RNA m6A demethylase ALKBH5 regulates the development of γδ T cells.

γδ T cells are an abundant T cell population at the mucosa and are important in providing immune surveillance as well as maintaining tissue homeostasis. However, despite γδ T cells' origin in the thymus, detailed mechanisms regulating γδ T cell development remain poorly understood. N6-methyladenosine (m6A) represents one of the most common posttranscriptional modifications of messenger RNA (mRNA) in mammalian cells, but whether it plays a role in γδ T cell biology is still unclear. Here, we show that depletion of the m6A demethylase ALKBH5 in lymphocytes specifically induces an expansion of γδ T cells, which confers enhanced protection against gastrointestinal Salmonella typhimurium infection. Mechanistically, loss of ALKBH5 favors the development of γδ T cell precursors by increasing the abundance of m6A RNA modification in thymocytes, which further reduces the expression of several target genes including Notch signaling components Jagged1 and Notch2. As a result, impairment of Jagged1/Notch2 signaling contributes to enhanced proliferation and differentiation of γδ T cell precursors, leading to an expanded mature γδ T cell repertoire. Taken together, our results indicate a checkpoint role of ALKBH5 and m6A modification in the regulation of γδ T cell early development.

Prevention and treatment of HPV-related cancer through a mRNA vaccine expressing APC-targeting antigen.

Persistent human papillomavirus (HPV) infection is associated with multiple malignancies. Developing therapeutic vaccines to eliminate HPV-infected and malignant cells holds significant value. In this study, we introduced a lipid nanoparticle encapsulated mRNA vaccine expressing tHA-mE7-mE6. Mutations were introduced into E6 and E7 of HPV to eliminate their tumourigenicity. A truncated influenza haemagglutinin protein (tHA), which binds to the CD209 receptor on the surface of dendritic cells (DCs), was fused with mE7-mE6 in order to allow efficient uptake of antigen by antigen presenting cells. The tHA-mE7-mE6 (mRNA) showed higher therapeutic efficacy than mE7-mE6 (mRNA) in an E6 and E7+ tumour model. The treatment resulted in complete tumour regression and prevented tumour formation. Strong CD8+ T-cell immune response was induced, contributing to preventing and curing of E6 and E7+ tumour. Antigen-specific CD8+ T were found in spleens, peripheral blood and in tumours. In addition, the tumour infiltration of DC and NK cells were increased post therapy. In conclusion, this study described a therapeutic mRNA vaccine inducing strong anti-tumour immunity in peripheral and in tumour microenvironment, holding promising potential to treat HPV-induced cancer and to prevent cancer recurrence.

Numerical optimization of auxiliary biaxial receiver to detect blind zone of pulsed coherent wind lidar.

The conventional pulsed monostatic coaxial coherent Doppler wind lidar (CDWL) has a blind detection zone of tens of meters, causing the loss of near-field wind field data. While maintaining the long-range detection capabilities of pulsed lidar, we introduce a novel auxiliary biaxial receiver (ABR) aimed at acquiring dependable coherent signals within blind zones. This is achieved by incorporating a receiver in close proximity to the monostatic coaxial transceiver (MCT), thereby mitigating end-face reflections and laser pulse tailing effects. A specific model of multiple aperture coherent wind detection is established for the ABR system without blind zone problem (BZP). The numerical simulations demonstrate that the biaxial receiver with reasonable design can meet the detection needs of the entire range of the blind zone. By using an ABR with a smaller focal length under appropriate transceiver pointing and general pointing accuracy, the BZP can be solved. The study also exhaustively obtained all parameter combinations that can solve the near-field BZP for a specific system. The results provide a new idea and engineering design guidance for the optical system design of pulsed CDWL without BZP.

Improving Vehicle Heading Angle Accuracy Based on Dual-Antenna GNSS/INS/Barometer Integration Using Adaptive Kalman Filter.

High-accuracy heading angle is significant for estimating autonomous vehicle attitude. By integrating GNSS (Global Navigation Satellite System) dual antennas, INS (Inertial Navigation System), and a barometer, a GNSS/INS/Barometer fusion method is proposed to improve vehicle heading angle accuracy. An adaptive Kalman filter (AKF) is designed to fuse the INS error and the GNSS measurement. A random sample consensus (RANSAC) method is proposed to improve the initial heading angle accuracy applied to the INS update. The GNSS heading angle obtained by a dual-antenna orientation algorithm is additionally augmented to the measurement variable. Furthermore, the kinematic constraint of zero velocity in the lateral and vertical directions of vehicle movement is used to enhance the accuracy of the measurement model. The heading errors in the open and occluded environment are 0.5418° (RMS) and 0.636° (RMS), which represent reductions of 37.62% and 47.37% compared to the extended Kalman filter (EKF) method, respectively. The experimental results demonstrate that the proposed method effectively improves the vehicle heading angle accuracy.

Metabolites and gene expression in the myocardium of fasting rats in an acute hypoxic environment.

With the rising demand for entry to extremely high altitudes (HAs), rapid adaptability to extremely hypoxic environments is a challenge that we need to explore. Fasting was used to evaluate acute hypoxia tolerance at HA and was proven to be an effective method for improving the survival rate at extreme HA. Our experiments also showed that fasting pretreatment for 72 h significantly increased the 24 h survival rate of rats at 7620 m from 10 to 85% and protected the myocardium cells of rats. Here, we compared the metabolites and gene expression in the myocardium of SD rats pretreated with fasting and nonfasting at normal altitude and extreme HA. Our findings demonstrated that the dynamic contents of detected differential metabolites (DMs) between different rat groups were consistent with the expression of differentially expressed genes (DEGs), and DM clusters also showed strong correlations with DEG clusters. DM clusters related to amino acids and lipids were significantly lower in the fasting groups, and the correlated DEG clusters were enriched in mitotic pathways, including CDK1, CDC7, NUF2, and MCM6, suggesting that fasting can attenuate mitotic processes in cardiac tissues and reduce the synthesis of amino acids and lipids. L-Glutamine-related metabolites were particularly low at extreme HA without pretreatment but were normal in the fasting groups. The DEGs in the cluster related to L-glutamine-related metabolites were enriched for T-cell receptor V(D)J recombination, the Hippo signaling pathway, the Wnt signaling pathway, the cGMP-PKG signaling pathway, and the mTOR signaling pathway and were significantly downregulated, indicating that the content of L-glutamine decreased at extreme HA, while fasting increased it to adapt to the environment. Moreover, abundant fatty acids were detected when rats were exposed to extreme HA without pretreatment. Our study revealed the fasting and hypoxic environment-related factors in SD rats and provided new insights into the genetic and molecular characteristics in the myocardium, which is critical to developing more potential rapid adaptation methods to extreme HA.

A Review of Skin-Wearable Sensors for Non-Invasive Health Monitoring Applications.

The early detection of fatal diseases is crucial for medical diagnostics and treatment, both of which benefit the individual and society. Portable devices, such as thermometers and blood pressure monitors, and large instruments, such as computed tomography (CT) and X-ray scanners, have already been implemented to collect health-related information. However, collecting health information using conventional medical equipment at home or in a hospital can be inefficient and can potentially affect the timeliness of treatment. Therefore, on-time vital signal collection via healthcare monitoring has received increasing attention. As the largest organ of the human body, skin delivers significant signals reflecting our health condition; thus, receiving vital signals directly from the skin offers the opportunity for accessible and versatile non-invasive monitoring. In particular, emerging flexible and stretchable electronics demonstrate the capability of skin-like devices for on-time and continuous long-term health monitoring. Compared to traditional electronic devices, this type of device has better mechanical properties, such as skin conformal attachment, and maintains compatible detectability. This review divides the health information that can be obtained from skin using the sensor aspect's input energy forms into five categories: thermoelectrical signals, neural electrical signals, photoelectrical signals, electrochemical signals, and mechanical pressure signals. We then summarize current skin-wearable health monitoring devices and provide outlooks on future development.

Fasting improves tolerance to acute hypoxia in rats.

Acute high-altitude illness seriously threatens the health and lives of people who rapidly ascend to high altitudes, but there is currently no particularly effective method for the prevention or treatment of acute high-altitude illness. In the present study, we found that fasting preconditioning effectively improved the survival rate of rats exposed to a simulated altitude of 7620 m for 24 h, and a novel animal model of rapid adaptation to acute hypoxia was established. Compared with control treatment, fasting preconditioning activated AMPK, induced autophagy, decreased ROS levels, and inhibited NF-κB signaling in the cardiac tissues of rats. Our results suggested that fasting effectively improved the acute hypoxia tolerance of rats, which was gradually enhanced with prolongation of fasting. In addition, the acute hypoxia tolerance of young rats was significantly higher than that of adult rats. These experimental results lay the foundation for achieving rapid adaptation to acute hypoxia in humans.

Unpaired Underwater Image Synthesis with a Disentangled Representation for Underwater Depth Map Prediction.

As one of the key requirements for underwater exploration, underwater depth map estimation is of great importance in underwater vision research. Although significant progress has been achieved in the fields of image-to-image translation and depth map estimation, a gap between normal depth map estimation and underwater depth map estimation still remains. Additionally, it is a great challenge to build a mapping function that converts a single underwater image into an underwater depth map due to the lack of paired data. Moreover, the ever-changing underwater environment further intensifies the difficulty of finding an optimal mapping solution. To eliminate these bottlenecks, we developed a novel image-to-image framework for underwater image synthesis and depth map estimation in underwater conditions. For the problem of the lack of paired data, by translating hazy in-air images (with a depth map) into underwater images, we initially obtained a paired dataset of underwater images and corresponding depth maps. To enrich our synthesized underwater dataset, we further translated hazy in-air images into a series of continuously changing underwater images with a specified style. For the depth map estimation, we included a coarse-to-fine network to provide a precise depth map estimation result. We evaluated the efficiency of our framework for a real underwater RGB-D dataset. The experimental results show that our method can provide a diversity of underwater images and the best depth map estimation precision.

Elevated ROS depress mitochondrial oxygen utilization efficiency in cardiomyocytes during acute hypoxia.

Mitochondria are important sites for the production of ATP and the generation of ROS in cells. However, whether acute hypoxia increases ROS generation in cells or affects ATP production remains unclear, and therefore, monitoring the changes in ATP and ROS in living cells in real time is important. In this study, cardiomyocytes were transfected with RoGFP for ROS detection and MitGO-Ateam2 for ATP detection, whereby ROS and ATP production in cardiomyocytes were respectively monitored in real time. Furthermore, the oxygen consumption rate (OCR) of cardiomyocytes was measured. Similar results were produced for adult and neonatal rat cardiomyocytes. Hypoxia (1% O2) reduced the basal OCR, ATP-linked OCR, and maximal OCR in cardiomyocytes compared with these OCR levels in the cardiomyocytes in the normoxic group (21% O2). However, ATP-linked OCR, normalized to maximal OCR, was increased during hypoxia, indicating that the electron leakage of complex III exacerbated the increase of ATP-linked oxygen consumption during hypoxia and vice versa. Combined with the result that cardiomyocytes expressing MitGO-Ateam2 showed a significant decrease in ATP production during hypoxia compared with that of normoxic group, acute hypoxia might depress the mitochondrial oxygen utilization efficiency of the cardiomyocytes. Moreover, cardiomyocytes expressing Cyto-RoGFP or IMS-RoGFP showed an increase in ROS generation in the cytosol and the mitochondrial intermembrane space (IMS) during hypoxia. All of these results indicate that acute hypoxia generated more ROS in complex III and increased mitochondrial oxygen consumption, leading to less ATP production. In conclusion, acute hypoxia depresses the mitochondrial oxygen utilization efficiency by decreasing ATP production and increasing oxygen consumption as a result of the enhanced ROS generation at mitochondrial complex III.

First Simultaneous Lidar Observations of Thermosphere-Ionosphere Fe and Na (TIFe and TINa) Layers at McMurdo (77.84°S, 166.67°E), Antarctica With Concurrent Measurements of Aurora Activity, Enhanced Ionization Layers, and Converging Electric Field.

We report the first simultaneous, common-volume lidar observations of thermosphere-ionosphere Fe (TIFe) and Na (TINa) layers in Antarctica. We also report the observational discovery of nearly one-to-one correspondence between TIFe and aurora activity, enhanced ionization layers, and converging electric fields. Distinctive TIFe layers have a peak density of ~384 cm-3 and the TIFe mixing ratio peaks around 123 km, ~5 times the mesospheric layer maximum. All evidence shows that Fe+ ion-neutralization is the major formation mechanism of TIFe layers. The TINa mixing ratio often exhibits a broad peak at TIFe altitudes, providing evidence for in situ production via Na+ neutralization. However, the tenuous TINa layers persist long beyond TIFe disappearance and reveal gravity wave perturbations, suggesting a dynamic background of neutral Na, but not Fe, above 110 km. The striking differences between distinct TIFe and diffuse TINa suggest differential transport between Fe and Na, possibly due to mass separation.

TumorGAN: A Multi-Modal Data Augmentation Framework for Brain Tumor Segmentation.

The high human labor demand involved in collecting paired medical imaging data severely impedes the application of deep learning methods to medical image processing tasks such as tumor segmentation. The situation is further worsened when collecting multi-modal image pairs. However, this issue can be resolved through the help of generative adversarial networks, which can be used to generate realistic images. In this work, we propose a novel framework, named TumorGAN, to generate image segmentation pairs based on unpaired adversarial training. To improve the quality of the generated images, we introduce a regional perceptual loss to enhance the performance of the discriminator. We also develop a regional L1 loss to constrain the color of the imaged brain tissue. Finally, we verify the performance of TumorGAN on a public brain tumor data set, BraTS 2017. The experimental results demonstrate that the synthetic data pairs generated by our proposed method can practically improve tumor segmentation performance when applied to segmentation network training.

Comparison of hypoxic effects induced by chemical and physical hypoxia on cardiomyocytes.

The degree and duration of chemical hypoxia induced by sodium dithionite (Na2S2O4) have not been reported. It is not yet clear how much reduction in the O2 concentration (physical hypoxia) can lead to hypoxia in cultured cardiomyocytes. In this study, oxygen microelectrodes were used to measure changes in the O2 concentration in media containing different concentrations of Na2S2O4. Then, hypoxic effects of 0.8, 1.0, and 2.0 mM Na2S2O4 or 1%, 3%, and 5% O2 in cultured cardiomyocytes from neonatal rats were observed and compared. The results showed that the O2 concentration failed to remain constant by Na2S2O4 treatment during the 180-minute observation period. Only the 2.0 mM Na2S2O4 group significantly increased the expression of hypoxia-inducible factor 1α (HIF-1α) and hypoxic responses. Notably, 3% O2 only significantly increased the expression of HIF-1α in cardiomyocytes, while 1% O2 not only increased the expression of HIF-1α but also increased the apoptotic rate in cardiomyocytes. These results suggest that Na2S2O4 is not suitable for establishing a hypoxic model in cultured neonatal rat cardiomyocytes, and neonatal rat cardiomyocytes cultured at or below 1% O2 induced significant hypoxic effects, which can be used as a starting O2 concentration for establishing a hypoxic cell model.

Glycosylated CD147 reduces myocardial collagen cross-linking in cardiac hypertrophy.

The mechanism of transition from chronic pressure overload-induced cardiac hypertrophy to heart failure is still unclear. Angiotensin II (Ang II) may be an important factor that mediates the transition in the end-stage of cardiac hypertrophy. In the present study, Goldblatt two-kidney one-clip (2K1C) rat model was used to simulate Ang II-induced hypertension. The elevated Ang II not only induced the concentric hypertrophy of left ventricle and cardiac fibrosis, but also increased the expression and glycosylation of CD147 in 2K1C rats. The left ventricular structure and function detected by echocardiogram showed a sign of the transition from cardiac hypertrophy to heart failure in 16 weeks of 2K1C rats. Ang II can activate N-acetylglucosamine transferase V (GnT-V), a key enzyme for CD147 glycosylation. Retinoic acid, an agonist of GnT-V, further increased glycosylated CD147, and activated matrix metalloproteinase-2/-9 (MMP-2 and MMP-9) in the hypertrophied left ventricle of 2K1C rat. Meanwhile, collagen cross-linking in the hypertrophied left ventricle significantly reduced in 2K1C rats. On the contrary, tunicamycin, an inhibitor of N-glycan biosynthesis, inhibited glycosylation of CD147 and activity of MMP-2 and MMP-9, and then maintained a stable of collagen cross-linking in the 2K1C rat hearts. The above results suggested that Ang II increased glycosylated CD147 which activated MMP-2 and MMP-9. Collagens were degraded by the activated MMPs and then reduced collagen cross-linking. Finally, the hypertrophied left ventricle was progressively dilated in chronic pressure overload due to losing the limitation of collagen cross-linking. Therefore, the compensated hypertrophy of left ventricle gradually transited to congestive heart failure.

Automatic plankton image classification combining multiple view features via multiple kernel learning.

BACKGROUND: Plankton, including phytoplankton and zooplankton, are the main source of food for organisms in the ocean and form the base of marine food chain. As the fundamental components of marine ecosystems, plankton is very sensitive to environment changes, and the study of plankton abundance and distribution is crucial, in order to understand environment changes and protect marine ecosystems. This study was carried out to develop an extensive applicable plankton classification system with high accuracy for the increasing number of various imaging devices. Literature shows that most plankton image classification systems were limited to only one specific imaging device and a relatively narrow taxonomic scope. The real practical system for automatic plankton classification is even non-existent and this study is partly to fill this gap. RESULTS: Inspired by the analysis of literature and development of technology, we focused on the requirements of practical application and proposed an automatic system for plankton image classification combining multiple view features via multiple kernel learning (MKL). For one thing, in order to describe the biomorphic characteristics of plankton more completely and comprehensively, we combined general features with robust features, especially by adding features like Inner-Distance Shape Context for morphological representation. For another, we divided all the features into different types from multiple views and feed them to multiple classifiers instead of only one by combining different kernel matrices computed from different types of features optimally via multiple kernel learning. Moreover, we also applied feature selection method to choose the optimal feature subsets from redundant features for satisfying different datasets from different imaging devices. We implemented our proposed classification system on three different datasets across more than 20 categories from phytoplankton to zooplankton. The experimental results validated that our system outperforms state-of-the-art plankton image classification systems in terms of accuracy and robustness. CONCLUSIONS: This study demonstrated automatic plankton image classification system combining multiple view features using multiple kernel learning. The results indicated that multiple view features combined by NLMKL using three kernel functions (linear, polynomial and Gaussian kernel functions) can describe and use information of features better so that achieve a higher classification accuracy.

Feeble object detection of underwater images through LSR with delay loop.

Feeble object detection is a long-standing problem in vision based underwater exploration work. However, because of the complicated light propagation situation and high background noise, underwater images are highly degraded. Noise is not always detrimental. Logical stochastic resonance (LSR) can be a useful tool for amplifying feeble signals by utilizing the constructive interplay of noise and a nonlinear system. In the present study, an appropriate LSR structure with a delay loop is proposed to process a low-quality underwater image for enhancing the vision detection accuracy of underwater feeble objects. Ocean experiments are conducted to demonstrate the effectiveness of the proposed structure. We also give explicit numerical results to illustrate the relationship between the structure of LSR and the correct detection probability. Methods presented in this paper are quite general and can thus be potentially extended to other applications for obtaining better performance.

Simulated microgravity increases myocardial susceptibility to ischemia-reperfusion injury via a deficiency of AMP-activated protein kinase.

Gravitation is an important factor in maintaining cardiac contractility. Our study investigated whether simulated microgravity increases myocardial susceptibility to ischemia-reperfusion (IR) injury. Using the Langendorff-perfused heart model with 300 beats/min pacing, 4-week tail suspension (SUS) and control (CON) male Sprague-Dawley rats (n = 10 rats/group) were subjected to 60 min of left anterior descending coronary artery (LAD) occlusion followed by 120 min of reperfusion. Left ventricular end-systolic pressure (LVESP), left ventricular end-diastolic pressure (LVEDP), creatine kinase (CK) and lactate dehydrogenase (LDH) activity, and infarct size were assessed. Data demonstrated that there were significantly increased LVEDP, CK, LDH, and infarct size in SUS compared with CON (P < 0.05), accompanied by decreased LVESP (P < 0.05). Furthermore, TUNEL-positive cardiomyocytes were higher in SUS than that in CON (P < 0.01), and AMP-activated protein kinase (AMPK) phosphorylation and Bcl-2/Bax in SUS were less compared with CON (P < 0.05). Similarly, isolated hearts pre-treated with A-769662 exhibited better recovery of cardiac function, increased AMPK phosphorylation, and reduced necrosis and apoptosis. Furthermore, AMPKα protein showed a significant suppression in 4-week hindlimb unweighting rats. These results suggest that AMPK deficiency increases myocardial susceptibility to IR injury in rats subjected to simulated microgravity.

Highly sensitive electronic whiskers based on patterned carbon nanotube and silver nanoparticle composite films.

Mammalian whiskers present an important class of tactile sensors that complement the functionalities of skin for detecting wind with high sensitivity and navigation around local obstacles. Here, we report electronic whiskers based on highly tunable composite films of carbon nanotubes and silver nanoparticles that are patterned on high-aspect-ratio elastic fibers. The nanotubes form a conductive network matrix with excellent bendability, and nanoparticle loading enhances the conductivity and endows the composite with high strain sensitivity. The resistivity of the composites is highly sensitive to strain with a pressure sensitivity of up to ∼8%/Pa for the whiskers, which is >10× higher than all previously reported capacitive or resistive pressure sensors. It is notable that the resistivity and sensitivity of the composite films can be readily modulated by a few orders of magnitude by changing the composition ratio of the components, thereby allowing for exploration of whisker sensors with excellent performance. Systems consisting of whisker arrays are fabricated, and as a proof of concept, real-time two- and three-dimensional gas-flow mapping is demonstrated. The ultrahigh sensitivity and ease of fabrication of the demonstrated whiskers may enable a wide range of applications in advanced robotics and human-machine interfacing.

Doppler Radar Vital Signs Detection Method Based on Higher Order Cyclostationary.

Due to the non-contact nature, using Doppler radar sensors to detect vital signs such as heart and respiration rates of a human subject is getting more and more attention. However, the related detection-method research meets lots of challenges due to electromagnetic interferences, clutter and random motion interferences. In this paper, a novel third-order cyclic cummulant (TOCC) detection method, which is insensitive to Gaussian interference and non-cyclic signals, is proposed to investigate the heart and respiration rate based on continuous wave Doppler radars. The k-th order cyclostationary properties of the radar signal with hidden periodicities and random motions are analyzed. The third-order cyclostationary detection theory of the heart and respiration rate is studied. Experimental results show that the third-order cyclostationary approach has better estimation accuracy for detecting the vital signs from the received radar signal under low SNR, strong clutter noise and random motion interferences.

NGL-2 Is a New Partner of PAR Complex in Axon Differentiation.

Neuronal polarization is pivotal for neural network formation during brain development. Axon differentiation is a hallmark of initial neuronal polarization. Here, we report that the leucine-rich repeat-containing protein netrin-G ligand-2 (NGL-2) as a polarity regulator that localizes asymmetrically in rat hippocampal neurons and is required for differentiation of the future axon. NGL-2 was associated with PAR complex, and this interaction resulted in local stabilization of axonal microtubules. Further study showed that the C terminal of NGL-2 binds to the PDZ domain of PAR6, and NGL-2 interacts with PAR3 and atypical PKCζ (aPKCζ), with PAR6 acting as a bridge or modifier. Then, NGL-2 regulates the local stabilization of microtubules and promotes axon differentiation by the aPKCζ/microtubule affinity-regulating kinase 2 pathway. These findings reveal the critical role of NGL-2 in regulating axon differentiation in rat hippocampal neurons and reveal a novel partner of the PAR complex.

Object extraction from underwater images through logical stochastic resonance.

Logical stochastic resonance (LSR), the phenomenon in which the interplay of noise and nonlinearity can raise the accurate probability of response to feeble input signals, is studied in this Lettter to extract objects from highly degraded underwater images. Images captured under water, especially in the turbid areas, always suffer from interference through heavy noise caused by the suspended particles. Inherent noise and nonlinearity cause difficulty in processing these images through conventional image processing methods. However, LSR can optimally address such issues. A heavily degraded image is first extended to a 1D form in the direction determined by the illumination condition, and then normalized to be placed in the LSR system as an input signal. Additional Gaussian noise is added to the system as the auxiliary power to help separate the object and the background. Results in the natural offshore area demonstrate the effect of LSR on image processing, and the proposed method creates an interesting direction in the processing of heavily degraded images.