Serum fatty acid and lipoprotein subclass concentrations and their associations in prepubertal healthy Norwegian children

Introduction The lipid metabolism is one of the most important and complex processes in the body. Serum concentrations of 18 fatty acids (FAs) and 24 lipoprotein features, i.e. concentrations of lipoprotein main and subclasses and average particle size in main classes, in 195 ethnic Norwegian children from the rural Fjord region were quantified by chromatography. Objectives To assess gender differences in prepubertal children and reveal predictive FA patterns for lipoprotein features. Methods Lipoprotein features were modelled from FA profiles using multivariate regression. Results Contrary to observations for adults from the same region, gender differences in prepubertal children were generally small. However, higher concentrations of C16–C18 FAs for girls compared to boys correlated to higher concentrations of triglycerides (TG) and very low density lipoprotein (VLDL) particles and larger average size of VLDL particles. Concentrations of high density lipoprotein (HDL) and its subclass of medium particle size were higher in boys than in girls. These findings are opposite to observations in adults from the same region, but reflect that prepubertal boys are more physically active than girls. Furthermore, children possessed only half the serum levels of eicosapentaenoic acid and docosahexaenoic acid measured in adults. Since sampling was done after 12 h of fasting, these differences may reflect higher rate of utilization of these crucial FAs in children. Conclusion Good predictive models were obtained for TGs, VLDL and chylomicrons with C14–C18 FAs as major contributors. Weak predictive associations were observed for HDL and Apolipoprotein A1 (ApoA1) with C20–C24 FAs as contributors.publishedVersio

Predictive associations between serum fatty acids and lipoproteins in healthy non-obese Norwegians: implications for cardiovascular health

A battery of methods for multivariate data analysis has been used to assess the associations between concentrations of fatty acids (FAs) and lipoprotein subclasses and particle size in serum for a normolipidemic population of ethnic Norwegians living in the rural Fjord region. Significant gender differences were found in the lipoprotein and FA patterns. Predictive FA patterns were revealed for lipoprotein features of importance for cardiovascular (CV) health. Thus, the subclasses of atherogenic small and very small low density lipoprotein (LDL) particles and the same subclasses of high density lipoprotein (HDL) particles were associated with a pattern of saturated FAs and mono-unsaturated C16-C18 FAs. Eicosapentaenoic acid (EPA) and the ratio of EPA to arachidonic acid (AA) had strongest associations to features that promotes CV health: (i) large average size of HDL and LDL particles, and, (ii) small average size of very low density lipoprotein (VLDL) particles. Total concentration of HDL in both genders correlated to EPA, but docosahexaenoic acid (DHA) correlated just as strongly for women. For men, docosapentaenoic acid (DPA) showed stronger association to HDL concentration than EPA. For both genders, concentration of large LDL particles showed associations to levels of EPA, but stronger to DHA and DPA. High values of EPA/AA seem to be the strongest single biomarker for good CV health in both men and women.publishedVersio

Sonority bias in Rugao di-syllabic syllable contraction

Two analyses, vowel sonority and the linear order of pre-contraction vowels, have been proposed to account for the vowel selection between two competing vowels in Chinese syllable contraction. An experiment was run to test whether sonority and/or linear order bias the vowel selection in Rugao syllable contraction. Our results confirmed the role of vowel sonority, and did not present supporting evidence for the linear order analysis. Sonority hierarchies along the dimensions of both height and centrality exhibit the same consistent and robust pattern, providing a new perspective to look at competing vowels in vowel-related phonological processes

Intensive lifestyle intervention provides rapid reduction of serum fatty acid levels in women with severe obesity without lowering omega-3 to unhealthy levels

Serum fatty acid (FA) levels were monitored in women with severe obesity during intensive lifestyle intervention. At baseline, total FA levels and most individual FAs were elevated compared to a matching cohort of normal and overweight women (healthy controls). After 3 weeks of intensive lifestyle intervention, total level was only 11–12% higher than in the healthy controls and with almost all FAs being significantly lower than at baseline, but with levels of omega-3 being similar to the healthy controls. This is contrary to observations for patients subjected to bariatric surgery where omega-3 levels dropped to levels significantly lower than in the lifestyle patients and healthy controls. During the next 3 weeks of treatment, the FA levels in lifestyle patients were unchanged, while the weight loss continued at almost the same rate as in the first 3 weeks. Multivariate analysis revealed that weight loss and change of serum FA patterns were unrelated outcomes of the intervention for lifestyle patients. For bariatric patients, these processes were associated probably due to reduced dietary input and increased input from the patients’ own fat deposits, causing a higher rate of weight loss and simultaneous reduction of the ratio of serum eicosapentaenoic to arachidonic acid.publishedVersio

Design strategies of tumor-targeted delivery systems based on 2D nanomaterials

Conventional chemotherapy and radiotherapy are nonselective and nonspecific for cell killing, causing serious side effects and threatening the lives of patients. It is of great significance to develop more accurate tumor-targeting therapeutic strategies. Nanotechnology is in a leading position to provide new treatment options for cancer, and it has great potential for selective targeted therapy and controlled drug release. 2D nanomaterials (2D NMs) have broad application prospects in the field of tumor-targeted delivery systems due to their special structure-based functions and excellent optical, electrical, and thermal properties. This review emphasizes the design strategies of tumor-targeted delivery systems based on 2D NMs from three aspects: passive targeting, active targeting, and tumor-microenvironment targeting, in order to promote the rational application of 2D NMs in clinical practice.This work was supported by the Guangdong Basic and Applied Basic Research Foundation (Nos. 2021A1515110657 and 2022A1515010056), Shenzhen Science and Technology Program (Grant No. RCBS20210609104513023), National Natural Science Foundation of China (No. 81922037), and Shanghai Biomedical Science and Technology Support Project (No. 19441903600)

Organelle-specific anchored delivery system stretching a reversal of tumor hypoxia microenvironment to a combinational chemo-photothermal therapy

Direct delivery to an organelle-specific point can boost the efficacy of therapy procedures to new heights. Among other subcellular organelles, mitochondria generate ATP as intracellular powerhouse, and are associated with multiple aspects of tumorigenesis and tumor development. Here, a mitochondrial anchored biomimetic nanoplatform (CZACN) is designed and its reversal of tumor hypoxia microenvironment underlying the mitochondria-located chemo-photothermal therapy is studied. After shuttling into cancer cells, therapeutic payloads including cisplatin (CDDP) and Au nanozymes are controllably released in the ATP-overexpressed mitochondria. CDDP generates O2â ¢â , forms H2O2 for a chemical fuel in the next reaction, and damages mitochondrial DNA. Meanwhile, the catalase-like Au nanozymes catalyze the produced hydrogen peroxide for oxygen supply to relieve hypoxic tumor microenvironment, offering cytotoxic singlet oxygen against cancer cells under NIR treatment. As a result of cancer-cell self-recognition, mitochondria-targeted therapy, and photothermal conversion ability, the fabricated CZACNs obtained 89.2 ± 3.70% of tumor growth inhibition under NIR irradiation and constrained the dose-limiting toxicity of CDDP, as well. These findings reinforce the synergistic effect of organelle-specific navigation and in situ oxygen self-sufficiency for combinational chemo-photothermal therapy.X.C., X.Y., and L.Z. contributed equally to this work. This work has been supported by the National Natural Science Foundation of China (22003038, 81922037, and 11575107), the Shanghai University-Universal Medical Imaging Diagnostic Research Foundation (19H00100), Shanghai Biomedical Science and Technology Support Project (19441903600), the Program for Changjiang Scholars and Innovative Research Team in University (IRT13078). The authors would like to thank the workers from Shiyanjia Lab (www.shiyanjia.com) for the ICP-OES analysis

STC3141 improves acute lung injury through neutralizing circulating histone in rat with experimentally-induced acute respiratory distress syndrome

Background: Acute respiratory distress syndrome (ARDS) remains a challenge because of its high morbidity and mortality. Circulation histones levels in ARDS patients were correlated to disease severity and mortality. This study examined the impact of histone neutralization in a rat model of acute lung injury (ALI) induced by a lipopolysaccharide (LPS) double-hit.Methods: Sixty-eight male Sprague-Dawley rats were randomized to sham (N = 8, received saline only) or LPS (N = 60). The LPS double-hit consisted of a 0.8 mg/kg intraperitoneal injection followed after 16 h by 5 mg/kg intra-tracheal nebulized LPS. The LPS group was then randomized into five groups: LPS only; LPS +5, 25, or 100 mg/kg intravenous STC3141 every 8 h (LPS + L, LPS + M, LPS + H, respectively); or LPS + intraperitoneal dexamethasone 2.5 mg/kg every 24 h for 56 h (LPS + D). The animals were observed for 72 h.Results: LPS animals developed ALI as suggested by lower oxygenation, lung edema formation, and histological changes compared to the sham animals. Compared to the LPS group, LPS + H and +D groups had significantly lower circulating histone levels and lung wet-to-dry ratio, and the LPS + D group also had lower BALF histone concentrations; the blood neutrophils and platelets counts in LPS + D group did not change, meanwhile, the LPS + L, +M and +H groups had significantly lower neutrophil counts and higher platelet counts in the blood; the total number of BALF WBC, platelet counts, MPO and H3 were significantly lower in the LPS + L, +M, +H and +D groups than in the LPS only group; and the degree of inflammation was significantly less in the LPS + L, +M, +H and +D groups, moreover, inflammation in the LPS + L, +M and +H animals showed a dose-dependent response; finally, the LPS + L, +M, +H and +D groups had improved oxygenation compared to the LPS group, and there were no statistical differences in PCO2 or pH among groups. All animals survived.Conclusion: Neutralization of histone using STC3141, especially at high dose, had similar therapeutic effects to dexamethasone in this LPS double-hit rat ALI model, with significantly decreased circulating histone concentration, improved acute lung injury and oxygenation

Prior Antithrombotic Therapy Is Associated With Cerebral Microbleeds in Ischemic Stroke Patients With Atrial Fibrillation and/or Rheumatic Heart Disease

Background and purpose: Cerebral microbleeds (CMBs) could contribute to an increased risk of intracerebral hemorrhage in patients with antithrombotic therapy (antiplatelets or anticoagulants). Antithrombotic agents are commonly prescribed to the patients with atrial fibrillation (AF) and/or rheumatic heart disease (RHD) for preventing ischemic stroke. However, the impact of antithrombotic therapy on CMBs remained controversial. We aimed to explore the association between the prevalence of CMBs and prior antithrombotic therapy in ischemic stroke patients with AF and/or RHD.Materials and Methods: Ischemic stroke patients with AF and/or RHD within 7 days of onset from two hospitals were enrolled. Clinical information, prior use of antiplatelets or anticoagulation, presence and location of CMBs on susceptibility weighted imaging were recorded. We investigated the association of antithrombotic use with the presence or location of CMBs using multivariable logistic regression.Results: A total of 160 patients (68 males; median age, 71 years) were included. CMBs were observed in 90 (56.3%) patients, of whom 37 were with strictly lobar CMBs and 53 were with deep or infratentorial CMBs. There was a significant difference in antiplatelet use between patients with and without CMBs (33.3 vs. 11.4%, P = 0.001), but not found in anticoagulants. Prior use of antiplatelets was independently associated with the presence of CMBs (OR 3.075, 95% CI 1.175–8.045, P = 0.022) and especially strictly lobar CMBs (OR 2.635, 95% CI 1.050–6.612, P = 0.039) in multivariate analysis.Conclusions: The present study suggests that CMBs are common in ischemic stroke patients with AF and/or RHD and prior antiplatelet use may relate to the presence of CMBs predominantly in the strictly lobar region. Whether anticoagulants could cause CMBs need to be determined in future longitudinal studies