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Abstract Objective Coronary artery ectasia (CAE) is a condition characterized by the localized or widespread dilation of one or more coronary arteries. The majority of CAE patients do not present with clinical symptoms, and the exact cause of CAE remains unclear. Therefore, a retrospective analysis was conducted to explore the potential causes of CAE. Methods This study was a retrospective analysis of patients who underwent coronary angiography at Guangdong Provincial People’s Hospital between January 2017 and July 2022, of whom 679 patients were ultimately enrolled in the study. Among them, 260 patients were diagnosed with CAE, whereas 419 patients with normal coronary results composed the control group. Remnant cholesterol (RC) was calculated as total cholesterol (TC) minus high-density lipoprotein cholesterol (HDL-C) minus low-density lipoprotein cholesterol (LDL-C). The association between RC levels and the risk of CAE was assessed via multivariable logistic models. Results Out of the 679 patients who participated in this study, with an average age of 59.9 years, 38.3% were diagnosed with CAE. Patients with CAE had higher RC levels than did those without CAE (P = 0.001). A significant positive association was observed between RC levels and the risk of CAE, with a multivariable adjusted odds ratio (OR) of 1.950 (95% confidence interval [CI]: 1.163–3.270). There was a significant positive association between RC levels and the risk of CAE in both single-vessel and multivessel dilation cases, as well as in isolated CAE and dilation secondary to coronary atherosclerosis. According to the subgroup analyses, RC levels were positively associated with the risk of CAE in participants with hypertension (OR, 1.065; 95% CI, 1.034–1.098). Conclusion RC levels are positively correlated with CAE, implying that a focus on RC could be beneficial in CAE research.

Abstract The meninges are critical for the brain functions, but the diversity of meningeal cell types and intercellular interactions have yet to be thoroughly examined. Here we identify a population of meningeal lymphatic supporting cells (mLSCs) in the zebrafish leptomeninges, which are specifically labeled by ependymin. Morphologically, mLSCs form membranous structures that enwrap the majority of leptomeningeal blood vessels and all the mural lymphatic endothelial cells (muLECs). Based on its unique cellular morphologies and transcriptional profile, mLSC is characterized as a unique cell type different from all the currently known meningeal cell types. Because of the formation of supportive structures and production of pro-lymphangiogenic factors, mLSCs not only promote muLEC development and maintain the dispersed distributions of muLECs in the leptomeninges, but also are required for muLEC regeneration after ablation. This study characterizes a newly identified cell type in leptomeninges, mLSC, which is required for muLEC development, maintenance, and regeneration.

Abstract Acute myeloid leukemia (AML) with mixed-lineage leukemia (MLL) gene rearrangements (MLL-r) is an aggressive subtype of blood cancer with dismal prognosis, underscoring the urgent need for novel therapeutic strategies. E1A-binding protein (EP300) and CREB-binding protein (CREBBP) function as essential transcriptional coactivators and acetyltransferases, governing leukemogenesis through diverse mechanisms. Targeting EP300/CREBBP holds great promise for treating leukemia with some certain cytogenetic abnormalities. Here, we demonstrated that EP300 and CREBBP are core epigenetic regulators in the pathogenesis of MLL-r AML through assaying the transposase-accessible chromatin with high-throughput sequencing (ATAC-seq). Knocking-out EP300/CREBBP and inhibitor (A-485) treatment depressed the MLL-r cells proliferation, while the MLL wild-type cells remained uninfluenced. We found that the CDK4/RB/E2F axis was downregulated specifically in MLL-r AML cell after A-485 treatment by RNA-seq, western blot and cut-tag analyses. EP300/CREBBP inhibitor selectively exerted potent anti-leukemia activity through blocking the MLL-r-BET complex binding to H3K27Ac modification on critical genes loci, distinct from global histone acetylation. Collectively, our study identified EP300/CREBBP as a critical epigenetic driver of MLL-r leukemia and validated their therapeutic potential through targeting inhibition, offering a promising avenue for improving clinical outcomes in this aggressive leukemia.

The construction of 14 large-scale coal bases and 89 demonstration bases for the comprehensive utilization of bulk solid waste in China marks that the utilization of bulk solid waste in mining areas has been incorporated into the national strategic development layout. The long-term high-intensity development and utilization of coal resources has caused the near depletion of shallow-buried coal seam resources in mining areas, and the large-scale solid waste accumulation and surface subsidence of coal power and chemical bases has become a problem restricting the green, low-carbon and high-quality development of mining areas. Co-operative utilization of bulk coal-based solid waste and green filling is an effective way to liberate the “three down and one up” pressed coal, extend the service life of mines, and realize the harmless, resourceful, and large-scale “three” utilization of solid waste. Based on the types and production of coal-based solid waste in Shanxi Province, the “East China Energy Granary” Anhui Lianghuai Base and Ningdong Energy and Chemical Base, it elaborates in detail the harmless disposal of coal-based solid waste through heavy metal adsorption and desorption and complexation passivation technology with coal gangue, fly ash, furnace slag, gasification slag and desulphurization gypsum as the main materials, listing the classification and application of coal-based solid waste, and the application of coal gangue, fly ash, furnace slag, gasification slag and desulphurization gypsum as the main materials. List the ways of resource utilization of coal-based solid waste classified and applied to low calorific value coal-based solid waste for power generation, preparation of building materials such as cement, bricks and tiles, etc. Comparatively analyze the ways of reclamation and backfilling of coal mining subsidence area and downhole filling and large-scale utilization of coal-based solid waste, highlighting the superiority of downhole filling of coal-based solid waste. Based on the deep coal resources of coal electrification bases, the theory and key technologies of green filling mining are proposed, including the synergistic technology of deep coal gangue source reduction and mining and filling, the technology of efficient preparation and deep underground transportation of filling materials, and the deep multi-field coupling mechanism of coal-based solid waste filling materials, and the technological principles and methods of the whole process of deep filling mining of multi-source coal-based solid waste from the source, process to the end are investigated to solve the technical problems of deep underground filling of mining areas. The technical problems of filling are solved. According to the geological conditions and filling purposes of Renjiazhuang Coal Mine in Ningdong Base, Huoerxinhe Coal Mine in Shanxi Province and Huaibei Mining Area, the key technologies of low-level filling by overdrilling, multi-separation layer stepped grouting under the conditions of atypical characteristics of key layers and synergistic utilization of coal-based solid wastes have been proposed, which comprehensively combine the advantages of disposal and utilization of solid wastes from mines, development and utilization of deep coal resources, control of subsidence of the ground surface, and ecological environment protection, and form a comprehensive plan for the disposal and utilization of bulk solid wastes from coal power and chemical bases. Coal power and chemical base bulk solid waste synergistic utilization and green mining mode, providing reference for high quality coal mining and low damage to the environment.

Abstract For expanding the amplitude-frequency response range of the differential cross-phase multiply (DCM) algorithm in the φ-OTDR system, a temporal spline interpolation (TSI) method is proposed to pre-process Rayleigh backscattering (RBS) signals. Through the TSI method, the discrete temporal signals characterizing RBS traces are subjected to interpolation, facilitating a reduction in differential approximation errors. This, in turn, establishes a heightened level of precision in phase demodulation, especially relevant across extensive sensing distances. By comparing the recovered time-domain waveforms and the corresponding power spectral densities without and with the TSI, the above improvement effect has been experimentally validated by utilizing the TSI. The results show that, with the TSI, the amplitude-frequency response range of the DCM algorithm is enlarged by 2.78 times, and the new relationship among f pulse, f, and D under the root mean square error (RMSE) tolerance less than 0.1 can be expressed as 1.9(D+1)f ≤ f pulse. This contribution underscores a substantial advancement in the capabilities of the DCM algorithm, holding promise for refined performance in optical fiber sensing applications.

In order to study the consolidation bearing capacity of coal-based solid waste paste backfill in deep high ground temperature environment of coal mine, uniaxial compression and acoustic emission tests were used to test the strength and failure characteristics of paste backfill under different curing temperature conditions (20 ℃, 35 ℃ and 50 ℃) and ages (3 d, 7 d, 14 d and 28 d). The microstructure and mineral composition of the filling cement were measured by SEM, and the influence of curing temperature on the hydration reaction was revealed from the microscopic point of view. The results show that: with the increase of curing temperature, its influence on hydration reaction gradually changes from promotion to inhibition, and the 28 d compressive strength reaches the maximum at 35 ℃; acoustic emission events mainly occur in the compaction and failure stages. The increase of curing temperature promotes the activity of acoustic emission in advance, and the failure mode of filling body gradually changes from ductile failure to brittle failure; due to the thermal damage, high temperature curing accelerates the early hydration reaction rate of the filling body, and causes damage to the C-S-H and pore structure of the filling body in the later stage of curing, which has an adverse effect on the increase of its long-term strength.

Abstract Scientific analysis of excavated pottery reveals critical archaeological insights, yet data on Han Dynasty pottery remains limited. This study focuses on pottery artifacts excavated from the Daqu burial site in Beijing, renowned for their polychrome decorations and size. Utilizing optical microscopy (OM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and X-ray Fluorescence (XRF), this study examined five substrate samples sourced from fragments of pottery towers and ellipse-shaped dishes. All samples exhibited similar inclusions and the same firing atmosphere. The mineralogical analysis indicated that quartz and feldspar are predominant components, with minor constituents like chlorite and kaolinite observed in the coarse pottery of the ellipse-shaped dish. Minor mineral variations suggest differences in firing temperatures. The resemblance between low-value pottery cups and delicate polychrome towers suggests they were crafted locally. These findings advance our understanding of ceramic materials and techniques in late Eastern Han Dynasty Beijing, providing crucial insights for future studies on ancient Chinese economy and society.

To further improve the spectral efficiency of the cooperative non-orthogonal multiple access (NOMA) network with half-duplex (HD) relaying and avoid the zero diversity gain due to the imperfect self interference estimation at high signa-to-noise ratio (SNR) value with full-duplex (FD) relaying, this paper developed a novel two-stage relay selection for a two-user multi-relay cooperative NOMA systems with adaptive-duplex (AD) relaying which can switch opportunistically between HD and FD relaying modes. An adaptive duplex based on fixed power allocation factor relay selection (AD-FPA-RS) scheme for cooperative NOMA networks is proposed in this paper, the relay can switch the work mode to the FD or HD state adaptively according to the current channel state information and the result of decode at the relay. Futhermore, the exact outage probability for the proposed AD-FPA-RS scheme is obtained in closed-form expression. The simulation and numerical results show that the proposed AD-FPA-RS scheme not only outperforms the existing HD-FPARS and FD-FPA-RS schemes in terms of outage behavior significantly, but also can obtain full diversity gain without the floor outage performance at high SNR region.

Abstract Background Breast cancer has the highest incidence rate of cancer worldwide, and brain metastases (BrM) are among the most malignant cases. While some patients have benefited from immune checkpoint inhibitors (ICIs), the complex anatomical structure of the brain and the heterogeneity of metastatic tumors have made it difficult to characterize the tumor immune microenvironment (TME) of metastatic tumors. Methods To address this, we used single‐cell RNA sequencing (scRNA‐seq) to analyze immune cells in the cerebrospinal fluid (CSF) of BrM patients with breast cancer, thereby providing a comprehensive view of the immune microenvironment landscape of BrM. Results Based on canonical marker genes, we identified nine cell types, and further identified their subtypes through differential expression gene (DEG) analysis. We compared the changes in cells and functions in the immune microenvironment of patients with different prognoses. Our analysis revealed a series of genes that promote tumor immune function (CCR5, LYZ, IGKC, MS4A1, etc.) and inhibit tumor immune function (SCGB2A2, CD24, etc.). Conclusions The scRNA‐seq in CSF provides a noninvasive method to describe the TME of breast cancer patients and guide immunotherapy.

Abstract The mix proportion of multi-source coal-based solid waste (CSW) for underground backfilling affects transportation and support performance of backfill materials, and even the backfilling cost. In this study, the optimal mix proportion of desulfurization gypsum (DG), furnace bottom slag (FBS) and gasification fine slag (GFS) is determined by the Response Surface Methodology–Box Behnken Design (RSM-BBD). Then the fluidity, bleeding rate, 3-day strength, 7-day strength and preparation cost are evaluation indicators, the optimal mix proportion of backfill materials is determined by the multi-objective decision-making method (MDM). Finally, the microstructure of the backfill material with optimal mix proportion was studied by TGA, MIP, SEM–EDS and XRD. The results show that the mix proportion of CSW with the optimal comprehensive index is coal gangue (CG): coal fly ash (CFA): DG: FBS: GFS = 1:1.5:0.2:0.1:0.1, the mass concentration is 78%, and ordinary Portland cement (OPC)/CSW = 7.5%. The weight loss phenomenon of the backfill material with the optimal mix proportion occurs continuously during the heating process, mainly due to the evaporation of crystal water, structural water and hydroxyl water. There are dense narrow-necked pores in the backfill material, and the pore connectivity is poor. There is no hydration reaction occurs between CSW particles, and the strength increase of the backfill material mainly depends on the hydration reaction of cement. In ettringite, part of Al2O3 is replaced by SiO2, and part of CaSO4 is replaced by CaCO3. This study provides a reference for the engineering application of underground backfilling with multi-source CSW.

Abstract The complexity of the tumor microenvironment (TME) is a crucial factor in lung adenocarcinoma (LUAD) progression. To gain deeper insights into molecular mechanisms of LUAD, we perform an integrative single-cell RNA sequencing (scRNA-seq) data analysis of 377,574 cells from 117 LUAD patient samples. By linking scRNA-seq data with bulk gene expression data, we identify a cluster of prognostic-related UPP1high tumor cells. These cells, primarily situated at the invasive front of tumors, display a stronger association with the immunosuppressive components in the TME. Our cytokine array analysis reveals that the upregulation of UPP1 in tumor cells leads to the increased release of various immunosuppressive cytokines, with TGF-β1 being particularly prominent. Furthermore, this UPP1 upregulation also elevates the expression of PD-L1 through the PI3K/AKT/mTOR pathway, which contributes to the suppression of CD8 + T cells. Cytometry by time-of-flight (CyTOF) analysis provides additional evidence of the role of UPP1 in shaping the immunosuppressive nature of the TME. Using patient-derived organoids (PDOs), we discover that UPP1high tumors exhibit relatively increased sensitivity to Bosutinib and Dasatinib. Collectively, our study highlights the immunosuppressive role of UPP1 in LUAD, and these findings may provide insights into the molecular features of LUAD and facilitate the development of personalized treatment strategies.

Abstract Background Exposure to PM2.5 has been implicated in a range of detrimental health effects, particularly affecting the respiratory system. However, the precise underlying mechanisms remain elusive. Methods To address this objective, we collected ambient PM2.5 and administered intranasal challenges to mice, followed by single-cell RNA sequencing (scRNA-seq) to unravel the heterogeneity of neutrophils and unveil their gene expression profiles. Flow cytometry and immunofluorescence staining were subsequently conducted to validate the obtained results. Furthermore, we assessed the phagocytic potential of neutrophils upon PM2.5 exposure using gene analysis of phagocytosis signatures and bacterial uptake assays. Additionally, we utilized a mouse pneumonia model to evaluate the susceptibility of PM2.5-exposed mice to Pseudomonas aeruginosa infection. Results Our study revealed a significant increase in neutrophil recruitment within the lungs of PM2.5-exposed mice, with subclustering of neutrophils uncovering subsets with distinct gene expression profiles. Notably, exposure to PM2.5 was associated with an expansion of PD-L1high neutrophils, which exhibited impaired phagocytic function dependent upon PD-L1 expression. Furthermore, PM2.5 exposure was found to increase the susceptibility of mice to Pseudomonas aeruginosa, due in part to increased PD-L1 expression on neutrophils. Importantly, monoclonal antibody targeting of PD-L1 significantly reduced bacterial burden, dissemination, and lung inflammation in PM2.5-exposed mice upon Pseudomonas aeruginosa infection. Conclusions Our study suggests that PM2.5 exposure promotes expansion of PD-L1high neutrophils with impaired phagocytic function in mouse lungs, contributing to increased vulnerability to bacterial infection, and therefore targeting PD-L1 may be a therapeutic strategy for reducing the harmful effects of PM2.5 exposure on the immune system.

Biomineralization through microbial process has attracted great attention in the field of geotechnical engineering due to its ability to bind granular materials, clog pores, and seal fractures. Although minerals formed by biomineralization are generally the same as that by mineralization, their mechanical behaviors show a significant discrepancy. This study aims to figure out the differences between biomineralization and mineralization processes by visualizing and tracking the formation of minerals using microfluidics. Both biomineralization and mineralization processes occurred in the Y-shaped sand-containing microchip that mimics the underground sand layers. Images from different areas in the reaction microchannel of microchips were captured to directly compare the distribution of minerals. Crystal size and numbers from different reaction times were measured to quantify the differences between biomineralization and mineralization processes in terms of crystal kinetics. Results showed that the crystals were precipitated in a faster and more uncontrollable manner in the mineralization process than that in the biomineralization process, given that those two processes presented similar precipitation stages. In addition, a more heterogeneous distribution of crystals was observed during the biomineralization process. The precipitation behaviors were further explained by the classical nucleation crystal growth theory. The present microfluidic tests could advance the understanding of biomineralization and provide new insight into the optimization of biocementation technology.

In the 5G and beyond networks, low-latency digital signatures are essential to ensure the security, integrity, and non-repudiation of massive data in communication processes. The binary finite field-based elliptic curve digital signature algorithm (ECDSA) is particularly suitable for achieving low-latency digital signatures due to its carry-free characteristics. This paper proposes a low-latency and universal architecture for point multiplication (PM) and double point multiplication (DPM) based on the differential addition chain (DAC) designed for signing and verification in ECDSA. By employing the DAC, the area-time product of DPM can be decreased, and throughput efficiency can be increased. Besides, the execution pattern of the proposed architecture is uniform to resist simple power analysis and high-order power analysis. Based on the data dependency, two Karatsuba–Ofman multipliers and four non-pipeline squarers are utilized in the architecture to achieve a compact timing schedule without idle cycles for multipliers during the computation process. Consequently, the calculation latency of DPM is minimized to five clock cycles in each loop. The proposed architecture is implemented on Xilinx Virtex-7, performing DPM in 3.584, 5.656, and $7.453~\mu s$ with 8135, 13372, and 17898 slices over GF(2163), GF(2233), GF(2283), respectively. In the existing designs that are resistant to high-order analysis, our architecture demonstrates throughput efficiency improvements of 36.7% over GF(2233) and 9.8% over GF(2283), respectively.

The application of grazing-incidence total X-ray scattering (GITXS) for pair distribution function (PDF) analysis using >50 keV X-rays from synchrotron light sources has created new opportunities for structural characterization of supported thin films with high resolution. Compared with grazing-incidence wide-angle X-ray scattering, which is only useful for highly ordered materials, GITXS/PDFs expand such analysis to largely disordered or nanostructured materials by examining the atomic pair correlations dependent on the direction relative to the surface of the supporting substrate. A characterization of nanocrystalline In2O3-derived thin films is presented here with in-plane-isotropic and out-of-plane-anisotropic orientational ordering of the atomic structure, each synthesized using different techniques. The atomic orientations of such films are known to vary based on the synthetic conditions. Here, an azimuthal orientational analysis of these films using GITXS with a single incident angle is shown to resolve the markedly different orientations of the atomic structures with respect to the planar support and the different degrees of long-range order, and hence, the terminal surface chemistries. It is anticipated that orientational analysis of GITXS/PDF data will offer opportunities to extend structural analyses of thin films by providing a means to qualitatively determine the major atomic orientation within nanocrystalline and, eventually, non-crystalline films.

Fine particulate matter (PM2.5) has been extensively implicated in the pathogenesis of neurodevelopmental disorders, but the underlying mechanism remains unclear. Recent studies have revealed that PM2.5 plays a role in regulating iron metabolism and redox homeostasis in the brain, which is closely associated with ferroptosis. In this study, the role and underlying mechanism of ferroptosis in PM2.5-induced neurotoxicity were investigated in mice, primary hippocampal neurons, and HT22 cells. Our findings demonstrated that exposure to PM2.5 could induce abnormal behaviors, neuroinflammation, and neuronal loss in the hippocampus of mice. These effects may be attributed to ferroptosis induced by PM2.5 exposure in hippocampal neurons. RNA-seq analysis revealed that the upregulation of iron metabolism-related protein Heme Oxygenase 1 (HO-1) and the activation of mitophagy might play key roles in PM2.5-induced ferroptosis in HT22 cells. Subsequent in vitro experiments showed that PM2.5 exposure significantly upregulated HO-1 in primary hippocampal neurons and HT22 cells. Moreover, PM2.5 exposure activated mitophagy in HT22 cells, leading to the loss of mitochondrial membrane potential, alterations in the expression of autophagy-related proteins LC3, P62, and mTOR, as well as an increase in mitophagy-related protein PINK1 and PARKIN. As a heme-degradation enzyme, the upregulation of HO-1 promotes the release of excess iron, genetically inhibiting the upregulation of HO-1 in HT22 cells could prevent both PM2.5-induced mitophagy and ferroptosis. Furthermore, pharmacological inhibition of mitophagy in HT22 cells reduced levels of ferrous ions and lipid peroxides, thereby preventing ferroptosis. Collectively, this study demonstrates that HO-1 mediates PM2.5-induced mitophagy-dependent ferroptosis in hippocampal neurons, and inhibiting mitophagy or ferroptosis may be a key therapeutic target to ameliorate neurotoxicity following PM2.5 exposure.

BackgroundLower respiratory tract infections represent prevalent ailments. Nonetheless, current comprehension of the microbial ecosystems within the lower respiratory tract remains incomplete and necessitates further comprehensive assessment. Leveraging the advancements in metagenomic next-generation sequencing (mNGS) technology alongside the emergence of machine learning, it is now viable to compare the attributes of lower respiratory tract microbial communities among patients across diverse age groups, diseases, and infection types.MethodWe collected bronchoalveolar lavage fluid samples from 138 patients diagnosed with lower respiratory tract infections and conducted mNGS to characterize the lung microbiota. Employing various machine learning algorithms, we investigated the correlation of key bacteria in patients with concurrent bronchiectasis and developed a predictive model for hospitalization duration based on these identified key bacteria.ResultWe observed variations in microbial communities across different age groups, diseases, and infection types. In the elderly group, Pseudomonas aeruginosa exhibited the highest relative abundance, followed by Corynebacterium striatum and Acinetobacter baumannii. Methylobacterium and Prevotella emerged as the dominant genera at the genus level in the younger group, while Mycobacterium tuberculosis and Haemophilus influenzae were prevalent species. Within the bronchiectasis group, dominant bacteria included Pseudomonas aeruginosa, Haemophilus influenzae, and Klebsiella pneumoniae. Significant differences in the presence of Pseudomonas phage JBD93 were noted between the bronchiectasis group and the control group. In the group with concomitant fungal infections, the most abundant genera were Acinetobacter and Pseudomonas, with Acinetobacter baumannii and Pseudomonas aeruginosa as the predominant species. Notable differences were observed in the presence of Human gammaherpesvirus 4, Human betaherpesvirus 5, Candida albicans, Aspergillus oryzae, and Aspergillus fumigatus between the group with concomitant fungal infections and the bacterial group. Machine learning algorithms were utilized to select bacteria and clinical indicators associated with hospitalization duration, confirming the excellent performance of bacteria in predicting hospitalization time.ConclusionOur study provided a comprehensive description of the microbial characteristics among patients with lower respiratory tract infections, offering insights from various perspectives. Additionally, we investigated the advanced predictive capability of microbial community features in determining the hospitalization duration of these patients.

Optically pumped magnetometers can provide functionality for bio-magnetic field detection and mapping. This has attracted widespread attention from researchers in the biomedical science field. Magnetocardiography has been proven to be an effective method for examining heart disease. Notably, vector magnetocardiography obtains more spatial information than the conventional method by only taking a component that is perpendicular to the chest surface. In this work, a spin-exchange-relaxation-free (SERF) magnetometer with a compact size of 14 mm × 25 mm × 90 mm was developed. The device has a high sensitivity of 25 fT/ Hz. Meanwhile, in the multichannel working mode, synchronous sensor manipulation and data acquisition can be achieved through our control software without additional data acquisition boards. Since a typical SERF magnetometer only responds to dual-axis magnetic fields, two sensors are orthogonally arranged to form a vector detection channel. Our system consists of seven channels and allows 7 × 9 vector MCG mapping by scanning. High-quality heart vector signals are measured, and P peak, QRS peak, and T peak can be distinguished clearly. To better demonstrate the vectorial information, a vector scatter plot form is also provided. Through a basic bio-electric current model, it demonstrates that triaxial MCG measurements capture a richer spatial current information than traditional uniaxial MCG, offering substantial diagnostic potential for heart diseases and shedding more light on the inversion of cardiac issues.

The performance requirements of modern fighters meet multiple targets such as high speed, high mobility, stealth, lightweight and so on. The aircraft with a tailless flying wing configuration has the advantages of high aerodynamic efficiency, good mobility, low detectability, and flying integration. Such configuration adopts a structural design with wing and body fusion, multi-control surface and all-moving wing tip. The innovative structure of the wing tip highlights its aeroelasticity problem, in which the coupling effect between the structure of wing tip and the control surface makes the flutter behavior particularly prominent. This paper adopted the linear flutter method and the mode tracking method to study the flutter problem of all-moving wing tip. According to the study, the flutter coupling has three types for the aircraft with a tailless flying wing configuration: coupling between the first symmetrical bending of wing and the symmetric rotation of all-moving wing tip (symmetrical couple), coupling between the first anti-symmetrical bending of wing and the anti-symmetric rotation of all-moving wing tip (antisymmetric couple) and the fuselage mode in flutter. It is found that the flutter speed of the antisymmetric coupling type is lower than that of the symmetric coupling type. From the flutter result, the coupling flutter speed of the fuselage and wing is higher than that of the former two, and the coupling speed of the fuselage and the all-moving wing tip is lower than that of the former two. The main structural factors affecting the symmetric coupled flutter are wing bending stiffness and rotational stiffness of the all-moving tip, while the main structural factors affecting the antisymmetric coupled flutter are wing bending stiffness, fuselage rotational inertia and rotational stiffness of the all-moving tip. The all-moving wing tip structure is the internal factor that makes the tailless flying wing prone to flutter.

Abstract In 2013, several tombs were discovered and excavated in Southeastern Beijing, China, yielding various burial products. Among these were pottery towers, a representative artifact of the Han Dynasty rarely found in the area. Many studies on architectural aspects, such as construction type and construction situation, have been conducted based on the excavated pottery towers, but only a few have examined their raw materials or pigments. In this study, black, white, and red pigments were identified as carbon black, calcite, and cinnabar, respectively, through a multi-analysis approach. The manufacturing method of the pigment was established based on the crystal form and particle size of the pigment, by factoring in the pigment characteristics, which cannot be distinguished by component analysis and crystal structure analysis. We recommend that a continuous database be prepared and used in the future, not only for an interpretation of ancient pigments but also to identify the factors to be considered (physical characteristics, such as pigment particle size among others) when estimating the manufacturing process and conservation treatment.

Objectives: This review aims to summarize the current literature on recurrent and metastatic (r/m) cervical cancer, especially first-line and second-line immunotherapy. Clinical benefits including efficacy and safety of new therapeutic options are also reviewed. Mechanism: The published relevant articles were searched from multiple databases, including PubMed, Ovid, and Scopus. The key terms included recurrent cervical cancer, advanced cervical cancer, metastatic cervical cancer, and immunotherapy. The data of the latest clinical trials was retrieved from ClinicalTrials.gov (https://clinicaltrials.gov). Findings in Brief: In late 2021, pembrolizumab in combination with chemotherapy with or without bevacizumab was approved as the first-line treatment for recurrent and metastatic cervical cancer. Also tisotumab vedotin was approved as the second-line immunotherapy for r/m cervical cancer. Moreover, a plethora of clinical immunotherapy trials were approved in different countries, and some received as breakthrough therapy designations. Pembrolizumab, cemiplimab, atezolizumab, cadonilimab, zimberelimab, balstilimab and zalifrelimab, nivolumab, and tisotumab vedotin were reviewed with overall survival, progression-free survival, rate of objective response and adverse effects in order to review the efficacy and safety of different therapeutic option. Conclusions: The majority of trials indicated that immunotherapy can significantly improve the overall survival (OS) and progression-free survival (PFS) of r/m cervical cancer patients without negatively affecting health-related quality-of-life (HRQoL), and demonstrated that immunotherapy is an effective and safe treatment for r/m cervical cancer.

Due to the limitations of planar mode wharfs, this paper proposes a new type of wharf—the three-dimensional cantilevered wharf. The proposed wharf is defined as an improvement of the traditional wharf, extending the traditional wharf upward and cantilevering out to the sea. The three-dimensional cantilevered wharf is a composite truss structure that meets structural and functional requirements. The composite truss structure is formed by connecting the beams of frame structures as a whole. The material consumption of the three-dimensional cantilevered wharf is decreased by controlling stresses and optimizing components. A finite element model of the proposed wharf, with a length of 200 m, width of 105 m, and cantilever length of 80 m, was established to analyze the basic mechanical performance. In this paper, the force distribution of the pile foundation, the vertical force transfer efficiency of web members, the structural stiffness, and the natural frequencies of the proposed wharf are analyzed. Tests regarding the stress and stiffness of different plane cantilever trusses are carried out, and finite element analysis is used for comparison. The test results show that the high-rise cantilever truss has a great in-plane stiffness and a reasonable component stress distribution. Additionally, the three-dimensional cantilevered wharf significantly improves the utilization efficiency of the wharf.

Abstract In this work, a new type of ternary lead‐free ferroelectric ceramics (1−x)[0.94(Bi0.5Na0.5)TiO3‐0.06BaTiO3]‐xCa(Mg1/3Nb2/3)O3 is synthesized by traditional solid‐state reaction method (x = 0.02, 0.04, 0.06, 0.07, 0.08, 0.10, and 0.15). No phase transition is detected and all ceramics exhibited the perovskite structure consisting of the rhombohedral (R3c) and tetragonal (P4bm) phases. By increasing the Ca(Mg1/3Nb2/3)O3(CMN) content, the average grain size shows a slight change. More specifically, the grain size is 1.00 µm when x

In order to comprehend the underlying mechanisms contributing to the development and exacerbation of asthma resulting from exposure to fine particulate matter (PM2.5), we established an asthmatic model in fat mass and obesity-associated gene knockdown mice subjected to PM2.5 exposure. Histological analyses using hematoxylin-eosin (HE) and Periodic Acid-Schiff (PAS) staining revealed that the down-regulation of the fat mass and obesity-associated gene (Fto) expression significantly ameliorated the pathophysiological alterations observed in asthmatic mice exposed to PM2.5. Furthermore, the down-regulation of Fto gene expression effectively attenuated damage to the airway epithelial barrier. Additionally, employing in vivo and in vitro models, we elucidated that PM2.5 modulated FTO expression by inducing oxidative stress. Asthmatic mice exposed to PM2.5 exhibited elevated Fto expression, which correlated with increased levels of reactive oxygen species. Similarly, when cells were exposed to PM2.5, FTO expression was up-regulated in a ROS-dependent manner. Notably, the administration of N-acetyl cysteine successfully reversed the PM2.5-induced elevation in FTO expression. Concurrently, we performed transcriptome-wide Methylated RNA immunoprecipitation Sequencing (MeRIP-seq) analysis subsequent to PM2.5 exposure. Through the implementation of Gene Set Enrichment Analysis and m6A-IP-qPCR, we successfully identified inhibitor of nuclear factor kappa B kinase subunit beta (IKBKB) as a target gene regulated by FTO. Interestingly, exposure to PM2.5 led to increased expression of IKBKB, while m6A modification on IKBKB mRNA was reduced. Furthermore, our investigation revealed that PM2.5 also regulated IKBKB through oxidative stress. Significantly, the down-regulation of IKBKB effectively mitigated epithelial barrier damage in cells exposed to PM2.5 by modulating nuclear factor-kappa B (NF-κB) signaling. Importantly, we discovered that decreased m6A modification on IKBKB mRNA facilitated by FTO enhanced its stability, consequently resulting in up-regulation of IKBKB expression. Collectively, our findings propose a novel role for FTO in the regulation of IKBKB through m6A-dependent mRNA stability in the context of PM2.5-induced oxidative stress. Therefore, it is conceivable that the utilization of antioxidants or inhibition of FTO could represent potential therapeutic strategies for the management of asthma exacerbated by PM2.5 exposure.

Fibrotic hypersensitivity pneumonitis (FHP) is a fatal interstitial pulmonary disease with limited treatment options. Lung macrophages are a heterogeneous cell population that exhibit distinct subsets with divergent functions, playing pivotal roles in the progression of pulmonary fibrosis. However, the specific macrophage subpopulations and underlying mechanisms involved in the disease remain largely unexplored. In this study, a decision tree model showed that matrix metalloproteinase-14 (MMP14) had higher scores for important features in the up-regulated genes in macrophages from mice exposed to the Saccharopolyspora rectivirgula antigen (SR-Ag). Using single-cell RNA sequencing (scRNA-seq) analysis of hypersensitivity pneumonitis (HP) mice profiles, we identified MMP14high macrophage subcluster with a predominant M2 phenotype that exhibited higher activity in promoting fibroblast-to myofibroblast transition (FMT). We demonstrated that suppressing toll-like receptor 2 (TLR2) and nuclear factor kappa-B (NF-κB) could attenuate MMP14 expression and exosome secretion in macrophages stimulation with SR-Ag. The exosomes derived from MMP14-overexpressing macrophages were found to be more effective in regulating the transition of fibroblasts through exosomal MMP14. Importantly, it was observed that the transfer of MMP14-overexpressing macrophages into mice promoted lung inflammation and fibrosis induced by SR-Ag. NSC-405020 binding to the hemopexin domain (PEX) of MMP-14 ameliorated lung inflammation and fibrosis induced by SR-Ag in mice. Thus, MMP14-overexpressing macrophages may be an important mechanism contributing to the exacerbation of allergic reactions. Our results indicated that MMP14 in macrophages has the potential to be a therapeutic target for HP.

Background and objective Idiopathic pulmonary fibrosis (IPF) is an idiopathic chronic, progressive interstitial lung disease with a diagnosed median survival of 3-5 years. IPF is associated with an increased risk of lung cancer. Therefore, exploring the shared pathogenic genes and molecular pathways between IPF and lung adenocarcinoma (LUAD) holds significant importance for the development of novel therapeutic approaches and personalized precision treatment strategies for IPF combined with lung cancer. Methods Bioinformatics analysis was conducted using publicly available gene expression datasets of IPF and LUAD from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis was employed to identify common genes involved in the progression of both diseases, followed by functional enrichment analysis. Subsequently, additional datasets were used to pinpoint the core shared genes between the two diseases. The relationship between core shared genes and prognosis, as well as their expression patterns, clinical relevance, genetic characteristics, and immune-related functions in LUAD, were analyzed using The Cancer Genome Atlas (TCGA) database and single-cell RNA sequencing datasets. Finally, potential therapeutic drugs related to the identified genes were screened through drug databases. Results A total of 529 shared genes between IPF and LUAD were identified. Among them, SULF1 emerged as a core shared gene associated with poor prognosis. It exhibited significantly elevated expression levels in LUAD tissues, concomitant with high mutation rates, genomic heterogeneity, and an immunosuppressive microenvironment. Subsequent single-cell RNA-seq analysis revealed that the high expression of SULF1 primarily originated from tumor-associated fibroblasts. This study further demonstrated an association between SULF1 expression and tumor drug sensitivity, and it identified potential small-molecule drugs targeting SULF1 highly expressed fibroblasts. Conclusions This study identified a set of shared molecular pathways and core genes between IPF and LUAD. Notably, SULF1 may serve as a potential immune-related biomarker and therapeutic target for both diseases.

The grouting technology of bed separations has been proved to be a new method which can meet the requirements of non-destructive mining and solid waste reduction. To effectively control the subsidence of ground structures caused by mining, the whole process of bed separation grouting mining is analyzed in a steady state based on the key stratum theory. For the first time, a “four zones” control model for surface subsidence under grouting bed separation was proposed, which includes natural zone, transition zone, warning zone, and protection zone, and the calculation formula for the “four zones” range was derived. Based on the engineering back-ground of controlling the subsidence of the ground coking plant at the 3501 panel, the proposed “four zones” model was validated by combining physical modelling and field measurement of subsidence. The results show that the surface subsidence curve of bed separation grouting in physical modelling shows an irregular “V” shape, and the surface subsidence of the panel first increases rapidly. After reaching the maximum subsidence, the surface subsidence first decreases rapidly, and then the reduction rate gradually slows down. The subsidence curve shows a clear “four zones” distribution, with a maximum subsidence of 1589 mm, appearing at the contact boundary between the natural zone and the transition zone. The subsidence of the contact boundary between the transition zone and the warning zone is 497.94 mm, and there is basically no subsidence within the protection zone. The predicted surface subsidence, horizontal deformation, slope, and curvature caused by mining under grouting conditions based on probability integral method are consistent with the field measured results, but significantly smaller than the predicted values under non-grouting conditions. It is determined that the surface deformation under grouting conditions meets the requirements of Grade I damage level for structures. Based on the practical engineering geology and observed data of the mine, the natural area is 261.19 m, the transition area is 246.09 m, the warning area is 655.25 m, and the protection area is 199.53 m. The proposed “four zones” control model provides a fundamental theoretical basis for studying the subsidence of bed separation grouting mining.

In 2021, the price of most of the domestic coal skyrocketed, affecting the stable supply of electric power supply in some regions, while the price of Xinjiang Zhundong coal remains stable at a low level. Thus, the study of safe and stable large-scale combustion of Zhundong coal in boilers is more and more important for the energy supplyHowever, fouling and slagging often occur on the heating surfaces of the boiler due to the characteristics of Zhundong coal and the high temperature of the flue gas. The effects of the operating parameters, including the primary air velocity, operating oxygen content, air staging and coal fineness on the combustion temperature and NOx emission were investigated on a four-corner tangentially fired boiler of 660 MW capacity, which burned 95% Zhundong coal to get the relevant control criterion. Based on the research, the improvement of control function for contamination of heating surfaces was implemented under steady and dynamic working conditions. Finally, the influence of the improvement on the contamination of the heating surfaces was proved by the method of the contamination monitoring of heated surfaces. The results show that, at 660 MW load condition, the operating oxygen content had the most obvious influence on the flue gas temperature at the outlet of the furnace. The flue gas temperature decreased 99 °C when it increased from 2.0% to 3.5%. The reduction of the operating oxygen content and the local mean stoichiometric ratio of the main combustion zone could lead to a significant reduction of NOx emission and the change of the coal fineness had no obvious effect on NOx emission. After the improved control function was implemented, the rate of flue gas temperature decreased from 6.18 to 4.26 °C min−1 during the load increase process, the maximum temperature decreased from 1104 to 1023 °C under 660 MW. The heat absorption ratio of the platen superheater, low-temperature superheater and low-temperature reheater increased by 0.6%, 1.6% and 0.9%, respectively, indicating that the fouling and slagging was significantly reduced. At 330 MW load condition, increasing the coal fineness R90 to around 4.9% of the uppermost mill could effectively reduce the flue gas temperature near the bottom of the high-temperature reheater, reduce the deposition of combustible matter and fly ash, and inhibit the formation of fouling and slagging.

Abstract In order to deeply study the basic characteristics, diffusion laws, and flow laws of coal gangue and coal gangue slurry, the basic characteristic parameters of coal gangue and coal gangue slurry were obtained through particle size distribution test, electron microscope scanning test, X-ray diffraction test, X-ray fluorescence spectrum test, and angle of repose test. The conveying performance test of coal gangue slurry was carried out, and based on this, a simulation test of coal gangue slurry caving areas was designed. The diffusion and flow laws of coal gangue slurry under the same inclination angle were summarized, and the field test of fluidization filling in the caving areas was conducted. The results show that: (1) The water-to-gangue ratio was the main controlling factor for the conveying performance of coal gangue slurry. The extensibility, slump, and bleeding rate of the coal gangue slurry increased with the increase of the water-to-gangue ratio. (2) The diffusion profile of coal gangue slurry at different dip angles was arc-shaped, and the diffusion distance of slurry increased with the increase of infiltration time. However, there were differences in the sustained diffusion ability of different dip angles. (3) At the same time interval, the spatial accumulation patterns of scattered gangue in different regions will lead to differences in the diffusion speed of the slurry. (4) Both burying and hanging pipes in the falling area can safely and efficiently fill the gangue slurry. The diffusion distance of the caving areas in the test working face was basically consistent with the diffusion distance of the slurry in the simulation test of the coal gangue slurry caving areas.

Abstract In the present study, we investigated how the perception of auditory duration could be modulated by a task-irrelevant, concurrent visual apparent motion, induced by visual bars alternating between left and right sides. Moreover, we examined the influence of the speed and temporal frequency of visual apparent motion on the perception of auditory duration. In each trial, the standard visual stimuli (two vertical bars) were presented sequentially, except that visual apparent motion was included in the fourth stimulus. A tone was presented simultaneously with each visual stimulus, while the fourth tone was presented with varied duration. Participants judged whether the fourth tone lasted longer than the other four tones. In Experiment 1, the speed of visual apparent motion (Fast vs. Slow) was manipulated by changing the interval between two bars. The mean point of subjective equality (PSE) in the Slow apparent motion condition was larger than that in the Static condition. Moreover, participants tended to overestimate the duration only in the Static condition, i.e., time dilation effect, which disappeared under apparent motion conditions. In Experiment 2, in addition to speed, we controlled the temporal frequency of apparent motion by manipulating the number of bars, generating four conditions of visual apparent motion (Physical-fast, Perceived-fast, Perceived-slow, vs. Static). The mean PSE was significantly smaller in the Physical-fast condition than in the Static and Perceived-slow conditions. Moreover, we found a time compression effect in both the Perceived-slow and Static conditions but not in the Perceived-fast and Physical-fast conditions. These results suggest that the auditory duration could be modulated by the concurrent, contextual visual apparent motion, and both the speed and temporal frequency of the task-irrelevant visual apparent motion contribute to the bias in perceiving the auditory duration.

Abstract Background The risk factors for mortality might differ between patients with acute exacerbation of chronic pulmonary heart disease in plains and plateaus, while there is a lack of evidence. Method Patients diagnosed with cor pulmonale at Qinghai Provincial People’s Hospital were retrospectively included between January 2012 and December 2021. The symptoms, physical and laboratory examination findings, and treatments were collected. Based on the survival within 50 days, we divided the patients into survival and death groups. Results After 1:10 matching according to gender, age, and altitude, 673 patients were included in the study, 69 of whom died. The multivariable Cox proportional hazards analysis showed that NYHA class IV (HR = 2.03, 95%CI: 1.21–3.40, P = 0.007), type II respiratory failure (HR = 3.57, 95%CI: 1.60–7.99, P = 0.002), acid-base imbalance (HR = 1.82, 95%CI: 1.06–3.14, P = 0.031), C-reactive protein (HR = 1.04, 95%CI: 1.01–1.08, P = 0.026), and D-dimer (HR = 1.07, 95%CI: 1.01–1.13, P = 0.014) were risk factors for death in patients with cor pulmonale at high altitude. Among patients living below 2500 m, cardiac injury was a risk factor for death (HR = 2.47, 95%CI: 1.28–4.77, P = 0.007), while no significant association was observed at ≥ 2500 m (P = 0.057). On the contrary, the increase of D-dimer was only a risk factor for the death of patients living 2500 m and above (HR = 1.23, 95% CI: 1.07–1.40, P = 0.003). Conclusion NYHA class IV, type II respiratory failure, acid-base imbalance, and C- reactive protein may increase the risk of death in patients with cor pulmonale. Altitude modified the association between cardiac injury, D-dimer, and death in patients with cor pulmonale.

The surface of marine fluid operating machinery is commonly damaged by cavitation, and the protection of its surface is one of the key technologies in contemporary marine industry. Bimodal grain weaving is an important means to enhance the cavitation erosion (CE) resistance of materials. Traditional bimodal grain fabrication methods are based on the grain refinement-recrystallization principle or on the mixed powder sintering principle, which are too tedious. In this paper, laser shock peening (LSP), a convenient technique, is innovatively utilized to fabricate bimodal grain weaving on the surface of nickel-aluminum bronze (NAB), a material with excellent cavitation erosion resistance, by using the principle of inhomogeneity Gaussian beam laser shock peening. The mechanism of its cavitation erosion resistance is also investigated. The results show that the depth of the affected layer induced by laser shock peening can reach 460 μm. At a laser power density of 5.37∗107 J/cm2, a bimodal grain weave with a large number of micron-sized grains interwoven with ultrafine grains is formed on the NAB surface. The results of ultrasonic cavitation experiments show that the cavitation erosion resistance of bimodal grain surface fabricated by laser shock peening is improved by approximately 2.18 times than that of matrix. The synergy of strength and toughness of bimodal grains is one of the important reasons for the improved cavitation erosion resistance of NAB. This research is expected to further promote the application of bimodal grain weaving in the marine high-speed flow-passing components.

Variations in the thickness of retinal layers serve as early diagnostic indicators for various fundus diseases, and precise segmentation of these layers is essential for accurately measuring their thickness. Optical Coherence Tomography (OCT) is an important non-invasive tool for diagnosing various eye diseases through the acquisition and layering of retinal images. However, noise and artifacts in images present significant challenges in accurately segmenting retinal layers. We propose a novel method for retinal layer segmentation that addresses these issues. This method utilizes ConvNeXt as the backbone network to enhance multi-scale feature extraction and incorporates a Transformer–CNN module to improve global processing capabilities. This method has achieved the highest segmentation accuracy on the Retina500 dataset, with a mean Intersection over Union (mIoU) of 81.26% and an accuracy (Acc) of 91.38%, and has shown excellent results on the public NR206 dataset.

Physically unclonable functions (PUFs) are crucial for enhancing cybersecurity by providing unique, intrinsic identifiers for electronic devices, thus ensuring their authenticity and preventing unauthorized cloning. The SRAM-PUF, characterized by its simple structure and ease of implementation in various scenarios, has gained widespread usage. The soft-decision Reed–Muller (RM) code, an error correction code, is commonly employed in these designs. This paper introduces the design of an RM code soft-decision attack algorithm to reveal its potential security risks. To address this problem, we propose a soft-decision SRAM-PUF structure based on the elliptic curve digital signature algorithm (ECDSA). To improve the processing speed of the proposed secure SRAM-PUF, we propose a custom ECDSA scheme. Further, we also propose a universal architecture for the critical operations in ECDSA, elliptic curve scalar multiplication (ECSM), and elliptic curve double scalar multiplication (ECDSM) based on the differential addition chain (DAC). For ECSMs, iterations can be performed directly; for ECDSMs, a two-dimensional DAC is constructed through precomputation, followed by iterations. Moreover, due to the high similarity of ECSM and ECDSM data paths, this universal architecture saves hardware resources. Our design is implemented on a field-programmable gate array (FPGA) and an application-specific integrated circuit (ASIC) using a Xilinx Virtex-7 and an TSMC 40 nm process. Compared to existing research, our design exhibits a lower bit error rate (2.7×10−10) and better area–time performance (3902 slices, 6.615 μs ECDSM latency).

Highlights The recent development and implementation of metal–organic frameworks (MOFs) and MOF-based materials in electrochemical water applications are reviewed. The critical factors that affect the performances of MOFs in the electrochemical reactions, sensing, and separations are highlighted. Advanced tools, such as pair distribution function analysis, are playing critical roles in unraveling the functioning mechanisms, including local structures and nanoconfined interactions. Abstract Metal–organic frameworks (MOFs), a family of highly porous materials possessing huge surface areas and feasible chemical tunability, are emerging as critical functional materials to solve the growing challenges associated with energy–water systems, such as water scarcity issues. In this contribution, the roles of MOFs are highlighted in electrochemical-based water applications (i.e., reactions, sensing, and separations), where MOF-based functional materials exhibit outstanding performances in detecting/removing pollutants, recovering resources, and harvesting energies from different water sources. Compared with the pristine MOFs, the efficiency and/or selectivity can be further enhanced via rational structural modulation of MOFs (e.g., partial metal substitution) or integration of MOFs with other functional materials (e.g., metal clusters and reduced graphene oxide). Several key factors/properties that affect the performances of MOF-based materials are also reviewed, including electronic structures, nanoconfined effects, stability, conductivity, and atomic structures. The advancement in the fundamental understanding of these key factors is expected to shed light on the functioning mechanisms of MOFs (e.g., charge transfer pathways and guest–host interactions), which will subsequently accelerate the integration of precisely designed MOFs into electrochemical architectures to achieve highly effective water remediation with optimized selectivity and long-term stability.

Abstract Sensing and recognizing invisible ultraviolet (UV) light is vital for exploiting advanced artificial visual perception system. However, due to the uncertainty of the natural environment, the UV signal is very hard to be detected and perceived. Here, inspired by the tetrachromatic visual system, we report a controllable UV-ultrasensitive neuromorphic vision sensor (NeuVS) that uses organic phototransistors (OPTs) as the working unit to integrate sensing, memory and processing functions. Benefiting from asymmetric molecular structure and unique UV absorption of the active layer, the as fabricated UV-ultrasensitive NeuVS can detect 370 nm UV-light with the illumination intensity as low as 31 nW cm−2, exhibiting one of the best optical figures of merit in UV-sensitive neuromorphic vision sensors. Furthermore, the NeuVS array exbibits good image sensing and memorization capability due to its ultrasensitive optical detection and large density of charge trapping states. In addition, the wavelength-selective response and multi-level optical memory properties are utilized to construct an artificial neural network for extract and identify the invisible UV information. The NeuVS array can perform static and dynamic image recognition from the original color image by filtering red, green and blue noise, and significantly improve the recognition accuracy from 46 to 90%.

Summary: Targeting lysine-specific histone demethylase 1A (LSD1) can improve tumor immunogenicity of poorly immunogenic tumors, such as non-small cell lung cancer (NSCLC), with elevated T cell infiltration and sensitize tumors to anti-PD-1 therapy. However, the lack of reliable biomarkers limits utilization of LSD1 inhibitors in cancer therapy. Here, we identify an E3 ligase, Trim35, as an effective biomarker for high activity of LSD1 to predict prognosis of LSD1-targeted therapy as well as immunotherapy. Mechanistically, Trim35 represses LSD1 demethylase activity by mediating K63 ubiquitination at lysine site 422 of LSD1. Suppressed LSD1 activity facilitates ERGIC1 transcription, followed by autophagy inhibition and IFNGR1 stabilization to activate IFN-γ signaling, leading to increased MHC class I expression and immune surveillance of NSCLC cells. Furthermore, combinational use of an LSD1 inhibitor and anti-PD-1 therapy can significantly eradicate poorly immunogenic lung cancer with low Trim35. These findings strongly suggest that Trim35 is a promising biomarker for prediction of immunotherapy outcome in NSCLC.

ABSTRACTArtificial synaptic devices are the cornerstone of neuromorphic electronics. The development of new artificial synaptic devices and the simulation of biological synaptic computational functions are important tasks in the field of neuromorphic electronics. Although two-terminal memristors and three-terminal synaptic transistors have exhibited significant capabilities in the artificial synapse, more stable devices and simpler integration are needed in practical applications. Combining the configuration advantages of memristors and transistors, a novel pseudo-transistor is proposed. Here, recent advances in the development of pseudo-transistor-based neuromorphic electronics in recent years are reviewed. The working mechanisms, device structures and materials of three typical pseudo-transistors, including tunneling random access memory (TRAM), memflash and memtransistor, are comprehensively discussed. Finally, the future development and challenges in this field are emphasized.

Background & aimsThis multicenter retrospective study evaluated the efficacy and safety of transarterial chemoembolization (TACE) combined with donafenib and a programmed death-1 (PD-1) inhibitor (TACE+DP) and TACE combined with donafenib (TACE+D) for unresectable hepatocellular carcinoma (uHCC).MethodsThe clinical data of 388 patients with uHCC who received TACE+DP or TACE+D as first-line treatment at six Chinese academic centers from July 2021 to July 2022 were collected and analyzed retrospectively. Patients in the TACE+DP group received an intravenous administration of a PD-1 inhibitor every three weeks and oral donafenib (0.2 g) twice daily until intolerable toxicity or disease progression. Patients in the TACE+D group received the same dose of donafenib for 3–5 days after TACE. Overall survival (OS) and progression-free survival (PFS)were analyzed by Kaplan-Meier method and log-rank test. The tumor response was compared between the two groups according to modified RECIST criteria. Adverse events were also analyzed between the two groupsResultsThe TACE+D group included 157 patients and the TACE+DP group included 166 patients. Patients in the TACE+DP group had a longer median OS (18.1 vs. 13.2 months, P

Abstract Craquelure is the most common defect on ancient polychrome paintings, which may deteriorate further to paint loss. Previous image processing methods, which can accurately recognize paint loss, have limited precision and efficiency in segmenting craquelure. This paper proposes a semantic segmentation method, Res-UNet, for the recognition of craquelure and paint loss in the Palace Museum, Beijing. The residual structure of ResNet-50 enables the avoidance of network degradation, and image features can be fully extracted. Using the unique skip connection module of U-Net, features of different levels are fused to improve segmentation accuracy and provide smoother craquelure edges. Three loss functions are combined to accelerate stable convergence. The model was tested on a newly built dataset based on 600 images. Experimental results supported by statistical tests show that Res-UNet is a capable method of craquelure recognition, with an accuracy rate of 98.19%, and F1-score of 93.42%. Hence, the proposed hybrid approach is a promising tool to support the preservation and restoration of valuable traditional Chinese polychrome architectural paintings.

This paper presents an FPGA-based lightweight and real-time infrared image processor based on a series of hardware-oriented lightweight algorithms. The two-point correction algorithm based on blackbody radiation is introduced to calibrate the non-uniformity of the sensor. With precomputed gain and offset matrices, the design can achieve real-time non-uniformity correction with a resolution of 640×480. The blind pixel detection algorithm employs the first-level approximation to simplify multiple iterative computations. The blind pixel compensation algorithm in our design is constructed on the side-window-filtering method. The results of eight convolution kernels for side windows are computed simultaneously to improve the processing speed. Due to the proposed side-window-filtering-based blind pixel compensation algorithm, blind pixels can be effectively compensated while details in the image are preserved. Before image output, we also incorporated lightweight histogram equalization to make the processed image more easily observable to the human eyes. The proposed lightweight infrared image processor is implemented on Xilinx XC7A100T-2. Our proposed lightweight infrared image processor costs 10,894 LUTs, 9367 FFs, 4 BRAMs, and 5 DSP48. Under a 50 MHz clock, the processor achieves a speed of 30 frames per second at the cost of 1800 mW. The maximum operating frequency of our proposed processor can reach 186 MHz. Compared with existing similar works, our proposed infrared image processor incurs minimal resource overhead and has lower power consumption.

A good safety and immunogenicity profile was reported in Phase I and II clinical trials of inactivated SARS-CoV-2 vaccines. Here, we report two cases associated with vaccine-associated adverse events, including one patient with fever and another with anaphylactic shock resulting from inactivated SARS-CoV-2 vaccination. Cell sub-types and the importance of genetic characteristics were assessed using single-cell mRNA sequencing and machine learning. Overall, the patient with fever showed a significant increase in the numbers of cytotoxic CD8 T cells and MKI67high CD8 T cells. A potential concurrent infection with the Epstein–Barr virus enhanced interferon type I responses to vaccination against the virus. STAT1, E2F1, YBX1, and E2F7 played a key role in the transcription regulation of MKI67high CD8 T cells. In contrast, the patient with allergic shock displayed predominant increases in the numbers of S100A9high monocytes, activated CD4 T cells, and PPBPhigh megakaryocytes. The decision tree showed that LYZ and S100A8 in S100A9high monocytes contributed to the degranulation of neutrophils and activation of neutrophils involved in allergic shock. PPBP and PF4 were major contributors to platelet degranulation. These findings highlight the diversity of adverse reactions following inactivated SARS-CoV-2 vaccination and show the emerging role of cellular subtypes and central genes in vaccine-associated adverse reactions.

Transient receptor potential (TRP) channels are a class of transmembrane proteins that can sense a variety of physical/chemical stimuli, participate in the pathological processes of various diseases and have attracted increasing attention from researchers. Recent studies have shown that some TRP channels are involved in the development of pathological scarification (PS) and directly participate in PS fibrosis and re-epithelialization or indirectly activate immune cells to release cytokines and neuropeptides, which is subdivided into immune inflammation, fibrosis, pruritus and mechanical forces increased. This review elaborates on the characteristics of TRP channels, the mechanism of PS and how TRP channels mediate the development of PS, summarizes the important role of TRP channels in the different pathogenesis of PS and proposes that therapeutic strategies targeting TRP will be important for the prevention and treatment of PS. TRP channels are expected to become new targets for PS, which will make further breakthroughs and provide potential pharmacological targets and directions for the in-depth study of PS.

IntroductionGlobal HIV infections due to HIV-1 recombinants are increasing and impede prevention and treatment efforts. Key populations suffer most new HIV infections, but their role in the spread of HIV-1 recombinants is unknown. We conducted a global analysis of the associations between key populations and HIV-1 recombinants.MethodsWe searched PubMed, EMBASE, CINAHL, and Global Health for HIV-1 subtyping studies published from 1/1/1990 to 31/12/2015. Unpublished data was collected through a global survey. We included studies with HIV-1 subtyping data of key populations collected during 1990-2015. Key populations assessed were heterosexual people (HET), men who have sex with men (MSM), people who inject drugs (PWID), vertical transmissions (VERT), commercial sex workers (CSW), and transfusion-associated infections (BLOOD). Logistic regression was used to determine associations of key populations with HIV-1 recombinants. Subgroup analyses were performed for circulating recombinant forms (CRFs), unique recombinant forms (URFs), regions, and time periods.ResultsEight hundred and eighty five datasets including 77,284 participants from 83 countries were included. Globally, PWID were associated with the greatest odds of recombinants and CRFs (OR 2.6 [95% CI 2.46–2.74] and 2.99 [2.83–3.16]), compared to HET. CSW were associated with increased odds of recombinants and URFs (1.59 [1.44–1.75] and 3.61 [3.15–4.13]). VERT and BLOOD were associated with decreased odds of recombinants (0.58 [0.54–0.63] and 0.43 [0.33–0.56]). MSM were associated with increased odds of recombinants in 2010–2015 (1.43 [1.35–1.51]). Subgroup analyses supported our main findings.DiscussionAs PWID, CSW, and MSM are associated with HIV-1 recombinants, increased preventative measures and HIV-1 molecular surveillance are crucial within these key populations.Systematic review registrationPROSPERO [CRD42017067164].

Lung diseases are a major global health problem, affecting millions of people worldwide. Recent research has highlighted the critical role that mitochondrial quality control plays in respiratory-related diseases, including chronic obstructive pulmonary disease (COPD), lung cancer, and idiopathic pulmonary fibrosis (IPF). In this review, we summarize recent findings on the involvement of mitochondrial quality control in these diseases and discuss potential therapeutic strategies. Mitochondria are essential organelles for energy production and other cellular processes, and their dysfunction is associated with various diseases. The quality control of mitochondria involves a complex system of pathways, including mitophagy, mitochondrial biogenesis, fusion/fission dynamics, and regulation of gene expression. In COPD and lung cancer, mitochondrial quality control is often involved in disease development by influencing oxidative stress and apoptosis. In IPF, it appears to be involved in the disease process by participating in the cellular senescence process. Mitochondrial quality control is a promising target for therapeutic interventions in lung diseases. However, there are conflicting reports on different pathological processes, such as the role of mitochondrial autophagy in lung cancer, which pose difficulties in the study of targeted mitochondrial quality control drugs. Additionally, there seems to be a delicate balance between the mitochondrial quality control processes in the physiological state. Emerging evidence suggests that molecules such as PTEN-induced putative kinase 1 (PINK1), parkin RBR E3 ubiquitin protein ligase (PRKN), dynamin-related protein 1 (DRP1), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α), as well as the signaling pathways they affect, play an important role in respiratory-related diseases. Targeting these molecules and pathways could contribute to the development of effective treatments for lung diseases. In conclusion, the involvement of mitochondrial quality control in lung diseases presents a promising new avenue for disease treatment. Further research is needed to better understand the complex mechanisms involved in the pathogenesis of respiratory diseases and to develop targeted therapies that could improve clinical outcomes.

The combination of superabsorbent polymer (SAP) and expansive agent can effectively reduce the shrinkage deformation of ultra-high strength cement-based grouting materials (UHS-CGM) in dry environment. However, there are differences in the compensation shrinkage mechanism of SAP and expansive agent, and the presence of SAP may have adverse effects on the working and mechanical properties of grouting materials. In order to evaluate the synergistic effect of SAP with different water adsorption and release characteristics and MgO expansion agent (MEA), the influence of different SAP size and dosage on the compressive strength, restrained expansion rate, internal relative humidity (IRH) and hydration characteristics of UHS-CGM containing MEA were investigated, and then the composition and content of hydration products were analyzed by TG and XRD, the microstructures were observed by SEM in this paper. The results show that SAP improved the hydration degree of UHS-CGM and the expansion efficiency of MEA, and significantly increased the restrained expansion rate of UHS-CGM under standard curing and sealed curing, while reduced the compressive strength of UHS-CGM, and the decreasing degree was aggravated with increasing size and dosage of SAP. Overall, small size SAP has better inner curing efficiency and compensates shrinkage effect.

Abstract Background Drainage is indicated in many patients with a perinephric abscess (PA). Surgical drainage is associated with trauma and slow recovery, while percutaneous drainage can be ineffective in some patients. We report on 11 patients with PA treated by percutaneous nephroscopy combined with ultrasound-guided negative-pressure suction under local anesthesia. Methods This case series included 11 PA patients operated on from January 2013 to June 2020. All patients received percutaneous nephroscopy combined with ultrasound-guided negative-pressure suction. Data, including operation time, volume of intraoperative blood loss, volume of intraoperative pus suction, time of postoperative drainage tube indwelling, time to restore normal body temperature, length of postoperative hospital stay, and intraoperative and postoperative complications, were collected. Results The age of the patients was 59 (53–69) years. Eight, six, two, and two patients had hypertension, type 2 diabetes, rheumatoid arthritis, and renal calculi, respectively. The operations were successful forall11 patients. Eight, two, and one patients required one, two, and three channels, respectively, to clear their abscess. The average operation time was 44 (30–65) min, and intraoperative blood loss was 16 (10–20) ml. The volume of intraoperative pus suction was 280 (200–400) ml, time of postoperative drainage tube indwelling was 8.2 (6–12) days, and time to restoring normal body temperature was 0.8 (0.5–2) days. The average postoperative hospital stay was 9.8 (7–14) days. No severe intraoperative or postoperative complications occurred. The postoperative follow-up time was typically 4.8 (3–8) months, and there were no recurrences. Conclusion Percutaneous nephroscopy combined with ultrasound-guided negative-pressure suction might be a feasible method for treating PA.