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BackgroundSevere burns can lead to systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) due to inflammation-immunity dysregulation. This study aimed to identify key immune-related molecules and potential drugs for immune regulation in severe burn treatment.MethodMicroarray datasets GSE77791 and GSE37069 were analyzed to identify immune-related differentially expressed genes (DEGs), enriched pathways and prognosis-related genes. The DGIdb database was used to identify potentially clinically relevant small molecular drugs for hub DEGs. Hub DEGs were validated by total RNA from clinical blood samples through qPCR. The efficacy of drug candidates was tested in a severe burn mouse model. Pathologic staining was used to observe organ damage. Enzyme Linked Immunosorbent Assay (ELISA) was used to detect the serum IL-1b, IL-6, TNF-a and MCP-1 contents. Activation of the NF-κB inflammatory pathway was detected by western blotting. Transcriptome sequencing was used to observe inflammatory-immune responses in the lung.ResultsA total of 113 immune-related DEGs were identified, and the presence of immune overactivation was confirmed in severe burns. S100A8 was not only significantly upregulated and identified to be prognosis-related among the hub DEGs but also exhibited an increasing trend in clinical blood samples. Methotrexate, which targets S100A8, as predicted by the DGIdb, significantly reduces transcription level of S100A8 and inflammatory cytokine content in blood, organ damage (lungs, liver, spleen, and kidneys) and mortality in severely burned mice when combined with fluid resuscitation. The inflammatory-immune response was suppressed in the lungs.ConclusionS100A8 with high transcription level in blood is a potential biomarker for poor severe burn prognosis. It suggested that methotrexate has a potential application in severe burn immunotherapy. Besides, it should be emphasized that fluid resuscitation is necessary for the function of methotrexate.

Thalamic hemorrhage can lead to the development of central post-stroke pain. Changes in histone acetylation levels, which are regulated by histone deacetylases, affect the excitability of neurons surrounding the hemorrhagic area. However, the regulatory mechanism of histone deacetylases in central post-stroke pain remains unclear. Here, we show that iron overload leads to an increase in histone deacetylase 2 expression in damaged ventral posterolateral nucleus neurons. Inhibiting this increase restored histone H3 acetylation in the Kcna2 promoter region of the voltage-dependent potassium (Kv) channel subunit gene in a rat model of central post-stroke pain, thereby increasing Kcna2 expression and relieving central pain. However, in the absence of nerve injury, increasing histone deacetylase 2 expression decreased Kcna2 expression, decreased Kv current, increased the excitability of neurons in the ventral posterolateral nucleus area, and led to neuropathic pain symptoms. Moreover, treatment with the iron chelator deferiprone effectively reduced iron overload in the ventral posterolateral nucleus after intracerebral hemorrhage, reversed histone deacetylase 2 upregulation and Kv1.2 downregulation, and alleviated mechanical hypersensitivity in central post-stroke pain rats. These results suggest that histone deacetylase 2 upregulation and Kv1.2 downregulation, mediated by iron overload, are important factors in central post-stroke pain pathogenesis and could serve as new targets for central post-stroke pain treatment.

Abstract The overall picture of degloving skin and soft tissue injuries (DSTI) remains a blank space in China. Therefore, a retrospective study was designed to summarize the current situation of this injury. Patients diagnosed with DSTI hospitalized between 2013 and 2018 were identified from the Hospital Quality Monitoring System (HQMS) database, of whom demographics, injury characteristics, hospitalization and cost information were analyzed. A total of 62,709 patients were enrolled in this study. Male sex predominated, with a mean age of 43.01 ± 19.70 years. Peasants seemed to be the most vulnerable. East China and Hubei province had the most patients. The most and least frequently injured anatomic site were lower extremity and torso, respectively. Traffic-related accidents and summer accounted for the highest proportion in terms of injury mechanism and season. The operation rate of DSTI roughly showed a growing trend, and the average length of stay was 22.02 ± 29.73 days. At discharge, 0.93% of DSTI patients ended up in death. Medicine accounted mostly for hospitalization cost, while the proportion decreased year by year. More than half DSTI patients paid at their own charge. This study made a relatively detailed description of DSTI patients nationwide, and might provide enlightenments for better prevention and treatment.

Abstract Neutrophil extracellular traps (NETs) seriously impede diabetic wound healing. The disruption or scavenging of NETs using deoxyribonuclease (DNase) or cationic nanoparticles has been limited by liberating trapped bacteria, short half‐life, or potential cytotoxicity. In this study, a positive correlation between the NETs level in diabetic wound exudation and the severity of wound inflammation in diabetic patients is established. Novel NETs scavenging bio‐based hydrogel microspheres ‘micro‐cage’, termed mPDA‐PEI@GelMA, is engineered by integrating methylacrylyl gelatin (GelMA) hydrogel microspheres with cationic polyethyleneimine (PEI)‐functionalized mesoporous polydopamine (mPDA). This unique ‘micro‐cage’ construct is designed to non‐contact scavenge of NETs between nanoparticles and the diabetic wound surface, minimizing biological toxicity and ensuring high biosafety. NETs are introduced into ‘micro‐cage’ along with wound exudation, and cationic mPDA‐PEI immobilizes them inside the ‘micro‐cage’ through a strong binding affinity to the cfDNA web structure. The findings demonstrate that mPDA‐PEI@GelMA effectively mitigates pro‐inflammatory responses associated with diabetic wounds by scavenging NETs both in vivo and in vitro. This work introduces a novel nanoparticle non‐contact NETs scavenging strategy to enhance diabetic wound healing processes, with potential benefits in clinical applications.

We measure the green technology innovation efficiency of 288 cities in China from static and dynamic dimensions using the super−SBM model and Malmquist−Luenberger index, and employ ''Difference in Difference'' (DID) model to evaluate the impact of FTZs construction on green technology innovation efficiency using panel data from 288 prefecture-level cities from 2008 to 2020. The findings show: (1) The FTZs significantly improve green technology innovation efficiency. The decomposition indexes promote the green technology innovation efficiency more from the dynamic productivity dimension (GTFP) functioning on technological advancement. (2) The FTZs can boost the efficiency of green technology innovation through industrial agglomeration, digital economy, and government financial support; (3) The effect of FTZs on the efficiency of green technology innovation differs based on the size and location of the city. Green technology innovation will reach maximum potential when promoting FTZ policy in less developed central, western, and interior regions. This study addresses whether FTZ policies can genuinely support regional green innovation and policy insights to expand opening up and enhance high-quality economic growth.

Abstract Trauma and its associated complications, including dysregulated inflammatory responses, severe infection, and disseminated intravascular coagulation (DIC), continue to pose lethal threats worldwide. Following injury, cell‐free nucleic acids (cfNAs), categorized as damage‐associated molecular patterns (DAMPs), are released from dying or dead cells, triggering local and systemic inflammatory responses and coagulation abnormalities that worsen disease progression. Harnessing cfNA scavenging strategies with biomaterials has emerged as a promising approach for treating posttrauma systemic inflammation. In this study, the effectiveness of cationic hyperbranched polyaminoglycosides derived from tobramycin (HPT) and disulfide‐included HPT (ss‐HPT) in scavenging cfNAs to mitigate posttrauma inflammation and hypercoagulation is investigated. Both cationic polymers demonstrate the ability to suppress DAMP‐induced toll‐like receptor (TLR) activation, inflammatory cytokine secretion, and hypercoagulation by efficiently scavenging cfNAs. Additionally, HPT and ss‐HPT exhibit potent antibacterial efficacy attributed to the presence of tobramycin in their chemical composition. Furthermore, HPT and ss‐HPT exhibit favorable modulatory effects on inflammation and therapeutic outcomes in a cecal ligation puncture (CLP) mouse abdominal trauma model. Notably, in vivo studies reveal that ss‐HPT displayed high accumulation and retention in injured organs of traumatized mice while maintaining a higher biodegradation rate in healthy mice, contrasting with findings for HPT. Thus, functionalized ss‐HPT, a bioreducible polyaminoglycoside, holds promise as an effective option to enhance therapeutic outcomes for trauma patients by alleviating posttrauma inflammation and coagulation complications.

Objective To investigate the effect of imatinib on the growth of A549 non-small cell lung cancer transplanted tumors and the expression of PDGFB and PDGFRβ proteins in tumor tissues and stroma in nude mice and to explore the underlying tumor suppression mechanism. Methods A transplantation tumor model of A549 non-small cell lung cancer was established in nude mice. The mice were then randomly divided into four groups: control group (0.9%NaCl), low-dose imatinib group (50 mg/(kg·d)), medium-dose imatinib group (100 mg/(kg·d)), and high-dose imatinib group (200 mg/(kg·d)). The effect of different concentrations of imatinib administered by continuous gavage on tumor growth was observed for 28 days. HE staining was performed to observe the pathological changes of tumor tissues. The expression of PDGF/PDGFR pathway-related proteins and the phosphorylation levels of AKT and ERK1/2 proteins in tumor tissues were detected by Western blot analysis. Double immunofluorescence staining was used to detect the expression of PDGFB and PDGFRβ proteins in the tumor stroma. Results Imatinib inhibited the growth of A549 non-small cell lung cancer cells in nude mice, suppressed the expression of PDGFB in tumor tissues, and decreased the phosphorylation levels of PDGFRβ, AKT, and ERK1/2. The expression of PDGFB and PDGFRβ in tumor stromal fibroblasts of the administered group was significantly lower than that of the control group. Conclusion Imatinib exhibits a pronounced inhibitory effect on A549 xenografts of nude mice with non-small cell lung cancer, and its antitumor mechanism may involve the downregulation of PDGFB and PDGFRβ expression in tumor stromal fibroblasts.

With limited number of labeled samples, hyperspectral image (HSI) classification is a difficult Problem in current research. The graph neural network (GNN) has emerged as an approach to semi-supervised classification, and the application of GNN to hyperspectral images has attracted much attention. However, in the existing GNN-based methods a single graph neural network or graph filter is mainly used to extract HSI features, which does not take full advantage of various graph neural networks (graph filters). Moreover, the traditional GNNs have the problem of oversmoothing. To alleviate these shortcomings, we introduce a deep hybrid multi-graph neural network (DHMG), where two different graph filters, i.e., the spectral filter and the autoregressive moving average (ARMA) filter, are utilized in two branches. The former can well extract the spectral features of the nodes, and the latter has a good suppression effect on graph noise. The network realizes information interaction between the two branches and takes good advantage of different graph filters. In addition, to address the problem of oversmoothing, a dense network is proposed, where the local graph features are preserved. The dense structure satisfies the needs of different classification targets presenting different features. Finally, we introduce a GraphSAGE-based network to refine the graph features produced by the deep hybrid network. Extensive experiments on three public HSI datasets strongly demonstrate that the DHMG dramatically outperforms the state-of-the-art models.

The purpose of this study is to analyze the spatiotemporal variations in wind field measurements obtained from the Chinese FengYun-3E (FY-3E) Wind Radar (WindRAD) scatterometer. To assess the performance of the wind field retrievals, we compare the FY-3E WindRAD measurements to ERA5 winds, which is the fifth-generation reanalysis global atmosphere dataset from the European Centre for Medium-Range Weather Forecasts (ECMWF). The comparative analysis between FY-3E and ERA5 for the period from June 1, 2022, to December 31, 2022, reveals that FY-3E wind speed retrievals have a bias of −0.42 m/s and a standard deviation (STD) of 1.45 m/s. In comparison to the TAO/TRITON array observations, the wind speed retrievals show a bias of −0.70 m/s and a STD of 1.37 m/s. Further improvements in wind direction retrieval precision are necessary for the FY-3E WindRAD scatterometer to meet operational requirements, aiming for an error within 20°. Temporal variations in the bias and STD of FY-3E wind speed retrievals exhibit two states, primarily attributed to the improved precision in wind field accuracy resulting from the implementation of the ocean calibration bias correction and advanced inversion algorithms. The spatial distribution analysis reveals regions characterized by relatively high bias and STD values, which could be associated with the presence of sea ice contamination near the ice shelves in these areas. These findings have the potential to offer valuable insights for improving Earth’s climate monitoring capabilities and enhancing the applications of oceanographic satellite observation systems.

Highlights The majority of KDM6A targets are regulated from one allele or the other with allelic downregulation showing a maternal allele bias. Kdm6a knockout affects genes that have been implicated in phenotypes of Kabuki syndrome caused by KDM6A mutations in human. KDM6A facilitates sex-biased gene expression, particularly female-biased expression.

Abstracts Background Dietary phytoestrogens have been suggested to influence puberty timing, a critical stage for well-being in adulthood. We hypothesized that childhood soy intake might prospectively influence puberty timing and that dietary fibre and the key isoflavone metabolite equol might play roles. Methods Cox proportional hazard regression models were performed in 4781 children (2152 girls and 2629 boys) aged 6–8 years old from the Chinese Adolescent Cohort Study for whom a food frequency questionnaire at baseline and information about potential confounders were available. Anthropometry and pubertal status including age at Tanner stage 2 for breast development (B2) or age at the initiation of gonadal growth (G2), and age at menarche (M) or voice break (VB) were assessed annually. Equol excretion was determined by urine samples from 1311 participants. Results Among girls and boys, higher soy intake was associated with later puberty timing (hazard ratio (HR)-B2: 0.88 (95% CI, 0.80–0.96), p=0.02; HR-M, 0.87 (0.77–0.94), p=0.01; HR-G2, 0.91 (0.82–0.98), p=0.013; HR-VB, 0.90 (0.82–0.9), p=0.02), independent of prepubertal body fatness and fibre intake. These associations were more pronounced among children with a high urinary equol level (p for-interaction ≤ 0.04) or with a high cereal fibre intake (p for-interaction ≤ 0.06). Intake of dietary fibre or its subtype was not prospectively associated with puberty onset after adjusting for dietary soy intake (p≥0.06). Conclusion Higher childhood soy intake is prospectively associated with later puberty timing in both Chinese girls and boys, independent of prepubertal body fatness, and the association is particularly pronounced among individuals with a higher urinary equol level.

Offshore wind speed is a critical factor that influences various aspects of human life, and accurate forecasting is of utmost importance for the efficient utilization of offshore resources. In this paper, we present a novel deep-learning-based model for multisite offshore wind speed forecasting along the US East Coast. The proposed model is trained using the collected 2018–2020 National Data Buoy Center buoy data and tested using the 2021–2022 data. By inputting historical wind speed data into the model, simultaneous forecasting results can be obtained for multiple buoy sites through the embedding layer, feature extraction layer, and long short-term memory layer. Notably, the embedding layer, which is specifically engineered to capture spatial dependencies between multiple sites, proves to be highly effective in the context of multisite wind speed forecasting, as substantiated by our conducted ablation experiments. The evaluation metrics display satisfactory results: The 12-h average root mean square error at 1-h forecasting intervals is 2.09 m/s, the correlation coefficient is 0.7, and the mean absolute error is 1.24 m/s. Through case studies, the proposed model demonstrates its effectiveness in forecasting wind speeds during hurricanes, underscoring its potential for use in the offshore wind energy assessment and maritime disaster warning domains.

Sepsis is one of the most severe complications and causes of mortality in the clinic. It remains a great challenge with no effective treatment for clinicians worldwide. Inhibiting the release of proinflammatory cytokines during sepsis is considered as an important strategy for treating sepsis and improving survival. In the present study, we have observed the effect of dimethyl fumarate (DMF) on lipopolysaccharide- (LPS-) induced sepsis and investigated the possible mechanism. By screening a subset of the Johns Hopkins Drug Library, we identified DMF as a novel inhibitor of nitric oxide synthesis in LPS-stimulated RAW264.7 cells, suggesting that DMF could be a potential drug to treat sepsis. To further characterize the effect of DMF on LPS signaling, TNF-α, MCP-1, G-CMF, and IL-6 expression levels were determined by using cytokine array panels. In addition, an endotoxemia model with C57BL/6 mice was used to assess the in vivo efficacy of DMF on sepsis. The survival rate was assessed, and HE staining was performed to investigate histopathological damage to the organs. DMF was found to increase the survival of septic mice by 50% and attenuate organ damage, consistent with the reduction in IL-10, IL-6, and TNF-α (inflammatory cytokines) in serum. In vitro experiments revealed DMF’s inhibitory effect on the phosphorylation of p65, IκB, and IKK, suggesting that the primary inhibitory effects of DMF can be attributed, at least in part, to the inhibition of phosphorylation of IκBα, IKK as well as nuclear factor-κB (NF-κB) upon LPS stimulation. The findings demonstrate that DMF dramatically inhibits NO and proinflammatory cytokine production in response to LPS and improves survival in septic mice, raising the possibility that DMF has the potential to be repurposed as a new treatment of sepsis.

The COMMD proteins are a highly conserved protein family with ten members that play a crucial role in a variety of biological activities, including copper metabolism, endosomal sorting, ion transport, and other processes. Recent research have demonstrated that the COMMD proteins are closely associated with a wide range of disorders, such as hepatitis, myocardial ischemia, cerebral ischemia, HIV infection, and cancer. Among these, the role of COMMD proteins in tumors has been thoroughly explored; they promote or inhibit cancers such as lung cancer, liver cancer, gastric cancer, and prostate cancer. COMMD proteins can influence tumor proliferation, invasion, metastasis, and tumor angiogenesis, which are strongly related to the prognosis of tumors and are possible therapeutic targets for treating tumors. In terms of molecular mechanism, COMMD proteins in tumor cells regulate the oncogenes of NF-κB, HIF, c-MYC, and others, and are related to signaling pathways including apoptosis, autophagy, and ferroptosis. For the clinical diagnosis and therapy of malignancies, additional research into the involvement of COMMD proteins in cancer is beneficial.

Six-generation (6G) networks will contain a higher density of users, base stations, and communication equipment, which poses a significant challenge to secure communications and collaborations due to the complex network and environment as well as the number of resource-constraint devices used. Trust evaluation is the basis for secure communications and collaborations, providing an access criterion for interconnecting different nodes. Without a trust evaluation mechanism, the risk of cyberattacks on 6G networks will be greatly increased, which will eventually lead to the failure of network collaboration. For the sake of performing a comprehensive evaluation of nodes, this paper proposes a novel multiple role fusion trust evaluation framework that integrates multiple role fusion trust calculation and blockchain-based trust management. In order to take advantage of fused trust values for trust prediction, a neural network fitting method is utilized in the paper. This work further optimizes the traditional trust management framework and utilizes the optimized model for node trust prediction to better increase the security of communication systems. The results show that multiple role fusion has better stability than a single role evaluation network and better performance in anomaly detection and evaluation accuracy.

Taking the flood inundation event in Linhai, Taizhou, Zhejiang Province caused by the super severe typhoon (1909) Lekima for example, we have verified and evaluated the 5km real-time data (CMPAS-5km) from the CMA Multi-source Precipitation Analysis System by using the precipitation data obtained by hydrological and meteorological stations over Zhejiang Province. In addition, we haveconductedflood simulations under the rainstorm scenarios based on the spatial distribution with weighted grid of area precipitation and accumulated precipitation calculated by CMPAS-5km to drive the FloodArea two-dimensional hydrodynamic inundation model, and performed verification of the simulated flooding by using Sentinel-1 SAR images and representative flooded points. The results show that the precipitation from CMPAS-5km and that from the stations have good temporal and spatial consistency, and the correlation coefficient (R) ofprecipitation from CMPAS-5km with those from hydrological stations and"hydrological + meteorological"stations are both 0.89. Rand root mean square error (RSME) of precipitation from CMPAS-5km with the hourly averaged precipitation from hydrological stations are 0.79 and 1.7 mm·h-1, respectively. The hourly area rainfall among CMPAS-5km, hydrological stations and meteorological stations have more consistent variation trend in Taizhou flooded simulation area, and the accumulated area rainfall in the whole simulation process is 305.5 mm, 304.1 mm and 283.7 mm, respectively. CMPAS-5km is superior to the other two sets of data from ground stations in stability, timeliness, precision and data interface. The newly-increased water area in SAR images matches the FloodArea simulation results well, and the relative bias between the maximum simulated water depth and the actual water depth at the four verification points is within ±22%.

A 66 years old male was admitted to our hospital after a serious car accident. The patient presented with severe shock after admission. After the examination, the patient was diagnosed with hemopneumothorax and myocardial contusion, accompanied by spleen rupture. After emergency surgery and a series of symptomatic treatments, the patient’s condition gradually stabilized. One week later, the patient suddenly presented with severe shock. Massive hemothorax was found on the left side of the chest. Surgical exploration revealed cardiac rupture and accidental absence of congenital pericardium. According to the literature review, congenital absence of pericardium (CAP) is relatively rare. Although there are certain imaging features, the clinical diagnosis is very difficult. However, this patient did not show the characteristics in the literature and had some other atypical features. The role of CAP in the occurrence and development of the patient’s heart injury and rupture is worthy of discussion. What we learned from this case is that we should look for potential risks in the telltale signs of a patient’s condition.

The reprogramming of cellular metabolism is frequently linked to tumorigenesis. Glucose, fatty acids, and amino acids are the specific substrates involved in how an organism maintains metabolic equilibrium. The HADH gene codes for the short-chain L-3-hydroxyacyl-CoA dehydrogenase (HADH), a crucial enzyme in fatty acid oxidation that catalyzes the third phase of fatty acid oxidation in mitochondria. Increasing data suggest that HADH is differentially expressed in various types of malignancies and is linked to cancer development and progression. The significance of HADH expression in tumors and its potential mechanisms of action in the onset and progression of certain cancers are summarized in this article. The possible roles of HADH as a target and/or biomarker for the detection and treatment of various malignancies is also described here.

Abstract Background Mammalian development is associated with extensive changes in gene expression, chromatin accessibility, and nuclear structure. Here, we follow such changes associated with mouse embryonic stem cell differentiation and X inactivation by integrating, for the first time, allele-specific data from these three modalities obtained by high-throughput single-cell RNA-seq, ATAC-seq, and Hi-C. Results Allele-specific contact decay profiles obtained by single-cell Hi-C clearly show that the inactive X chromosome has a unique profile in differentiated cells that have undergone X inactivation. Loss of this inactive X-specific structure at mitosis is followed by its reappearance during the cell cycle, suggesting a “bookmark” mechanism. Differentiation of embryonic stem cells to follow the onset of X inactivation is associated with changes in contact decay profiles that occur in parallel on both the X chromosomes and autosomes. Single-cell RNA-seq and ATAC-seq show evidence of a delay in female versus male cells, due to the presence of two active X chromosomes at early stages of differentiation. The onset of the inactive X-specific structure in single cells occurs later than gene silencing, consistent with the idea that chromatin compaction is a late event of X inactivation. Single-cell Hi-C highlights evidence of discrete changes in nuclear structure characterized by the acquisition of very long-range contacts throughout the nucleus. Novel computational approaches allow for the effective alignment of single-cell gene expression, chromatin accessibility, and 3D chromosome structure. Conclusions Based on trajectory analyses, three distinct nuclear structure states are detected reflecting discrete and profound simultaneous changes not only to the structure of the X chromosomes, but also to that of autosomes during differentiation. Our study reveals that long-range structural changes to chromosomes appear as discrete events, unlike progressive changes in gene expression and chromatin accessibility.

Synthetic Aperture Radar (SAR) imagery plays an important role in observing tropical cyclones (TCs). However, the C-band attenuation caused by rain bands and the problem of signal saturation at high wind speeds make it impossible to retrieve the fine structure of TCs effectively. In this paper, a dual-level contextual attention generative adversarial network (DeCA-GAN) is tailored for reconstructing SAR wind speeds in TCs. The DeCA-GAN follows an encoder–neck–decoder architecture, which works well for high wind speeds and the reconstruction of a large range of low-quality data. A dual-level encoder comprising a convolutional neural network and a self-attention mechanism is designed to extract the local and global features of the TC structure. After feature fusion, the neck explores the contextual features to form a reconstructed outline and up-samples the features in the decoder to obtain the reconstructed results. The proposed deep learning model has been trained and validated using the European Centre for Medium-Range Weather Forecasts (ECMWF) atmospheric model product and can be directly used to improve the data quality of SAR wind speeds. Wind speeds are reconstructed well in regions of low-quality SAR data. The root mean square error of the model output and ECMWF in these regions is halved in comparison with the existing SAR wind speed product for the test set. The results indicate that deep learning methods are effective for reconstructing SAR wind speeds.

While the unmanned aerial vehicles (UAVs) swarm travels under a dynamic environment, the cluster head (CH) switching is unavoidable due to the mitigation of mobility, quality of service, and energy consumption. If an attacker becomes the new CH, the entire swarm will be controlled and the sensitive data will be leaked. Unlike the other mobile networks with constant network connectivity, the authentication in the UAV swarm suffers from intermittent connection with the ground station under a hostile environment or spectrum constraint condition. Hence, this paper proposes a novel CH safeguarding mechanism enabled by edge intelligence utilizing a situational-aware authentication scheme. This low-latency mechanism provides extra security at the CH selection and switching without cloud server support. By adopting the unique cross-layer attributes, the system security is significantly improved based on the extracted multi-dimensional information. The Linear Discriminant Analysis (LDA) algorithm fuses the authentication decision accurately by projecting the high dimensional estimations into a low dimensional space for maximum separability by only keeping the necessary attributes. A situation-aware cross-layer attribute selection algorithm is developed to select a minimum number of attributes so that the time required for attribute estimation and computation overhead of authentication can be reduced. The simulation results demonstrate that our scheme performs better under a dynamic environment compared with the physical layer authentication scheme and some existing state-of-the-art authentication techniques.

The X-linked SMC1A gene encodes a core subunit of the cohesin complex that plays a pivotal role in genome organization and gene regulation. Pathogenic variants in SMC1A are often dominant-negative and cause Cornelia de Lange syndrome (CdLS) with growth retardation and typical facial features; however, rare SMC1A variants cause a developmental and epileptic encephalopathy (DEE) with intractable early-onset epilepsy that is absent in CdLS. Unlike the male-to-female ratio of 1:2 in those with CdLS associated with dominant-negative SMC1A variants, SMC1A-DEE loss-of-function (LOF) variants are found exclusively in females due to presumed lethality in males. It is unclear how different SMC1A variants cause CdLS or DEE. Here, we report on phenotypes and genotypes of three females with DEE and de novo SMC1A variants, including a novel splice-site variant. We also summarize 41 known SMC1A-DEE variants to characterize common and patient-specific features. Interestingly, compared to 33 LOFs detected throughout the gene, 7/8 non-LOFs are specifically located in the N/C-terminal ATPase head or the central hinge domain, both of which are predicted to affect cohesin assembly, thus mimicking LOFs. Along with the characterization of X-chromosome inactivation (XCI) and SMC1A transcription, these variants strongly suggest that a differential SMC1A dosage effect of SMC1A-DEE variants is closely associated with the manifestation of DEE phenotypes.

Working memory means a lot in incidental vocabulary learning and retention. The present study examines the correlation between two types of working memory—complex working memory and phonological short-term memory—and incidental vocabulary learning from captioned videos. After conducting an empirical research to 125 young learners of English as a foreign language with two working memory tests: an operation span test, which measured complex working memory, and a non-word repetition test, which measured phonological short-term memory. It showed that complex working memory did not significantly predict the effects of captioning types on incidental vocabulary learning and retention. However, phonological working memory significantly affects incidental vocabulary learning and retention. The findings suggest that the role of working memory varies as a function of captioning types. Complex working memory and phonological short-term memory may have different predictive effects in incidental vocabulary learning and retention under different captioning types.

Firre encodes a lncRNA involved in nuclear organization in mammals. Here, the authors find that allelic deletion of Firre on the active X chromosome (Xa) results in dose-dependent loss of histone H3K27me3 on the inactive X chromosome (Xi), along with other trans-acting effects, including disruption of the perinuclear location and minor dysregulation of gene expression.

C22H22N10Cl2Hg, triclinic, P1‾$P‾{1}$ (no. 2), a = 8.2034(4) Å, b = 12.7859(7) Å, c = 13.5026(7) Å, α = 66.069(5)°, β = 79.964(4)°, γ = 84.465(4)°, V = 1274.18(12) Å3, Z = 2, Rgt(F) = 0.0372, ωRref(F2) = 0.0670, T = 291.15 K.

Abstract Wireless communications between two devices can be protected by secret keys. However, existing key generation schemes suffer from the high bit disagreement rate and low bit generation rate. In this paper, we propose an efficient physical layer key generation scheme by exploring the Received Signal Strength (RSS) of signals. In order to reduce the high mismatch rate of the measurements and to increase the key generation rate, a pair of transmitter and receiver separately apply adaptive quantization algorithm for quantifying the measurements. Then, we implement a randomness extractor to further increase key generation rate and ensure randomness of generated of keys. Several real-world experiments are implemented to verify the effectiveness of the proposed scheme. The results show that compared with the other related schemes, our scheme performs better in bit generation rate, bit disagreement rate, and randomness.

Several C2 domain-containing proteins play key roles in tumorigenesis, signal transduction, and mediating protein–protein interactions. Tandem C2 domains nuclear protein (TC2N) is a tandem C2 domain-containing protein that is differentially expressed in several types of cancers and is closely associated with tumorigenesis and tumor progression. Notably, TC2N has been identified as an oncogene in lung and gastric cancer but as a tumor suppressor gene in breast cancer. Recently, a large number of tumor-associated antigens (TAAs), such as heat shock proteins, alpha-fetoprotein, and carcinoembryonic antigen, have been identified in a variety of malignant tumors. Differences in the expression levels of TAAs between cancer cells and normal cells have led to these antigens being investigated as diagnostic and prognostic biomarkers and as novel targets in cancer treatment. In this review, we summarize the clinical characteristics of TC2N-positive cancers and potential mechanisms of action of TC2N in the occurrence and development of specific cancers. This article provides an exploration of TC2N as a potential target for the diagnosis and treatment of different types of cancers.

Hepatocellular carcinoma (HCC) has a poor prognosis due to its high malignancy, rapid disease progression, and the presence of chemotherapy resistance. Long-stranded non-coding RNAs (lncRNAs) affect many malignant tumors, including HCC. However, their mechanism of action in HCC remains unclear. This study aimed to clarify the role of DUXAP8 in regulating the malignant phenotype and chemotherapy resistance in HCC. Using an in vivo xenograft tumor model, the regulatory functions and mechanisms of lncRNA DUXAP8 in the progression and response of HCC to chemotherapy were explored. It was found that DUXAP8 was significantly upregulated in a patient-derived xenograft tumor model based on sorafenib treatment, which is usually associated with a relatively poor prognosis in patients. In HCC, DUXAP8 maintained its upregulation in the expression by increasing the stability of m6A methylation-mediated RNA. DUXAP8 levels were positively correlated with the proliferation, migration, invasion, and chemotherapy resistance of HCC in vivo and in vitro. In the mechanistic study, it was found that DUXAP8 competitively binds to miR-584-5p through a competing endogenous RNA (ceRNA) mechanism, thus acting as a molecular sponge for miR-584-5p to regulate MAPK1 expression, which in turn activates the MAPK/ERK pathway. These findings can provide ideas for finding new prognostic indicators and therapeutic targets for patients with HCC.

Objective: We conducted a systematic review and meta-analysis to comprehensively estimate the incidence and mortality of acute respiratory distress syndrome (ARDS) in overall and subgroups of patients with burns.Data sources: Pubmed, Embase, the Cochrane Library, CINAHL databases, and China National Knowledge Infrastructure database were searched until September 1, 2021.Study selection: Articles that report study data on incidence or mortality of ARDS in patients with burns were selected.Data extraction: Two researchers independently screened the literature, extracted data, and assessed the quality. We performed a meta-analysis of the incidence and mortality of ARDS in patients with burns using a random effects model, which made subgroup analysis according to the study type, inclusion (mechanical ventilation, minimal burn surface), definitions of ARDS, geographic location, mean age, burn severity, and inhalation injury. Primary outcomes were the incidence and mortality of burns patients with ARDS, and secondary outcomes were incidence for different subgroups.Data synthesis: Pooled weighted estimate of the incidence and mortality of ARDS in patients with burns was 0.24 [95% confidence interval (CI)0.2–0.28] and 0.31 [95% CI 0.18−0.44]. Incidences of ARDS were obviously higher in patients on mechanical ventilation (incidence = 0.37), diagnosed by Berlin definition (incidence = 0.35), and with over 50% inhalation injury proportion (incidence = 0.41) than in overall patients with burns. Patients with burns who came from western countries and with inhalation injury have a significantly higher incidence of ARDS compared with those who came from Asian/African countries (0.28 vs. 0.25) and without inhalation injury (0.41 vs. 0.24).Conclusion: This systematic review and meta-analysis revealed that the incidence of ARDS in patients with burns is 24% and that mortality is as high as 31%. The incidence rates are related to mechanical ventilation, location, and inhalation injury. The patients with burns from western countries and with inhalation injury have a significantly higher incidence than patients from Asian/African countries and without inhalation injury.Systematic Review Registration: identifier: CRD42021144888.

Understanding the response of tropospheric ozone (O3) to nitrogen dioxide (NO2) change is important for local O3 control. The relationship between O3 and NO2 at county scale in China has been extensively studied using models, but there is a lack of results from direct measurements. In this study, we used measurements of O3, NO2 and meteorological conditions from a dense network in the Yangtze River Delta (YRD), and satellite observed formaldehyde (HCHO) and NO2 column densities for the analysis of O3 variabilities and its relationship to NO2. As a result, severe O3 pollution occurred mainly in Shanghai city, southern Jiangsu and northern Zhejiang provinces in YRD during April–September. In addition, meteorological conditions could explain 54% the diurnal O3 variation over YRD. During April–September 2015–2021, O3 showed a significant positive relationship (r = 0.61 ± 0.10) with NO2 after removing the impact from meteorological conditions. However, the relationship could be reversed with NO2 concentration change. Our result suggested that the controllable O3 related to NO2 change is up to 100 μg·m−3 in megacities over Shanghai and northern Zhejiang province. The O3 is much more sensitive to the NO2 reduction in megacities than surrounding areas. Our results evaluate the different impacts of NO2 changes on O3 formation, which provides explanation for the simultaneously alleviated O3 pollution and reduced NO2 in 2020 in Shanghai and northern Zhejiang, as well as the increased O3 in most counties before 2019 with reduced NO2 during October–March. The driving mechanism as revealed from this study for O3 and NO2 will be valuable for the O3 abatement through NO2 reduction at sub-county scale over YRD in China.

To ensure the reliability and integrity of data in the cloud storage server, some scholars provided various data integrity auditing schemes. However, the most existing data integrity auditing schemes only support the static data and may be unsuitable for the dynamic operations of data. To overcome this difficulty, we propose a fuzzy identity-based dynamic auditing of big data, which combines the structure of the Merkle hash tree (MHT) with the Index logic table (ILT). Our scheme not only performs the dynamic operations of data block in the ILT, namely modification, insertion and deletion, but also efficiently executes dynamic operations of the ILT on the structure of the MHT. We also elaborate the security, characteristics and performance analysis of the proposed scheme separately. The analysis results show that the proposed scheme costs less time than the structure of the original MHT to generate the root node hash value during the metadata generation phase and update the root node hash value during the dynamic operations. Furthermore, when users store the new ILT in local storage, they require lower communication cost to update root node hash value than users without storing the ILT, and fewer interactions between the cloud storage server and users in the dynamic operations process.

The damage of vascular endothelial barrier function induced by sepsis is critical in causing multiple organ dysfunctions. Previous studies showed that dexmedetomidine (Dex) played a vital role in protecting organ functions. However, whether Dex participates in protecting vascular leakage of sepsis and the associated underlying mechanism remains unknown yet. We used cecal ligation and puncture induced septic rats and lipopolysaccharide stimulated vascular endothelial cells (VECs) to establish models in vivo and in vitro, then the protective effects of Dex on the vascular endothelial barrier function of sepsis were observed, meanwhile, related mechanisms on regulating mitochondrial fission were further studied. The results showed that Dex could significantly reduce the permeability of pulmonary veins and mesenteric vessels, increase the expression of intercellular junction proteins, enhance the transendothelial electrical resistance and decrease the transmittance of VECs, accordingly protected organ functions and prolonged survival time in septic rats. Besides, the mitochondria of VECs were excessive division after sepsis, while Dex could significantly inhibit the mitochondrial fission and protect mitochondrial function by restoring mitochondrial morphology of VECs. Furthermore, the results showed that ER-MITO contact sites of VECs were notably increased after sepsis. Nevertheless, Dex reduced ER-MITO contact sites by regulating the polymerization of actin via α2 receptors. The results also found that Dex could induce the phosphorylation of the dynamin-related protein 1 through down-regulating extracellular signal-regulated kinase1/2, thus playing a role in the regulation of mitochondrial division. In conclusion, Dex has a protective effect on the vascular endothelial barrier function of septic rats. The mechanism is mainly related to the regulation of Drp1 phosphorylation of VECs, inhibition of mitochondrial division by ER-MITO contacts, and protection of mitochondrial function.

Background The role of tumor necrosis factor (TNF)-α small interfering (si)RNA alveolar epithelial cell (AEC)-targeting nanoparticles in lung injury is unclear. Methods Sixty C57BL/6J mice with sepsis were divided into normal, control, sham, 25 mg/kg, 50 mg/kg, and 100 mg/kg siRNA AEC-targeting nanoparticles groups (n = 10 per group). The wet:dry lung weight ratio, and hematoxylin and eosin staining, western blotting, and enzyme-linked immunosorbent assays for inflammatory factors were conducted to compare differences among groups. Results The wet:dry ratio was significantly lower in control and sham groups than other groups. TNF-α siRNA AEC-targeting nanoparticles significantly reduced the number of eosinophils, with significantly lower numbers in the 50 mg/kg group than in 25 mg/kg and 100 mg/kg groups. The nanoparticles also significantly reduced the expression of TNF-α, B-cell lymphoma-2, caspase 3, interleukin (IL)-1β, and IL-6, with TNF-α expression being significantly lower in the 50 mg/kg group than in 25 mg/kg and 100 mg/kg groups. Conclusion TNF-α siRNA AEC-targeting nanoparticles appear to be effective at improving lung injury-related sepsis, and 50 mg/kg may be a preferred dose option for administration.

The rapid development of urbanization and population growth in China has posed a major threat to the green sustainable development of the ecological environment. However, the impact of urbanization on the eco-environmental quality (EEQ) in China remains to be developed. Understanding their interactive coupling mechanism is of great significance to achieve the urban sustainable development goals. By using multi-source remote sensing data and the coupling coordination degree model (CCDM), we intended to answer the question “What are the temporal and spatial characteristics of urbanization and EEQ in China on the pixel scale during 2000–2013, and what is the coupling mechanism between the urbanization and the EEQ?”. To answer these questions, we explored the coupling mechanism between urbanization and the EEQ in China with a combined mathematical and graphics model. The results show that the urbanization and the coupling coordination degree (CCD) of the whole region continually increased from 2000 to 2013, especially in the three major urban agglomerations, with a spatial distribution pattern that was “high in the east and low in the west”. Most importantly, from 2000 to 2013, the CCD type of cities in China gradually evolved from uncoordinated cities to coordinated cities. Additionally, the decisive factor affecting the CCD from 2000 to 2013 was the development of urbanization, and the degree at which urbanization had an impact on CCD was about 8.4 times larger than that of the EEQ. At the same time, the rapid urbanization that has occurred in some areas has led to a significant decline in the EEQ, thus indicating that China needs to increase its protection of the ecological environment while pursuing social and economic development in the future. This study makes up for the deficiencies in the existing literature and investigates the long-term coupling of the EEQ and urbanization in China, thereby providing a new research perspective for the sustainable development of China and even the world in the future.

BackgroundHypergonadotropic hypogonadism (HH) is characterized by low sex steroid levels and secondarily elevated gonadotropin levels with either congenital or acquired etiology. Genetic factors leading to HH have yet to be fully elucidated.MethodsHere, we report on genome and transcriptome data analyses from a male patient with HH and history of growth delay who has an inherited deletion of chromosome Xq28. Expression analyses were done for this patient and his unaffected family members and compared to normal controls to identify dysregulated genes due to this deletion.ResultsOur patient’s Xq28 deletion is 44,806 bp and contains only two genes, FUNDC2 and CMC4. Expression of both FUNDC2 and CMC4 are completely abolished in the patient. Gene ontology analyses of differentially expressed genes (DEGs) in the patient in comparison to controls show that significantly up-regulated genes in the patient are enriched in Sertoli cell barrier (SCB) regulation, apoptosis, inflammatory response, and gonadotropin-releasing regulation. Indeed, our patient has an elevated follicle stimulating hormone (FSH) level, which regulates Sertoli cell proliferation and spermatogenesis. In his mother and sister, who are heterozygous for this deletion, X-chromosome inactivation (XCI) is skewed toward the deleted X, suggesting a mechanism to avoid FSH dysregulation.ConclusionCompared to the previously reported men with variable sized Xq28 deletions, our study suggests that loss of function of FUNDC2 and CMC4 results in dysregulation of apoptosis, inflammation, and FSH, and is sufficient to cause Xq28-associated HH.

X inactivation represents a complex multi-layer epigenetic mechanism that profoundly modifies chromatin composition and structure of one X chromosome in females. The heterochromatic inactive X chromosome adopts a unique 3D bipartite structure and a location close to the nuclear periphery or the nucleolus. X-linked lncRNA loci and their transcripts play important roles in the recruitment of proteins that catalyze chromatin and DNA modifications for silencing, as well as in the control of chromatin condensation and location of the inactive X chromosome. A subset of genes escapes X inactivation, raising questions about mechanisms that preserve their expression despite being embedded within heterochromatin. Escape gene expression differs between males and females, which can lead to physiological sex differences. We review recent studies that emphasize challenges in understanding the role of lncRNAs in the control of epigenetic modifications, structural features and nuclear positioning of the inactive X chromosome. Second, we highlight new findings about the distribution of genes that escape X inactivation based on single cell studies, and discuss the roles of escape genes in eliciting sex differences in health and disease.

C22H22N10I2Cd, triclinic, P1̄ (no. 2), a = 10.5476(8) Å, b = 11.1759(9) Å, c = 12.7735(10) Å, α = 103.372(7)°, β = 105.811(7)°, γ = 100.270(6)°, V = 1361.85(18) Å3, Z = 2, Rgt(F) = 0.0324, wRref(F2) = 0.0661, T = 291(2) K.

C24H22N12S2Zn, monoclinic, C2/c (no. 15), a = 27.6123(9) Å, b = 9.6238(4) Å, c = 21.1748(8) Å, β = 101.088(4)°, Z = 8, V = 5521.8(4) Å3, Rgt(F) = 0.0481, wRref(F2) = 0.1047, T = 291(2) K.