Search

Abstract Fear memory is essential for survival and adaptation, yet excessive fear memories can lead to emotional disabilities and mental disorders. Despite previous researches have indicated that histamine H1 receptor (H1R) exerts critical and intricate effects on fear memory, the role of H1R is still not clarified. Here, we show that deletion of H1R gene in medial septum (MS) but not other cholinergic neurons selectively enhances contextual fear memory without affecting cued memory by differentially activating the dentate gyrus (DG) neurons in mice. H1R in cholinergic neurons mediates the contextual fear retrieval rather than consolidation by decreasing acetylcholine release pattern in DG. Furthermore, selective knockdown of H1R in the MS is sufficient to enhance contextual fear memory by manipulating the retrieval-induced neurons in DG. Our results suggest that H1R in MS cholinergic neurons is critical for contextual fear retrieval, and could be a potential therapeutic target for individuals with fear-related disorders.

Rheumatoid arthritis is a widely prevalent autoimmune bone disease that imposes a significant burden on global healthcare systems due to its increasing incidence. In recent years, attention has focused on the interaction between gut homeostasis and the immune system, particularly in relation to bone health. Dysbiosis, which refers to an imbalance in the composition and function of the gut microbiota, has been shown to drive immune dysregulation through mechanisms such as the release of pro-inflammatory metabolites, increased gut permeability, and impaired regulatory T cell function. These factors collectively contribute to immune system imbalance, promoting the onset and progression of Rheumatoid arthritis. Dysbiosis induces both local and systemic inflammatory responses, activating key pro-inflammatory cytokines such as tumor necrosis factor-alpha, Interleukin-6, and Interleukin-17, which exacerbate joint inflammation and damage. Investigating the complex interactions between gut homeostasis and immune regulation in the context of Rheumatoid arthritis pathogenesis holds promise for identifying new therapeutic targets, revealing novel mechanisms of disease progression, and offering innovative strategies for clinical treatment.

Abstract Studying brain‐wide hemodynamic responses to different stimuli at high spatiotemporal resolutions can help gain new insights into the mechanisms of neuro‐ diseases and ‐disorders. Nonetheless, this task is challenging, primarily due to the complexity of neurovascular coupling, which encompasses interdependent hemodynamic parameters including cerebral blood volume (CBV), cerebral blood flow (CBF), and cerebral oxygen saturation (SO2). The current brain imaging technologies exhibit inherent limitations in resolution, sensitivity, and imaging depth, restricting their capacity to comprehensively capture the intricacies of cerebral functions. To address this, a multimodal functional ultrasound and photoacoustic (fUSPA) imaging platform is reported, which integrates ultrafast ultrasound and multispectral photoacoustic imaging methods in a compact head‐mountable device, to quantitatively map individual dynamics of CBV, CBF, and SO2 as well as contrast agent enhanced brain imaging at high spatiotemporal resolutions. Following systematic characterization, the fUSPA system is applied to study brain‐wide cerebrovascular reactivity (CVR) at single‐vessel resolution via relative changes in CBV, CBF, and SO2 in response to hypercapnia stimulation. These results show that cortical veins and arteries exhibit differences in CVR in the stimulated state and consistent anti‐correlation in CBV oscillations during the resting state, demonstrating the multiparametric fUSPA system's unique capabilities in investigating complex mechanisms of brain functions.

Objective This study aimed to investigate the influence of peripapillary atrophy (PPA) area and axial elongation on the longitudinal changes in macular choroidal thickness (ChT) in young individuals with myopia.Methods and analysis In this longitudinal investigation, 431 eyes—342 categorised as non-high myopia (non-HM) and 89 as HM—were examined for 2 years. Participants were examined with swept-source optical coherence tomography. The macular ChT, PPA area and axial length (AL) were measured at baseline and follow-up visits. Multiple regression analysis was performed to identify factors associated with ChT changes. The areas under the receiver operating characteristic curves were analysed to ascertain the predictive capacity of the PPA area and axial elongation for the reduction in macular ChT.Results Initial measurements revealed that the average macular ChT was 240.35±56.15 µm in the non-HM group and 198.43±50.27 µm in the HM group (p

As the Internet of Things (IoT) becomes increasingly prevalent, there is a surge in wireless-connected devices. In this context, one technique that has garnered significant attention is visible light communication (VLC) due to its ultra-wide and license-free frequency resource. However, a critical issue in utilizing VLC in IoT lies in its lack of smooth cooperation with ubiquitous radio frequency (RF)-based wireless networks. RF signals can use duplex techniques to transmit and receive bidirectional signals with one antenna. In contrast, VLC's light-emitting diodes (LEDs) and PIN diodes cannot operate in duplex mode, posing challenges in establishing two unidirectional VLC links. To address the mismatch between VLC and RF, we propose a light-based RF transceiver design called LiRF, capable of smooth transmission of RF signals through VLC for IoT devices. To verify its feasibility, we first build a prototype using 802.11ax (WiFi-6) network interface cards (NICs) in the 5 GHz channel. Experimental results show that LiRF is compatible with the 802.11bb standard, supporting TCP/IP data streams at 750 Mbps with a 200 MHz Superluminescent Diode-PIN (SLD-PIN) transceiver and at 600 Mbps with a 180 MHz LED-PIN transceiver. To the best of our knowledge, this is the first real-time bidirectional VLC system utilizing WiFi NICs capable of achieving near-Gbps data rates for a single spatial stream without altering the RF designs. LiRF paves the way for seamlessly integrating VLC into upcoming IoT networks, supporting high-speed, low-latency applications like Virtual Reality and Augmented Reality.

Visible light communications (VLC) utilizing LEDs for transmissions have been widely considered a revolutionary solution for next-generation networks such as 6G. Frequency response (FR) is of great importance for LEDs, but the inherent internal quantum efficiency (IQE) of LEDs is often disregarded, resulting in imprecise FR models. Although it is widely known that IQE varies with the injected direct current (DC), the impact of IQE on the frequency response has not been thoroughly analyzed. To address this issue, we have developed a precise electro-optical (E-O) FR model by incorporating the ABC model of IQE, named IQE-FR. To validate the accuracy of IQE-FR, we conducted the experiments using commercial off-the-shelf (COTS) LEDs including a tri-color LED and three monochromatic LEDs. The IQE-FR model aligns well with the experimental findings in terms of the maximum FR value, while state-of-the-art FR models that ignore the IQE effects do not yield consistent results. Specifically, we discovered that the red LEDs exhibit a stable DC gain when the biasing current rises to 300 mA, but the highest DC gain for green and blue LEDs can only be achieved under 100 mA. For green and blue LEDs, the biasing currents are much lower than their typical working currents (350 mA and 500 mA). To address the trade-off between luminance and DC gain, we propose cascading multiple LEDs operating at a low current corresponding to the maximum response. Experimental results demonstrate that four cascaded monochromatic LEDs exhibit similar bandwidth and response gain larger than 11 dB compared to a single LED at the same biasing current while delivering four times the emission power, which is very close to the theoretical value of 12 dB. Furthermore, we find that the DC gain improvement by cascading multiple LEDs is nonlinear and bounded by an upper limit as the number of LEDs increases, and as a cost-effective solution, a few tens of LEDs is recommended. To the best of our knowledge, this is the first attempt to apply the IQE model to study the LEDs’ precise FR performances for VLC. We believe that the precise IQE-FR model opens new avenues for optimizing VLC system performance by considering the effects of IQE.

Visible light communications (VLC) has experienced rapid development in recent years as a strong competitor for next-generation wireless applications due to its wider bandwidth, higher security, and better electromagnetic immunity compared with conventional radio frequency (RF) microwaves. Although state-of- the-art VLC systems can achieve Gbps data rates by employing equalization schemes, designing a general low-complexity VLC transmitter with hundreds of MHz 3-dB bandwidth is still challenging due to the narrow modulation bandwidth nature of light emitting diodes (LEDs). In this paper, we first present a second-order equivalent circuit model for the LED, based on which we propose a general second-order equalizer (GSE) with low complexities, consisting of less than 5 passive capacitors, inductors, and resistors. We show that the GSE can enlarge the LED transmitter's bandwidth to a few hundred MHz. To validate our GSE, we build a broadband VLC transmitter using commercial-off-the-shelf (COTS) red, green and blue (RGB) LEDs, whose bandwidth is 14 MHz, by summing up three colours. Experimental results show that our proposed GSE can extend the transmitter's 3-dB bandwidth from 14 MHz to 1.5 GHz. Furthermore, we demonstrate that a VLC system utilizing the proposed GSE transmitter can achieve 1.15 Gbps data rates at a distance of 250 cm with a bit error ratios (BERs) below the forward error correction (FEC) limit $3.8 \times 10^{-3}$.

Vehicle detection (VD) on remote sensing (RS) images has gained impressive achievements these years, mainly thanks to the development of popular learning-based object detection architectures [e.g., faster R-convolutional neural network (CNN), YOLO series, etc.]. However, for RS images, mutiscale VD with tiny size still remains challenging. Particularly, vehicles as tiny objects typically contain only a few pixels with very rare information for model training and validation, which can result in inaccurate localization and intricate classification. In this article, we present a new detection model called faster transformer-DS, in which two improvements are proposed and discussed as follows. 1) Instead of CNN-based ResNet50, a transformer-based backbone—pyramid vision transformer v2-b0 that can extract global context information, is investigated as feature extraction backbone for both object classification and bounding box regression. (2) In contrast to the conventional paradigm based and intersection over union based loss functions, to further fine-tune the localization of predicted bounding box, we proposed a novel distance-scale loss function—the distance loss is directly related to the absolute value of the length and width of the bounding box together with its center position, while the scale loss refers to the geometric shape ratio between the bounding box and the ground truth box. To demonstrate the efficacy of our model, comprehensive experiments are conducted to show that both the proposed methods can boost the performance of multiscale VD on RS images and the best result, all of which are confirmed by experimental data indicators and visual detection results. Additionally, several state-of-the-art methods are compared and consequently, our model is notably superior to many common detection models.

Abstract Despite recent advances in the development of computational methods of modeling thrombosis, relatively little effort has been made in developing methods of modeling blood clot embolization. Such a model would provide substantially greater understanding of the mechanics of embolization, as in-vitro and in-vivo characterization of embolization is difficult. Here, a method of computationally simulating embolization is developed. Experiments are performed of blood clots formed in a polycarbonate tube, where phosphate-buffered saline is run through the tube at increasing flow rates until the clot embolizes. The experiments revealed embolization can be initiated by leading edge and trailing edge detachment or by non-uniform detachment. Stress-relaxation experiments are also performed to establish values of constitutive parameters for subsequent simulations. The embolization in the tube is reproduced in silico using a multiphase volume-of-fluid approach, where the clot is modeled as viscoelastic. By varying the constitutive parameters at the wall, embolization can be reproduced in-silico at varying flow rates, and a range of constitutive parameters fitting the experiments is reported. Here, the leading edge embolization is simulated at flow rates consistent with the experiments demonstrating excellent agreement in this specific behavior.

Abstract Temporal lobe epilepsy (TLE), one common type of medically refractory epilepsy, is accompanied with altered adult-born dentate granule cells (abDGCs). However, the causal role of abDGCs in recurrent seizures of TLE is not fully understood. Here, taking advantage of optogenetic and chemogenetic tools to selectively manipulate abDGCs in a reversible manner, combined with Ca2+ fiber photometry, trans-synaptic viral tracing, in vivo/vitro electrophysiology approaches, we aimed to test the role of abDGCs born at different period of epileptogenic insult in later recurrent seizures in mouse TLE models. We found that abDGCs were functionally inhibited during recurrent seizures. Optogenetic activation of abDGCs significantly extended, while inhibition curtailed, the seizure duration. This seizure-modulating effect was attributed to specific abDGCs born at a critical early phase after kindled status, which experienced specific type of circuit re-organization. Further, abDGCs extended seizure duration via local excitatory circuit with early-born granule cells (ebDGCs). Repeated modulation of “abDGC-ebDGC” circuit may easily induce a change of synaptic plasticity, and achieve long-term anti-seizure effects in both kindling and kainic acid-induced TLE models. Together, we demonstrate that abDGCs born at a critical period of epileptogenic insult maintain seizure duration via local aberrant excitatory circuits, and inactivation of these aberrant circuits can long-termly alleviate severity of seizures. This provides a deeper and more comprehensive understanding of the potential pathological changes of abDGCs circuit and may be helpful for the precise treatment in TLE.

Nonverbal behaviors could play a crucial role in detecting deception, yet existing studies on deception cues have largely centered on Western populations, predominantly university students, thus neglecting the influence of cultural and sample diversity. To address this gap, our study explored deception cues within an Asian cultural setting, utilizing a mock crime paradigm. Our sample comprised Chinese participants, including both men and women with various socioeconomic status (SES) backgrounds. Our findings revealed that compared to truth tellers, liars exhibited heightened emotions and an increased cognitive load. Furthermore, liars showed a higher frequency of self-adaptors and a longer duration of gaze aversion. Our findings contribute to a more profound understanding of deception cues within Asian culture and have implications for practical fields such as criminal interrogation.

Introduction: Depression is a common illness worldwide. However, the current treatments available for depression only achieve relative success, often come with several side effects, and are associated with high costs. Aurantii Fructus Immaturus (AFI) has a rich historical legacy in Traditional Chinese Medicine (TCM) for its traditional use as a treatment for depression. In this research, our primary objective is to examine the potential antidepressant properties and the mechanisms at play behind a particular bioactive compound found in AFI, which is referred to as carbon dots derived from AFI Carbonisata (AFIC-CDs).Methods: Extracted and isolated the AFIC-CDs from the decoction of AFIC, then characterized the morphological structure and functional groups comprehensively. We then utilized two distinct models to investigate the anti-depressive properties of AFIC-CDs: the chronic unpredictable mild stress (CUMS) model and the reserpine-induced pain-depression dyad model. In the CUMS model, we assessed immobile time and measured neurotransmitter levels in the mouse brain cortex. In the pain-depression dyad model, we evaluated immobile time, neurotransmitter levels, interleukin-1 (IL-1β) and tumor necrosis factor-α (TNF-α) levels, and the expression of mRNA of brain-derived neurotrophic factor (BDNF) and tryptophan hydroxylase 2 (Tph2).Results: AFIC-CDs were found to have abundant chemical groups, and their diameter ranged from 2 to 10 nm. In the CUMS model, AFIC-CDs demonstrated significant effects. They reduced the immobile time of the mice and increased the levels of serotonin (5-HT), dopamine (DA), and norepinephrine (NE) in the mouse brain cortex. In the pain-depression dyad model, the AFIC-CDs groups decreased the immobile time, showed effect in increasing both the neurotransmitters’ levels and the expression of mRNA of BDNF and Tph2, and decreased the IL-1β and TNF-α levels in mouse brain cortex. Taken together, these results strongly indicate that AFIC-CDs possess significant antidepressant activity.Conclusion: AFIC-CDs demonstrate promising therapeutic potential in the treatment of depression, suggesting that they may become a valuable candidate for depression management. This not only extends the understanding of the biological activity of carbon dots (CDs) but also opens up new possibilities for the development of effective depression treatment strategies.

Background: Liver fibrosis represents an intermediate stage in the progression of liver disease, and as of now, there exists no established clinical therapy for effective antifibrotic treatment.Purpose: Our aim is to explore the impact of Carbon dots derived from Vaccaria Semen Carbonisata (VSC-CDs) on carbon tetrachloride-induced liver fibrosis in mice.Methods: VSC-CDs were synthesized employing a modified pyrolysis process. Comprehensive characterization was performed utilizing various techniques, including transmission electron microscopy (TEM), multiple spectroscopies, X-ray photoelectron spectroscopy (XPS), and high-performance liquid chromatography (HPLC). A hepatic fibrosis model induced by carbon tetrachloride was utilized to evaluate the anti-hepatic fibrosis effects of VSC-CDs.Results: VSC-CDs, exhibiting a quantum yield (QY) of approximately 2.08%, were nearly spherical with diameters ranging from 1.0 to 5.5 nm. The VSC-CDs prepared in this study featured a negative charge and abundant chemical functional groups. Furthermore, these particles demonstrated outstanding dispersibility in the aqueous phase and high biocompatibility. Moreover, VSC-CDs not only enhanced liver function and alleviated liver damage in pathomorphology but also mitigated the extent of liver fibrosis. Additionally, this study marks the inaugural demonstration of the pronounced activity of VSC-CDs in inhibiting inflammatory reactions, reducing oxidative damage, and modulating the TGF-β/Smad signaling pathway.Conclusion: VSC-CDs exerted significant potential for application in nanodrugs aimed at treating liver fibrosis.

Abstract Seizures due to cortical dysplasia are notorious for their poor prognosis even with medications and surgery, likely due to the widespread seizure network. Previous studies have primarily focused on the disruption of dysplastic lesions, rather than remote regions such as the hippocampus. Here, we first quantified the epileptogenicity of the hippocampus in patients with late-stage cortical dysplasia. We further investigated the cellular substrates leading to the epileptic hippocampus, using multiscale tools including calcium imaging, optogenetics, immunohistochemistry and electrophysiology. For the first time, we revealed the role of hippocampal somatostatin-positive interneurons in cortical dysplasia-related seizures. Somatostatin-positive were recruited during cortical dysplasia-related seizures. Interestingly, optogenetic studies suggested that somatostatin-positive interneurons paradoxically facilitated seizure generalization. By contrast, parvalbumin-positive interneurons retained an inhibitory role as in controls. Electrophysiological recordings and immunohistochemical studies revealed glutamate-mediated excitatory transmission from somatostatin-positive interneurons in the dentate gyrus. Taken together, our study reveals a novel role of excitatory somatostatin-positive neurons in the seizure network and brings new insights into the cellular basis of cortical dysplasia.

Numerous natural compounds exhibit low bioavailability due to suboptimal water solubility. The solubilization methods of the modern pharmaceutical industry in contemporary pharmaceutical research are restricted by low efficiency, sophisticated technological requirements, and latent adverse effects. There is a pressing need to elucidate and implement a novel solubilizer to ameliorate these challenges. This study identified natural biomass-derived carbon dots as a promising candidate. We report on natural fluorescent carbon dots derived from Aurantia Fructus Immatures (AFI-CDs), which have exhibited a remarkable solubilization effect, augmenting naringin (NA) solubility by a factor of 216.72. Subsequent analyses suggest that the solubilization mechanism is potentially contingent upon the oration of a nanostructured complex (NA-AFI-CDs) between AFI-CDs and NA, mediated by intermolecular non-covalent bonds. Concomitantly, the synthesized NA-AFI-CDs demonstrated high biocompatibility, exceptional stability, and dispersion. In addition, NA-AFI-CDs manifested superior free radical scavenging capacity. This research contributes foundational insights into the solubilization mechanism of naringin-utilizing AFI-CDs and proffers a novel strategy that circumvents the challenges associated with the low aqueous solubility of water-insoluble drugs in the field of modern pharmaceutical science.

To explore the flow, heat transfer and oxidative regeneration mechanism of the porous media of the catalytic diesel particulate filter at the pore scale, catalytic diesel particulate filter and particulate layer structure were built using three-dimensional reconstruction technology of Micro-CT and the Quartet Structure Generation Set. A heat source term was added to the mathematical model to simulate the temperature field during the oxidative regeneration of the particulate layer. The effects of different wall structures at five different positions, air inlet velocities and particulate layer parameters on the porous media were analyzed. The results show that in the clean cordierite porous medium structures, the larger the structural porosity, the greater the average velocity at the inlet of the porous medium wall. In the porous medium wall structures loaded with particulate layers, the particulate layer has a weakening effect on the velocity field above the particulate layer porous media. As the porosity of the particulate layer decreases, the temperature rise increases. When the particulate layers are oxidized, a temperature peak is generated at the inlet of the wall porous media. As the porosity of the particulate layer decreases, the temperature peak increases during oxidative regeneration.

E-cigarettes, also known as electronic nicotine delivery systems (ENDS), are mainly used among adolescents and young adults. Similar to traditional cigarettes, different concentrations of nicotine are also added to E-cigarette's liquid (E-liquid), but due to the supplementation of chemicals such as propylene glycol (PG), vegetable glycerin (VG) and flavors, it is difficult to determine the risk after using E-cigarettes. And given to the specificity of the aerosol particle composition and atomization process of E-cigarettes, it is necessary to assess the neurotoxic effects of long-term E-cigarettes use. In this study, two commercial nicotine-containing (5%) and nicotine-free E-liquids were diluted to investigate the neurobehavioral changes and addictive tendencies of developing C. elegans after sub-chronic exposure to E-liquid. The results showed that sub-chronic exposure of E-liquid could lead to impaired growth and development of nematodes, abnormal general neuromotor behavior and advanced learning and memory behavior, and nicotine-containing E-liquid could also lead to increased addiction tendency of nematodes. Although the damage effect of nicotine free E-liquid is smaller than that of the nicotine-containing group, its toxic effect cannot be ignored. Further analysis of the neurotoxicity mechanism found that redox imbalance-mediated mitochondrial stress and aging may be important causes of E-liquid-induced biological damage. The biosafety of e-cigarette aerosols was also included in the assessment. The study found that the heated atomization process did not alter the E-liquid components, and E-cigarette aerosols still have the effect of interfering with the growth and development of nematodes and neurobehavior, and its addictive nature is also of concern. This study can provide new ideas for future studies on the neurotoxic effects and safety assessment of the E-cigarettes, and provide theoretical reference for the study on the injury mechanism of E-cigarettes.

The spatial organisation of diffuse midline glioma-H3K27M mutant (DMG) and glioblastoma (GBM) remains to be investigated. Here, the authors integrate short-read and long-read spatial profiling of DMG and GBM to identify regulatory programs and cellular ecosystems in distinct glioma niches.

In order to promote multi-energy complementation and low carbonization, an optimal scheduling model of virtual power plant (VPP) with carbon capture and waste incineration considering power-to-gas coordination is proposed. By introducing the collaborative utilization framework with a carbon capture plant-power to gas (P2G)-gas unit system, the CO2 in the carbon capture can be used as the raw material of P2G, which produces natural gas to be supplied to the gas unit. In addition, the power consumption of the carbon capture and the flue gas treatment can be transferred through joint dispatching to smooth the fluctuation of renewable energy output, so that the wind power and photovoltaic can be indirectly dispatchable and flexibly utilized. In view of the high dimensional nonlinearity of the proposed optimization model and the difficulty in solving it, a new Gaussian compound differential evolution algorithm is designed to solve the model. The simulation results show that the proposed model and method can provide peak load shifting capacity and improve renewable energy consumption, effectively reducing the cost and carbon emission of VPP.

Abstract Metasurface can use artificial microstructures to manipulate electromagnetic waves more accurately and flexibly. All-dielectric metalens have a wide range of materials and low cost so it has a wide application prospect. Herein, we propose a all-dielectric achromatic metalens built with Si as the structural unit that can operate over a broadband of wavelengths in the visible region. It controls the wavefront of light through the Pancharatnam–Berry phase and propagation phase to eliminate the chromatic aberration. Meanwhile, we also use Gerchberg–Saxton algorithm and its improved algorithm to iterate over multiple design wavelengths and obtain holographic phases suitable for broadband. Thus, both the metalenses and holographic metasurfaces can achieve achromatic broadband in the visible light range, which provides a new method for the development of meta-optical imaging devices.

Background: Sarcopenia, defined as the loss of muscle mass and strength, has been associated with increased hospitalization and mortality. Dietary pattern analysis is a whole diet approach which in this study was used to investigate the relationship between diet and sarcopenia. This study aims to estimate the prevalence of sarcopenia and explore possible factors associated with it among a large population in Beijing, China.Methods: A cross-sectional study with 1,059 participants aged more than 50 years was performed. Sarcopenia was defined based on the guidelines of the Asian Working Group for Sarcopenia. The total score of the MNA-SF questionnaire was used to analyse nutrition status. The baseline demographic information, diet structure and eating habits were collected by clinicians trained in questionnaire data collection and anthropometric and bioimpedance measurements.Results: The overall prevalence of sarcopenia was 8.8% and increased with age: 5%, 5.8%, 10.3% and 26.2% in the 50–59, 60–69, 70–79, and ≥80 years groups, respectively. Marital status (with or without a spouse) was not an independent factor associated with sarcopenia adjusted by age and sex. However, nutritional risk or malnutrition, vegetable diet, advanced age and spicy eating habits were risk factors for sarcopenia. Meanwhile, daily fruit, dairy and nut consumption were protective factors against sarcopenia adjusted by age, sex, income status and spouse status.Conclusion: Although further studies are required to explore the association between healthy dietary patterns and the risk of sarcopenia, the present study provides basic data for identifying correlates of sarcopenia in elderly Chinese individual.

Introduction: Anxiety disorders have emerged as a predominant health concern, yet existing pharmacological treatments for anxiety still present various challenges. Chrysanthemum morifolium Ramat Carbonisata (CMRC) has been utilized in China for approximately 400 years as a therapeutic intervention for anxiety disorders. In this study, a novel type of carbon dots derived from the decoction of Chrysanthemum morifolium Ramat Carbonisata (CMRC-CDs) was identified and isolated, and their morphological structure and functional groups were characterized. Furthermore, the effects of CMRC-CDs on m-chlorophenylpiperazine (mCPP)-induced anxiety-like behaviour in mice were examined and quantified. In order to investigate the potential mechanisms of their anxiolytic effects, concentrations of hypothalamic-pituitary-adrenal (HPA) axis hormones, amino acid neurotransmitters, and monoamine neurotransmitters were measured.Methods: In this study, we synthesized CMRC-CDs and evaluated their potential anti-anxiety effects in a controlled experiment involving 48 male ICR mice. The mice were randomly divided into six groups, treated with CMRC-CDs at different doses for 14 days, and subjected to Open-Field (OF) and Elevated Plus Maze (EPM) tests. Post-behavioral evaluations, blood samples and brain tissues were collected for neurotransmitter and Hypothalamic-Pituitary-Adrenal (HPA) axis hormone quantification via ELISA. Additionally, cytotoxicity of CMRC-CDs was assessed using a Cell Counting Kit-8 (CCK-8) assay on RAW 264.7 cells.Results and Discussion: CMRC-CDs were spherical and homogeneously dispersed, with diameters ranging from 1.4 to 4.0 nm and an abundance of chemical groups on their surface. In the open-field (OF) test, mice pre-treated with CMRC-CDs demonstrated an increased proportion of time spent in the central area and a higher frequency of entries into the central area. In the elevated plus maze (EPM) test, mice pre-treated with CMRC-CDs exhibited a greater number of entries into the open arm and an extended duration spent in the open arm. CMRC-CDs were observed to decrease serum concentrations of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT). Furthermore, CMRC-CDs were found to increase γ-aminobutyric acid (GABA) and 5-hydroxytryptamine (5-HT) levels, while concurrently reducing glutamic acid (Glu) concentrations in brain tissue. CMRC-CDs demonstrated anxiolytic effects, which may be attributed to their modulation of hormones and neurotransmitters. This finding suggests the potential therapeutic value of CMRC-CDs in the clinical treatment of anxiety disorders.

The steganography theory of computing security has been proposed for a long time, but it has not been widely adopted for mainstream steganography using multimedia data as a carrier.The reason is that the prerequisite for calculating secure steganography is to obtain the accurate distribution of the carrier or to accurately sample according to the carrier distribution.However, naturally collected images and audio/video cannot meet this prerequisite.With the development of deep learning technology, various machine-generated media such as image generation and synthesized speech, have become more and more common on the Internet and then generated media has become a reasonable steganography carrier.Steganography can use normal generated media to cover up secret communications, and pursue in distinguishability from normal generated media.The distribution learned by some generative models is known or controllable, which provides an opportunity to push computational security steganography for practical use.Taking the widely used synthetic speech model as an example, a computationally secure symmetric key steganography algorithm was designed and implemented.The message was decompressed into the synthetic audio according to the decoding process of arithmetic coding based on the conditional probability of sample points, and the message receiver had the same generation model to complete the message extraction by reproducing the audio synthesis process.The public key steganography algorithm was additionally designed based on this algorithm, which provided algorithmic support for the realization of full-flow steganographic communication.Steganographic key exchange ensured the security of steganographic content and the security of steganographic behavior was also achieved.The theoretical analysis showed that the security of the proposed algorithm is determined by the randomness of the embedded message.And the steganography analysis experiment further verified that the attacker cannot distinguish the synthesized carrier audio from the encrypted audio.

MicroRNAs (miRNAs) are important regulators of gene expression. The large-scale detection and profiling of miRNAs have been accelerated with the development of high-throughput small RNA sequencing (sRNA-Seq) techniques and bioinformatics tools. However, generating high-quality comprehensive miRNA annotations remains challenging due to the intrinsic complexity of sRNA-Seq data and inherent limitations of existing miRNA prediction tools. Here, we present iwa-miRNA, a Galaxy-based framework that can facilitate miRNA annotation in plant species by combining computational analysis and manual curation. iwa-miRNA is specifically designed to generate a comprehensive list of miRNA candidates, bridging the gap between already annotated miRNAs provided by public miRNA databases and new predictions from sRNA-Seq datasets. It can also assist users in selecting promising miRNA candidates in an interactive mode, contributing to the accessibility and reproducibility of genome-wide miRNA annotation. iwa-miRNA is user-friendly and can be easily deployed as a web application for researchers without programming experience. With flexible, interactive, and easy-to-use features, iwa-miRNA is a valuable tool for the annotation of miRNAs in plant species with reference genomes. We also illustrate the application of iwa-miRNA for miRNA annotation using data from plant species with varying genomic complexity. The source codes and web server of iwa-miRNA are freely accessible at http://iwa-miRNA.omicstudio.cloud/.

Abstract The optimal scheduling problem of integrated energy system (IES) has the characteristics of high-dimensional nonlinearity. Using the traditional Grey Wolf Optimizer (GWO) to solve the problem, it is easy to fall into a local optimum in the process of optimization, resulting in a low-quality scheduling scheme. Aiming at the dispatchability of electric and heat loads, this paper proposes an electric and heat comprehensive demand response model considering the participation of dispatchers. On the basis of incentive demand response, the group aggregation model of electrical load is constructed, and the electric load response model is constructed with the goal of minimizing the deviation between the dispatch signal and the load group aggregation characteristic model. Then, a heat load scheduling model is constructed according to the ambiguity of the human body's perception of temperature. On the basis of traditional GWO, the Fuzzy C-means (FCM) clustering algorithm is used to group wolves, which increases the diversity of the population, uses the Harris Hawk Optimizer (HHO) to design the prey to search for the best escape position, and reduces the local The optimal probability, and the use of Particle Swarm Optimizer (PSO) and Bat Optimizer (BO) to design the moving modes of different positions, increase the ability to find the global optimum, so as to obtain an Improved Gray Wolf Optimizer (IGWO), and then efficiently solve the model. IGWO can improve the defect of insufficient population diversity in the later stage of evolution, so that the population diversity can be better maintained during the entire evolution process. While taking into account the speed of optimization, it improves the algorithm's ability to jump out of the local optimum and realizes continuous deep search. Compared with the traditional intelligent Optimizer, IGWO has obvious improvement and achieved better results. At the same time, the comprehensive demand response that considers the dispatcher's desired signal improves the accommodation of new energy and reduces the operating cost of the system, and promotes the benign interaction between the source and the load.

Tartaric acid (TA) is the primary organic acid present in grapes and a fundamental constituent of wine, responsible for shaping its taste, aroma, and overall quality. This review presents a comprehensive overview of the advances made in previous investigations on grape tartaric acid. It elucidates the structural properties, distribution characteristics, biosynthesis, catabolism, and transcriptional regulation of grape tartaric acid, and also speculates on the regulatory mechanism of tartaric acid based on the modulation of ascorbic acid-related transcription factors. Furthermore, this review provides insights into the future research directions and objectives, with the goal of providing a reference for the analysis of the complete biosynthetic pathway of grape tartaric acid, thereby enabling precise regulation of tartaric acid.

A new triple cascade waste heat recovery system coupled with a supercritical CO2 power cycle and transcritical CO2 regenerative cycle is proposed for the high temperature exhaust waste heat generated during the operation of gas turbine, and thermodynamic and economic models are established to analyze the performance of the system, with the following performance indicators: the net output power is 5.67 MW, the thermal efficiency is 24.94 %, the exergy efficiency is 46.08 %, the total investment cost rate is 126.06$/h, and the per unit energy cost is 6.31$/GJ. The thermal performance of the integrated system consisting of the gas turbine unit and the proposed triple cascade waste heat recovery system is evaluated, and the results show that the integrated system effectively utilizes the waste heat compared with the gas turbine unit alone, while the net output power of the integrated system is 22.17 MW and the thermal efficiency is 47.7 %. Each component's exergy and cost analysis is performed. The heat exchanger accounts for a large percentage of the exergy destruction, and the investment cost rate of the turbine, compressor and other work-making components is high, indicating the direction of system optimization. The sensitivity analysis of the system's key parameters was carried out through the control variables method to reveal the influence of individual setting parameters on the system performance. Based on the research range of the set parameters, the system is optimized with multiple objectives, and the net output power, exergy efficiency and per unit energy cost are selected as the objective functions. The optimization results show that the combination of exergy efficiency and per unit energy cost resulted in better economic performance, with exergy efficiency of 50.37 % and per unit energy cost of 4.66$/GJ. Comparing the system with the other two configurations proves the superiority of the proposed system.

Abstract Background Shoot branching is one of the important agronomic traits affecting yields and quality of tea plant (Camellia sinensis). Cytokinins (CTKs) play critical roles in regulating shoot branching. However, whether and how differently alternative splicing (AS) variant of CTKs-related genes can influence shoot branching of tea plant is still not fully elucidated. Results In this study, five AS variants of CTK biosynthetic gene adenylate isopentenyltransferase (CsA-IPT5) with different 3′ untranslated region (3ˊ UTR) and 5ˊ UTR from tea plant were cloned and investigated for their regulatory effects. Transient expression assays showed that there were significant negative correlations between CsA-IPT5 protein expression, mRNA expression of CsA-IPT5 AS variants and the number of ATTTA motifs, respectively. Shoot branching processes induced by exogenous 6-BA or pruning were studied, where CsA-IPT5 was demonstrated to regulate protein synthesis of CsA-IPT5, as well as the biosynthesis of trans-zeatin (tZ)- and isopentenyladenine (iP)-CTKs, through transcriptionally changing ratios of its five AS variants in these processes. Furthermore, the 3′ UTR AS variant 2 (3AS2) might act as the predominant AS transcript. Conclusions Together, our results indicate that 3AS2 of the CsA-IPT5 gene is potential in regulating shoot branching of tea plant and provides a gene resource for improving the plant-type of woody plants.

Promoting the efficient use of renewable energy and realizing the low-carbon operation of the integrated energy system has become an important direction for the reform of the integrated energy system. In this paper, we firstly construct a microgrid model containing electricity, heat and gas multi-energy synergy, consider the optimal operation mechanism of carbon trading with reward and punishment ladder, and improve the model of CHP units by adding carbon capture system and power-to-gas facility to reduce carbon emissions. Then, a cooperative operation model of multi-microgrid electric energy sharing is established, which is then decomposed into the subproblem of maximizing the benefits of microgrid alliances and the subproblem of distributing cooperative benefits, and the alternating direction multiplier method is selected for distributed solution, so as to effectively protect the privacy of each subject. In the cooperative benefit distribution subproblem, a method is proposed to quantify the contribution size of each participating entity by a nonlinear energy mapping function, and each microgrid negotiates with each other by the size of its electric energy contribution in the cooperation as the bargaining power to achieve a fair distribution of cooperative benefits. Finally, the simulation results verify the effectiveness of the proposed method. The results show that the benefits of the microgrid alliance are maximized by the proposed multi-microgrid power sharing method; moreover, the cooperative benefits of the microgrid alliance are equitably distributed based on the magnitude of the energy contribution of each microgrid; in terms of carbon emissions, the results demonstrate that the carbon capture joint power-to-gas system, as well as the energy sharing method among microgrids, can effectively reduce the carbon emissions during the microgrid operation.

ABSTRACT Cronobacter is a foodborne pathogen associated with severe infections in restricted populations and particularly with high mortality in neonates and infants. The prevalence and antimicrobial resistance (AMR) phenotype of Cronobacter cultured from powdered infant formula and supplementary food were studied. The virulence factors, AMR genes, and genomic environments of the multidrug-resistant isolates were further studied. A total of 1,055 Cronobacter isolates were recovered from 12,105 samples of powdered infant formula and supplementary food collected from 29 provinces between 2018 and 2019 in China. Among these, 1,048 isolates were from infant supplementary food and 7 were from powdered infant formula. Regarding antimicrobial resistance susceptibility, 11 (1.0%) isolates were resistant and two showed resistance to four antimicrobials (ampicillin [AMP], tetracycline [TET], sulfamethoxazole-trimethoprim [SXT], and chloramphenicol [CHL]), defined as MDR. These two MDR isolates were subsequently identified as Cronobacter sakazakii sequence type 4 (ST4) (C. sakazakii Crono-589) and ST40 (C. sakazakii Crono-684). Both MDR isolates contain 11 types of virulence genes and 7 AMR genes on their genomes. Meanwhile, the IncFIB plasmids of both MDR C. sakazakii isolates also harbored 2 types of virulence genes. Results of the genomic comparative analysis indicated that food-associated C. sakazakii could acquire antimicrobial resistance determinants through horizontal gene transfer (HGT). IMPORTANCE As a foodborne pathogen, Cronobacter can cause serious infections in restricted populations and lead to death or chronic sequelae. Although a number of investigations showed that Cronobacter isolates are susceptible to most antimicrobial agents, MDR Cronobacter isolates, isolated mainly from clinical cases but occasionally from foods, have been reported in recent years. In this study, we successfully identified two MDR Cronobacter sakazakii isolates from infant foods based on nationwide surveillance and genome sequencing in China. Genomic analysis revealed that these two MDR C. sakazakii strains acquired resistance genes from other species via different evolution and transmission routes. It is important to monitor MDR C. sakazakii isolates in infant foods, and appropriate control measures should be taken to reduce the contamination with and transmission of this MDR bacterium.

Recently, the emerging technology known as Interlaced Magnetic Recording (IMR) has been receiving widespread attention from both industry and academia. IMR-based disks incorporate interlaced track layouts and energy-assisted techniques to dramatically increase areal densities. The interlaced track layout means that in-place updates to the bottom track require rewriting the adjacent top track to ensure data consistency. However, at high disk utilization, frequent track rewrites degrade disk performance. To address this problem, we propose a solution called Balloon to reduce the frequency of track rewrites. First, an adaptive write interference data placement policy is introduced, which judiciously places data on tracks with low rewrite probability to avoid unnecessary rewrites. Next, an on-demand data shuffling mechanism is designed to reduce user-requests write latency by implicitly migrating data and promptly swapping tracks with high update block coverage to the top track. Finally, a write-interference-free persistent buffer design is proposed. This design dynamically adjusts buffer admission constraints and selectively evicts data blocks to improve the cooperation between data placement and data shuffling. Evaluation results show that Balloon significantly improves the write performance of IMR-based disks at medium and high utilization compared with state-of-the-art studies.

Accurate and timely estimation of grass yield is crucial for understanding the ecological conditions of grasslands in the Mongolian Plateau (MP). In this study, a new artificial neural network (ANN) model was selected for grassland yield inversion after comparison with multiple linear regression, K-nearest neighbor, and random forest models. The ANN performed better than the other machine learning models. Simultaneously, we conducted an analysis to examine the spatial and temporal characteristics and trends of grass yield in the MP from 2000 to 2020. Grassland productivity decreased from north to south. Additionally, 92.64% of the grasslands exhibited an increasing trend, whereas 7.35% exhibited a decreasing trend. Grassland degradation areas were primarily located in Inner Mongolia and the central Gobi region of Mongolia. Grassland productivity was positively correlated with land surface temperature and precipitation, although the latter was less sensitive than the former in certain areas. These findings indicate that ANN model-based grass yield estimation is an effective method for grassland productivity evaluation in the MP and can be used in a larger area, such as the Eurasian Steppe.

In order to address the issue of battery cell disparity in lithium-ion battery systems, battery balancing techniques are required. This paper proposes an improved battery balancing strategy within a reconfigurable converter system. The strategy is based on the state of charge (SOC) of batteries, and utilizes the reconfigurable converter system to transfer energy from battery modules with high SOC to those with lower SOC. Additionally, it allows for battery module balancing while supplying power to loads. A MATLAB/Simulink simulation model with five batteries was built to validate the effectiveness of the proposed balancing strategy under unloaded and loaded conditions. The simulation results demonstrate that the proposed strategy achieves more efficient and accurate battery module balancing compared to the previous balancing modes.

Generalized logistic distribution, as the generalized form of the symmetric logistic distribution, plays an important role in reliability analysis. This article focuses on the statistical inference for the stress–strength parameter R=P(Y

Globally, Late Permian to Early Triassic carbonate rocks record several pronounced positive and negative C-isotope excursions, indicating a dramatic reorganization of the global carbon cycle. These C-isotopic anomalies provide important constraints on environmental changes that occurred during the end-Permian extinction and the subsequent delayed biotic recovery. In this study, we present high-resolution carbonate C-isotopic data (δ13Ccarb) spanning the Permian-Triassic transition at Dajiang, South China. Our results reveal a general decrease in δ13Ccarb of ∼3.3‰ during the microbialite formation which was followed by an increase. C-isotopic chemostratigraphic correlation between the Dajiang section and the Global Boundary Stratotype Section and Point (GSSP) at Meishan suggest a hiatus of several thousands of years between the pre-extinction skeletal limestones and the microbialite deposition in the aftermath of the end-Permian extinction in South China. We suggest that multiple sources of 13C-depleted dissolved carbon are required to explain the negative δ13Ccarb excursions as well as the δ13Ccarb differences among microbialites deposited in various paleogeographic locations. Our study shows that carbon cycles during the formation of microbialite may have been more complex than previously thought, and cessation of microbialite formation may have been controlled by both global and local environmental changes.

ABSTRACT Sequence type 88 (ST88) methicillin-resistant Staphylococcus aureus (MRSA) has been recognized as an important pathogen that causes infections in humans, especially when it has strong biofilm production and multidrug resistance (MDR). However, knowledge of the determinants of resistance or virulence and genomic characteristics of ST88 MRSA from China is still limited. In this study, we employed the antimicrobial resistance (AMR), biofilm formation, and genomic characteristics of ST88 MRSA collected from various foods in China and estimated the worldwide divergence of ST88 MRSA with publicly available ST88 genomes. All ST88 isolates studied were identified as having resistance genes, while 50% (41/82) harbored MDR genes. All isolates carried core virulence genes related to immune modulation, adherence, secreted enzymes, and hemolysin. In addition, all 20 Chinese ST88 isolates showed biofilm production capacity, three strongly so. Bayesian phylogenetic analysis showed that Chinese ST88 clones formed an independent MRSA lineage, with two subclades associated with acquisition of type IVc staphylococcal cassette chromosome mec (SCCmec) elements. In contrast, all African ST88 strains were subtyped as SCCmecIVa, where the African clades were mixed with a few European and American isolates, suggesting potential transmission from Africa to these regions. In summary, our results revealed the evolution of ST88 MRSA in humans, animals, and foods in Africa and Asia. The food-associated ST88 genomes in this study will remedy the lack of food-associated ST88 isolates, and the study in general will extend the discussion of the potential exchanges of ST88 between humans and foods or food animals. IMPORTANCE ST88 MRSA has frequently been detected in humans, animals, and foods mainly in Africa and Asia. It can colonize and cause mild to severe infections in humans, especially children. Several studies from African countries have described its genotypic characteristics but, limited information is available on the evolution and characterization of ST88 MRSA in Asia, especially China. Meanwhile, the molecular history of its global spread remains largely unclear. In this study, we analyzed the genomic evolution of global ST88 MRSA strains in detail and identified key genetic changes associated with specific hosts or regions. Our results suggested geographical differentiation between ST88 MRSA’s evolution in Africa and its evolution in Asia, with a more recent clonal evolution in China. The introduction of ST88 MRSA in China was aligned with the acquisition of SCCmecIVc elements, specific virulent prophages, and AMR genes.

The end-Permian mass extinction was the most severe extinction event in the past 540 million years, and the Siberian Traps large igneous province is widely hypothesized to have been the primary trigger for the environmental catastrophe. In this study, Ni isotopes provide the link between Siberian Traps magmatism and early environmental degradation, ultimately leading to the end-Permian extinction.

Abstract Water level conditions are the key factors that affect the growth and distribution of wetland plants. Using Carex cinerascens (C. cinerascens) as the study species, we employ indoor simulations and field surveys. Our results show that C. cinerascens can adapt to rhythmic changes in the water level through different adaptation strategies. Compared to that of the control group, plant growth was better with a 0–0.4 cm/d water level rate, and plant growth was in the 42–56 cm range to that a 1.0–1.4 cm/d water level rate. Furthermore, it was observed that 0–0.4 cm/d was the most suitable growth rate, with 0.6–1.0 cm/d and 0–32 cm being the ideal plant tolerance ranges, and increasing to 1.0–1.4 cm/d and 32–56 cm exceeds the plant tolerance threshold. In the middle and late period of the experiment (25–45 d), the ecological characteristics of the plants changed significantly. For example, the root-to-shoot ratio of the plant in the stable water level reached 26.1. In our field observations, plant biomass can be influenced by a variety of environmental factors. The frequency of the species was the largest at an elevation of 15 m, and the growth status of the dominant and companion species of C. cinerascens was weakened with an increase in soil moisture content. The suitable water content for C. cinerascens growth was 27.6–57.3%, the distribution elevation was 12.54–16.59 m, and the optimum elevation was 13.56–15.54 m. The study is expected to provide a reference for wetland ecology research and wetland protection and restoration, a theoretical reference for the coordination of water resource development and utilization of Poyang Lake and ecological protection of important lakes and wetlands, and an important scientific basis for wetland hydrologic regulation, ecological restoration and biodiversity conservation.

Identification of stratospheric volcanic eruptions in the geological record and their link to mass extinction events during the past 540 million years remains challenging. Here, the authors report unexpected, large mass-independent sulphur isotopic compositions of pyrite in Late Ordovician sedimentary rocks, which they suggest originates from stratospheric volcanism linked to the first pulse of the Late Ordovician mass extinction.

Graph is an important model to describe various networks, and its scale becomes larger and larger with the development of communication and information technology. The analysis of large-scale graphs requires distributed graph processing systems, and graph partition is the basis of these systems. The existing graph partitioning algorithms are almost proposed for homogeneous clusters, which don't consider the differences among computing nodes in heterogeneous clusters. This paper proposes GAP, a Genetic Algorithm based graph Partitioning algorithm to solve this problem. GAP aims to reduce the total processing time on a heterogeneous cluster by partitioning graphs according to the computing powers of computing nodes. GAP balanced partition the graph initially, and then utilizes genetic algorithm to transfer vertices to reduce cut edges. GAP can balance the processing time of computing nodes, and reduce the communication time among computing nodes. The experiments performed on a heterogeneous cluster demonstrate the outperformance of GAP than Hash.

The power-to-gas (P2G) technology transforms the unidirectional coupling of power network and natural gas network into bidirectional coupling, and its operational characteristics provide an effective way for wind and solar energy accommodation. The paper proposes a bi-level optimal dispatch model for the integrated energy system with carbon capture system and P2G facility. The upper model is an optimal allocation model for coal-fired units, and the lower model is an economic dispatch model for the integrated energy system. Moreover, the upper model is solved by transforming the model into a mixed-integer linear programming problem and calling CPLEX, and the lower model is a multi-objective planning problem, which is solved by improving the small-habitat particle swarm algorithm. Finally, the simulation is validated by the MATLAB platform, and the results show that the simultaneous consideration of carbon capture system and P2G facility improves the economics of the integrated energy system and the capacity of wind and solar energy accommodation.

Cronobacter is a foodborne pathogen associated with severe infections and high mortality in neonates. The bacterium may also cause gastroenteritis, septicemia, and urinary tract and wound infectious in adults. A total of 15 Cronobacter isolates collected from 617 raw materials and environment samples from Powdered Infant Formula manufacturing factories during 2016 in Shaanxi, China, were analyzed for antimicrobial susceptibilities, species identification, biofilm formation, and whole-genome sequencing. The results showed that all 15 isolates were Cronobacter sakazakii, while the antimicrobial susceptibility test showed that all 15 C. sakazakii were pan susceptible. Most isolates were able to produce a weak biofilm, and two isolates from soil samples produced a strong biofilm formation. All isolates were classified into seven STs including ST4, ST40, ST64, ST93, ST148, ST256, and ST494, with ST64 (4/15, 26.7%) being dominant, and most were clinically related. The isolates harbored at least 11 virulence genes and two plasmids, with one isolate being positive for all virulence genes. Phylogenetic and ANI analysis showed strong clustering by sequence types and isolates from different sources or regions with a similar genomic background. The fact that isolates were obtained from raw materials and environment samples of PIF facilities shared a close phylogeny with one another suggests that cross-contamination events may have occurred between the processing room and external environments, which may give rise to a recurring risk of a continuous contamination during production.

Listeria innocua are Gram-positive rod-shaped bacteria, which are not generally infectious as opposed to Listeria monocytogenes. However, the comparatively high genomic similarity between both along with on occasion, their coexistence in similar ecological niches may present the opportunity for resistance or virulence gene transfer. In this study, three multi-drug resistant L. innocua originally cultured from food were put forward for long-read genome sequencing. Chromosome and plasmid genomes were assembled and annotated. Analysis demonstrated that the resistant phenotypes correlated well with genotypes. Three plasmids pLI42, pLI203, and pLI47-1 were identified which harbor resistance islands. Sequence alignments suggested that plasmids pLI42 and pLI203 were highly similar to a previously sequenced L. monocytogenes plasmid pLR1. Similarly, another three types of resistance gene islands were observed on chromosome, including tet(M) gene islands (transposon Tn916 orthologs), dfrG gene islands and optrA-erm(A) gene islands. All three L. innocua isolates possessed listeria pathogenicity island-4 (LIPI-4) which is linked to cases of mengitis. Further genome environment and phylogenic analysis of regions flanking LIPI-4 of L. innocua and L. monocytogenes showed that these may have common origins and with the potential to transmit from the former. Our findings raise the possible need to include both L. monocytogenes and L. innocua in food surveillance programs so as to further understand of the origins of antimicrobial resistance and virulence markers of public health importance in L. monocytogenes.

ABSTRACT Staphylococcus aureus is a worldwide leading cause of numerous diseases ranging from food-poisoning to lethal infections. Methicillin-resistant S. aureus (MRSA) has been found capable of acquiring resistance to most antimicrobials. MRSA is ubiquitous and diverse even in terms of antimicrobial resistance (AMR) profiles, posing a challenge for treatment. Here, we present a comprehensive study of S. aureus in China, addressing epidemiology, phylogenetic reconstruction, genomic characterization, and identification of AMR profiles. The study analyzes 673 S. aureus isolates from food as well as from hospitalized and healthy individuals. The isolates have been collected over a 9-year period, between 2010 and 2018, from 27 provinces across China. By whole-genome sequencing, Bayesian divergence analysis, and supervised machine learning, we reconstructed the phylogeny of the isolates and compared them to references from other countries. We identified 72 sequence types (STs), of which, 29 were novel. We found 81 MRSA lineages by multilocus sequence type (MLST), spa, staphylococcal cassette chromosome mec element (SCCmec), and Panton-Valentine leukocidin (PVL) typing. In addition, novel variants of SCCmec type IV hosting extra metal and antimicrobial resistance genes, as well as a new SCCmec type, were found. New Bayesian dating of the split times of major clades showed that ST9, ST59, and ST239 in China and European countries fell in different branches, whereas this pattern was not observed for the ST398 clone. On the contrary, the clonal transmission of ST398 was more intermixed in regard to geographic origin. Finally, we identified genetic determinants of resistance to 10 antimicrobials, discriminating drug-resistant bacteria from susceptible strains in the cohort. Our results reveal the emergence of Chinese MRSA lineages enriched of AMR determinants that share similar genetic traits of antimicrobial resistance across human and food, hinting at a complex scenario of evolving transmission routes. IMPORTANCE Little information is available on the epidemiology and characterization of Staphylococcus aureus in China. The role of food is a cause of major concern: staphylococcal foodborne diseases affect thousands every year, and the presence of resistant Staphylococcus strains on raw retail meat products is well documented. We studied a large heterogeneous data set of S. aureus isolates from many provinces of China, isolated from food as well as from individuals. Our large whole-genome collection represents a unique catalogue that can be easily meta-analyzed and integrated with further studies and adds to the library of S. aureus sequences in the public domain in a currently underrepresented geographical region. The new Bayesian dating of the split times of major drug-resistant enriched clones is relevant in showing that Chinese and European methicillin-resistant S. aureus (MRSA) have evolved differently. Our machine learning approach, across a large number of antibiotics, shows novel determinants underlying resistance and reveals frequent resistant traits in specific clonal complexes, highlighting the importance of particular clonal complexes in China. Our findings substantially expand what is known of the evolution and genetic determinants of resistance in food-associated S. aureus in China and add crucial information for whole-genome sequencing (WGS)-based surveillance of S. aureus.