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The effect of a tilted-dipole three-dimensional corotating interaction region (CIR) on the transport and acceleration of solar energetic particles (SEPs) is studied. In this work, we discussed how the particle intensity longitudinal and radial dependence might be influenced by the background structures. Moreover, we investigate how the spectral index distribution is modulated by the CIR structure. We use the focused transport equation (FTE) to describe the propagation and acceleration of SEPs in a tilt-dipole 3D CIR, generated by the high-resolution 3D magnetohydrodynamic (MHD) model. The forward stochastic differential method is used to solve the FTE. The protons with the \begin{document}$ E^{-4.4} $\end{document} spectrum from 0.5 to 15 MeV are injected uniformly at the heliographic equator of 0.15 AU. Physical quantities are extracted along each interplanetary magnetic field (IMF) line to show the results. In the tilted-dipole CIR background, if injected from the solar equator at the inner boundary, particles in the slow flow are transported to higher latitudes due to the extension of the IMF lines to higher latitudes. The longitudinal patterns of the particles are dominated by the density of IMF lines. The focusing effect modulates the longitudinal variation of the particle intensity and gives rise to new longitudinal intensity peaks. The adiabatic effect largely increases the intensity fluctuation along the longitude. The structure of the solar wind can also lead to the difference of the index \begin{document}$ \alpha $\end{document} in the empirical function \begin{document}$ I_{{\mathrm{max}}}=kR^{-\alpha} $\end{document}, describing the radial variation of peak intensity according to our simulation. Under the influence of the CIR structure, the index \begin{document}$ \alpha $\end{document} varies from 1.9 to 3.4 at 0.3−1.0 AU. The variation of the solar wind speed should be considered when estimating the radial dependence of the SEP peak intensity. The spectra indices rise near the CIR boundaries and drop near the stream interface (SI). The adiabatic effect makes the spatial variability of the spectral index larger. The spectral index could be similar at different radial distances in the CIR structure.

Abstract The non-coordination between the socio-economic systems and ecosystems of a region is a crucial obstacle to sustainable development. To reveal the relationships between complex urban systems and achieve the goal of sustainable and coordinated urban development, we constructed a coupling coordination degree model (CCDM) and coupling angle model (CAM) and analyzed the degree of coupling coordination and evolution process among the population, water resources, economy, and ecology (PWEE) system of the Tuha region for 2005–2020. The results indicated that: (1) During 2005–2020, the comprehensive development index (CDI) of the population, water resources and economy subsystems was 0.21–0.65, with the three subsystems portraying an overall increase; the average values of the RSEI at five-year intervals were 0.29, 0.28, 0.28, and 0.26, indicating a downward trend in the environmental quality. (2) The coupling coordination effect of the PWEE system portrayed a low level; the coupling coordination degree (CCD) values were 0.28–0.58, portraying a fluctuating upward trend. The level of CCD increased from low disorder to marginal coordination. (3) The PWEE system’s scissor difference reflects large evolutionary characteristics. The ecological support capacity was not observed until the late stage. We conclude that the PWEE composite system of the region is in a stage of disordered development. These findings significantly bolster the theoretical underpinnings of sustainable development studies, offering essential scientific theories and methodological frameworks for crafting sustainable development policies tailored to urban systems in the Tuha region.

BackgroundBecker muscular dystrophy (BMD) is an X-linked recessive inherited disorder characterized by slowly progressing muscle weakness of the legs and pelvis, caused by mutations in the DMD gene, which encodes dystrophin protein. Different from Duchenne Muscular Dystrophy (DMD), in which dystrophin is completely absent in muscle tissue, while in BMD, the dystrophin gene can express some protein, but not enough. It has also been shown that a proportion of patients with DMD suffer from attention deficit hyperactivity disorder (ADHD), and the use of the stimulant methylphenidate has been suggested for the treatment of patients with DMD in combination with ADHD. However, there are no case reports on the treatment of co-occurring ADHD in BMD.Case presentationThe patient was a 9-year-old boy who presented with elevated serum creatine kinase levels and inattention. The magnetic resonance imaging of the thigh muscles of both lower limbs suggested partial fatty infiltration of the gluteus maximus muscle bilaterally, and a novel heterozygous mutation (c.31 + 6 T > C) was identified in the DMD gene by Next Generation Sequencing (NGS) and the sequencing results were verified by using the Sanger method. The child was also diagnosed with co-morbid ADHD after a thorough evaluation and considering this new diagnosis, we started treatment with methylphenidate at a dose of 18 mg/day, and after 6 months of treatment, he showed a significant improvement in his attention span.ConclusionWe identified a novel heterozygous mutation in the DMD gene, which will expand the spectrum of pathogenic variants in BMD. Simultaneously, methylphenidate treatment significantly improved attention in children with BMD co-morbid with ADHD, and this study provides value for future therapeutic protocols for BMD combined with ADHD. However, to the best of our knowledge, this is the only reported case report on the treatment of BMD co-morbid ADHD. So further studies are needed to determine the interrelationship between these disorders and their treatment.

Abstract Marine heatwaves (MHWs) represent anomalously warm temperature conditions of seawater that may affect marine life and ocean biogeochemistry. Under such conditions, phytoplankton communities may modify their structure and functions, and their resilience is not assured. This study characterizes the impact of MHWs on the phytoplankton spring bloom in the North‐Western Mediterranean Sea. Here, we synergistically combine autonomous observations from BioGeoChemical‐Argo floats, satellite‐based and marine ecosystem model data, and show that MHW events occurring during winter drastically inhibit phytoplankton carbon biomass in spring by up to 70%. Such reduction is related to the enhanced stratification of the water column under MHWs which hinders the renewal of nutrients from deep‐ocean reservoirs, thus preventing surface phytoplankton from blooming. This process negatively impacts particulate organic carbon stocks within the mixed layer, while severe events cause an earlier shift of phytoplankton phenology that provokes changes in zooplankton biomass distribution.

Abstract River sediments play a critical role in sustaining deltaic wetlands. Therefore, concerns are raised about wetlands’ fate due to the decline of river sediment supply to many deltas. However, the dynamics and drivers of suspended sediment near deltaic coasts are not comprehensively assessed, and its response to river sediment supply changes remains unclear. Here we examine patterns of coastal suspended sediment concentration (SSC) and river sediment plume area (RPA) for 349 deltas worldwide using satellite images from 2000 to 2020. We find a global increase in SSC and RPA, averaging +0.46% and +0.48% yr−1, respectively, with over 59.0% of deltas exhibiting an increase in both SSC and RPA. SSC and RPA increases are prevalent across all continents, except for Asia. The relationship between river sediment supply and coastal SSCs varies between deltas, with as much as 45.2% of the deltas showing opposing trends between river sediments and coastal SSCs. This is likely because of the impacts of tides, waves, salinity, and delta morphology. Our observed increase in SSCs near river delta paints a rare promising picture for wetland resilience against sea-level rise, yet whether this increase will persist remains uncertain.

Abstract With the formation and popularization of the 5G-enabled industrial internet, cybersecurity risks are increasing, and the limited number of attack samples, such as zero-day, leaves a short response time for security protectors, making it substantially more difficult to protect industrial control systems from new types of malicious attacks. Traditional supervised intrusion detection models rely on a large number of samples for training and their performance needs to be improved. Therefore, there is an urgent need for few-shot intrusion detection. Aiming at the above problems, this paper proposes a detection model based on a meta-learning framework, which aims to effectively improve the accuracy and real-time performance of intrusion detection, and designs a meta-learning intrusion detection model containing a sample generation module, a feature mapping module and a feature metric module. Among them, the sample generation module introduces the residual block into the Natural GAN and proposes a new method to generate high-quality antagonistic samples—Res-Natural GAN, which is used to enhance the antagonism of the generated samples and the feature mining degree, to improve the accuracy of malicious traffic detection; the feature mapping module proposes a new attention mechanism, the multi-head fast attention mechanism, which is applied to the encoder structure of the transformer and combined with a parameter optimization algorithm based on particle swarm mutation to shorten the mapping time and improve the real-time performance of the model while mapping the features effectively; the feature metric module proposes a prototype structure based on a prototype storage update algorithm and combines it with a prototype network to achieve correct classification by measuring the Euclidean distance between the detected samples and the class of prototypes, and to shorten the inference time while ensuring the detection accuracy; finally, the three modules are combined to form a real-time meta-learning intrusion detection model. To evaluate the proposed model, five different types of experiments are conducted on multiple public datasets. The experimental results show that the model has higher detection accuracy than the traditional model for both few-shot and zero-shot malicious attacks, and is not only applicable to 5G-enabled industrial internet, but also generalized to different network environments and attack types.

Abstract Northwest China has great natural resource endowment to develop its economy, but factors such as geographic remoteness and technological backwardness result in lower economic levels and higher carbon emissions. This study calculated the energy-related carbon emissions of five provinces in this region, and the evolutionary characteristics of energy-related carbon emissions were analysed from the spatiotemporal perspective. The Kaya identity was applied to decompose the factors influencing energy-related carbon emissions, and the logarithmic mean divisia index (LMDI) and refined Laspeyres index were combined to calculate the role of each influencing factor on energy-related carbon emissions. Finally, the Tapio and LMDI models were used to analyse the evolution of the decoupling relationship between energy-related carbon emissions and economic growth and the role of various influencing factors. The energy-related carbon emissions in Northwest China showed an increasing trend. In terms of influencing factors, economic growth and urban expansion had the highest contributions to carbon emissions and decoupling inhibition, whereas population agglomeration had the opposite effect. Northwest China showed great decoupling trends between energy-related carbon emissions and economic growth.

Biomechanic studies can provide a powerful theoretical and scientific basis for studies on knee osteoarthritis (OA), which is of great significance for clinical management as it provides new concepts and methods in clinical and research settings. This study aimed to discuss and summarize biomechanical research on lower extremities in individuals with knee OA in the past ten years. The methodology of this review followed the framework outlined in the Joanna Briggs Institute (JBI) guidelines and strictly followed the checklist for drafting the findings. A literature search was conducted using PubMed, Scopus, Cochrane Library, Embase, Web of Science, Grey literature search in Open Library, and Google Academic databases. Relevant literature was searched from 2011 to 2023. Sixteen studies were included in this scoping review. Biomechanical research on knee OA in the last decade demonstrates that the biomechanics of the hip, knee, and ankle have a profound influence on the pathogenesis and treatment of knee OA. Individuals with knee OA have biomechanical changes in hip, knee, and ankle joints such as a significant defect in the strength of ankle varus muscles, weakness of hip abductor muscle, walking with toes outwards, increased knee adduction moment and angle, and decreased knee extensor moment. As the severity of knee OA increases, the tendency of hip abduction positions also increases. Further research with a longitudinal study design should focus on the determination of the relative importance of different biomechanical and neuromuscular factors in the development and progression of the disease.

Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in children, characterized by age-inappropriate inattention, hyperactivity, and impulsivity, which can cause extensive damage to children's academic, occupational, and social skills. This review will present current advancements in the field of attention deficit hyperactivity disorder, including genetics, environmental factors, epigenetics, and neuroimaging features. Simultaneously, we will discuss the highlights of promising directions for further study.

This study demonstrates the existence of an evanescent electron wave outside both finite and infinite quantum wells by solving the Dirac equation and ensuring the continuity of the spinor wavefunction at the boundaries. We show that this evanescent wave shares the spin characteristics of the wave confined within the well, as indicated by analytical expressions for the current density across all regions. Our findings suggest that the electron cannot be confined to a mathematical singularity and that quantum information, or quantum entropy, can leak through any quantum confinement. These results emphasize that the electron wave, fully characterized by Lorentz-invariant charge and current densities, should be considered the true and sole entity of the electron.

Solar energetic particles (SEPs) are bursts of high-energy particles that originate from the Sun and can last for hours or even days. The aim of this study is to understand how the characteristics of energetic particles ware affected by the characteristic parameters of corotating interaction regions (CIRs). In particular, the particle intensity distribution with time and space in CIRs with different characteristics were studied. The propagation and acceleration of particles were described by the focused transport equation (FTE). We used a three-dimensional magnetohydrodynamic (MHD) model to simulate the background solar wind with CIRs. By changing the inner boundary conditions, we constructed CIRs with different solar wind speeds, angles between the polar axis and rotation axis, and the azimuthal widths of the fast streams. Particles were impulsively injected at the inner boundary of the MHD model. We then studied the particle propagation and compression acceleration in different background solar wind. The results showed that the CIR widths are related to the solar wind speed, tilt angles, and the azimuthal widths of the fast stream. The acceleration of particles in the reverse and forward compression regions are mainly influenced by the solar wind speed difference and the slow solar wind speed, respectively. Particles with lower energy (sub-MeV) are more sensitive to the solar wind speed difference and the tilt angle. The particle intensity variation with time and the radial distance is mainly influenced by the solar wind speed. The longitudinal distribution of particle intensity is affected by the solar wind speed, tilt angles, and the azimuthal widths of the fast stream.

In recent years, increasing urbanization has profoundly impacted the quality of regional habitats, presenting a severe risk to the ability of a region to develop in a high-quality manner. Therefore, the scientific assessment of the features of habitat quality (HQ) evolution over time and space and the prediction of future trends in changes in the HQ are of great significance for the formulation of effective ecological protection policies. Based on five periods of land use and land cover (LULC) data from 2000 to 2020, InVEST model was used to estimate both geographical and chronological trends in the HQ in the Tuha region, China. Spatial autocorrelation analysis methods were used to assess HQ and spatial aggregation of habitat degradation, and ecological zoning was delineated in conjunction with the Human Footprint Index (HFI). Based on the results of ecological zoning, the study predicted changes in habitat quality (HQ) in 2040 under three scenarios: natural development (ND), ecological preservation (EP), and urban development (UD) by applying the Patch-Generating Land Use Simulation (PLUS) model. The results demonstrated that (1) from 2000 to 2020, the habitat quality in the Tuha region exhibited a downward trend, with the proportion of low HQ increasing from 83.63% to 84.24%. Spatially, high habitat quality (HQ) is mainly concentrated in the Tianshan Mountains. From 2000 to 2020, the Moran index for habitat quality (HQ) decreased from 0.967 to 0.959, while the Moran index for habitat degradation declined from 0.805 to 0.780. The habitat quality (HQ) and degradation exhibit significant spatial aggregation, and the degree of degradation has increased incrementally. (2) From 2000 to 2020, human activities in the Tuha area increased continuously and were mainly concentrated in Tuha district and counties. The proportion of high Human Footprint Index (HFI) increased from 0.66% to 1.32%, while the proportion of medium HFI increased from 3.13% to 7.46%. (3) The expansion of urbanized land has exacerbated habitat degradation. The proportion of high HQ in the EP scenario is higher than that in ND and UD scenario. The results show that the ecological protection scenario is more conducive to the sustainable development of habitat quality in the Tuha region. The results can provide a scientific basis for ecological management and protection in the Tuha area.

Background: ANXA2 has been extensively documented in relation to cancer. Nevertheless, the involvement of ANXA2 in lung carcinoma remains uncertain. Methods: Data from The Cancer Genome Atlas (TCGA) database was downloaded using open-access methods. The examination of publicly available data was conducted utilizing the R software. The mRNA level of specific molecules was detected using Real-time Quantitative PCR (qPCR). The protein level of specific molecules was detected using the Western blot assay. The cell proliferation ability of cancer cells was assessed using the CCK8 assay. The invasion and migration capability of cancer cells was assessed using the Transwell assay. Validation of exosomes extraction was conducted using electron microscopy and particle size analysis. Results: In this study, based on series experiments, we found that ANXA2 can promote the activation of neuroastrocytes cells CP-H122 through the exosome pathway. Also, we found that ANXA2 can be transmitted from A549 cells to CP-H122 through the exosomes pathway and further promote the activation of CP-H122. Activated CP-H122 cells further enhance the proliferation, invasion and metastasis of A549 cells. Meanwhile, we performed transcriptome sequencing to explore the downstream genes of ANXA2 to screen potential targets for follow-up studies. Analysis based on public data showed that ANXA2 was related to the worse survival performance and clinical features of lung cancer. Gene set enrichment analysis based on the Hallmark gene set indicated that the patient with high ANXA2 expression might have a higher activity of the apical surface, reactive oxygen species pathway, angiogenesis, TGF-β signaling, MYC target, but lower activity of pancreas-β cells. More important, our results showed that ANXA2 can affects immunotherapy response and reshape immune microenvironment of lung cancer. Conclusions: This study demonstrates that ANXA2 activates CP-H122 cells, affects A549 cell behavior, and impacts lung cancer prognosis and immunotherapy response.

Exosomes have been demonstrated to exert momentous roles in autism spectrum disorder (ASD). However, few studies have reported a correlation between exosomal microRNAs (miRNAs) and ASD. To date, our understanding of crucial competing endogenous RNA (ceRNA) networks in ASD remains limited. Herein, the exosomal miRNA profile in the peripheral blood of children with ASD and healthy controls was investigated and the level of immune cell infiltration in ASD was evaluated to determine the distribution of immune cell subtypes. Exosomes were isolated from the peripheral blood of ten children with ASD and ten healthy controls, and further identified using transmission electron microscopy and western blot analysis. RNA sequencing was conducted to investigate exosomal miRNA profiles in patients with ASD. The mRNA and circular RNA (circRNA) expression profiles were acquired from the Gene Expression Omnibus (GEO) database. Differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs), and circRNAs (DEcircRNAs) were identified and ceRNA regulatory networks were constructed. Furthermore, the immune cell infiltration levels in patients with ASD were evaluated. Exosomes were spherical, approximately 100 nm in size, and were confirmed via western blot analysis using exosome-associated markers CD9, CD63, and CD81. Thirty-five DEmRNAs, 63 DEmiRNAs, and 494 DEcircRNAs were identified in patients with ASD. CeRNA regulatory networks, including 6 DEmRNAs, 14 DEmiRNAs, and 86 DEcircRNAs, were established. Correlation analysis indicated that leucine-rich glioma inactivated protein 1 (LGI1) expression was significantly positively correlated with the content of CD8+ T cells. Our findings may be conducive to offering novel insights into this disease and providing further evidence of transcriptomic abnormalities in ASD.

Accumulating evidence has highlighted a strong association between gut microbiota and the occurrence, development, prevention, and treatment of atopic dermatitis (AD). The regulation of gut microbial dysbiosis by oral traditional Chinese medicine (TCM) has garnered significant attention. In the treatment of AD, the TCM formula Qingre-Qushi Recipe (QRQS) has demonstrated clinical efficacy. However, both the therapeutic mechanisms of QRQS and its impact on gut microbiota remain unclear. Thus, our study aimed to assess the efficacy of QRQS and evaluate its influence on the composition and diversity of gut microbiota in AD animal models. First, we investigated the therapeutic effect of QRQS on AD using two animal models: filaggrin-deficient mice (Flaky tail, ft/ft) and MC903-induced AD-like mice. Subsequently, we explored its influence on the composition and diversity of gut microbiota. Our results demonstrated that QRQS treatment ameliorated the symptoms in both ft/ft mice and MC903-induced AD-like mice. It also reduced the levels of serum IgE and pro-inflammatory cytokines, including IL-1β, IL-4, IL-5, IL-9, IL-13, IL-17A, and TNF-α. Furthermore, QRQS remarkably regulated gut microbiota diversity by increasing Lactobacillaceae and decreasing Bacteroidales. The inflammatory factors in peripheral serum of ft/ft mice showed a close correlation with gut microbiota, as determined using the Spearman correlation coefficient. Additionally, PICRUSt analysis revealed an enrichment in ascorbate and aldarate metabolism, fatty acid metabolism and biosynthesis, and propanoate metabolism in the QRQS group compared to the ft/ft group. Finally, we identified liquiritin as the primary active ingredient of QRQS using ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS). Our findings revealed that QRQS improved AD-like symptoms and alleviated skin inflammation in ft/ft and MC903-induced mice. This suggests that modulating the gut microbiota may help elucidate its anti-inflammation activation mechanism, highlighting a new therapeutic strategy that targets the intestinal flora to prevent and treat AD.

A Ni-15Cr-5Al-6Ge alloy was prepared using powder metallurgy technology. The effect of Ge on the oxidation resistance of Ni-Cr-Al alloy at 1000°C was investigated. The results indicate that the addition of Ge reduces the oxidation rate of the alloy interface in the range of 0 to 6 wt.% Ge. When the Ge content reaches 6 wt.%, a continuous and dense oxide film forms on the surface of the matrix, imparting the alloy with the best oxidation resistance. The addition of Ge improves the selective oxidation of Al and inhibits the diffusion rate of Ni and Cr elements to the alloy surface, resulting in the formation of a single, uniform Al2O3 oxide film on the alloy surface with a thickness of approximately 1.45 micrometers. An appropriate amount of Ge (6 wt.%) reduces surface defects, while an excessive amount of Ge (8 wt.%) increases surface defects, thereby adversely affecting the oxidation resistance of the alloy.

Summary: In this study, we report on mosaic variegated aneuploidy (MVA) syndrome with tetraploidy and predisposition to infertility in a family. Sequencing analysis identified that the CEP192 biallelic variants (c.1912C>T, p.His638Tyr and c.5750A>G, p.Asn1917Ser) segregated with microcephaly, short stature, limb-extremity dysplasia, and reduced testicular size, while CEP192 monoallelic variants segregated with infertility and/or reduced testicular size in the family. In 1,264 unrelated patients, variant screening for CEP192 identified a same variant (c.5750A>G, p.Asn1917Ser) and other variants significantly associated with infertility. Two lines of Cep192 mice model that are equivalent to human variants were generated. Embryos with Cep192 biallelic variants arrested at E7 because of cell apoptosis mediated by MVA/tetraploidy cell acumination. Mice with heterozygous variants replicated the predisposition to male infertility. Mouse primary embryonic fibroblasts with Cep192 biallelic variants cultured in vitro showed abnormal morphology, mitotic arresting, and disruption of spindle formation. In patient epithelial cells with biallelic variants cultured in vitro, the number of cells arrested during the prophase increased because of the failure of spindle formation. Accordingly, we present mutant CEP192, which is a link for the MVA syndrome with tetraploidy and the predisposition to male infertility.

With the formation and popularity of the Internet of Things(IoT), the difficulty of protecting IoT infrastructure and smart devices from a few-shot of ever-changing malicious attacks has increased significantly. Traditional intrusion detection models in static mode cannot defend against intelligent attacks that change in real time and are good at reconnaissance, and it is difficult to achieve effective detection of few-shot attacks. Therefore, to solve the above problems, this paper proposes a variable few-shot intrusion detection model GDE Model for IoT, which contains a data processing module consisting of an improved Gramian Angular Fields(GAF), a data augmentation module consisting of an improved Denoising Diffusion Probabilistic Models(DDPM), and an image classification module consisting of a variable network ETNet V2 obtained from a neural architecture search based on efficient net v2. The one-dimensional network traffic data collected from a real network environment is converted into two-dimensional images and fed into the above model for learning and training, so as to construct a variable intrusion detection model that combines accuracy and inference speed. To evaluate the work of this paper, different categories of evaluation metrics were selected and experiments were conducted on each module and the overall model separately. The experimental results show that the proposed intrusion detection model achieves variable functionality with an accuracy of up to 99.20% for few-shot detection and an average inference time as low as 23ms, which can be used not only for IoT but also for different network environments and attack types.

ABSTRACTImmune checkpoint inhibitors that overcome T cell suppressive mechanisms in tumors have revolutionized the treatment of cancer but are only efficacious in a small subset of patients. Targeting suppressive mechanisms acting on innate immune cells could significantly improve the incidence of clinical response by facilitating a multi-lineage response against the tumor involving both adaptive and innate immune systems. Here, we show that intra-tumoral interleukin (IL)-38 expression is a feature of a large frequency of head and neck, lung and cervical squamous cancers and correlates with reduced immune cell numbers. We generated IMM20324, an antibody that binds human and mouse IL-38 proteins and inhibits the binding of IL-38 to its putative receptors, interleukin 1 receptor accessory protein-like 1 (IL1RAPL) and IL-36R. In vivo, IMM20324 demonstrated a good safety profile, delayed tumor growth in a subset of mice in an EMT6 syngeneic model of breast cancer, and significantly inhibited tumor expansion in a B16.F10 melanoma model. Notably, IMM20324 treatment resulted in the prevention of tumor growth following re-implantation of tumor cells, indicating the induction of immunological memory. Furthermore, exposure of IMM20324 correlated with decreased tumor volume and increased levels of intra-tumoral chemokines. Together, our data suggest that IL-38 is expressed in a high frequency of cancer patients and allows tumor cells to suppress anti-tumor immunity. Blockade of IL-38 activity using IMM20324 can re-activate immunostimulatory mechanisms in the tumor microenvironment leading to immune infiltration, the generation of tumor-specific memory and abrogation of tumor growth.

The coastal environment is characterized by high, multi-scale dynamics and the corresponding observations from a single remote sensing sensor are still facing challenges in achieving both high temporal and spatial resolution. This study proposed a spatiotemporal fusion model for coastal environments, which could fully enhance the efficiency of remote sensing data use and overcome the shortcomings of traditional spatiotemporal models that are insensitive to small-scale disturbances. The Enhanced Deep Super-Resolution Network (EDSR) was used to reconstruct spatial features in the lower spatial resolution GOCI-II data. The spatial features obtained instead of GOCI-II data were fed into the spatiotemporal fusion model, which enabled the fusion data to achieve an hour-by-hour observation of the water color and morphology information changes at 30 m resolution, including the changes in the spatial and temporal distributions of suspended particulate matter (SPM), the characterization of the vortex street caused by the bridge piers, the inundation process of the tidal flats, and coastline changes. In addition, this study analyzed the various factors affecting fusion accuracy, including spectral difference, errors in both temporal difference and location distance, and the structure of the EDSR model on the fusion accuracy. It is demonstrated that the location distance error and the spectral difference have the most significant impact on the fusion data, which may lead to the introduction of some ambiguous or erroneous spatial features.

The magnetic orientation of coronal mass ejections (CMEs) is of great importance to understand their space weather effects. Although plenty of evidence suggests that CMEs can undergo significant rotation during the early phases of evolution in the solar corona, there are few reports that CMEs rotate in the interplanetary space. In this work, we use multispacecraft observations and a numerical simulation starting from the lower corona close to the solar surface to understand the CME event on 2021 December 4, with an emphatic investigation of its rotation. This event is observed as a partial halo CME from the back side of the Sun by coronagraphs and reaches the BepiColombo spacecraft and the Mars Atmosphere and Volatile EvolutioN/Tianwen-1 as a magnetic flux-rope-like structure. The simulation discloses that in the solar corona the CME is approximately a translational motion, while the interplanetary propagation process evidences a gradual change of axis orientation of the CME’s flux-rope-like structure. It is also found that the downside and the right flank of the CME moves with the fast solar wind, and the upside does in the slow-speed stream. The different parts of the CME with different speeds generate the nonidentical displacements of its magnetic structure, resulting in the rotation of the CME in the interplanetary space. Furthermore, at the right flank of the CME exists a corotating interaction region, which makes the orientation of the CME alter and also deviates from its route due to the CME. These results provide new insight into interpreting CMEs’ dynamics and structures during their traveling through the heliosphere.

The timely and precise prediction of the arrival time of coronal mass ejections (CMEs) is crucial in mitigating their potential adverse effects. In this study, we present a novel prediction method utilizing a deep-learning framework coupled with physical characteristics of CMEs and background solar wind. Time series images from synchronized solar white-light and EUV observations of 156 geoeffective CME events during 2000–2020 are collected for this study, according to the Richardson and Cane interplanetary CME directory and the SOHO/LASCO CME catalog of NASA/CDAW. The CME parameters are obtained from the CDAW website and the solar wind parameters are from OMNI2 website. The observational images are first fed into a convolutional neural network (CNN) to train a regression model as Model A. The results generated by the original CNN are then integrated with 11 selected physical parameters in additional neural network layers of Model B to improve the predictions. Under optimal configurations, Model A achieves a minimum mean absolute error (MAE) of 7.87 hr, whereas Model B yields a minimum MAE of 5.12 hr. During model training, we employed tenfold cross validation to reduce the occasionality of biased data. The average MAE of Model B on 10 folds is 33% lower than that of model A. The results demonstrate that combining the imaging observations with the physical properties of CMEs and background solar wind to train a machine-learning model can benefit the forecasting of CME arrival times.

Combined with data assimilation methods, a three-dimensional magnetohydrodynamic (MHD) numerical model is an effective tool to explore the mechanism of space weather. As a driver of space weather, the dynamic development of stream interaction regions (SIRs) near the orbit of Mars is an area of active research. In this study, we use the interplanetary total variation diminishing (TVD) MHD model to simulate solar wind parameters and model SIRs near Mars from 2021 November 15 to 2021 December 31. In this model, the MHD equations are solved by the conservation TVD Lax–Friedrichs scheme in a rotating spherical coordinate system with six component meshes used on the spherical shell. Solar wind velocity, density, temperature, and magnetic field strength are given at the inner boundary due to the characteristic waves propagating outward. We compared modeled results with observations from Mars Atmospheric Volatile EvolutioN (MAVEN) and Tianwen-1 (China’s first Mars exploration mission). Statistical analysis shows that the simulated results can capture SIRs and are in good agreement with observations; moreover, the assimilated results based on the Kalman filter improve the accuracy of numerical prediction compared with simulated results. This paper is the first attempt to simulate SIR events combined with MAVEN and Tianwen-1 in situ observations. Our work demonstrates that using the MHD model with the Kalman filter to reconstruct solar wind parameters can help us study the characteristics of SIRs near Mars, improve the capabilities of space weather forecasting, and understand the background solar wind environment.

Coronal mass ejections (CMEs) constitute the major source of severe space weather events, with the potential to cause enormous damage to humans and spacecraft in space. It is becoming increasingly important to detect and track CMEs, since there are more and more space activities and facilities. We have developed a new algorithm to automatically derive a CME’s kinematic parameters based on machine learning. Our method consists of three steps: recognition, tracking, and the determination of parameters. First, we train a convolutional neural network to classify images from Solar and Heliospheric Observatory Large Angle Spectrometric Coronagraph observations into two categories, containing CME(s) or not. Next, we apply the principal component analysis algorithm and Otsu’s method to acquire binary-labeled CME regions. Then, we employ the track-match algorithm to track a CME’s motion in time-series images and finally determine the CME’s kinematic parameters, e.g., velocity, angular width, and central position angle. The results of four typical CME events with different morphological characteristics are presented and compared with a manual CME catalog and several automatic CME catalogs. Our algorithm shows some advantages in the recognition of CME structure and the accuracy of the kinematic parameters. This algorithm can be helpful for real-time CME warnings and predictions. In the future, this algorithm is capable of being applied to CME initialization in magnetohydrodynamic simulations to study the propagation characteristics of real CME events and to provide more efficient predictions of CMEs’ geoeffectiveness.

We continue the numerical modeling of a corotating interaction region (CIR) and the effects it has on solar-rotational recurrent variations of galactic cosmic rays (GCRs). A magnetohydrodynamic model is adapted to simulate the background solar wind plasma with a CIR structure in the inner heliosphere, which is incorporated into a comprehensive Parker-type transport model. The focus is on the simulation of the effects of a CIR on GCR protons and the two helium isotopes as a function of heliolongitude. This is to establish whether the difference in composition affects how they are modulated by the CIR in terms of their distribution in longitude. It is demonstrated that particle diffusion and drift influence the effects of the CIR with increasing rigidity from 100 MV up to 15 GV. It is found that protons and helium isotopes are modulated differently with longitude by the CIR and that particle drift influences the modulation effects in longitude. These differences dissipate with increasing rigidity. The final results are focused on the simulated amplitude of these GCR flux variations as a function of rigidity. The amplitude displays a power-law behavior above ∼1 GV with an index similar to the power index of the rigidity dependence of the assumed diffusion coefficients. The simulations further show that below this rigidity, the amplitude at first flattens off, displaying a plateau-like profile, but it then increases systematically with decreasing rigidity below ∼0.3 GV. Again, a power-law behavior is displayed, but it is completely different from that above 1 GV.

Coronal mass ejection (CME) is a kind of space weather phenomenon caused by the intense activity of the sun. Important issues of concern to the space weather community include understanding the propagation and evolution of a particular CME in the corona and interplanetary space, forecasting whether and when it will reach the earth orbit, and predicting the change of solar wind state in near-earth space. CME always carries a vast amount of energy. When it reaches space near the earth, it will cause a severe disturbance, and trigger catastrophic space weather events, such as the geomagnetic storm. In order to utilize space resources and develop space science more deeply, avoid the damage of severe space weather caused by CME, it is important to improve the accuracy and efficiency of CME forecasting. Numerical simulation is one of the practical tools for the study and prediction of CME's propagation.This review introduces the different models used in the CME propagation simulations and their latest research progress. Firstly, we summarize the various CME propagation simulation models including background solar wind models, CME initialization models, and coronal magnetic field reconstruction models. The outline of the application and research progress of these models in the propagation simulation is also presented. Then, we review the simulation studies on the deflection of CME, including the deflection in the corona and its interaction with CIR. The relationship between CMEs and their simulation is then discussed. Finally, based on this research, we propose the problems that need to be solved in the CME propagation simulation research and give a few prospects.

Numerous chemical compounds used in cancer treatment have been isolated from natural herbs to address the ever-increasing cancer incidence worldwide. Therein is icariin, which has been extensively studied for its therapeutic potential due to its anti-inflammatory, antioxidant, antidepressant, and aphrodisiac properties. However, there is a lack of comprehensive and detailed review of studies on icariin in cancer treatment. Given this, this study reviews and examines the relevant literature on the chemopreventive and therapeutic potentials of icariin in cancer treatment and describes its mechanism of action. The review shows that icariin has the property of inhibiting cancer progression and reversing drug resistance. Therefore, icariin may be a valuable potential agent for the prevention and treatment of various cancers due to its natural origin, safety, and low cost compared to conventional anticancer drugs, while further research on this natural agent is needed.

CD24 is a glycosylphosphatidylinositol linked molecular which expressed in diverse malignant tumor cells, particular in ovarian carcinoma cells and ovarian carcinoma stem cells. The CD24 expression is associated with increased metastatic potential and poor prognosis of malignancies. CD24 on the surface of tumor cells could interact with Siglec-10 on the surface of immune cells, to mediate the immune escape of tumor cells. Nowadays, CD24 has been identified as a promising focus for targeting therapy of ovarian cancer. However, the roles of CD24 in tumorigenesis, metastasis, and immune escape are still not clearly demonstrated systematically. In this review, we i) summarized the existing studies on CD24 in diverse cancers including ovarian cancer, ii) illustrated the role of CD24-siglec10 signaling pathway in immune escape, iii) reviewed the existing immunotherapeutic strategies (targeting the CD24 to restore the phagocytic effect of Siglec-10 expressing immune cells) based on the above mechanisms and evaluated the priorities in the future research. These results might provide support for guiding the CD24 immunotherapy as the intervention upon solid tumors.

The human papillomavirus (HPV) vaccine reduces the prevalence of genital warts and the cancers they are associated with in males. However, the vaccination of males has always been neglected. Here, we performed a meta-analysis to comprehend the acceptability of the HPV vaccine in men and the factors impacting vaccination intentions. We searched PubMed, Web of Science, Embase, Ovid, CNKI, and Wan Fang up to 5 July 2023 for studies that reported HPV vaccine acceptance among men. A random effects model was used to obtain the pooled acceptance rate, and subgroup analysis was performed. Then, the influencing factors of HPV vaccination in males were analyzed. A total of 57 studies with 32,962 samples were included in the analysis. The overall acceptance rate of the HPV vaccine in general men was 47.04% (95% confidence interval [95%CI]: 39.23–54.93%), and 62.23% (95% CI: 52.93–71.10%) among those whose sexual orientation contained men. HPV vaccine acceptance rates differed significantly between the two populations (p = 0.01). The population with a medical background (46.23%, 95% CI: 40.28–52.24%) was more willing to be vaccinated. In comparison to the employed population (66.93%, 95% CI: 48.79–82.81%) and the unemployed (68.44%, 95% CI: 52.82–82.23%), vaccination acceptance rates were lower among students (47.35%, 95% CI: 37.00–57.81%) (p = 0.04). The most significant barriers to vaccination were perceived low risk of infection for themselves (45.91%, 95% CI: 31.73–60.43%), followed by vaccine cost (43.46%, 95% CI: 31.20–56.13%). Moreover, the recommendations from medical professionals (60.90%, 95%CI: 44.23–76.37%) and sexual partners (60.09%, 95%CI: 27.11–88.67%) were significant factors in promoting vaccination. Overall, acceptance of the HPV vaccine among general men was at a lower level, despite being slightly higher among men with a same-sex orientation. Popularizing knowledge about diseases and vaccines, encouraging medical professionals to recommend vaccines to men, or reducing the cost of vaccines may promote HPV vaccination.

The predictions of plasma parameters in the interplanetary medium are the core of space weather forecasts, and the magnetohydrodynamics (MHD) numerical simulation is an important tool in the prediction of plasma parameters. Operational space weather forecasts are commonly produced by a heliosphere model whose inner boundary is set at 18 Rs or beyond. Such predictions typically use empirical/physics-based inner boundary conditions to solve the MHD equations for numerical simulation. In recent years, significant progress has been made in the numerical modeling of the inner heliosphere. In this paper, the numerical modeling of solar wind and coronal mass ejection in the inner heliosphere is reviewed. In particular, different inner boundary conditions used in the simulation are investigated since the MHD solutions are predetermined by the treatment of the inner boundary conditions to a large extent. Discussion is made on further development of the heliosphere model.

Abstract The high Zn ion desolvation energy, sluggish Zn deposition kinetics, and top Zn plating pattern are the key challenges toward practical Zn anodes. Herein, these key issues are addressed by introducing zinc pyrovanadate (ZVO) as a solid zinc‐ion conductor interface to induce smooth and fast Zn deposition underneath the layer. Electrochemical studies, computational analysis, and in situ observations reveal the boosted desolvation and deposition kinetics, and uniformity by ZVO interface. In addition, the anti‐corrosion ability of Zn anodes is improved, resulting in high Zn stripping/plating reversibility. Consequently, the ZVO layer renders fast rechargeability and durable life in both Zn symmetric cells (1050 h at 10 mA cm−2, 1 mAh cm−2) and Zn/V2O5 batteries (79.1% capacity retention after 1000 cycles at 2 A g−1) with low electrode polarization. This work provides insights into the design of solid zinc‐ion conductor interface to enhance the interface stability and kinetics of Zn metal anodes.

Purpose: Fermented camel milk from Xinjiang is rich in probiotics and has immunomodulatory effects as an important source of bioactive peptides. However, it is not clear whether it is the probiotic or the bioactive peptide that acts. The present study aimed to extract and identify bioactive peptides from fermented camel milk in Xinjiang and investigate their immunomodulatory effects and mechanisms based on network pharmacology and molecular docking.Methods: Four probiotic bacteria were used to ferment the fresh camel milk and the bioactive peptides were extracted and isolated by ultrafiltration and column chromatography. Network pharmacology predicts targets and pathways of action. GeneCards and OMIM-GENE-MAP database were used in order to search disease target genes and screen common target genes. Then we used STRING web to construct a protein-protein interaction (PPI) interaction network of the common target protein. The key targets were analyzed by GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis through the David database. The "drug (bioactive peptide)-disease-targets-pathway" network was established and molecular docking was used for prediction.Results: Two fractions were obtained by UV spectrophotometer; whey acidic protein, α-lactalbumin, and peptidoglycan recognition protein 1 were the main protein-like components of Xinjiang fermented camel milk-derived bioactive peptides. The repeat sequence of peptidoglycan recognition protein 1 was selected and then seven bioactive peptides were obtained. Bioactive peptides had 222 gene targets, anti-inflammatory diseases had 2598 gene targets, and immune regulation had 866 gene targets, the intersection of which was 66 in common gene targets. Gene ontology and KEGG analysis reveals that bioactive peptides mainly play a vital role in the signaling pathways of lipid and atherosclerosis, pathways in cancer. The molecular docking results showed that the seven bioactive peptides bound well to the top four scoring proteins.Conclusion: The immunomodulatory and anti-inflammatory effects and mechanisms of Xinjiang fermented camel milk-derived bioactive peptides were initially investigated by network pharmacology and molecular docking, providing a scientific basis for future studies.

A preliminary analysis to the current situation of the power grid optical transmission network was made.The power grid optical transmission network is facing huge challenges such as the increasing transmission capacity, the increasingly complex topology, the flexible scheduling of services and the evolution of network intelligence.By adopting photoelectric layered cross processing, electric layer cross focus on small particles business convergence and long distance electric regeneration, optical layer routing provides the flexible wavelength routing, based on colorless, directionless, and contention less flexible grid configurable add/drop architecture CDC-F ROADM technology to optimize network structure, improve the network transmission efficiency, reducing energy consumption and space, which also benefits the evolution of network intelligence, and greatly save the construction and operational costs.

Abstract This review article summarizes the advancement in the studies of Earth-affecting solar transients in the last decade that encompasses most of solar cycle 24. It is a part of the effort of the International Study of Earth-affecting Solar Transients (ISEST) project, sponsored by the SCOSTEP/VarSITI program (2014–2018). The Sun-Earth is an integrated physical system in which the space environment of the Earth sustains continuous influence from mass, magnetic field, and radiation energy output of the Sun in varying timescales from minutes to millennium. This article addresses short timescale events, from minutes to days that directly cause transient disturbances in the Earth’s space environment and generate intense adverse effects on advanced technological systems of human society. Such transient events largely fall into the following four types: (1) solar flares, (2) coronal mass ejections (CMEs) including their interplanetary counterparts ICMEs, (3) solar energetic particle (SEP) events, and (4) stream interaction regions (SIRs) including corotating interaction regions (CIRs). In the last decade, the unprecedented multi-viewpoint observations of the Sun from space, enabled by STEREO Ahead/Behind spacecraft in combination with a suite of observatories along the Sun-Earth lines, have provided much more accurate and global measurements of the size, speed, propagation direction, and morphology of CMEs in both 3D and over a large volume in the heliosphere. Many CMEs, fast ones, in particular, can be clearly characterized as a two-front (shock front plus ejecta front) and three-part (bright ejecta front, dark cavity, and bright core) structure. Drag-based kinematic models of CMEs are developed to interpret CME propagation in the heliosphere and are applied to predict their arrival times at 1 AU in an efficient manner. Several advanced MHD models have been developed to simulate realistic CME events from the initiation on the Sun until their arrival at 1 AU. Much progress has been made on detailed kinematic and dynamic behaviors of CMEs, including non-radial motion, rotation and deformation of CMEs, CME-CME interaction, and stealth CMEs and problematic ICMEs. The knowledge about SEPs has also been significantly improved. An outlook of how to address critical issues related to Earth-affecting solar transients concludes this article.

ObjectivesThe aim of the current study is to explore the association between extended adjuvant endocrine treatment and prognosis of women with hormone receptor-positive (HR+) early breast cancer.MethodsDatabases including PubMed, Web of Science, Embase and the Cochrane Library databases were electronically searched to identify randomized controlled trials (RCTs) that reported extended endocrine therapy for women with HR+ early breast cancer. The retrieval time was limited from inception to September 2022. Two reviewers independently screened literature, extracted data, and assessed risk bias of included studies. Meta-analysis was performed by using R software Version 4.1.2 and STATA Version 12.0.ResultsA total of 15 RCTs involving 29497 cases were included. The overall analysis showed that compared with the control, extended adjuvant endocrine therapy increased disease-free survival (DFS) (HR=0.814, 95% CI: 0.720-0.922, 95% PI: 0.556-1.194), overall survival (OS) (HR=0.885, 95% CI: 0.822-0.953, 95% PI: 0.771-1.035), relapse-free survival (RFS) (HR=0.833, 95% CI: 0.747-0.927, 95% PI: 0.575-1.159), distant metastatic-free survival (DMFS) (HR=0.824, 95% CI: 0.694-0.979, 95% PI: 0.300-2.089) and reduced new breast cancer cumulative incidence (NBCCI) (HR=0.484, 95% CI: 0.403-0.583, 95% PI: 0.359-0.654). For adverse events, extended adjuvant endocrine treatment was associated with a significantly higher risk of bone fracture (RR=1.446, 95% CI: 1.208-1.730, 95% PI: 1.154-1.854) and osteoporosis (RR=1.377, 95% CI: 1.018-1.862, 95% PI: 0.347-5.456).ConclusionOur study showed that extended adjuvant endocrine therapy increased DFS, OS, RFS, DMFS, the incidence of bone fracture and osteoporosis, and reduced NBCCI.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero, identifier (CRD42022351295)

Metformin is a first-line drug for type 2 diabetes, and its anticancer effects have also been widely studied in recent years. The Sonic hedgehog (Shh) signaling pathway is involved in the initiation and progression of medulloblastoma. In order to develop a new treatment strategy for medulloblastoma (MB), this study investigated the inhibitory effect of metformin on MB and the underlying mechanism of metformin on the Shh signaling pathway. The effect of metformin on proliferation was evaluated by the cell counting kit-8 (CCK-8) test and colony formation experiment. The effect of metformin on metastasis was assessed by the scratch-wound assay and transwell invasion assay. Cell cycle and apoptosis were evaluated by flow cytometry, and the associated proteins were examined by western blotting. The mRNA and protein expression levels related to the Shh pathway were measured by quantitative PCR, western blotting, and immunofluorescence staining. The xenograft murine model was carried out to evaluate the anticancer effect of metformin on medulloblastoma in vivo. Metformin inhibited proliferation and metastasis of the Shh subgroup MB cell line, and the inhibitory effect on proliferation was related to apoptosis and the block of the cell cycle at the G0/G1 phase. Animal experiments showed that metformin inhibits medulloblastoma growth in vivo. Moreover, metformin decreased mRNA and protein expression levels of the Shh pathway, and this effect was reversed by the AMP-activated protein kinase (AMPK) siRNA. Furthermore, the pro-apoptotic and cell cycle arrest effects of metformin on Daoy cells could be reversed by the Shh pathway activators. Our findings demonstrated that metformin could inhibit medulloblastoma progression in vitro and in vivo, and this effect was associated with AMPK-mediated inhibition of the Shh signaling pathway in vitro studies.

BackgroundIntravenous thrombolysis (IVT) is a standard procedure for the treatment of patients with acute ischemic stroke (AIS). Improving the therapeutic efficacy of IVT is an important task for neurologists. The aim of this study was to evaluate the efficacy and safety of early low-dose tirofiban treatment in AIS patients with early neurological deterioration (END) after IVT.MethodsIn this prospective and randomized pilot study, 73 AIS patients with END were recruited from a local hospital in China. Of these, 14 patients were treated with regular antiplatelet agents (aspirin plus clopidogrel) and 59 patients were treated with tirofiban within 24 h of IVT, followed by regular antiplatelet therapy. Neurological deficits and functional recovery were assessed with NIHSS and modified Rankin Scale (mRS) at 7 and 90 days. During the 90-day follow-up period, both hemorrhagic (e.g., intracerebral hemorrhage) and non-hemorrhagic (e.g., pneumonia) events were recorded.ResultsTreatment with tirofiban compared with regular antiplatelet therapy: (1) improved functional recovery of AIS patients to mRS (≤2) at both 7 and 90 days (odds ratios [ORs], 1.37 and 1.64; 95% confidence interval [CI], 1.16–1.61 and 1.26–2.12; P = 0.008 and < 0.001, respectively), and (2) reduced NIHSS scores from 11.14 ± 2.38 to 5.95 ± 3.48 at day 7 (P < 0.001) and from 8.14 ± 2.74 to 4.08 ± 3.50 at day 90 (P < 0.001). Tirofiban treatment did not increase the risk of hemorrhagic complications. Multivariate regression analysis showed that tirofiban treatment independently predicted a favorable functional outcome (P ≤ 0.001).ConclusionEarly treatment with low-dose tirofiban in AIS patients with neurologic deterioration after IVT potentially improved functional recovery and attenuated neurologic deficits as early as 7 days and did not increase the risk of various hemorrhagic complications. However, the therapeutic efficacy of tirofiban treatment in END patients needs to be determined by future randomized clinical trials with a large study population.Clinical trial registrationhttp://www.chictr.org.cn/, Identifier ChiCTR2200058513.

Abstract Background The COVID-19 pandemic has become a global health catastrophe. By far, there has been no specific antiviral treatment for COVID-19. Developing a vaccine against COVID-19 appeared to be the most cost-effective strategy to stop the repeated outbreak. This study aimed to investigate the attitudes of psychiatric patients with regards to COVID-19 vaccination and potential factors that might influence their decision-making process. Methods Psychiatric patients participated in this cross-sectional survey in China. Family caregivers, usually a guardian or next of kin completed the questionnaire when the patient is unable to consent. Data was collected via an online self-administered questionnaire. This questionnaire focused on four main attributes: (1) sociology-demographic characteristics, such as age and sex; (2) questions relating to the COVID-19 pandemic, such as perceived risk of COVID-19; (3) Flu vaccination history; and (4) attitude towards COVID-19 vaccination and affected factors, such as preferred vaccine type and vaccination site. The associated factors that influenced vaccination acceptance were analyzed by Chi-square analysis and binary logistic regression. Results In total, 416 individuals were recruited, from which 408: 229 patients and 179 family caregivers completed the online survey (response rate: 98.1%). 78.7% of the participants (178 patients and 143 family caregivers) said they intended to receive vaccination once the COVID-19 vaccine became available on the market. Our results showed that participants would have a greater likelihood of joining the COVID-9 immunization programme if the people they knew (community residents or their friends and relatives) presented with high vaccine coverage (OR = 0.24; 95% CI:0.09–0.59). If the pandemic returns, participants were also more likely to accept vaccination (OR = 0.21; 95% CI:0.07–0.62). Moreover, those who believed that the vaccination was an important way to control the COVID-19 pandemic also showed a tendency to receive vaccination (OR = 0.21; 95% CI:0.11–0.40). For those who did not intend to get vaccinated either for themselves or their psychiatric family member, the safety of vaccine was their main concern (71.3%). Conclusions This study showed a high acceptance rate for COVID-19 vaccination amongst psychiatric patients, while worries about the safety of vaccine led to refusal towards vaccination. To increase vaccination uptake amongst this vulnerable group, the public health messaging should include updated vaccination coverage in local communities, and the number of newly COVID-19 infected cases. Specific information about vaccine safety concerning psychiatric patients; as well as the importance of vaccination in controlling the pandemic should be explained in detail.

Diabetes increases the occurrence and severity of atherosclerosis. When plaques form in brain vessels, cerebral atherosclerosis causes thickness, rigidity, and unstableness of cerebral artery walls, leading to severe complications like stroke and contributing to cognitive impairment. So far, the molecular mechanism underlying cerebral atherosclerosis is not determined. Moreover, effective intervention strategies are lacking. In this study, we showed that polarization of microglia, the resident macrophage in the central nervous system, appeared to play a critical role in the pathological progression of cerebral atherosclerosis. Microglia likely underwent an M2c-like polarization in an environment long exposed to high glucose. Experimental suppression of microglia M2c polarization was achieved through transduction of microglia with an adeno-associated virus (serotype AAV-PHP.B) carrying siRNA for interleukin-10 (IL-10) under the control of a microglia-specific TMEM119 promoter, which significantly attenuated diabetes-associated cerebral atherosclerosis in a mouse model. Thus, our study suggests a novel translational strategy to prevent diabetes-associated cerebral atherosclerosis through in vivo control of microglia polarization.

Abstract During late 2019 and early 2020, Australia experienced one of the most active bushfire seasons that advected large emissions over the adjacent ocean. Herein, we present a comprehensive research on mixed atmospheric aerosol particulate pollution emitted by wildfires in the atmosphere and the ocean. Based on a wide range of physical and biochemical data, including the Aerosol Robotic Network, multi-satellite observations, and Argo floats, we investigated the spatio-temporal variations and mixed compositions of aerosol particles, deposition in the coastal waters of eastern Australia and the South Pacific Ocean, and biogeochemical responses in the water column. Four types of wildfire-derived mixed particles were classified by using the optical properties of aerosols into four types, including the background aerosols, mineral dust, wildfire smoke particles, and residual smoke. The coarse particles accounted for more than 60% of the mineral dust on 22 November 2019 in the Tasman Sea; afterwards, during the wildfire smoke episode from December 2019 to January 2020, the particles affected large areas of the atmosphere such as eastern Australia, the South Pacific Ocean, and South America. The maximum value of the aerosol optical depth reached 2.74, and the proportion of fine particles accounted for 98.9% in the smoke episode. Mineral dust and smoke particles from the fire emissions changed the particle composition in the surface ocean. Particle deposition accounted for increases in chlorophyll-a concentration (Chla) standardized anomaly up to maximum of 23.3 with a lag time of less than 8 days. In the vertical direction, float observations showed the impact of exogenous particles on the water column could up to 64.7 m deep, resulting in Chla of 1.85 mg/m3. The high Chla lasted for a minimum period of two months until it returned to normal level.

Abstract Alzheimer’s disease (AD) is a common neurodegenerative disease with poor prognosis. New options for drug discovery targets are needed. We developed an imaging based arrayed CRISPR method to interrogate the human genome for modulation of in vitro correlates of AD features, and used this to assess 1525 human genes related to tau aggregation, autophagy and mitochondria. This work revealed (I) a network of tau aggregation modulators including the NF-κB pathway and inflammatory signaling, (II) a correlation between mitochondrial morphology, respiratory function and transcriptomics, (III) machine learning predicted novel roles of genes and pathways in autophagic processes and (IV) individual gene function inferences and interactions among biological processes via multi-feature clustering. These studies provide a platform to interrogate underexplored aspects of AD biology and offer several specific hypotheses for future drug discovery efforts.

Hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) has recently aroused increasing attention, especially ST11, the predominant CRKP clone in China. Here, we report a case of hv-CRKP-associated infection and reveal the in-host evolution of its mechanism of resistance to tigecycline and polymyxin under clinical therapy. A total of 11 K. pneumoniae carbapenemase (KPC)-producing CRKP strains were consecutively isolated from a male patient who suffered from continuous and multisite infections. String and antimicrobial susceptibility tests identified seven hypermucoviscous strains and three tigecycline-resistant and four colistin-resistant strains. Galleria mellonella larvae infection model confirmed the hypervirulence. Pulsed-field gel electrophoresis (PFGE) separated three PFGE clusters among all strains, and further Southern blotting detected that blaKPC-2 was located on the same-sized plasmid. Whole-genome sequencing showed that all strains belonged to the hv-CRKP ST11-KL64 clone. Diverse hypervirulence factors and resistance genes were identified. Further sequencing with the Nanopore platform was performed on the CRKP-Urine1 strain, which contained one virulence plasmid (pVi-CRKP-Urine1) and two resistance plasmids (pKPC-CRKP-Urine1 and pqnrS1-CRKP-Urine1). The gene mutations responsible for tigecycline or colistin resistance were then amplified with PCR followed by sequencing, which indicated that mutations of ramR and lon were the potential loci for tigecycline resistance and that the pmrB, phoQ and mgrB genes for colistin resistance. A novel frameshift mutation of lon was identified in the high-level tigecycline-resistant strain (MIC, 128 mg/L). The results indicate that the hypervirulent ST11-KL64 clone is a potential threat to antiinfection treatment and is capable of rapid and diverse evolution of resistance during tigecycline and polymyxin treatment.

B3GALT6 is a well-documented disease-related gene. Several B3GALT6-recessive variants have been reported to cause Ehlers–Danlos syndrome (EDS). To the best of our knowledge, no dominant B3GALT6 variant that causes human disease has been reported. In 2012, we reported on a three-generation, autosomal-dominant family with multiple members who suffered from radioulnar joint rotation limitation, scoliosis, thick vermilion of both lips, and others, but the genetic cause was unknown. Here, exome sequencing of the family identified mutant B3GALT6 as the cause of the multiplex affected family. We observed that, in the compound heterozygous pattern (i.e., c.883C>T:p.R295C and c.510_517del:p.L170fs*268), mutant B3GALT6 led to severe consequences, and in the dominant pattern, an elongated B3GALT6 variant co-segregated with moderate phenotypes. The functional experiments were performed in vitro. The R295C variant led to subcellular mislocalization, whereas the L170fs*268 showed normal subcellular localization, but it led to an elongated protein. Given that most of the catalytic galactosyltransferase domain was disrupted for the L170fs*268 (it is unlikely that such a protein has activity), we propose that the L170fs*268 occupies the normal B3GALT6 protein position in the Golgi and exerts a dominant-negative effect.

Abstract is missing (Short communication)

Objective: To investigate the effects of mirror neuron theory-based visual feedback therapy (VFT) on restoration of upper limb function of stroke patients and motor-related cortical function using functional magnetic resonance imaging (fMRI). Methods: Hemiplegic stroke patients were randomly divided into two groups: a VFT group and a control (CTL) group. Sixteen patients in the VFT group received conventional rehabilitation (CR) and VFT for 8 weeks, while 15 patients in the CTL group received only CR. The Barthel Index (BI) was used to assess the activities of daily living at baseline and the 8th week of the recovery training period. The Fugl–Meyer assessment (FMA) scale, somatosensory evoked potential (SEP), and fMRI were used to evaluate the recovery effect of the training therapies. The latencies and amplitudes of N9 and N20 were measured. Before recovery training, fMRI was performed for all patients in the VFT and CTL groups. In addition, 17 patients (9 in the VFT group and 8 in the CTL group) underwent fMRI for follow-up 2 months after treatment. Qualitative data were analyzed using the χ2 test. The independent sample t-test was used to compare normally distributed data among different groups, the paired sample t-test was used to compare data between groups, and the non-parametric test was used to comparing data without normal distribution among groups. Results: There were no significant differences between the VFT and CTL group in all indexes. However, after 8 weeks of recovery training, these indexes were all significantly improved (P

The carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) poses a severe therapeutic challenge to global public health, and research on CR-hvKP in older patients remain limited. In this study, we aimed to investigate the clinical and molecular characteristics and risk factors of CR-hvKP infections in older patients. We retrospectively investigated older patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in the intensive care unit (ICU) between January 2020 and December 2020. The clinical data, and microbiological data including antimicrobial susceptibility testing, phenotype experiment and detection of carbapenemases, string test, virulence genes, capsular serotype-specific (cps) genes, and multilocus sequence typing, of the CR-hvKP group defined by the presence of any one of the virulence genes, including rmpA, rmpA2, iucA, iroN, and peg-344 were compared with those of CR-non-hvKP strains. Of the 80 CRKP strains, 51 (63.8%) met the definition of CR-hvKP. The main mechanism of resistance to carbapenems was the presence of the blaKPC−2 gene. Sequence type (ST)11 (81.3%, 65/80) and ST15 (16.3%, 13/80) were the most common STs in CRKP strains. The minimum inhibitory concentration (MIC)50 values of the CR-hvKP group against the six tested antibiotics (ceftazidime, ceftazidime-avibactam, imipenem-avibactam, tigecycline, levofloxacin, and Cefoperazone-Sulbactam) exhibited elevated levels than the CR-non-hvKP group. Ceftazidime and imipenem by combining avibactam (4 μg/mL) significantly decreased the MIC90 values more than 16-fold than ceftazidime and imipenem alone against Klebsiella pneumoniae carbapenemase (KPC)-2-producing K. pneumoniae. Cardiovascular disease [odds ratio (OR) = 11.956] and ST11-K64 (OR = 8.385) appeared to be independent variables associated with CR-hvKP infection by multivariate analysis. In conclusion, higher MICs of the last line antibiotic agents (ceftazidime-avibactam, tigecycline) might be a critical consideration in the clinical management of older patients where the concentration of these toxic antibiotics matters because of underlying comorbidities. Caution regarding KPC-2-producing ST11-K64 CR-hvKP as being new significant “superbugs” is required as they are widespread, and infection control measures should be strengthened to curb further dissemination in nosocomial settings in China.

Abstract Background SMAD6 variants have been reported in patients with radioulnar synostosis (RUS). This study aimed to investigate the genotypes and phenotypes for a large cohort of patients with RUS having mutant SMAD6. Methods Genomic DNA samples were isolated from 251 RUS sporadic patients (with their parents) and 27 RUS pedigrees. Sanger sequencing was performed for the SMAD6 coding regions. For positive probands, co‐segregation and parental‐origin analysis of SMAD6 variants and phenotypic re‐evaluation were performed for their family members. Results We identified 50 RUS probands with SMAD6 variants (13 co‐segregated with RUS in pedigrees and 37 in RUS‐sporadic patients). Based on the new and previous data, we identified SMAD6 mutated in 16/38 RUS pedigrees and 61/393 RUS sporadic patients, respectively. Overall, 93 SMAD6 mutant patients with RUS were identified, among which 29 patients had unilateral RUS, where the left side was more involved than the right side (left:right = 20:9). Female protective effects and non‐full penetrance were observed, in which only 6.90% mothers (vs. ~50% fathers) of SMAD6 mutant RUS probands had RUS. Pleiotropy was observed as a re‐evaluation of SMAD6 mutant families identified: (a) three families had axial skeletal malformations; (b) two families had polydactyly; and (c) eight families had other known malformations. Conclusion SMAD6 was mutated in 42.11% RUS pedigrees and 15.52% RUS sporadic patients. The RUS patients with SMAD6 variants exhibit both non‐full‐penetrance, variable expressivity, pleiotropy, female protective effects, and the left side is more susceptible than the right side.