemical analysis and luciferase Genetic experiments to confirm its downstream target gene of. After using Lentivirus-ATG5 (LV-sh-ATG5) to effectively inhibit autophagy, in order to further clarify the possible mechanism of autophagy leading to ferroptosis in H9C2 cells, we have tested the relevant indicators ferroptosis. RESULTS: We first found that miR-30d expression was down-regulated in myocardial tissue after MI, while autophagy increased, and autophagy was reduced when miR-30d was overexpressed, and then analyzed by biochemical analysis and luciferase Genetic experiments confirmed that ATG5 was a downstream target gene of miR-30d. After using Lentivirus-ATG5 (LV-shATG5) to effectively inhibit autophagy and up-regulate the expression of FTH1 and GPX4 in H9C2 cells, reduce the content of MDA, increase the content of GSH, and increase the activity of GPX4, suggesting that autophagy after MI may promote ferroptosis in H9C2 cells. CONCLUSIONS: The expression of miR-30d decreased in cardiomyocytes after MI and which can inhibit autophagy by binding to ATG5. Furthermore, autophagy after MI may promote ferroptosis.

A case study of Chlorophyll a response to tropical cyclone Wind Pump considering Kuroshio invasion and air-sea heat exchange.

New evidences provided that the tropical cyclone (TC) Linfa in 2015 induced looping path of Kuroshio invasion into the northeastern South China Sea (NESCS) through the northwestern Luzon Strait (LS), based on the in-situ measurements, satellite data and model output data. This TC-enhanced Kuroshio invasion with low nutrients and denser waters suppressed the TC "Wind Pump" induced upwelling and nutrients uptake, and therefore inhibited the Chlorophyll a concentration (Chl-a) increase from surface to ~50 m in the open ocean of the NESCS. The TC-induced Kuroshio invasion promoted the generation of the strong cyclonic eddy to its left side where weak Ekman Pumping Velocity was observed. This enhancing cyclonic eddy then dominated the nutrients uplift and increased the surface and subsurface (0-50 m) Chl-a through eddy pumping rather than Ekman Pumping. The TC-declined anti-cyclonic eddy, which shoaled the Mixed Layer Depth (MLD), benefited to the nutrient uptake through TC-induced upwelling and thereby increased the surface Chl-a and raised the Chl-a Maximum Layer (CML) to ~20 m over the southwestern LS. The temporal Chl-a variations were also influenced by TC intensities and biochemical processes. The air-sea heat budget analysis indicated that, the air-sea heat exchange contributed to nearly 80% of the sea surface cooling (SST cooling) over the northwestern LS with Kuroshio invasion, while eddy-induced upwelling dominated the SST cooling over the western LS, and the wind-driven upwelling (and mixing) controlled the SST cooling over the southwestern LS. These different formations of SST cooling then played important role in Chl-a variations. This study is the first case of TC "Wind Pump" induced Chl-a variations considering air-sea heat exchange, Kuroshio invasion and mesoscale eddies over LS, which would help to evaluate the influence of TCs over the other major heat transport arteries of the world ocean: The Gulf Stream area.

Coronavirus disease 2019 (COVID-19): current status and future perspectives.

Coronavirus disease 2019 (COVID-19) originated in the city of Wuhan, Hubei Province, Central China, and has spread quickly to 72 countries to date. COVID-19 is caused by a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [previously provisionally known as 2019 novel coronavirus (2019-nCoV)]. At present, the newly identified SARS-CoV-2 has caused a large number of deaths with tens of thousands of confirmed cases worldwide, posing a serious threat to public health. However, there are no clinically approved vaccines or specific therapeutic drugs available for COVID-19. Intensive research on the newly emerged SARS-CoV-2 is urgently needed to elucidate the pathogenic mechanisms and epidemiological characteristics and to identify potential drug targets, which will contribute to the development of effective prevention and treatment strategies. Hence, this review will focus on recent progress regarding the structure of SARS-CoV-2 and the characteristics of COVID-19, such as the aetiology, pathogenesis and epidemiological characteristics.

Variation of pCO2 concentrations induced by tropical cyclones "Wind-Pump" in the middle-latitude surface oceans: A comparative study.

The Bermuda Testbed Mooring (BTM) and Bay of Bengal Ocean Acidification (BOBOA) mooring measurements were used to identify changes in the partial pressure of CO2 at the sea surface (pCO2sea) and air-sea CO2 fluxes (FCO2) associated with passage of two tropical cyclones (TCs), Florence and Hudhud. TC Florence passed about 165 km off the BTM mooring site with strong wind speeds of 24.8 m s-1 and translation speed of 7.23 m s-1. TC Hudhud passed about 178 km off the BOBOA mooring site with wind speeds of 14.0 m s-1 and translation speed of 2.58 m s-1. The present study examined the effect of temperature, salinity, dissolved inorganic carbon (DIC), total alkalinity (TA), air-sea CO2 flux, and phytoplankton chlorophyll a change on pCO2sea as a response to TCs. Enhanced mixed layer depths were observed due to TCs-induced vertical mixing at both mooring sites. Decreased pCO2sea (-15.16±5.60 µatm) at the BTM mooring site and enhanced pCO2sea (14.81±7.03 µatm) at the BOBOA mooring site were observed after the passage of Florence and Hudhud, respectively. Both DIC and TA are strongly correlated with salinity in the upper layer of the isothermal layer depth (ILD). Strong (weak) vertical gradient in salinity is accompanied by strong (weak) vertical gradients in DIC and TA. Strong vertical salinity gradient in the upper layer of the ILD (0.031 psu m-1), that supply much salinity, dissolved inorganic carbon and total alkalinity from the thermocline was the cause of the increased pCO2sea in the BOBOA mooring water. Weak vertical salinity gradient in the upper layer of the ILD (0.003 psu m-1) was responsible for decreasing pCO2sea in the BTM mooring water. The results of this study showed that the vertical salinity gradient in the upper layer of the ILD is a good indicator of the pCO2sea variation after the passages of TCs.

Pregnancy-Associated Plasma Protein-A Accelerates Atherosclerosis by Regulating Reverse Cholesterol Transport and Inflammation.

BACKGROUND: Recent studies have suggested that pregnancy-associated plasma protein-A (PAPP-A) is involved in the pathogenesis of atherosclerosis. This study aim is to investigate the role and mechanisms of PAPP-A in reverse cholesterol transport (RCT) and inflammation during the development of atherosclerosis. Methods and Results: PAPP-A was silenced in apolipoprotein E (apoE-/-) mice with administration of PAPP-A shRNA. Oil Red O staining of the whole aorta root revealed that PAPP-A knockdown reduced lipid accumulation in aortas. Oil Red O, hematoxylin and eosin (HE) and Masson staining of aortic sinus further showed that PAPP-A knockdown alleviated the formation of atherosclerotic lesions. It was found that PAPP-A knockdown reduced the insulin-like growth factor 1 (IGF-1) levels and repressed the PI3K/Akt pathway in both aorta and peritoneal macrophages. The expression levels of LXRα, ABCA1, ABCG1, and SR-B1 were increased in the aorta and peritoneal macrophages from apoE-/-mice administered with PAPP-A shRNA. Furthermore, PAPP-A knockdown promoted RCT from macrophages to plasma, the liver, and feces in apoE-/-mice. In addition, PAPP-A knockdown elevated the expression and secretion of monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), tumor necrosis factor-α, and interleukin-1ß through the nuclear factor kappa-B (NF-κB) pathway. CONCLUSIONS: The present study results suggest that PAPP-A promotes the development of atherosclerosis in apoE-/-mice through reducing RCT capacity and activating an inflammatory response.