CD47 serves as a ligand for signaling regulatory protein α (SIRPα) and as a receptor for thrombospondin‐1 (TSP‐1). Although CD47, TSP‐1, and SIRPα are thought to be involved in the clearance of aged ...red blood cells (RBCs), aging‐associated changes in the expression and interaction of these molecules on RBCs have been elusive. Using direct stochastic optical reconstruction microscopy (dSTORM)‐based imaging and quantitative analysis, we can report that CD47 molecules on young RBCs reside as nanoclusters with little binding to TSP‐1, suggesting a minimal role for TSP‐1/CD47 signaling in normal RBCs. On aged RBCs, CD47 molecules decreased in number but formed bigger and denser clusters, with increased ability to bind TSP‐1. Exposure of aged RBCs to TSP‐1 resulted in a further increase in the size of CD47 clusters via a lipid raft‐dependent mechanism. Furthermore, CD47 cluster formation was dramatically inhibited on thbs1−/− mouse RBCs and associated with a significantly prolonged RBC lifespan. These results indicate that the strength of CD47 binding to its ligand TSP‐1 is predominantly determined by the distribution pattern and not the amount of CD47 molecules on RBCs, and offer direct evidence for the role of TSP‐1 in phagocytosis of aged RBCs. This study provides clear nanoscale pictures of aging‐associated changes in CD47 distribution and TSP‐1/CD47 interaction on the cell surface, and insights into the molecular basis for how these molecules coordinate to remove aged RBCs.
On young RBCs (Top), CD47 molecules reside as nanoclusters with minimal binding to TSP‐1 trimmers. On aged RBCs (Bottom), CD47 proteins form bigger and denser clusters and gain increased ability to bind TSP‐1, thus promoting phagocytosis of aged RBCs.
Background and Aims
Although the prevalence of NAFLD has risen dramatically to 25% of the adult population worldwide, there are as yet no approved pharmacological interventions for the disease ...because of uncertainty about the underlying molecular mechanisms. It is known that mitochondrial dysfunction is an important factor in the development of NAFLD. Mitochondrial antiviral signaling protein (MAVS) is a critical signaling adaptor for host defenses against viral infection. However, the role of MAVS in mitochondrial metabolism during NAFLD progression remains largely unknown.
Approach and Results
Based on expression analysis, we identified a marked down‐regulation of MAVS in hepatocytes during NAFLD progression. By using MAVS global knockout and hepatocyte‐specific MAVS knockout mice, we found that MAVS is protective against diet‐induced NAFLD. MAVS deficiency induces extensive mitochondrial dysfunction during NAFLD pathogenesis, which was confirmed as impaired mitochondrial respiratory capacity and membrane potential. Metabolomics data also showed the extensive metabolic disorders after MAVS deletion. Mechanistically, MAVS interacts with the N‐terminal stretch of voltage‐dependent anion channel 2 (VDAC2), which is required for the ability of MAVS to influence mitochondrial function and hepatic steatosis.
Conclusions
In hepatocytes, MAVS plays an important role in protecting against NAFLD by helping to regulate healthy mitochondrial function. These findings provide insights regarding the metabolic importance of conventional immune regulators and support the possibility that targeting MAVS may represent an avenue for treating NAFLD.
•A colorimetric gas sensor array was developed containing four natural pigments.•The sum of putrescine and cadaverine (BAI) was used as a measure of meat freshness.•The colour changes of the sensors ...were correlated with BAI and total viable counts.•The natural pigment sensors were useful for quality evaluation of meat.
A new colorimetric gas-sensor array based on four natural pigments, that were extracted from spinach (Spinacia oleracea), red radish (Raphanus sativus L.), winter jasmine (Jasminum nudiflorum), and black rice (Oryza sativa L. indica), was developed for pork freshness evaluation. A colour change profile for each sample was obtained by differentiating the images of the sensor array before and after exposure to the odour of sample. The total viable count (TVC) per gram of pork was obtained by classical microbiological plating methods, and the biogenic amines were measured by HPLC. Biogenic amine index (BAI) for the determination of meat freshness was developed from the sum of putrescine and cadaverine. The colour change profiles were analysed using principal component analysis and correlated with conventional methods (BAI, TVC). A partial least squares (PLS) prediction model was obtained with r=0.854 and 0.933 for BAI and TVC, respectively.
The disadvantages of poor selectivity, thermal instability and nonlinear output for metal oxide semiconductor (MOS) gas sensors restrict their detection accuracy for flammable and toxic gases. In ...this paper, a low frequency dynamic temperature modulation detection method using rectangular wave was designed and first proposed herein. The temperature modulation detection mechanism was also provided in detail. The flammable gases CH 4 and CO were detected successfully using this method by self-made indirectly Pt/SnO 2 sensors. The results show that the response time of the Pt/SnO 2 sensors is 9 s and 8 s, and the recovery time is 25 s and 23 s for 100 ppm CH 4 and CO, using the rectangular wave temperature modulation with a working temperature of 335-382 °C and an optimized frequency of 100 mHz. The temperature modulation has more advantages than steady-state constant temperature method in power consumption and working temperature. The temperature-modulated response for CH 4 and CO, are highly linear with the gas concentration without using the log coordinates. The selectivity of the Pt/SnO 2 sensors for 500 ppm CH 4 and CO is enhanced from 2.03 using the traditional steady-state constant temperature detection to 2.56 using the temperature modulation method. Compared with the steady-state constant temperature method, both the selectivity and linearity of the response output for the Pt/SnO 2 sensors are improved by this method, and an effective detection can be realized for a wide gas concentration range of 0-500 ppm CH 4 and CO. It provides a new potential detection pathway for MOS-based gas sensors.
Atrazine is widely used in agriculture and is a known endocrine disrupting chemical. Atrazine can seep into the water body through surface, posing a potential threat to the aquatic ecological ...environment and human drinking water source. In vertebrate, studies have shown that it can affect reproduction and development seriously, but its molecular mechanism for aquatic animals is unknown. Aquaculture is very common in China, especially common carp, whose females grow faster than males. However, the effects of atrazine on the reproduction of carp, especially miRNA, have not been investigated.
In this study, common carp (Cyprinus carpio) at two key developmental stages were exposed to atrazine in vitro. Sex ratio was observed to analyze the effect of atrazine on the sex. MiRNA expression profiles were analysed to identify miRNAs related to gonad development and to reveal the atrazine mechanisms interfering with gonad differentiation. The results showed that the sex ratio was biased towards females. Atrazine exposure caused significant alteration of multiple miRNAs. Predicted targets of differently-expressed miRNAs were involved in many reproductive biology signalling pathways.
Our results indicate that atrazine promoted the expression of female-biased genes by decreasing miRNAs in primordial gonad. In addition, our results indicate that atrazine can up-regulate aromatase expression through miRNAs, which supports the hypothesis that atrazine has endocrine-disrupting activity by altering the gene expression profile of the Hypothalamus-Pituitary-Gonad axis through its corresponding miRNAs.
Whereas there are many pharmacological interventions prescribed for patients with advanced anaplastic lymphoma kinase (ALK)- rearranged non-small cell lung cancer (NSCLC), comparative data between ...novel generation ALK-tyrosine kinase inhibitors (TKIs) remain scant. Here, we indirectly compared the efficacy and safety of first-line systemic therapeutic options used for the treatment of ALK-rearranged NSCLC.
We included all phase 2 and 3 randomised controlled trials (RCTs) comparing any two or three treatment options. Eligible studies reported at least one of the following outcomes: progression free survival (PFS), overall survival (OS), objective response rate (ORR), or adverse events of grade 3 or higher (Grade ≥ 3 AEs). Subgroup analysis was conducted according to central nervous system (CNS) metastases.
A total of 9 RCTs consisting of 2484 patients with 8 treatment options were included in the systematic review. Our analysis showed that alectinib (300 mg and 600 mg), brigatinib, lorlatinib and ensartinib yielded the most favorable PFS. Whereas there was no significant OS or ORR difference among the ALK-TKIs. According to Bayesian ranking profiles, lorlatinib, alectinib 600 mg and alectinib 300 mg had the best PFS (63.7%), OS (35.9%) and ORR (37%), respectively. On the other hand, ceritinib showed the highest rate of severe adverse events (60%).
Our analysis indicated that alectinib and lorlatinib might be associated with the best therapeutic efficacy in first-line treatment for major population of advanced NSCLC patients with ALK-rearrangement. However, since there is little comparative evidence on the treatment options, there is need for relative trials to fully determine the best treatment options as well as the rapidly evolving treatment landscape.
Air pollution is one of the major threats to human health. The monitoring of toxic NO2 gas in urban air emission pollution is becoming increasingly important. Thus, the development of an NO2 sensor ...with low power consumption, low cost, and high performance is urgent. In this paper, a planar structural micro hotplate gas sensor based on an AlN ceramic substrate with an annular Pt film heater was designed and prepared by micro-electro-mechanical system (MEMS) technology, in which Pt/Nb/In2O3 composite semiconductor oxide was used as the sensitive material with a molar ratio of In:Nb = 9:1. The annular thermal isolation groove was designed around the heater to reduce the power consumption and improve the thermal response rate. Furthermore, the finite element simulation analysis of the thermal isolation structure of the sensor was carried out by using ANSYS software. The results show that a low temperature of 94 °C, low power consumption of 150 mW, and low concentration detection of 1 to 10 ppm NO2 were simultaneously realized for the Nb-doped In2O3-based gas sensor. Our findings provide a promising strategy for the application of In2O3-based sensors in highly effective and low concentration NO2 detection.
The temperature of an object provides important somatosensory information for animals performing tactile tasks. Humans can perceive skin cooling of less than one degree, but the sensory afferents and ...central circuits that they engage to enable the perception of surface temperature are poorly understood. To address these questions, we examined the perception of glabrous skin cooling in mice. We found that mice were also capable of perceiving small amplitude skin cooling and that primary somatosensory (S1) cortical neurons were required for cooling perception. Moreover, the absence of the menthol-gated transient receptor potential melastatin 8 ion channel in sensory afferent fibers eliminated the ability to perceive cold and the corresponding activation of S1 neurons. Our results identify parts of a neural circuit underlying cold perception in mice and provide a new model system for the analysis of thermal processing and perception and multimodal integration.
► NIR coupled with LS-SVM was used to detection quality of 95 Chinese vinegars. ► White vinegar and fruit vinegar were separated from traditional vinegar categories by PCA. ► LS-SVM was firstly ...applied to identify mature vinegar, aromatic vinegar and ric vinegar. ► LS-SVM also be used to predication total acid content in all vinegar samples.
More than 3.2millionlitres of vinegar is consumed every day in China. There are many types of vinegar in China. How to control the quality of vinegar is problem. Near infrared spectroscopy (NIR) transmission technique was applied to achieve this purpose. Ninety-five vinegar samples from 14 origins covering 11 provinces in China were collected. They were classified into mature vinegar, aromatic vinegar, rice vinegar, fruit vinegar, and white vinegar. Fruit vinegar and white vinegar were separated from the other traditional categories in the two-dimension principal component space of NIR after principle component analysis (PCA). Least-squares support vector machine (LS-SVM) as the pattern recognition was firstly applied to identify mature vinegar, aromatic vinegar, rice vinegar in this study. The top two principal components (PCs) were extracted as the input of LS-SVM classifiers by principal component analysis (PCA). The best experimental results were obtained using the radial basis function (RBF) LS-SVM classifier with σ=0.8. The accuracies of identification were more than 85% for three traditional vinegar categories. Compared with the back propagation artificial neural network (BP-ANN) approach, LS-SVM algorithm showed its excellent generalisation for identification results. As total acid content (TAC) is highly connecting with the quality of vinegar, NIR was used to prediction the TAC of samples. LS-SVM was applied to building the TAC prediction model based on spectral transmission rate. Compared with partial least-square (PLS) model, LS-SVM model gave better precision and accuracy in predicting TAC. The determination coefficient for prediction (Rp) of the LS-SVM model was 0.919 and root mean square error for prediction (RMSEP) was 0.3226. This work demonstrated that near infrared spectroscopy technique coupled with LS-SVM could be used as a quality control method for vinegar.
Ni-B alloy coatings were electrodeposited using a Ni plating bath containing dimethylamine borane (DMAB) as boron sources. Hard chromium coatings were electrodeposited from conventional Cr (VI) bath ...for comparison. Ni-B alloy coatings were heat treated at different temperature from 200°C to 400°C using vacuum annealing furnace. Crystal structures and surface morphologies of coatings were evaluated by XRD, SEM and TEM, respectively. Their mechanical and tribological properties were tested by microhardness tester, scratch tester and friction wear testing machine, respectively. Wear tracks morphologies were observed through SEM to analyze the wear mechanism of coatings. Nano-hardness and elastic modulus were tested by Nanoindenter. Results show that the hardness of as-plated Ni-B alloy coatings is 700–800Hv, and it increases to 980±28Hv after heat treatment at 300°C for 20min. The scratch tests show that the Ni-B coatings have a good adhesion to the substrate in both as-plated and heat-treated conditions. Tribological tests show that the 300°C-heat-treated Ni-B coatings exhibit a lowest wear rate under different oil-lubricated sliding conditions, the wear resistance of which is higher than that of hard chromium coatings. The excellent wear resistance is attributed to its high ratio of hardness to elastic modulus (H/E).
•High hardness Ni-B coatings were prepared as alternative for Cr coatings.•The wear resistance of 300°C-heat-treated Ni-B coatings is obviously higher than that of hard chromium coatings.•Coatings with high H/E exhibit good resistance to both abrasion and fatigue.•Ni-B coatings heat-treated at 300°C and having the highest H/E exhibit best wear resistance.
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