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Abstract Background The lipid-lowering effects of Omega-3 fatty acids have been widely reported, yet their impact on ischemic stroke remains controversial. Reports on the protective effects of unsaturated fatty acids, such as Omega-6 and Omega-7, as well as saturated fatty acids in cardiovascular diseases, including hypertension and ischemic stroke, are less frequent. Objectives This study aims to identify fatty acids associated with blood pressure and ischemic stroke through Mendelian randomization. Besides, it seeks to determine whether specific fatty acids can prevent ischemic stroke by managing blood pressure and revealing the specific mechanisms of this action. Methods This research involved downloading relevant data from websites and extracting SNPs that met the standard criteria as instrumental variables. Simultaneously, the ‘MR-PRESSO’ package and ‘Mendelian Randomization’ package were used to eliminate confounding SNPs that could bias the study results. Then, inverse variance weighting and the weighted median were employed as primary analysis methods, accompanied by sensitivity analysis to assess the validity of the causal relationships. Initially, multivariable Mendelian randomization was used to identify fatty acids linked to blood pressure and the incidence of ischemic stroke. The causal link between certain fatty acids and the initiation of ischemic stroke was then investigated using bidirectional and mediator Mendelian randomization techniques. Stepwise Regression and the Product of Coefficients Method in mediator Mendelian randomization were utilized to ascertain whether specific fatty acids reduce ischemic stroke risk by lowering blood pressure. Results Multivariable Mendelian randomization analysis indicated a potential inverse correlation between Omega-3 intake and both blood pressure and ischemic stroke. Consequently, Omega-3 was selected as the exposure, with blood pressure and ischemic stroke-related data as outcomes, for further bidirectional and mediation Mendelian Randomization analyses. Bidirectional Mendelian Randomization revealed that Omega-3 significantly influences DBP (P = 1.01e-04) and IS (P = 0.016). It also showed that DBP and SBP significantly affect LAS, SVS, CES, IS, and LS. Mediator Mendelian Randomization identified five established mediating pathways: Omega-3-Diastolic blood pressure-Small vessel stroke, Omega-3-Diastolic blood pressure-Cardioembolic stroke, Omega-3-Diastolic blood pressure-Lacunar stroke, Omega-3-Diastolic blood pressure-Large artery atherosclerosis stroke, and Omega-3-Diastolic blood pressure-Ischemic stroke. Of these, four pathways are complete mediation, and one pathway is partial mediation. Conclusions The findings suggest that Omega-3 may indirectly reduce the incidence of ischemic stroke by lowering blood pressure. Thus, blood pressure modulation might be one of the mechanisms through which Omega-3 prevents ischemic stroke. In summary, incorporating an increased intake of Omega-3 in the diet can serve as one of the dietary intervention strategies for patients with hypertension. Additionally, it can act as an adjunctive therapy for the prevention of ischemic strokes and their complications.

Bile acid (BA) play an important role in nutrient absorption and are key regulators of antioxidant and immune response homeostasis. The purpose of this study was to evaluate the effects of dietary supplementation with 0 (CON), 100 (BA100), 200 (BA200), 300 (BA300) and 400 (BA400) mg/kg BA on the growth, digestive enzyme activity, antioxidant capacity and immune response of loach. The results of serum biochemical analysis showed that the serum markers of liver damage (ALT, AST, ALP and LDH) of loach were decreased by adding BA. The BA diets mainly affected the lipase activity in the liver and intestine of loach, but there was no significant difference on protease. Histological section results showed that dietary supplementation with 100, 200 and 300 mg/kg BA increased the number of liver nuclei, liver vacuolation, intestinal wall muscle thickness and intestinal villi. In addition, BA enhanced the antioxidant capacity of loach by increasing the activities of GSH, GSH-Px, CAT, SOD and GST in their tissues (liver and intestine) and the mRNA expression levels of antioxidant-related genes (cat, gsh-px, sod and nrf2). At the same time, BA increased serum immune parameters (C3, C4, IgM and LYS), up-regulated the mRNA expression levels of anti-inflammatory factors (il-10), key immune genes (lys) and down-regulated the mRNA expression levels of pro-inflammatory factors (il-1β and tnf-α) in tissues (liver and intestine). In conclusion, dietary BA supplementation could improve the liver and intestinal digestive enzyme activities, enhance the antioxidant capacity and immune function, and promote the healthy growth of loach. Based on the results of these studies, the optimal supplementation of BA in loach diets was 200–300 mg/kg.

IntroductionDue to the high mortality rate and increasing severity of antibiotic resistance, there is a growing interest in new treatments for Klebsiella pneumoniae (KP)-induced pneumonia. Research has shown that the single herbs of SiHuangQingXinWan (SHQXW) are effective in treating pneumonia caused by KP. The PI3K/AKT signaling pathway has garnered attention for its potential role in the management of bacterial infections. This study aimed to evaluate the anti-pneumonia effect of SHQXW and to investigate its mechanism of action.Materials and MethodsThe potential plant metabolites and molecular targets of SHQXW in the context of pneumonia were determined through ultra-high performance liquid chromatography-tandem mass-spectrometry (UHPLC-MS/MS) and bioinformatics analysis. The therapeutic effect of SHQXW was evaluated in a KP-induced pneumonia murine model with imipenem/cilastatin as a positive control. Transcriptomics and non-targeted metabolomics were carried out to unveil potential mechanisms and targets for anti-pneumonia effects. Additionally, an in-depth exploration on the PI3K/AKT signaling pathway was conducted in this study.ResultsA total of 24 potential plant metabolites and 285 SHQXW-pneumonia-related targets selected by Homo sapiens were identified in this study. The tested doses of SHQXW significantly reduced mortality, improved body weight, decreased the lung index, reduced the bacterial load, and alleviated lung pathological damage in the KP-induced pneumonia murine model (p < 0.05). Notably, 1.3 g/kg/day of SHQXW provided the most effective protective outcome. Furthermore, SHQXW demonstrated the ability to suppress the production of inflammatory factors such as IL-1α, IL-1β, IL-3, IL-6, IL-12p70, G-CSF, GM-CSF, MCP-1, KC, and TNF-α. Analysis of transcriptomic and metabolomic data revealed that SHQXW could modulate inflammation-related signaling pathways (TNF, HIF-1, NF-κB, and PI3K/AKT) and metabolites to regulate pulmonary inflammation. Additional experiments using RT-qPCR and western blotting indicated that SHQXW may exert anti-inflammatory effects by activating the PI3K/AKT pathway.DiscussionThe findings indicate that SHQXW effectively reduces inflammation in mice with KP-induced pneumonia by modulating inflammatory signaling pathways and metabolites, rather than by directly inhibiting the growth of KP. This study introduces a novel treatment approach for KP-induced pneumonia and presents a new outlook on drug development.

Abstract Background the mortality associated with severe malaria due to Plasmodiun falciparum remains high despite improvements in malaria management. Case prensentation: this case series aims to describe the efficacy and safety of the exchange transfusion combined with artesunate (ET-AS) regimen in severe P. falciparum malaria. Eight patients diagnosed with severe P. falciparum malaria were included. All patients underwent ET using the COBE Spectra system. The aimed for a post-exchange hematocrit of 30%. Half the estimated blood volume was removed and replaced using fresh frozen plasma. The regimen was well-tolerated without complications. The parasite clearance time ranged from 1 ~ 5 days. Five patients with cerebral malaria exhibited full improved consciousness within 3 days, while patient2 with hemolysis improved on day 2. Liver function improved within 1 ~ 6 days, and patient 1 and patient 6 showed improvements renal function on days 18 and 19, respectively. The length of intensive care unit stay range from 2 ~ 10 days, and all patients treated with ET-AS remained in the hospital for 3 ~ 19 days. Conclusions: these preliminary results suggest that ET-AS regimens are a safe and effective therapy for severe P. falciparum malaria and can benefit patients in clinical settings.

Emergency response after earthquakes, especially rapid access to building damage information, is of great significance to ensure timely rescue and reduce casualties. However, manual field surveys of building damages are inefficient and dangerous, and optical satellite data are more susceptible to cloud interference after earthquakes. Synthetic aperture radar (SAR) is now widely used in disaster response efforts due to its full-time and all-weather capability. According to the change in coherence between SAR images before and after earthquakes, it is possible to identify damaged buildings that cause coherence loss. However, the accuracy of traditional coherence-based damage detection methods is relatively low due to biases in coherence estimation and inconsistency in spatio-temporal baselines. In this study, we propose a new method to produce a postearthquake building damage proxy map (BDPM) based on multitemporal Sentinel-1 coherence, which incorporates homogeneous SAR pixel coherence estimation and histogram matching techniques. The former is used to reduce estimation biases and the latter to reduce the effect of baseline inconsistencies in adjacent coherence maps. We successfully applied this method to the 2022 Mw 6.2 Afghanistan earthquake, the 2023 strong earthquake sequence in Turkey, and the 2023 Ms 6.2 Jishishan, China earthquake. We also verified its accuracy (over 80%) by comparing the BDPM with results from the United Nations Institute for Training and Research and analyzed various factors affecting the distribution of damaged buildings. These analyses confirm the effectiveness of our method for generating BDPM using free medium-resolution Sentinel-1 data, which will greatly assist in earthquake emergency response.

Abstract Bilayer graphene (BLG) is intriguing for its unique properties and potential applications in electronics, photonics, and mechanics. However, the chemical vapor deposition synthesis of large-area high-quality bilayer graphene on Cu is suffering from a low growth rate and limited bilayer coverage. Herein, we demonstrate the fast synthesis of meter-sized bilayer graphene film on commercial polycrystalline Cu foils by introducing trace CO2 during high-temperature growth. Continuous bilayer graphene with a high ratio of AB-stacking structure can be obtained within 20 min, which exhibits enhanced mechanical strength, uniform transmittance, and low sheet resistance in large area. Moreover, 96 and 100% AB-stacking structures were achieved in bilayer graphene grown on single-crystal Cu(111) foil and ultraflat single-crystal Cu(111)/sapphire substrates, respectively. The AB-stacking bilayer graphene exhibits tunable bandgap and performs well in photodetection. This work provides important insights into the growth mechanism and the mass production of large-area high-quality BLG on Cu.

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by abnormal cell proliferation, apoptosis repression and myeloid differentiation blockade of hematopoietic stem/progenitor cells. Developing and identifying novel therapeutic agents to reverse the pathological processes of AML are of great significance. Here in this study, we found that a fungus-derived histone deacetylase inhibitor, Apicidin, presents promising therapeutic effect on AML by inhibiting cell proliferation, facilitating apoptosis and inducing myeloid differentiation of AML cells. Mechanistic investigation revealed that QPCT is identified as a potential downstream target of Apicidin, which exhibits significantly decreased expression in AML samples compared with the normal controls and is remarkably up-regulated in AML cells upon Apicidin management. Functional study and rescue assay demonstrated that QPCT depletion further promotes cell proliferation, inhibits apoptosis and impairs myeloid differentiation of AML cells, alleviating the anti-leukemic effect of Apicidin on AML. Our findings not only provide novel therapeutic target for AML, but also lay theoretical and experimental foundation for the clinical application of Apicidin in AML patients.

Summary: Increased propensity of bone marrow-derived mesenchymal stem cells (BM-MSCs) toward adipogenic differentiation at the expense of osteogenesis has been implicated in obesity, diabetes, and age-related osteoporosis as well as various hematopoietic disorders. Defining small molecules with role in rectifying the adipo-osteogenic differentiation imbalance is of great significance. Here, we unexpectedly found that Chidamide, a selective histone deacetylases inhibitor, exhibited remarkably suppressive effect on the in vitro induced adipogenic differentiation of BM-MSCs. Multifaceted alterations in the spectrum of gene expression were observed in Chidamide-managed BM-MSCs during adipogenic induction. Finally, we focused on REEP2, which presented decreased expression in BM-MSCs-mediated adipogenesis and was restored by Chidamide treatment. REEP2 was subsequently demonstrated as a negative regulator of adipogenic differentiation of BM-MSCs and mediated the suppressive effect of Chidamide on adipocyte development. Our findings provide the theoretical and experimental foundation for the clinical application of Chidamide for disorders associated with excessive marrow adipocytes.

Methylmercury (MeHg) is a ubiquitous environmental pollutant, which can cross the placenta and blood brain barrier, thus affecting fetal growth and development. Although previous studies have demonstrated that MeHg induces endoplasmic reticulum (ER) stress in rat cerebral cortex and primary neurons, the role of ER stress in MeHg-induced neurodevelopmental toxicity remains unclear. Here, we used ICR pregnant mice and hippocampal neurons cells (HT22 cells) to investigate the molecular mechanism by which MeHg exposure during pregnancy affects neurodevelopment. We found that prenatal MeHg exposure caused developmental delay in offspring, accompanied with ER stress, cell apoptosis, cell cycle arrest and abnormal DNA methylation. Then, we used ER stress specific inhibitor 4-PBA and CHOP siRNA to investigate the role of ER stress on HT22 cells damage caused by MeHg. The results showed that 4-PBA pretreatment restored MeHg-induced axonal shortening and alleviated apoptosis, cell cycle arrest and DNA methylation. At the same time, the activation of CHOP/c-Jun/GADD45A signaling pathway was inhibited, and the interaction between CHOP and c-Jun was weakened. In addition, CHOP siRNA reduced the expression of c-Jun and GADD45A, and relieved DNA methylation levels to some extent. In summary, our study suggested that ER stress induced by MeHg mediated cell apoptosis and cell cycle arrest, and may affect DNA methylation through activation of CHOP/c-Jun/GADD45A signaling pathway, thus leading to neuronal damage.

Autophagy is an important mechanism involved in the regulation of acute myeloid leukemia (AML) chemoresistance. The long noncoding RNA (lncRNA) differentiation antagonizing non‐protein coding RNA (DANCR) exhibits oncogenic activity in several types of human cancers, including AML, but it remains unclear whether it regulates autophagy and chemoresistance in AML. We report here that cytarabine (Ara‐C) treatment elevates DANCR expression in human AML cells. In addition, DANCR overexpression confers and its knockdown diminishes Ara‐C resistance in human AML cells, suggesting that DANCR positively regulates AML chemoresistance to Ara‐C. Moreover, DANCR promotes autophagy in Ara‐C‐treated human AML cells and acts as a sponge to decrease miR‐20a‐5p expression, thereby upregulating the expression of ATG16L1, a critical component of the autophagy machinery. Importantly, ATG16L1 silencing abrogates DANCR‐promoted autophagy and markedly restores DANCR‐conferred Ara‐C resistance, suggesting that DANCR promotes MIR‐874‐3P/ATG16L1 axis‐regulated autophagy to confer Ara‐C resistance in human AML cells. Together, this study identifies DANCR as a positive regulator of Ara‐C resistance in human AML cells, suggesting this lncRNA as a potential target for overcoming Ara‐C resistance in AML chemotherapy.

Increased propensity of bone marrow-derived mesenchymal stem cells (BM-MSCs) toward adipogenic differentiation has been implicated in the fatty bone marrow and defective hematopoiesis of aplastic anemia (AA). However, the underlying molecular mechanism remains to be investigated. In this study, we found that microRNA 199a-5p (miR-199a-5p) exhibits significantly higher expression in AA BM-MSCs compared with the normal control and is demonstrated to facilitate adipogenic differentiation of BM-MSCs through lentivirus-mediated miR-199a overexpression. Mechanistic investigation reveals that miR-199a-5p could be regulated by PPAR gamma (PPARγ) in a transcription-independent manner and regulates adipogenic differentiation by targeting the expression of transforming growth factor beta induced (TGFBI), which is subsequently validated as a negative regulator of adipogenesis. Besides, the positive correlation between PPARγ and miR-199a-5p expression as well as the inverse relationship between miR-199a-5p and TGFBI expression in normal and AA BM-MSCs was observed. Altogether, our work demonstrates that PPARγ-regulated miR-199a-5p promotes adipogenesis of BM-MSCs by inhibiting TGFBI expression, which might be a novel mechanism underlying the bone marrow adiposity in AA, and provides promising therapeutic targets for AA treatment. Keywords: Aplastic anemia, BM-MSCs, PPARγ, miR-199a-5p, TGFBI

InGaN materials are widely used in optoelectronic devices due to their excellent optical properties. Since the emission wavelength of the full-composition-graded InxGa1−xN films perfectly matches the solar spectrum, providing a full-spectrum response, this makes them suitable for the manufacturing of high-efficiency optoelectronic devices. It is extremely important to study the optical properties of materials, but there are very few studies of the luminescence of full-composition-graded InxGa1−xN ternary alloy. In this work, the optical properties of full-composition-graded InxGa1−xN films are studied by cathodoluminescence (CL). The CL spectra with multiple luminescence peaks in the range of 365–1000 nm were acquired in the cross-sectional and plan-view directions. The CL spectroscopy studies were carried out inside and outside of microplates formed under the indium droplets on the InGaN surface, which found that the intensity of the light emission peaks inside and outside of microplates differed significantly. Additionally, the paired defects structure is studied by using the spectroscopic method. A detailed CL spectroscopy study paves the way for the growth and device optimization of high-quality, full-composition-graded InxGa1−xN ternary alloy materials.

Aortopulmonary window is a rare congenital heart disease that can increase pulmonary vascular resistance, exacerbate left-to-right shunt and lead to heart failure and respiratory tract infections. Most patients die during childhood. We report a 53-year-old male patient with a large aortopulmonary window combined with anomalous origin of the right pulmonary artery from the aorta, with Eisenmenger syndrome and without surgery.

Abstract Mesenchymal stem cells (MSCs) have been widely used in regenerative medicine and cellular therapy due to their multi-lineage differentiation potential and immunomodulatory function. The applicability of MSCs also depends on their cellular sources and in vivo functions. Here in this study, we systematically compared the morphologic characteristics, immunophenotypes and the adipogenic differentiation of MSCs derived from umbilical cord (UC), adipose tissue (Ad) and bone marrow (BM). We found that the three tissues-derived MSCs displayed decreased adipogenic capacity in the order: Ad-MSC > BM-MSC > UC-MSC, and no morphologic and immunophenotypic differences were observed. Mechanistic investigation revealed a miR-301b~miR-130b—PPARγ axis, whose expression pattern in UC-MSC, Ad-MSC and BM-MSC significantly correlates with their adipogenic capacity. Our results come up with a potential mechanism to elucidate the differential adipogenesis of Ad-MSC, BM-MSC and UC-MSC, which would provide instructional advice for which source of MSCs to choose according to a certain clinical purpose. Furthermore, the miR-301b~miR-130b—PPARγ axis may also be used as a potential therapeutic target for the disorders associated with MSCs-mediated abnormal adipogenesis.

In this paper, the sodium salt of styrene-maleic anhydride copolymer (SMA) was used as a stabilizer in the process of graphite exfoliation to few-layer graphene using the technique of microfluidization in water. This method is simple, scalable, and cost-effective, and it produces graphene at concentrations as high as 0.522 mg mL−1. The generated high-quality graphene consists of few-layer sheets with a uniform size of less than 1 μm. The obtained graphene was uniformly dispersed and tightly integrated into a polyamide 66 (PA66) matrix to create high-performance multifunctional polymer nanocomposites. The tensile strength and thermal conductivity of 0.3 and 0.5 wt% EG/PA66 composites were found to be ~32.6% and ~28.8% greater than the corresponding values calculated for pure PA66, respectively. This confirms that the new protocol of liquid phase exfoliation of graphite has excellent potential for use in the industrial-scale production of high-quality graphene for numerous applications.

Good dispersion and interfacial compatibility are the key issues to realize the full potential of the physical−mechanical properties of nanocarbon-materials reinforced composites. Styrene−maleic-anhydride-copolymer (SMA)-treated graphene oxide (GO), carboxylated multiwalled carbon nanotubes (MWNTs-COOH), and solid-state shear milling (S3M) were applied to further improve the physical−mechanical properties of the nanocomposite fibers. The results show that a mixture of GO/MWNTs-COOH exhibits good dispersion and interfacial compatibility in polyamide-66 (PA66) matrix. Consequently, the physical−mechanical properties of the fibers, which were spun from the nanocomposite of GO/MWNTs-COOH treated using SMA and S3M methods, show a significant enhancement compared to the untreated fibers as well as better crystallization and thermal properties. In particular, the tensile strength of the PA66/GO/MWNTs-COOH nanocomposite fibers with a loading of 0.3 wt % GO/MWNTs-COOH reaches a maximum (979 MPa), which is the highest among all of the reported literature values. Moreover, the fibers were fabricated by a facile process with efficiency, holding great potential for industrial applications.