Porcine Enteric Alphacoronavirus Entry through Multiple Pathways (Caveolae, Clathrin, and Macropinocytosis) Requires Rab GTPases for Endosomal Transport.

Porcine enteric alphacoronavirus (PEAV) is a new bat HKU2-like porcine coronavirus, and its endemic outbreak has caused severe economic losses to the pig industry. Its broad cellular tropism suggests a potential risk of cross-species transmission. A limited understanding of PEAV entry mechanisms may hinder a rapid response to potential outbreaks. This study analyzed PEAV entry events using chemical inhibitors, RNA interference, and dominant-negative mutants. PEAV entry into Vero cells depended on three endocytic pathways: caveolae, clathrin, and macropinocytosis. Endocytosis requires dynamin, cholesterol, and a low pH. Rab5, Rab7, and Rab9 GTPases (but not Rab11) regulate PEAV endocytosis. PEAV particles colocalize with EEA1, Rab5, Rab7, Rab9, and Lamp-1, suggesting that PEAV translocates into early endosomes after internalization, and Rab5, Rab7, and Rab9 regulate trafficking to lysosomes before viral genome release. PEAV enters porcine intestinal cells (IPI-2I) through the same endocytic pathway, suggesting that PEAV may enter various cells through multiple endocytic pathways. This study provides new insights into the PEAV life cycle. IMPORTANCE Emerging and reemerging coronaviruses cause severe human and animal epidemics worldwide. PEAV is the first bat-like coronavirus to cause infection in domestic animals. However, the PEAV entry mechanism into host cells remains unknown. This study demonstrates that PEAV enters into Vero or IPI-2I cells through caveola/clathrin-mediated endocytosis and macropinocytosis, which does not require a specific receptor. Subsequently, Rab5, Rab7, and Rab9 regulate PEAV trafficking from early endosomes to lysosomes, which is pH dependent. The results advance our understanding of the disease and help to develop potential new drug targets against PEAV.

Identification and experimental validation of KMO as a critical immune-associated mitochondrial gene in unstable atherosclerotic plaque.

BACKGROUND: The heightened risk of cardiovascular and cerebrovascular events is associated with the increased instability of atherosclerotic plaques. However, the lack of effective diagnostic biomarkers has impeded the assessment of plaque instability currently. This study was aimed to investigate and identify hub genes associated with unstable plaques through the integration of various bioinformatics tools, providing novel insights into the detection and treatment of this condition. METHODS: Weighted Gene Co-expression Network Analysis (WGCNA) combined with two machine learning methods were used to identify hub genes strongly associated with plaque instability. The cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) method was utilized to assess immune cell infiltration patterns in atherosclerosis patients. Additionally, Gene Set Variation Analysis (GSVA) was conducted to investigate the potential biological functions, pathways, and mechanisms of hub genes associated with unstable plaques. To further validate the diagnostic efficiency and expression of the hub genes, immunohistochemistry (IHC), quantitative real-time polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA) were performed on collected human carotid plaque and blood samples. Immunofluorescence co-staining was also utilized to confirm the association between hub genes and immune cells, as well as their colocalization with mitochondria. RESULTS: The CIBERSORT analysis demonstrated a significant decrease in the infiltration of CD8 T cells and an obvious increase in the infiltration of M0 macrophages in patients with atherosclerosis. Subsequently, two highly relevant modules (blue and green) strongly associated with atherosclerotic plaque instability were identified. Through intersection with mitochondria-related genes, 50 crucial genes were identified. Further analysis employing least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine recursive feature elimination (SVM-RFE) algorithms revealed six hub genes significantly associated with plaque instability. Among them, NT5DC3, ACADL, SLC25A4, ALDH1B1, and MAOB exhibited positive correlations with CD8 T cells and negative correlations with M0 macrophages, while kynurenine 3-monooxygenas (KMO) demonstrated a positive correlation with M0 macrophages and a negative correlation with CD8 T cells. IHC and RT-qPCR analyses of human carotid plaque samples, as well as ELISA analyses of blood samples, revealed significant upregulation of KMO and MAOB expression, along with decreased ALDH1B1 expression, in both stable and unstable samples compared to the control samples. However, among the three key genes mentioned above, only KMO showed a significant increase in expression in unstable plaque samples compared to stable plaque samples. Furthermore, the expression patterns of KMO in human carotid unstable plaque tissues and cultured mouse macrophage cell lines were assessed using immunofluorescence co-staining techniques. Finally, lentivirus-mediated KMO silencing was successfully transduced into the aortas of high-fat-fed ApoE-/- mice, with results indicating that KMO silencing attenuated plaque formation and promoted plaque stability in ApoE-/- mice. CONCLUSIONS: The results suggest that KMO, a mitochondria-targeted gene associated with macrophage cells, holds promise as a valuable diagnostic biomarker for assessing the instability of atherosclerotic plaques.

Simultaneous improvement of the sensitivity and resolution of CPT magnetometers based on phase delay and differential method.

We report a method to enhance the sensitivity of coherent population trapping (CPT) magnetometers using a combination of left-handed and right-handed circularly polarized light phase-delay detection and a differential detection scheme. The approach can achieve a four third-fold enhancement of the CPT dispersion signal slope and a three-fold reduction in noises. The proposed method experimentally exhibits a four third-fold magnetic field resolution enhancement in CPT open-loop measurements, and the differential method could achieve a sensitivity of 1 p T/H z at 10 Hz and a sensitivity of 0.4 p T/H z at 50-100 Hz in the CPT closed-loop measurement, which is a four-fold sensitivity enhancement compared to the single-transmitted CPT magnetometer.

Timing Correlated-Electron Emission from Strong Field Atomic Double Ionization with Polarization-Gated Attoclock.

Attoclock provides a powerful tool for probing the ultrafast electron dynamics in strong laser fields. However, this technique has remained restricted to single electron or sequential double ionized electron dynamics. Here, we propose a novel attoclock scheme with a polarization-gated few-cycle laser pulse and demonstrate its application in timing the correlated-electron emission in strong field double ionization of argon. Our experimental measurements reveal that the correlated-electron emission occurs mainly through two channels with time differences of 234±22 as and 1043±73 as, respectively. Classical model calculations well reproduce the experimental results and deepen our understanding of ultrafast electron correlation dynamics.

Causal role of myeloid cells in Parkinson's disease: Mendelian randomization study.

BACKGROUND: Previous studies have observed elevated myeloid cells in the peripheral blood of patients with Parkinson's disease (PD), but the causal relationship between them remains to be elucidated. We investigated whether there is a causal relationship between different subtypes of peripheral blood myeloid cells and PD using Mendelian randomization (MR) combined with bioinformatics analysis. Exploring the etiology of PD from the perspective of genetics can remove confounding factors and provide a more reliable theoretical basis for elucidating the pathogenesis of PD. METHODS: Comprehensive two-sample MR analysis and sensitivity analyses were conducted to explore the causal associations between 64 myeloid cell signatures and PD risk. The Venn diagram and protein-protein interaction network analysis of instrumental variables (IV) corresponding genes were used to further investigate the potential mechanism of myeloid cells influencing the pathogenesis of PD. RESULTS: We investigated the impact of four immunophenotypes on the risk of PD, including Im MDSC% CD33dim HLA DR- CD66b- (relative count), CD33dim HLA DR+ CD11b+% CD33dim HLA DR+ (relative count), and CD11b on Mo MDSC (MFI) and CD11b on CD33br HLA DR+ CD14dim (MFI), while an immunophenotype's protective effect on PD was observed CD45 on Im MDSC (MFI). The results of bioinformatics analysis showed that CD33, NTRK2, PLD2, GRIK2 and RELN had protein interactions with the risk genes of PD. CONCLUSIONS: Our study has demonstrated a close genetic correlation between different subtypes of myeloid cells and PD, providing guidance for early identification and immunotherapeutic development in patients with PD.

Learning Temporal-Spatial Contextual Adaptation for Three-Dimensional Human Pose Estimation.

Three-dimensional human pose estimation focuses on generating 3D pose sequences from 2D videos. It has enormous potential in the fields of human-robot interaction, remote sensing, virtual reality, and computer vision. Existing excellent methods primarily focus on exploring spatial or temporal encoding to achieve 3D pose inference. However, various architectures exploit the independent effects of spatial and temporal cues on 3D pose estimation, while neglecting the spatial-temporal synergistic influence. To address this issue, this paper proposes a novel 3D pose estimation method with a dual-adaptive spatial-temporal former (DASTFormer) and additional supervised training. The DASTFormer contains attention-adaptive (AtA) and pure-adaptive (PuA) modes, which will enhance pose inference from 2D to 3D by adaptively learning spatial-temporal effects, considering both their cooperative and independent influences. In addition, an additional supervised training with batch variance loss is proposed in this work. Different from common training strategy, a two-round parameter update is conducted on the same batch data. Not only can it better explore the potential relationship between spatial-temporal encoding and 3D poses, but it can also alleviate the batch size limitations imposed by graphics cards on transformer-based frameworks. Extensive experimental results show that the proposed method significantly outperforms most state-of-the-art approaches on Human3.6 and HumanEVA datasets.

Mechanisms of the Masquelet technique to promote bone defect repair and its influencing factors.

The Masquelet technique, also known as the induced membrane technique, is a surgical technique for repairing large bone defects based on the use of a membrane generated by a foreign body reaction for bone grafting. This technique is not only simple to perform, with few complications and quick recovery, but also has excellent clinical results. To better understand the mechanisms by which this technique promotes bone defect repair and the factors that require special attention in practice, we examined and summarized the relevant research advances in this technique by searching, reading, and analysing the literature. Literature show that the Masquelet technique may promote the repair of bone defects through the physical septum and molecular barrier, vascular network, enrichment of mesenchymal stem cells, and high expression of bone-related growth factors, and the repair process is affected by the properties of spacers, the timing of bone graft, mechanical environment, intramembrane filling materials, artificial membrane, and pharmaceutical/biological agents/physical stimulation.

Upregulation of Formaldehyde in Parkinson's Disease Found by a Near-Infrared Lysosome-Targeted Fluorescent Probe.

Parkinson's disease (PD) is one of the major neurodegenerative diseases caused by complex pathological processes. As a signal molecule, formaldehyde is closely linked to nervous systems, but the relationship between PD and formaldehyde levels remains largely unclear. We speculated that formaldehyde might be a potential biomarker for PD. To prove it, we constructed the first near-infrared (NIR) lysosome-targeted formaldehyde fluorescent probe (named NIR-Lyso-FA) to explore the relationship between formaldehyde and PD. The novel fluorescent probe achieves formaldehyde detection in vitro and in vivo, thanks to its excellent properties such as NIR emission, large Stokes shift, and fast response to formaldehyde. Crucially, utilizing the novel probe NIR-Lyso-FA, formaldehyde overexpression was discovered for the first time in cellular, zebrafish, and mouse PD models, supporting our guess that formaldehyde can function as a possible biomarker for PD. We anticipate that this finding will offer insightful information for PD pathophysiology, diagnosis, medication development, and treatment.

Niobium Oxide Anode with Lattice Structure Self-Optimization for High-Power and Nearly Zero-Degeneration Battery Operation.

Li+ insertion-induced structure transformation in crystalline electrodes vitally influence the energy density and cycle life of secondary lithium-ion battery. However, the influence mechanism of structure transformation-induced Li+ migration on the electrochemical performance of micro-crystal materials is still unclear and the strategy to profit from such structure transformation remains exploited. Here, an interesting self-optimization of structure evolution during electrochemical cycling in Nb2 O5 micro-crystal with rich domain boundaries is demonstrated, which greatly improves the charge transfer property and mechanical strength. The lattice rearrangement activates the Li+ diffusion kinetics and hinders the particle crack, thus enabling a nearly zero-degeneration operation after 8000 cycles. Full cell paired with lithium cobalt oxides displays an exceptionally high capacity of 176 mA h g-1 at 8000 mA g-1 and excellent long-term durability at 6000 mA g-1 with 63% capacity retention over 2000 cycles. Interestingly, a unique fingerprint based on the intensity ratio of two X-ray diffraction peaks is successfully extracted as a measure of Nb2 O5 electrochemical performance. The structure self-optimization for fast charge transfer and high mechanical strength exemplifies a new battery electrode design concept and opens up a vast space of strategy to develop high-performance lithium-ion batteries with high energy density and ultra-long cycle life.

Controllable Fabrication of Highly Uniform Sub-10 nm Nanoparticles from Spontaneous Confined Nanoemulsification.

Sub-10 nm nanoparticles are known to exhibit extraordinary size-dependent properties for wide applications. Many approaches have been developed for synthesizing sub-10 nm inorganic nanoparticles, but the fabrication of sub-10 nm polymeric nanoparticles is still challenging. Here, a scalable, spontaneous confined nanoemulsification strategy that produces uniform sub-10 nm nanodroplets for template synthesis of sub-10 nm polymeric nanoparticles is proposed. This strategy introduces a high-concentration interfacial reaction to create overpopulated surfactants that are insoluble at the droplet surface. These overpopulated surfactants act as barriers, resulting in highly accumulated surfactants inside the droplet via a confined reaction. These surfactants exhibit significantly changed packing geometry, solubility, and interfacial activity to enhance the molecular-level impact on interfacial instability for creating sub-10 nm nanoemulsions via self-burst nanoemulsification. Using the nanodroplets as templates, the fabrication of uniform sub-10 nm polymeric nanoparticles, as small as 3.5 nm, made from biocompatible polymers and capable of efficient drug encapsulation is demonstrated. This work opens up brand-new opportunities to easily create sub-10 nm nanoemulsions and advanced ultrasmall functional nanoparticles.

Construction and signal analysis of a reflective single-beam spin-exchange relaxation-free comagnetometer for rotation measurement.

The single-beam comagnetometer working in the spin-exchange relaxation-free (SERF) state is being developed into a miniaturized atomic sensor with extremely high precision in rotation measurement. In this paper, we propose a reflective configuration for the single-beam SERF comagnetometer. The laser light simultaneously used for optical pumping and signal extraction is designed to pass through the atomic ensemble twice. In the optical system, we propose a structure composed of a polarizing beam splitter and a quarter-wave plate. With this, the reflected light beam can be separated entirely from the forward propagating one and realize a complete light collection with a photodiode, making the least light power loss. In our reflective scheme, the length of interaction between light and atoms is extended, and because the power of the DC light component is attenuated, the photodiode can work in a more sensitive range and has a better photoelectric conversion coefficient. Compared with the single-pass scheme, our reflective configuration has a stronger output signal and performs better signal-to-noise ratio and rotation sensitivity. Our work has an important impact on developing miniaturized atomic sensors for rotation measurement in the future.

Atomic spin precession detection method based on the Mach-Zehnder interferometer in an atomic comagnetometer.

A new method for the detection of atomic spin precession based on the Mach-Zehnder interferometer (MZI) is proposed and experimentally demonstrated. Different from the conventional polarization detection methods which obtain the atomic spin precession signal by measuring the change of the probe laser power, the proposed method uses the laser modulated by an electro-optic phase modulator (EOM) as the source of the interferometer, and obtains the atomic spin precession signal by measuring the phase difference between the two arms of the MZI. The output of interferometer is independent of the probe laser power, which avoids the system error caused by the fluctuation of the probe laser power, and the long-term stability of the system is effectively improved. At the same time, the method adopts high-frequency electro-optic modulation, which can effectively suppress low-frequency noise, such as 1/f noise, and can significantly improve the detection sensitivity. The rotation sensitivity and long-term stability of the atomic comagnetometer were tested using the MZI detection method and a typical detection method, respectively. The comparison results show that the proposed method has the highest low frequency sensitivity and the potential to improve the long-term stability of the system.

Optimizing noble gas pressure for enhanced self-compensation in spin-exchange relaxation-free comagnetometers.

The coupling of electron spin and nuclear spin through spin-exchange collisions compensates for external magnetic field interference in the spin-exchange relaxation-free (SERF) comagnetometer. However, the compensation ability for magnetic field interference along the detection axis is limited due to the presence of nuclear spin relaxation. This paper aims to enhance the self-compensation capability of the system by optimizing the pressure of the noble gas during cell filling. Models are established to describe the relationships between the nuclear spin polarization, the polarizing magnetic field of nuclei, the magnetic field suppression factors, and the pressure of the noble gas in the K-Rb-21Ne atomic ensemble. Experiments are conducted using five cells with different pressure. The results indicate that in the positive pressure area, the nuclear spin polarization decreases while the equivalent magnetic field experienced by the noble gas increases with increasing pressure. The magnetic field suppression factor for transverse fields increases as the pressure increases, leading to a decrease in the ability to suppress low-frequency magnetic field interference. Moreover, at the cell temperature of 180°C and a transverse residual field gradient of 4.012 nT/cm, the system exhibits its strongest capability to suppress transverse magnetic field interference when the pressure of 21Ne is around 0.7 atm.

Effects of pump laser intensity on the cell temperature working point in a K-Rb-21Ne spin-exchange relaxation-free co-magnetometer.

The cell temperature working point optimization of the spin-exchange relaxation-free (SERF) co-magnetometer is studied theoretically and experimentally in this article. Based on the steady-state solution of the Bloch equations, the steady-state response model of the K-Rb-21Ne SERF co-magnetometer output signal with cell temperature is established in this paper. And combined with the model, a method to find the optimal working point of the cell temperature that incorporates the pump laser intensity is proposed. The scale factor of the co-magnetometer under different pump laser intensities and cell temperatures is obtained experimentally, and the long-term stability of the co-magnetometer at the different cell temperatures with corresponding pump laser intensities is measured. The results show that the bias instability of the co-magnetometer is reduced from 0.0311 deg/h to 0.0169 deg/h by obtaining the optimal working point of the cell temperature, which verifies the validity and accuracy of the theoretical derivation and the proposed method.

Comprehensive analysis of the effects of magnetic field gradient on the performance of the SERF co-magnetometer.

The magnetic field gradient affects the improvement of sensitivity and magnetic field suppression ability of the spin-exchange relaxation-free co-magnetometer. This paper proposes a response model of a co-magnetometer considering magnetic field gradient based on state-space method. The effects of transverse and longitudinal magnetic field gradients on the system's scale factor, bandwidth and magnetic field response are analyzed. The analysis shows that transverse gradient affects the whole frequency band of system response, including steady-state and dynamic performance, while longitudinal gradient only affects steady-state response. With the increase of the gradient, the effect becomes more significant. The test results are in agreement with the theory, proving the accuracy of the theoretical analysis. The rotational sensitivity at 1 Hz decreases from 6.51 ×10-6 °/s/Hz1/2 to 5.05×10-5 °/s/Hz1/2 in the presence of a magnetic field gradient of -40 nT/cm, so the effect of the magnetic field gradient is critical. This work provides an accurate model for evaluating the effects of magnetic field gradients and provides a method for suppressing gradients using gradient coils, which are important for improving the sensitivity and accuracy of co-magnetometers.

Fiber-coupled silicon carbide divacancy magnetometer and thermometer.

Divacancy in silicon carbide has become an important solid-state system for quantum metrologies. To make it more beneficial for practical applications, we realize a fiber-coupled divacancy-based magnetometer and thermometer simultaneously. First, we realize an efficient coupling between the divacancy in a silicon carbide slice with a multimode fiber. Then the optimization of the power broadening in optically detected magnetic resonance (ODMR) of divacancy is performed to obtain a higher sensing sensitivity of 3.9 µT/Hz1/2. We then use it to detect the strength of an external magnetic field. Finally, we use the Ramsey methods to realize a temperature sensing with a sensitivity of 163.2 mK/Hz1/2. The experiments demonstrate that the compact fiber-coupled divacancy quantum sensor can be used for multiple practical quantum sensing.

Single-beam NMOR atomic magnetometer based on a fiberized EOM.

The high-precision and portable nonlinear magneto-optical rotation (NMOR) atomic magnetometer has significant potential in the direction of magnetic field measurement under a geomagnetic environment. Here, we propose a single-beam NMOR atomic magnetometer with amplitude modulation based on a fiberized electro-optic modulator (EOM) for the first time, to the best of our knowledge, which provides a feasible scheme for the integrated design. A theoretical model of the system response signal as a function of the modulation amplitude is established by a Jones matrix. Based on the theoretical model, the influence mechanism of the modulation amplitude on the system response signal is further analyzed and the optimal modulation parameters can be determined. Finally, a sensitivity of 42.67 fT/Hz1/2 at 50-µT magnetic field is achieved. The proposed scheme is also applicable to other magnetometers under a geomagnetic environment.

Fiber-integrated silicon carbide silicon-vacancy-based magnetometer.

Silicon vacancies in silicon carbide have drawn much attention for various types of quantum sensing. However, most previous experiments are realized using confocal scanning systems, which limits their practical applications. In this work, we demonstrate a compact fiber-integrated silicon carbide silicon-vacancy-based magnetometer at room temperature. First, we effectively couple the silicon vacancy in a tiny silicon carbide slice with an optical fiber tip and realize the readout of the spin signal through the fiber at the same time. We then study the optically detected magnetic resonance spectra at different laser and microwave powers, obtaining an optimized magnetic field sensitivity of 12.3 µT/Hz 12. Based on this, the magnetometer is used to measure the strength and polar angle of an external magnetic field. Through these experiments, we have paved the way for fiber-integrated silicon-vacancy-based magnetometer applications in practical environments, such as geophysics and biomedical sensing.

Identification of QTL for reducing loss of grain yield under salt stress conditions in bi-parental populations derived from wheat landrace Hongmangmai.

KEY MESSAGE: A novel QTL (QSt.nftec-2BL) was mapped to a 0.7 cM interval on chromosome 2B. Plants carrying QSt.nftec-2BL produced higher grain yields by up to 21.4% than otherwise in salinized fields. Wheat yield has been limited by soil salinity in many wheat-growing areas globally. The wheat landrace Hongmangmai (HMM) possesses salt tolerance as it produced higher grain yields than other tested wheat varieties including Early Premium (EP) under salt stresses. To detect QTL underlying this tolerance, wheat cross EP × HMM was chosen to serve as mapping population that was homozygous at Ppd (photoperiod response gene), Rht (reduced plant height gene) and Vrn (vernalization gene); thus, interference with QTL detection by these loci could be minimized. QTL mapping was conducted firstly using 102 recombinant inbred lines (RILs) that were selected from the EP × HMM population (827 RILs) for similarity in grain yield under non-saline condition. Under salt stresses, however, the 102 RILs varied significantly in grain yield. These RILs were genotyped using a 90 K SNP (single nucleotide polymorphism) array; consequently, a QTL (QSt.nftec-2BL) was detected on chromosome 2B. Then, using 827 RILs and new simple sequence repeat (SSR) markers developed according to the reference sequence IWGSC RefSeq v1.0, location of QSt.nftec-2BL was refined to a 0.7 cM (6.9 Mb) interval flanked by SSR markers 2B-557.23 and 2B-564.09. Selection for QSt.nftec-2BL was performed based on the flanking markers using two bi-parental wheat populations. Trials for validating effectiveness of the selection were conducted in salinized fields in two geographical areas and two crop seasons, demonstrating that wheat plants with the salt-tolerant allele in homozygous status at QSt.nftec-2BL produced higher grain yields by up to 21.4% than otherwise.

Omnifarious fruit polyphenols: an omnipotent strategy to prevent and intervene diabetes and related complication?

Diabetes mellitus is a metabolic syndrome which cannot be cured. Recently, considerable interest has been focused on food ingredients to prevent and intervene in complications of diabetes. Polyphenolic compounds are one of the bioactive phytochemical constituents with various biological activities, which have drawn increasing interest in human health. Fruits are part of the polyphenol sources in daily food consumption. Fruit-derived polyphenols possess the anti-diabetic activity that has already been proved either from in vitro studies or in vivo studies. The mechanisms of fruit polyphenols in treating diabetes and related complications are under discussion. This is a comprehensive review on polyphenols from the edible parts of fruits, including those from citrus, berries, apples, cherries, mangoes, mangosteens, pomegranates, and other fruits regarding their potential benefits in preventing and treating diabetes mellitus. The signal pathways of characteristic polyphenols derived from fruits in reducing high blood glucose and intervening hyperglycemia-induced diabetic complications were summarized.