As mTOR/mTORC1 is a master regulator that integrates external signals with cellular responses, the study sheds light on how the cardiac monocytes and macrophages sense and respond to the ischemic environment..

Pediatric dilated cardiomyopathy (pDCM) is characterized by unique age-dependent molecular mechanisms that include myocellular responses to therapy. We previously showed that pDCM, but not adult DCM patients respond to phosphodiesterase 3 inhibitors (PDE3i) by increasing levels of the second messenger cAMP and consequent phosphorylation of phospholamban (PLN). However, the molecular mechanisms involved in the differential pediatric and adult response to PDE3i are not clear.

Quantification of serum response factor (SRF) isoforms from the left ventricle of explanted hearts showed that PDE3i treatment affects expression of SRF isoforms in pDCM hearts. An SRF isoform lacking exon 5 (SRFdel5) was highly expressed in the hearts of pediatric, but not adult DCM patients treated with PDE3i. To determine the functional consequence of expression of SRFdel5, we overexpressed full length SRF or SRFdel5 in cultured cardiomyocytes with and without adrenergic stimulation. Compared to a control adenovirus, expression of SRFdel5 increased phosphorylation of PLN, negatively affected expression of the phosphatase that promotes dephosphorylation of PLN (PP2Cε), and promoted faster calcium reuptake, whereas expression of full length SRF attenuated calcium reuptake through blunted phosphorylation of PLN.

Taken together, these data indicate that expression of SRFdel5 in pDCM hearts in response to PDE3i contributes to improved function through regulating PLN phosphorylation and thereby calcium reuptake.

Taken together, these data indicate that expression of SRFdel5 in pDCM hearts in response to PDE3i contributes to improved function through regulating PLN phosphorylation and thereby calcium reuptake.Chronic heart failure (HF) is often accompanied by systemic iron deficiency (ID). However, effects of ID on cardiac iron status and progression of HF are unknown. To investigate these effects rats underwent LAD ligation to induce post-myocardial infarction HF or sham operation. After 3 weeks the animals from both groups were randomized into three subgroups control, moderate ID and severe ID+anemia (IDA) by a combination of phlebotomy and low iron diet for 5 weeks. Serum and hepatic iron content were reduced by 55% and 70% (ID) and by 80% and 77% (IDA), respectively, while cardiac iron content was unchanged in HF rats. Changes in expression of all cardiomyocyte iron handling proteins indicating preserved cardiomyocytes iron status in HF and ID/IDA. Contractile function of LV cardiomyocytes, Ca2+ transient amplitude, sarcoplasmic reticulum Ca2+ release and SERCA2a function was augmented by ID and IDA and it was accompanied by an increase in serum catecholamines. Neither ID nor IDA affected left ventricular (LV) systolic or diastolic function or dimensions. To sum up, systemic ID does not result in cardiac ID and does not affect progression of HF and even improves contractile function and Ca2+ handling of isolated LV cardiomyocytes, however, at the cost of increased catecholamine level. This suggests that intravenous iron therapy should be considered as an additional therapeutic option in HF, preventing the increase of catecholaminergic drive with its well-known long-term adverse effects.

Since our troops had returned from the first Persian Gulf War in 1990-91, the veterans have reported chronic multisymptomatic illness widely referred to as Gulf War Illness (GWI). We aim to review the current directions of GWI pathology research in the context of chronic multisymptomatic illness and its possible gut microbiome targeted therapies. The veterans of Gulf War show symptoms of chronic fatigue, cognitive deficits, and a subsection report of gastrointestinal complications.

Efforts of finding a suitable treatment regimen and clinical management remain a challenge. More recently, we have shown that the pathology is connected to alterations in the gut microbiome, and efforts of finding a suitable regimen for gut-directed therapeutics are underway. We discuss the various clinical interventions and summarize the possible effectiveness of gut-directed therapies such as the use of short-chain fatty acids (SCFA), phenolic compounds, and their metabolites, use of probiotics, and fecal microbiota transfer.

The short review will be helpful to GWI researchers to expand their studies to the gut and find an effective treatment strategy for chronic multisymptomatic illness.

The short review will be helpful to GWI researchers to expand their studies to the gut and find an effective treatment strategy for chronic multisymptomatic illness.This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https//www.elsevier.com/about/our-business/policies/article-withdrawal.

Immune inflammatory dysfunction is a hallmark of abdominal aortic aneurysm (AAA). Granzyme K (GZMK) is involved in the regulation of inflammation. However, the correlation between GZMK expression and AAA risk remains unknown.

This case-control study included 112 AAA patients and 112 controls. Serum GZMK levels were determined by enzyme-linked immunosorbent assay and immunohistochemistry was utilized to determine GZMK expression in aortic tissues.

Compared with controls, AAA patients had higher levels of serum GZMK, and GZMK expression in AAA tissues was increased and positively associated with its serum levels (r = 0.688, P = 0.019). A positive association of serum GZMK levels with CRP or AAA diameter was confirmed, while there was a relationship between tissue GZMK expression and AAA diameter. The AUC of serum GZMK for AAA diagnosis was 0.78 with the sensitivity and specificity of 62.5% and 81.2%, whereas AUC for rupture detection was 0.76 with a sensitivity of 90.0% and specificity of 51.3%. A combination of clinically used inflammatory parameters with serum GZMK could enhance the accuracy of WBC or CRP alone in detecting AAA or rupture type. Multiple logistic analyses revealed an association of per unit increase of serum GZMK with AAA presence (OR = 1.046, P < 0.001) and its rupture risk (OR = 1.015, P = 0.048) after adjusting for confounding factors.

Our study provides proof that elevated GZMK expression both in serum and tissues is correlated with the presence of AAA, and serum GZMK may be a useful non-invasive marker that helps to identify AAA and its rupture risk in clinical practice.

Our study provides proof that elevated GZMK expression both in serum and tissues is correlated with the presence of AAA, and serum GZMK may be a useful non-invasive marker that helps to identify AAA and its rupture risk in clinical practice.

Computed tomography (CT) pulmonary angiography as the first-line diagnosis tool of acute pulmonary embolism (PE), might improve this discriminatory power. We aimed to developed a simply tool combining multi-CT parameters to complete individualized risk assessment of deterioration in non-high-risk patients with acute PE at admission.

Consecutive non-high-risk patients with acute PE who were treated in a Chinese center during 2010-2021, were collected.Prognosis-related CT parameters were reviewed. Deterioration was defined as any adverse event within 30 day after admission. Eligible patients were randomized into derivation and validation cohorts. In the derivation cohort, CT parameters were screened for importance using classification tree methodology and enrolled variables was partitioned via curve-fitting and dose-response analysis. A nomogram was developed and the predictive power in both cohorts was evaluated based on the area under the receiver operating characteristic curve (AUROC) and the corresponding 95% confidence interval (CI).

A total of 1001 patients were included. The preliminary analyses revealed that deterioration risk was related to the right-to-left ventricular diameter ratio at 4-chamber view, pulmonary vein filling abnormality. After a curve-fitting to deterioration risk, these parameters were partitioned and used to develop a nomogram, which had AUROC values of 0.91 (95% CI 0.87-0.96) in the derivation cohort and 0.89 (95% CI 0.81-0.97) in the validation cohort. A web-based version of the radiomics scoring tool was published online for use in clinical practice (https//acutepeprediction.shinyapps.io/Radiomics_Predictive_Tool/).

This simply tool can complete rapid estimation of deterioration risk among non-high-risk acute PE patients at admission.

This simply tool can complete rapid estimation of deterioration risk among non-high-risk acute PE patients at admission.Legacy per- and polyfluoroalkyl acids (PFASs) have received global concern over the scientific and public community since this century. However, the information on alternative PFASs pollution in the marine environment, especially in the subtropical marine environment is extremely limited. This study investigated the occurrence, partitioning, potential sources, and ecological risks of PFASs, including perfluoroalkane sulfonic acids (PFSAs), perfluoroalkyl carboxylic acids (PFCAs), and alternative PFASs, in surface water and sediments from the subtropical Beibu Gulf, South China. Concentrations of total PFASs (∑PFASs) were in the range of 0.98-2.64 ng/L in water and 0.19-0.66 ng/g (dry weight, dw) in sediment, respectively. Perfluorooctanoic acid (PFOA) was the most abundant PFAS in water, while PFASs in sediment were dominated by perfluorooctanesulfonic acid (PFOS) and PFOA. Among investigated environmental parameters (total organic carbon (TOC), grain size, water pH, sediment pH, and salinity), TOC and salinity were the dominant factors influencing the sediment-water distribution coefficient (Kd) of PFOA, perfluorodecanoic acid (PFDA), and perfluorononanoic acid (PFNA). Log Kd and log soil organic carbon-water distribution coefficient (Koc) both increase with increasing carbon chain length of PFASs. Significantly positive correlations between PFOS and perfluorohexanoic acid (PFHxA) (p less then 0.05), PFOA and perfluoro-1-butane-sulfonamide (FBSA) were observed, suggesting that these PFASs might have similar sources and transport routes. Preliminary environmental risk assessment showed that PFOA and PFOS would not pose risks to the marine aquatic environment. This is the first comprehensive survey of legacy and alternative PFASs in a subtropical area of the Beibu Gulf, which provides significant data and scientific basis to better understand the fate of PFASs and pollution control management.Wastewater management is becoming a serious issue worldwide. To enhance the reuse of wastewater, one has to remove toxic pollutants present in it. High amount of dye is present in wastewater, and to remove these dyes is the large scope of this research. Herein, we report production of pure and Ce-doped copper ferrite via hydrothermal route. The synthesized nanoparticles were collected and analyzed by basic characterization techniques. The bandgap energy calculated for pure, 1% Ce, and 2% Ce-doped CuFe2O4 was found to be 2.77, 2.57, and 2.36eV, respectively. Reduction in bandgap was attributed to the doping element. The shape and size of pure and Ce-doped products were investigated using a scanning electron microscope. Agglomeration was observed in the pure copper ferrite sample. In the Ce-doped sample, agglomeration was clearly reduced and the 2% Ce-doped CuFe2O4 sample showed growth of small nanoparticles. They showed complete growth and were arranged in a uniform manner without agglomeration. The surface area of the 2% Ce-CuFe2O4 sample was found to be 65.