Search

Statins are known to be anti-inflammatory, but the mechanism remains poorly understood. Here, we show that macrophages, either treated with statin in vitro or from statin-treated mice, have reduced cholesterol levels and higher expression of Jmjd3, a H3K27me3 demethylase. We provide evidence that lowering cholesterol levels in macrophages suppresses the adenosine triphosphate (ATP) synthase in the inner mitochondrial membrane and changes the proton gradient in the mitochondria. This activates nuclear factor kappa-B (NF-κB) and Jmjd3 expression, which removes the repressive marker H3K27me3. Accordingly, the epigenome is altered by the cholesterol reduction. When subsequently challenged by the inflammatory stimulus lipopolysaccharide (M1), macrophages, either treated with statins in vitro or isolated from statin-fed mice, express lower levels proinflammatory cytokines than controls, while augmenting anti-inflammatory Il10 expression. On the other hand, when macrophages are alternatively activated by IL-4 (M2), statins promote the expression of Arg1, Ym1, and Mrc1. The enhanced expression is correlated with the statin-induced removal of H3K27me3 from these genes prior to activation. In addition, Jmjd3 and its demethylase activity are necessary for cholesterol to modulate both M1 and M2 activation. We conclude that upregulation of Jmjd3 is a key event for the anti-inflammatory function of statins on macrophages.

The advent of immune-checkpoint inhibitors (ICIs) has revolutionized the treatment of malignant solid tumors in the last decade, producing lasting benefits in a subset of patients. However, unattended excessive immune responses may lead to immune-related adverse events (irAEs). IrAEs can manifest in different organs within the body, with pulmonary toxicity commonly referred to as immune checkpoint inhibitor-related pneumonitis (CIP). The CIP incidence remains high and is anticipated to rise further as the therapeutic indications for ICIs expand to encompass a wider range of malignancies. The diagnosis and treatment of CIP is difficult due to the large individual differences in its pathogenesis and severity, and severe CIP often leads to a poor prognosis for patients. This review summarizes the current state of clinical research on the incidence, risk factors, predictive biomarkers, diagnosis, and treatment for CIP, and we address future directions for the prevention and accurate prediction of CIP.

Abstract Herein, we analyzed total polyphenol content, total flavonoid content, and the antioxidant activity of the ethanol and distilled water extracted Houttuynia cordata perennial herb. Later, we investigated the possibility of producing Houttuynia cordata extract (HCE) loaded Polyurethane (PU) nanofibers via the electrospinning technique. The analysis confirmed that the total polyphenol, total flavonoid content, and antioxidant activity of the ethanol extracted HCE were higher than the distilled water extracted HCE. Therefore, the ethanol extracted HCE was used to prepare HCE/PU nanofibers by varying concentrations of HCE and PU. The HCE/PU nanofibers showed a mixed pattern of beads and fibers at a PU concentration of 10 wt%. However, at 12 wt% PU concentration, relatively uniform nanofibers with an average diameter of about 200 nm were formed at 1.0% and 1.5 wt% of HCE. The successful incorporation of HCE in PU nanofibrous matrix was confirmed by the presence of its characteristic bands in Fourier transform infrared (FTIR) and X-ray diffraction (XRD) spectra. The addition of HCE increased the crystallinity, the amount of heat required for pyrolysis, and the thermal stability of HCE/PU nanofibers, which must be credited to the HCE-derived quercitrin and quercetin crystallite solids.

Abstract Objectives To explore the causes of sudden unexpected death (SUD) and to search for high-risk people, whole exome sequencing (WES) was performed in families with SUDs. Methods Whole exome sequencing of 25 people from 14 SUD families were screened based on cardiac disease-associated gene variants, and their echocardiograms and electrocardiograms (ECG) were also examined. The protein function of mutated genes was predicted by SIFT, PolyPhen2 and Mutation Assessor. Results In the group of 25 people from 14 SUD families, 49 single nucleotide variants (SNVs) of cardiac disease-associated genes were found and verified by Sanger sequencing. 29 SNVs of 14 cardiac disorder-related genes were predicted as pathogens by software. Among them, 7 SNVs carried by two or more members were found in 5 families, including SCN5A (c.3577C > T), IRX4 (c.230A > G), LDB3 (c.2104 T > G), MYH6 (c.3G > A), MYH6 (c.3928 T > C), TTN (c.80987C > T) and TTN (c.8069C > T). 25 ECGs were collected. In summary, 4 people had J-point elevation, 2 people had long QT syndrome (LQTS), 4 people had prolonged QT interval, 3 people had T-wave changes, 3 people had sinus tachycardia, 4 people had sinus bradycardia, 4 people had left side of QRS electrical axis, and 3 people had P wave broadening. Echocardiographic results showed that 1 person had atrial septal defect, 1 person had tricuspid regurgitation, and 2 people had left ventricular diastolic dysfunction. Conclusions Of the 14 heart disease-associated genes in 14 SUDs families, there are 7 possible pathological SNVS may be associated with SUDs. Our results indicate that people with ECG abnormalities, such as prolonged QT interval, ST segment changes, T-wave change and carrying the above 7 SNVs, should be the focus of prevention of sudden death.

Wearable flexible sensors are widely used in several applications such as physiological monitoring, electronic skin, and telemedicine. Typically, flexible sensors that are made of elastomeric thin-films lack sufficient permeability, which leads to skin inflammation, and more importantly, affects signal detection and consequently, reduces the sensitivity of the sensor. In this study, we designed a flexible nanofibrous membrane with a high air permeability (6.10 mm/s), which could be effectively used to monitor human motion signals and physiological signals. More specifically, a flexible membrane with a point (liquid metal nanoparticles)-line (carbon nanotubes)-plane (liquid metal thin-film) multiscale conductive structure was fabricated by combining liquid metal (LM) and carbon nanotubes (CNTs) with a polyurethane (PU) nanofibrous membrane. Interestingly, the excellent conductivity and fluidity of the liquid metal enhanced the sensitivity and stability of the membrane. More precisely, the gauge factor (GF) values of the membrane is 3.0 at 50% strain and 14.0 at 400% strain, which corresponds to a high strain sensitivity within the whole range of deformation. Additionally, the proposed membrane has good mechanical properties with an elongation at a break of 490% and a tensile strength of 12 MPa. Furthermore, the flexible membrane exhibits good biocompatibility and can efficiently monitor human health signals, thereby indicating potential for application in the field of wearable electronic devices.

Abstract Artificial synapses and neurons are crucial milestones for neuromorphic computing hardware, and memristors with resistive and threshold switching characteristics are regarded as the most promising candidates for the construction of hardware neural networks. However, most of the memristors can only operate in one mode, that is, resistive switching or threshold switching, and distinct memristors are required to construct fully memristive neuromorphic computing hardware, making it more complex for the fabrication and integration of the hardware. Herein, we propose a flexible dual‐mode memristor array based on core–shell CsPbBr3@graphdiyne nanocrystals, which features a 100% transition yield, small cycle‐to‐cycle and device‐to‐device variability, excellent flexibility, and environmental stability. Based on this dual‐mode memristor, homo‐material‐based fully memristive neuromorphic computing hardware—a power‐free artificial nociceptive signal processing system and a spiking neural network—are constructed for the first time. Our dual‐mode memristors greatly simplify the fabrication and integration of fully memristive neuromorphic systems.

Introduction: Aconiti lateralis radix praeparata (ALRP), the sub root of Aconitum carmichaelii Debx., is a traditional Chinese medicine with good pharmacological effects. Heishunpian (HSP), prepared through the process of brine immersing, boiling, rinsing, dyeing, and steaming ALRP is one of the most widely used forms of decoction pieces in clinical practice. Objectives: This study aims to investigate the mechanisms of component changes and transformations during the processing from ALRP to HSP, and to screen for their quality markers through UHPLC‐QTOF‐MS analysis. Methods: Samples from ALRP to HSP during processing were prepared and analyzed by UHPLC‐QTOF‐MS. By comparing the differences between before and after each processing step, the purpose of processing and the transformation of components during processing were studied. In addition, multiple batches of ALRP and HSP were determined, and potential quality markers were screened. Results: Through the analysis of ALRP and five key processing samples, 55 components were identified. Immersing in brine, rinsing, and dyeing were the main factors of component loss, and boiling caused a slight loss of components. Some components were enhanced during the steaming process. Combining the screened differences components between multiple ALRP and HSP, 10 components were considered as potential quality biomarkers. Conclusion: This study found that the adjacent hydroxyl groups of the ester group may have a positive impact on the hydrolysis of the ester group, and 10 quality markers were preliminarily screened. It provides a reference for quality control and clinical application of ALRP and HSP. To screen quality markers based on the processing of Aconiti lateralis radix praeparata (ALRP) to Heishunpian (HSP), samples during processing and multiple batches of ALRP and HSP were prepared and analyzed by UHPLC‐QTOF‐MS. Fifty‐five components were identified, including diterpenoid alkaloids, isoquinoline alkaloids, and organic amine alkaloids. Immersing in brine, rinsing, and dyeing were the main factors of component loss, and some components were enhanced during the steaming process. Ten components were considered as potential quality markers. [ABSTRACT FROM AUTHOR]