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While Inconel 718 is a widely used engineering material in industrial fields such as the aerospace and automotive fields, the machined surface integrity has a significant effect on the performance of its components and parts. In this work, the laser-assisted micro-milling process of Inconel 718 is investigated using a combination of experiments and finite element simulations. Firstly, an experimental platform of laser-assisted milling is built, and a three-dimensional thermal–mechanical coupled finite element model of laser-assisted milling of Inconel 718 is then established. Secondly, laser-assisted milling experiments and finite element simulations are conducted to investigate the impact of laser assistance on cutting force, chip morphology, tool wear and surface topography of Inconel 718 under a milling process. The results indicate that laser-assisted milling results in a moderate reduction in cutting forces while enhancing surface integrity and chip continuity, as compared with ordinary milling. Thirdly, orthogonal experiments of laser-assisted milling of Inconel 718 are conducted to discover the optimal processing parameters, including spindle speed, feed per tooth, milling depth and laser parameters. Finally, single-factor experiments are conducted to investigate the effect of laser power on cutting force, chip morphology, tool wear, groove burr and surface roughness in the laser-assisted milling of Inconel 718. And, a minimal surface roughness Sa of 137 nm for Inconel 718 accompanied by minimal tool wear is experimentally obtained via laser-assisted milling. These findings highlight the effectiveness of applying laser assistance in enhancing the machinability of difficult-to-machine materials for achieving desirable machined surface integrity.

The authors present structures of the MtbEttA protein bound to or free of the ribosome from Mycobacterium tuberculosis under different nucleotide states, which provide insights into the mechanism of translational regulation by EttA-like proteins.

Marcasite (FeS2) is widespread in nature, its oxidation plays a vital role in acid mine drainage, mineral resource recovery, and photoelectric material applications. In this paper, the oxidation mechanism of marcasite has been studied for the first time using density functional theory (DFT). It is found that, unlike the oxidation of pyrite, the oxidation of marcasite merely occurs at surface S atoms. Under the coexistence of water and oxygen, S atoms around surface Fe atoms are replaced by O atoms. The surface S sites are initially oxidized to form S==O bonds, and continue to adsorb oxygen to gradually generate SO32−, SO42− species, and eventually FeSO4. In this process, H2O molecules participate in neither oxidation nor dissociation, and they are adsorbed on surface Fe sites in the form of molecules, i.e., all O atoms in SO42− derive from oxygen rather than water molecules.

Low-Density Parity-Check (LDPC) code is a type of forward error-correction code with excellent performance, and has been widely used in many modern communication standards. The second-generation satellite broadcasting standard (DVB-S2) and its extension (DVB-S2X) adopt a special Irregular Repeated Accumulate (IRA) LDPC code as inner coding scheme. However, due to the large block size, most of the architectures proposed so far use Random Access Memory (RAM) to store and update the encoding results, and the delay caused by address-controlled read and write operations and barrel shift during computation inevitably limits the upper bound of encoder throughput. In this paper, by extracting the periodicity of the parity-check matrix, we introduce a fast encoding algorithm that can efficiently process the multiplication of the information sequence and a large-dimensional sparse matrix, and propose an encoder architecture with low encoding delay and high throughput. The proposed architecture has been implemented and tested on a Xilinx Kintex-7 FPGA, and the result show that the encoder architecture can achieve the highest throughput of 47.5 Gbps at a clock frequency of 280 MHz.

Introduction: Flight muscle histolysis, as an important survival strategy, is a widespread phenomenon in insects and facilitates adaptation to the external environment in various insect taxa. However, the regulatory mechanism underlying this phenomenon in Orthoptera remains unknown.Methods: In this study, the flight muscle histolysis in the house cricket Acheta domesticus was investigated by transcriptomics and RNA interference.Results: The results showed that flight muscle histolysis in A. domesticus was standard and peaked within 9 days after eclosion of adult crickets, and there was no significant difference in the peak time or morphology of flight muscle histolysis between males and females. In addition, the differentially expressed genes between before and after flight muscle histolysis were studied, of which AdomFABP, AdomTroponin T and AdomActin were identified as candidate genes, and after injecting the dsRNA of these three candidates, only the downregulated expression of AdomFABP led to flight muscle histolysis in A. domesticus. Furthermore, the expression level of AdomFABP was compared between before and after flight muscle histolysis based on RT-qPCR.Disscussion: We speculated that AdomFABP might play a role in the degradation of flight muscle by inhibiting muscle development. Our findings laid a molecular foundation for understanding the flight muscle histolysis.

Abstract The advent of high-resolution electron and scanning probe microscopy imaging has opened the floodgates for acquiring atomically resolved images of bulk materials, 2D materials, and surfaces. This plethora of data contains an immense volume of information on materials structures, structural distortions, and physical functionalities. Harnessing this knowledge regarding local physical phenomena necessitates the development of the mathematical frameworks for extraction of relevant information. However, the analysis of atomically resolved images is often based on the adaptation of concepts from macroscopic physics, notably translational and point group symmetries and symmetry lowering phenomena. Here, we explore the bottom-up definition of structural units and symmetry in atomically resolved data using a Bayesian framework. We demonstrate the need for a Bayesian definition of symmetry using a simple toy model and demonstrate how this definition can be extended to the experimental data using deep learning networks in a Bayesian setting, namely rotationally invariant variational autoencoders.

Abstract Healthcare‐associated infections are a major problem in hospitals, and regular disinfection methods cannot guarantee that all pathogens are eliminated. Non‐contact human–computer interactions can effectively reduce the risk of contamination by preventing direct contact between medical staff and electronic products. In this study, a new type of flexible and highly malleable magnetic skin composed of a mixture of an elastic matrix and permanent magnetic powder is demonstrated. In addition, the relationship between the magnetic skin properties and the elastic matrix, magnetic powder material, and their ratio is studied. In addition, the application of magnetic skin in gesture recognition (representing discrete gesture input) and magnetic positioning (representing continuous input) is explored to easily achieve touchless human–computer interactions. Both perform well and provide a new way for future human–computer interaction.

ABSTRACT Japanese encephalitis virus (JEV) genotype V (GV) emerged in China in 2009, then South Korea, and has since spread to other regions in Asia and beyond, raising concern about its pathogenicity and the cross-protection offered by JEV vaccines against different genotypes. In this study, we replaced the structural proteins (C-prM-E) of an attenuated genotype I (GI) SD12-F120 strain with those of a virulent GV XZ0934 strain to construct a recombinant chimeric GI-GV JEV (JEV-GI/V) strain to determine the role of the structural proteins in virulence and cross-protection. The recombinant chimeric virus was highly neurovirulent and neuroinvasive in mice. This demonstrated the determinant role of the structural proteins in the virulence of the GV strain. Intracerebral or intraperitoneal inoculation of mice with JEV-GI/V-E5 harboring a combination of substitutions (N47K, L107F, E138K, H123R, and I176R) in E protein, but not mutants containing single substitution of these residues, resulted in decreased or disappeared mortality, suggesting that these residues synergistically, but not individually, played a role in determining the neurovirulence and neuroinvasiveness of the GV strain. Immunization of mice with attenuated strain JEV-GI/V-E5 provided complete protection and induced high neutralizing antibody titers against parental strain JEV-GI/V, but partial cross-protection and low cross-neutralizing antibodies titers against the heterologous GI and GIII strains in mice, suggesting the reduced cross-protection of JEV vaccines among different genotypes. Overall, these findings suggested the essential role of the structural proteins in determination of the virulence of GV strain, and highlighted the need for a novel vaccine against this newly emerged strain. IMPORTANCE The GV JEV showed an increase in epidemic areas, which exhibited higher pathogenicity in mice than the prevalent GI and GIII strains. We replaced a recombinant chimeric GI-GV JEV (JEV-GI/V) strain to determine the role of the structural proteins in virulence and cross-protection. It was found that the essential role of the structural proteins is to determinethe virulence of the GV strain. It is also suggested that there is reduced cross-protection of JEV vaccines among different genotypes, which provides basic data for subsequent JEV prevention, control, and new vaccine development.

Deficiency of oxygen supply is an inevitable problem in the treatment of bone defects or fractures. In addition, an adequate supply of major mineral elements (Ca and P) is also required for efficient new bone formation. In this study, we developed a novel nanofibrous membrane to provide oxygen and essential mineral elements for enhanced osteogenesis, which was fabricated from Poly L lactic-acid (PLLA), calcium peroxide (CPO) and black phosphorus (BP). The results in vitro demonstrated that the obtained composite nanofibers promoted the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) due to the sustained supply of oxygen, Ca and P element. And under the NIR exposure, the osteogenic properties of composite nanofibers were further improved. Furthermore, the results in vivo confirmed that the composite nanofibers has good biocompatibility and osteoinductive activity. Considering the unique oxygen-generating, osteogenic properties and NIR-responsive behavior, we believed that the developed composite nanofibers have great application potential in the field of bone regenerative medicine.

Artificial induction of polyploidy is an efficient technique for improving biological properties and developing new varieties of many plants. In this study, we analyzed and compared differences in characteristics (morphological and biological) of diploid and tetraploid Anoectochilus roxburghii plants. We found significant differences between tetraploid plants and their diploid counterparts. The tetraploid plants exhibited dwarfing and stockiness. They were also bigger and had more voluminous roots and larger stomata than the diploid plants. Moreover, the biochemical analyses showed that the contents of some amino acids and minerals elements were significantly higher in tetraploid plants. The chlorophyll content of the leaves exhibited no definitive changes, but the photosynthetic performance was higher in the tetraploid plants. In addition, contents of major bioactive compounds, such as kinsenoside and some flavonoids, were enhanced in tetraploids. This is the first detailed analysis of characteristics in diploid and tetraploid A. roxburghii plants. The results may facilitate breeding programs with the species.

Aging is an intricate biological event that occurs in both vertebrates and invertebrates. During the aging process, the brain, a vulnerable organ, undergoes structural and functional alterations, resulting in behavioral changes. The hippocampus has long been known to be critically associated with cognitive impairment, dementia, and Alzheimer’s disease during aging; however, the underlying mechanisms remain largely unknown. In this study, we hypothesized that altered metabolic and gene expression profiles promote the aging process in the hippocampus. Behavioral tests showed that exploration, locomotion, learning, and memory activities were reduced in aged mice. Metabolomics analysis identified 69 differentially abundant metabolites and showed that the abundance of amino acids, lipids, and microbiota-derived metabolites (MDMs) was significantly altered in hippocampal tissue of aged animals. Furthermore, transcriptomic analysis identified 376 differentially expressed genes in the aged hippocampus. A total of 35 differentially abundant metabolites and 119 differentially expressed genes, constituting the top 200 correlations, were employed for the co-expression network. The multi-omics analysis showed that pathways related to inflammation, microglial activation, synapse, cell death, cellular/tissue homeostasis, and metabolism were dysregulated in the aging hippocampus. Our data revealed that metabolic perturbations and gene expression alterations in the aged hippocampus were possibly linked to their behavioral changes in aged mice; we also provide evidence that altered MDMs might mediate the interaction between gut and brain during the aging process.

While the deformation behavior of grain boundaries has a strong impact on the mechanical response of polycrystalline materials, investigating the coupled thermal–mechanical properties of grain boundaries in their real formats is crucial for enhancing the ductile machinability of hard brittle polycrystalline ceramic materials. In the present work, we report the thermal softening-suppressed inter-granular fracture, accompanied with enhanced stacking fault formation, increased healing ability of grain boundaries and promoted ductile material removal, in diamond cutting of polycrystalline 3C-SiC at elevated temperatures by multi-scale simulations. Molecular dynamics simulations and experiments of high temperature nanoindentations are performed to derive the temperature-dependent mechanical properties of bulk polycrystalline 3C-SiC. Furthermore, molecular dynamics simulations of Mode I (tension) and Mode II (shearing) loading of a Σ9{122} symmetric tilt grain boundary at elevated temperatures are performed to extract the temperature-dependent mechanical properties of grain boundaries in polycrystalline 3C-SiC. A novel finite element model of heat treatment-assisted diamond cutting of polycrystalline 3C-SiC with the comprehensive consideration of thermal properties of both grains and grain boundaries at elevated temperatures is established to reveal the transition of material removal mode, grain boundary failure behavior, cutting force characteristics and chip profile with temperature.

Background Osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) is essential for bone formation, and its dysfunction is reported to be associated with osteoporosis (OP). Recent researches have determined that lncRNA PART1 participates in the pathogenesis of multiple diseases. However, its role in modulating osteogenic differentiation of hBMSCs is unclear. Methods PART1, miR-185-5p, and RUNX3 levels were assessed via RT-qPCR. The protein levels of OCN, OSN, and COL1A1 were measured by western blotting. The osteoblastic phenotype was evaluated via ALP activity and ARS staining. The relationship between miR-185-5p and PART1 or RUNX3 was validated by luciferase reporter, RIP assays. Results PART1 and RUNX3 expression were enhanced during hBMSC osteogenic differentiation. PART1 deletion decreased OCN, OSN, and COL1A1 levels and weakened ALP activity, but promoted the apoptosis of hBMSCs. Moreover, PART1 served as a ceRNA to influence the RUNX3 level via targeting miR-185-5p. In addition, RUNX3 was verified to activate the transcription of PART1 in hBMSCs. Finally, rescue assays indicated that suppression of miR-185-5p or addition of RUNX3 partially abolished the effects of PART1 knockdown on the levels of OCN, OSX, and COL1A1 levels, ALP activity, and apoptosis. Conclusion Our study elaborated that PART1/miR-185-5p/RUNX3 feedback contributed to osteogenic differentiation and inhibited the hBMSCs apoptosis, suggesting that PART1 might be a novel target for OP treatment.

Abstract Background Super typhoon Lekima had a maximum wind force of 16 (52 m/s) and hit Wenling city, Zhejiang province in China on August 10, 2019. The typhoon left many victims showing symptoms of posttraumatic stress disorder (PTSD). Objective This study aimed to assess the prevalence of full and partial PTSD to inform targeted interventions for adult victims. Method In total, four thousand seven hundred and forty-six adults who are parents of students in local primary and middle schools were recruited to participate in this study. Participants completed a trauma exposure scale and the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition PTSD Checklist. Logistic regression analysis was used to examine the factors of full and partial PTSD. Results Nine hundred and ten (19.2%) adults had full PTSD and 1775 (37.4%) had partial PTSD. Adults with a monthly income > 10,000 RMB (about 1530 dollars) and a high education level (bachelor’s degree or above) were less likely to have full or partial PTSD than those with lower income and lower education levels. In addition, married adults were less likely to have full PTSD than divorced or widowed ones. Higher rates of PTSD were observed among those aged ≥40 years, who were injured/trapped, whose family members/friends were injured/trapped, and who lost property. Conclusions Partial and full PTSD were common among adults following super typhoon Lekima, and high income, high education level, and married status were protective factors, whereas trauma exposure was a risk factor of PTSD. Target psychological intervention should be provided to these victims who are in low income and education level, divorced and widowed, and experienced more serious trauma.

Abstract Effectively promoting corneal allograft survival remains a challenge in corneal transplantation. The emerging therapeutic agents with high pharmacological activities and their appropriate administration routes provide attractive solutions. In the present study, a celastrol-loaded positive nanomedicine (CPNM) was developed to enhance corneal penetration and to promote corneal allograft survival. The in vitro, in vivo and ex vivo results demonstrated the good performance of CPNM prolonging the retention time on ocular surface and opening the tight junction in cornea, which resulted in enhanced corneal permeability of celastrol. Both in vitro and in vivo results demonstrated that celastrol inhibited the recruitment of M1 macrophage and the expression of TLR4 in corneal allografts through the TLR4/MyD88/NF-κB pathway, thereby significantly decreasing secretion of multiple pro-inflammatory cytokines to promote corneal allograft survival. This is the first celastrol-based topical instillation against corneal allograft rejection to provide treatment more potent than conventional eye drops for ocular anterior segment diseases. Graphical Abstract

Purpose – This paper aims to use active fine lane management methods to solve the problem of congestion in a weaving area and provide theoretical and technical support for traffic control under the environment of intelligent connected vehicles (ICVs) in the future. Design/methodology/approach – By analyzing the traffic capacities and traffic behaviors of domestic and foreign weaving areas and combining them with field investigation, the paper proposes the active and fine lane management methods for ICVs to optimal driving behavior in a weaving area. The VISSIM simulation of traffic flow vehicle driving behavior in weaving areas of urban expressways was performed using research data. The influence of lane-changing in advance on the weaving area was evaluated and a conflict avoidance area was established in the weaving area. The active fine lane management methods applied to a weaving area were verified for different scenarios. Findings – The results of the study indicate that ICVs complete their lane changes before they reach a weaving area, their time in the weaving area does not exceed the specified time and the delay of vehicles that pass through the weaving area decreases. Originality/value – Based on the vehicle group behavior, this paper conducts a simulation study on the active traffic management control-oriented to ICVs. The research results can optimize the management of lanes, improve the traffic capacity of a weaving area and mitigate traffic congestion on expressways.

Porcine reproductive and respiratory syndrome (PRRS) is an immunosuppressive disease caused by PRSS virus (PRRSV). PRRSV mainly causes reproductive disorders in pregnant sows and respiratory diseases in piglets. Recently, it has emerged as one of the most important diseases of the pig industry across the globe. In this study, we have collected 231 samples from differently sized pig farms in Eastern China from 2017 to 2022 to investigate the epidemic characteristics of the disease. All samples were screened by RT-PCR and analyzed further using Nsp2 and ORF5 genes. The result showed that the positive rate of PRRSV was 24% (54/231). Phylogenetic analysis (13 positive samples) revealed that all isolates belonged to genotype 2, and they were mainly distributed in four lineages (i.e., lineage 1, 3, 5, and 8). Nsp2 is the most variable protein among all PRRSV NSPs, several isolates from this study had amino acid deletions within Nsp2 compared to that of strain VR-2332. The major structural protein glycoprotein (GP5) protein is encoded by ORF5. Epitope analysis of the 13 isolated strains and additional reference strains revealed that all 13 strains had some mutations on the decoy epitope, the primary neutralizing epitope, T cell epitopes, and B cell epitopes. This study showed that the prevalent PRRSV strain in Eastern China was still HP-PRRSV, while the proportion of NADC30-like and NADC34-like strains have increased. This study further enriches the epidemiological data of PRRS in Eastern China and provides a theoretical basis for vaccine development and prevention and control of the disease across the region.

African Swine Fever (ASF) is an acute, highly contagious and deadly infectious disease that has a huge impact on the swine industry. It is caused by the African swine fever virus (ASFV). The most acute forms of ASF in domestic pigs have mortality rates of up to 100%. The lack of a commercial vaccine and effective therapeutic drugs has brought great challenges to the prevention and control of ASF. Current, the African swine fever virus requires a huge amount of detection, so there is a need for more sensitive and accurate detection technology. The protein pB602L, as a late non-structural protein, has a high corresponding antibody titer and strong antigenicity in infected swine. In this research, the B602L gene was constructed into the pColdI prokaryotic expression vector, and prokaryotic expression of the soluble pB602L protein was induced by IPTG. Western blot analysis demonstrated that the protein had strong immunogenicity. We established an indirect ELISA method for the detection of anti-ASFV using purified recombinant pB602L protein as antigen. The detection method showed excellent specificity without cross-reactions with antibodies against PRRSV, CSFV, JEV, and GETV. The method could detect anti-ASFV in serum samples that were diluted up to 6,400 times, showing high sensitivity. The coefficients of variation of the intra-assay and inter-assay were both

The Physical Exercise Rating Scale, Mindfulness Attention Awareness Scale (MAAS), Ruminative Thinking Scale (RRS), and Pittsburgh Sleep Quality Index (PSQI) are used to conduct the questionnaire among a sample of 1,006 college students (average age = 19.95 years, SD = 1.86 years) to figure out whether there is any correlation between physical exercise and sleep quality in college students as well as how the mechanism of mindfulness and ruminative thinking plays a role in them. For data analysis, the Harman single-factor test was used; for the common method deviation test, Pearson’s correlation analysis, and the mediating effect tested by using the bootstrap method were carried out. Results: (1) Overall, 34% (PSQI ≥ 8) of college students’ sleep quality is poor. (2) The PSQI is positively correlated with ruminative thinking, while both are negatively correlated with the level of physical exercise and mindfulness; the level of physical exercise is positively correlated with the level of mindfulness. (3) Physical exercise can significantly negatively predict sleep quality (β = −0.08, P < 0.05), significantly positively predict mindfulness (β = 0.12, P < 0.001), and significantly negatively predict ruminative thinking (β = −0.07, P < 0.05). When participate in physical exercise, mindfulness, and ruminative thinking enter the regression equation at the same time, only mindfulness and ruminative thinking can predict sleep quality(β = −0.15, P < 0.001) significantly negatively predicted sleep quality and ruminative thinking (β = 0.22, P < 0.001) significantly positively predicted sleep quality, while physical exercise (β = −0.04, P > 0.05) had no significant predictive effect on sleep quality. (4) After controlling for age and gender, physical exercise appears to have an impact on sleep quality of college students through the independent intermediary role of mindfulness and ruminative thinking and the chain intermediary role of mindfulness and ruminative thinking, with a total mediating effect value of −0.007. This study reveals the relationship between physical exercise and sleep quality, as well as its mechanism, thus guiding college students to actively participate in physical exercise. It also provides corresponding suggestions to improve sleep quality as well as physical and mental health in college students.

G protein–coupled receptors can signal through both G proteins and ß-arrestin2. For the µ-opioid receptor (MOR), early experimental evidence from a single study suggested that G protein signaling mediates analgesia and sedation, whereas ß-arrestin signaling mediates respiratory depression and constipation. Then, receptor mutations were used to clarify which residues interact with ligands to selectively regulate signals in a ligand-specific manner. However, there is no systematic study on how to determine these residues and clarify the molecular mechanism of their influence on signal pathways. We have therefore used molecular docking to predict the amino acid sites that affect the binding of ligands and MOR. Then, the corresponding sites were mutated to determine the effect of the structural determinant of MOR on Gi/o protein and ß-arrestin pathways. The pharmacological and animal behavioral experiments in combination with molecular dynamics simulations were used to elucidate the molecular mechanism of key residues governing the signaling. Without affecting ligand binding to MOR, MORY7.43A attenuated the activation of both Gi/o protein and ß-arrestin signaling pathways stimulated by fentanyl, whereas it did not change these two pathways stimulated by morphine. Likewise, the activation peak time of extracellular regulated protein kinases was significantly prolonged at MORY7.43A compared with that at MORwildtype stimulated by fentanyl, but there was no difference stimulated by morphine. In addition, MORY7.43A significantly enhanced analgesia by fentanyl but not by morphine in the mice behavioral experiment. Furthermore, the molecular dynamics simulations showed that H6 moves toward the cellular membrane. H6 of the fentanyl–Y7.43A system moved outward more than that in the morphine–Y7.43A system. Y7.43 mutation disrupted hydrophobic interactions between W6.48 and Y7.43 in the fentanyl–Y7.43A system but not in the morphine–Y7.43A system. Our results have disclosed novel mechanisms of Y7.43 mutation affecting MOR signaling pathways. Y7.43 mutation reduced the activation of the Gi/o protein pathway and blocked the ß-arrestin2 recruitment, increased the H6 outward movement of MOR, and disrupted hydrophobic interactions. This may be responsible for the enhanced fentanyl analgesia. These findings are conducive to designing new drugs from the perspective of ligand and receptor binding, and Y7.43 is also expected to be a key site to structure optimization of synthesized compounds.

Safety and efficient dispose of municipal solid waste incineration (MSWI) fly ash with high toxicity has emerged as a worldwide challenge. Vitrification provides the advantages of capacity reduction, detoxification, and solidification of heavy metals, which has the potential to dispose of hazardous waste on a large scale. Herein, co–vitrification of MSWI fly ash and bottom slag has been accomplished based on the characteristics of calcium and silicon composition. A novel approach for producing glass ceramic foams by alkaline activation–crystallization was developed to realize the disposal of the obtained glass. The effect of MSWI fly ash/bottom slag ratios on the glass network, crystallization ability of the basic glass, pore structure, and physical properties of the porous green body was investigated. The results revealed that with increasing MSWI fly ash proportion, the Si–O of [SiO4] in the basic glass changed significantly and the crystallization ability steadily reduced. Si–O and Al–O in basic glass are easy to corrode under alkaline conditions, releasing Ca2+ and forming a low solubility product, calcium silicate hydrate. When the crystallization temperature increases from 950 ℃ to 1150 ℃, it is more conducive to the precipitation of the gehlenite phase. Extending the crystallization time promotes three–dimensional growth of crystals that are coupled with each other to form a network structure and a multi–stage pore structure. The pore structure was developed with the help of NH3 and H2 generated by the secondary aluminum ash (SAA). Through the preparation of glass ceramic foams, the raw materials were detoxified. The toxic heavy metals showed extremely low leaching concentrations, which were smaller than the limit of TCLP. The prepared samples had 70.22–80.61% of porosity, 0.78–1.19 g/cm3 of low bulk density, and 0.54–7.86 MPa of compressive strength.

Sepsis-associated encephalopathy (SAE) is an intricated complication of sepsis that brings abnormal emotional and memory dysfunction and increases patients’ mortality. Patients’ alterations and abnormal function seen in SAE occur in the hippocampus, the primary brain region responsible for memory and emotional control, but the underlying pathophysiological mechanisms remain unclear. In the current study, we employed an integrative analysis combining the RNA-seq-based transcriptomics and liquid chromatography/mass spectrometry (LC-MS)-based metabolomics to comprehensively obtain the enriched genes and metabolites and their core network pathways in the endotoxin (LPS)-injected SAE mice model. As a result, SAE mice exhibited behavioral changes, and their hippocampus showed upregulated inflammatory cytokines and morphological alterations. The omics analysis identified 81 differentially expressed metabolites (variable importance in projection [VIP] > 1 and p < 0.05) and 1747 differentially expressed genes (Foldchange >2 and p < 0.05) were detected in SAE-grouped hippocampus. Moreover, 31 compounds and 100 potential target genes were employed for the Kyoto Encyclopedia of Genes and Genomes (KEGG) Markup Language (KGML) network analysis to explore the core signaling pathways for the progression of SAE. The integrative pathway analysis showed that various dysregulated metabolism pathways, including lipids metabolism, amino acids, glucose and nucleotides, inflammation-related pathways, and deregulated synapses, were tightly associated with hippocampus dysfunction at early SAE. These findings provide a landscape for understanding the pathophysiological mechanisms of the hippocampus in the progression of SAE and pave the way to identify therapeutic targets in future studies.

Alternative choices of anode materials in lithium-ion batteries (LiBs) have drawn great attention to the urgent demands of rapid charging, however, the severe interface problems remain a bottleneck for the anode development. Based on the high reducibility of halogen elements, herein a smart anode/liquid electrolyte interface is designed for the high energy density batteries that present large specific capacity retentions of about 510.5 mAh∙g−1 (Cl-matrix) and 429.6 mAh∙g−1 (Br-matrix) at the current density of 5 A∙g−1 after cycling 1000 times. As a novel anode material, the low-dimension halide perovskite microcrystals Cs4Pb(Cl/Br/I)6 embedded in the glass matrix present high ionic conductivities (10−5 ∼ 10−4 S∙cm−1) that enables fast charge transfer, besides the smooth interface benefits ionic transport reversibly. Most impressively, simple composite processing has significant economic benefits that might drive the crystal-in-glass composite material as a promising new generation anode for rechargeable LiBs.

There has emerged substantial research in addressing single-view 3D reconstruction and the majority of the state-of-the-art implicit methods employ CNNs as the backbone network. On the other hand, transformers have shown remarkable performance in many vision tasks. However, it is still unknown whether transformers are suitable for single-view implicit 3D reconstruction. In this paper, we propose the first end-to-end single-view 3D reconstruction network based on the Pyramid Vision Transformer (PVT), called ED2IF2-Net, which disentangles the reconstruction of an implicit field into the reconstruction of topological structures and the recovery of surface details to achieve high-fidelity shape reconstruction. ED2IF2-Net uses a Pyramid Vision Transformer encoder to extract multi-scale hierarchical local features and a global vector of the input single image, which are fed into three separate decoders. A coarse shape decoder reconstructs a coarse implicit field based on the global vector, a deformation decoder iteratively refines the coarse implicit field using the pixel-aligned local features to obtain a deformed implicit field through multiple implicit field deformation blocks (IFDBs), and a surface detail decoder predicts an enhanced displacement field using the local features with hybrid attention modules (HAMs). The final output is a fusion of the deformed implicit field and the enhanced displacement field, with four loss terms applied to reconstruct the coarse implicit field, structure details through a novel deformation loss, overall shape after fusion, and surface details via a Laplacian loss. The quantitative results obtained from the ShapeNet dataset validate the exceptional performance of ED2IF2-Net. Notably, ED2IF2-Net-L stands out as the top-performing variant, exhibiting the highest mean IoU, CD, EMD, ECD-3D, and ECD-2D scores, reaching impressive values of 61.1, 7.26, 2.51, 6.08, and 1.84, respectively. The extensive experimental evaluations consistently demonstrate the state-of-the-art capabilities of ED2IF2-Net in terms of reconstructing topological structures and recovering surface details, all while maintaining competitive inference time.

Dried distiller’s grains with solubles (DDGS) are rich in nutrients and can enhance animals’ growth and immunity. However, there are few reports on the effects of a diet of DDGS on plasma metabolism and the related action pathways in domestic animals. In this study, groups of Guanling yellow cattle (GY) and Guanling crossbred cattle (GC) having a basal diet served as the control groups (GY-CG and GC-CG), and DDGS replacing 25% of the diet of GY and GC served as the replacement groups (GY-RG and GC-RG), with three cattle in each group. Plasma samples were prepared for metabolomic analysis. Based on multivariate statistical and univariate analyses, differential metabolites and metabolic pathways were explored. Twenty-nine significantly different metabolites (p < 0.05) were screened in GY-RG compared with those in GY-CG and were found to be enriched in the metabolic pathways, including choline metabolism in cancer, linolenic acid metabolism, and amino acid metabolism. Nine metabolites showed significant differences (p < 0.05) between GC-RG and GC-CG and were mainly distributed in the metabolic pathways of choline metabolism in cancer, glycerophospholipid metabolism, prostate cancer metabolism, and gonadotropin-releasing hormone (GnRH) secretion. These results suggest that a DDGS diet may promote healthy growth and development of experimental cattle by modulating these metabolic pathways. Our findings not only shed light on the nutritional effects of the DDGS diet and its underlying mechanisms related to metabolism but also provide scientific reference for the feed utilization of DDGS.

The overpasses and the terrain under them in Chongqing, a mountainous city in China, are complex and diverse, and some spaces under the overpasses are integrated and reconstructed into the underpass green space for citizens to stroll about or have a rest. From the perspective of visitor perception, this paper constructs a perception evaluation system of the environmental characteristics of underpass green space in mountainous cities from the following five environmental perception dimensions: path organization, security, aesthetic value, physical environment, activities and cultural. The IPA-Kano model is used to quantify environmental perception, and the main environmental factors affecting the improvement of recreation satisfaction of underpass green space in three types of terrain are explored, with a view to improving the environment and service functions of underpass green spaces in high-density interchange networks in mountainous cities, and enhancing the attractiveness of underpass green spaces. It can be found from the study that: (1) Among the five environmental perception dimensions, visitors pay more attention to the physical environment quality of the underpass green space and their physical and psychological activity experience, while their demands for visual senses are relatively low. Due to the deficiency or lack of leisure facilities, sports facilities, children’s playgrounds and amusement equipment, the dimension of “activities and cultural perception” of the underpass green space has the lowest scores of all. (2) The existing sites, facilities and landscape resources of the underpass green space, different terrain types and underpass environment are the important reasons that affect the performance of environmental perception factors and their priority ranking results. (3) The improvement of security of the arrival path or sports facilities is beneficial to improve visitor satisfaction of underpass green space of three types of terrain. The number of environmental factors to be optimized of the three types of terrain are ranked as: mountainous green space > flat green space > concave green space. Among them, four environmental factors have a high priority in two kinds of underpass green space, which are the distribution and quantity of leisure facilities, the effect of noise reduction and sound insulation, the adequacy of activity venues and the distribution and quantity of sports facilities. Finally, according to the particularity of the underpass environment and the characteristics of three types of terrain, this paper puts forward some suggestions for optimizing the service function of underpass green space from five perceptual dimensions.

Conotoxins are a class of disulfide-rich peptides found in the venom of cone snails, which have attracted considerable attention in recent years due to their potent activity on ion channels and potential for therapeutics. Among them, α-conotoxin RgIA, a 13-residue peptide, has shown great promise as a potent inhibitor of α9α10 nAChRs for pain management. In this study, we investigated the effect of substituting the naturally occurring L-type arginine at position 11 of the RgIA sequence with its D-type amino acid. Our results indicate that this substitution abrogated the ability of RgIA to block α9α10 nAChRs, but instead endowed the peptide with the ability to block α7 nAChR activity. Structural analyses revealed that this substitution induced significant alteration of the secondary structure of RgIA[11r], which consequently affected its activity. Our findings underscore the potential of D-type amino acid substitution as a promising strategy for designing novel conotoxin-based ligands targeting different types of nAChRs.

Late Cretaceous granitoids are developed in the eastern and western districts of the Gejiu ore district, but tin deposits mainly occur in the eastern district, and the reasons for the difference in mineralization between the eastern and western districts are still controversial. Considering the main factors controlling granite Sn fertility, the whole-rock geochemical characteristics of granites on both sides are compared. LA-ICP-MS zircon U-Pb analyses of the Gejiu granites yielded two age periods: the early phase from 79.2 to 83.3 Ma and the later phase from 73.8 to 75.6 Ma. The western district granites have higher zircon εHf(t), CaO/Na2O, Ba, and Sr concentrations and lower Rb/Sr ratios than the eastern district granites, indicating that the western district granites have more mantle-derived materials in the source than the eastern district granites. Results of oxygen fugacity show that the western granites have a higher oxygen fugacity condition. More depleted Ba, Sr, P, Eu and Ti characteristics with obviously negative Eu anomalies in the eastern granites also have high Rb/Sr ratios and low Nb/Ta and Zr/Hf ratios, indicating that the eastern granites experienced highly magmatic differentiation, attributed to high volatile F contents that can reduce the viscosity and solidus of magma. Combined with the differences in field observations and structural styles, on the whole, the western district granites have higher oxygen fugacities and lower F contents and magmatic differentiation than those in the eastern district granites, indicating that the western district granites are not conducive to mineralization.

The TCP protocol is a connection-oriented and reliable transport layer communication protocol which is widely used in network communication. With the rapid development and popular application of data center networks, high-throughput, low-latency, and multi-session network data processing has become an immediate need for network devices. If only a traditional software protocol stack is used for processing, it will occupy a large amount of CPU resources and affect network performance. To address the above issues, this paper proposes a double-queue storage structure for a 10G TCP/IP hardware offload engine based on FPGA. Furthermore, a TOE reception transmission delay theoretical analysis model for interaction with the application layer is proposed, so that the TOE can dynamically select the transmission channel based on the interaction results. After board-level verification, the TOE supports 1024 TCP sessions with a reception rate of 9.5 Gbps and a minimum transmission latency of 600 ns. When the TCP packet payload length is 1024 bytes, the latency performance of TOE’s double-queue storage structure improves by at least 55.3% compared to other hardware implementation approaches. When compared with software implementation approaches, the latency performance of TOE is only 3.2% of the software approaches.

Glaesserella parasuis (Gps), Gram-negative bacteria, are a universal respiratory-disease-causing pathogen in swine that colonize the upper respiratory tract. Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus (HP-PRRSV2HP-PRRSV2) and Gps coinfections are epidemics in China, but little is known about the influence of concurrent coinfection on disease severity and inflammatory responses. Herein, we studied the effects of secondary HP-PRRS infection on clinical symptoms, pathological changes, pathogen load, and inflammatory response of Gps coinfection in the upper respiratory tract of piglets. All coinfected piglets (HP-PRRSV2 + Gps) displayed fever and severe lesions in the lungs, while fever was present in only a few animals with a single infection (HP-PRRSV2 or Gps). Additionally, HP-PRRSV2 and Gps loading in nasal swabs and blood and lung tissue samples was significantly increased in the coinfected group. Necropsy data showed that coinfected piglets suffered from severe lung damage and had significantly higher antibody titers of HP-PRRSV2 or Gps than single-infected piglets. Moreover, the serum and lung concentrations of inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-8) were also significantly higher in coinfected piglets than in those infected with HP-PRRSV2 or Gps alone. In conclusion, our results show that HP-PRRSV2 promotes the shedding and replication of Gps, and their coinfection in the upper respiratory tract aggravates the clinical symptoms and inflammatory responses, causing lung damage. Therefore, in the unavoidable situation of Gps infection in piglets, necessary measures must be made to prevent and control secondary infection with HP-PRRSV2, which can save huge economic losses to the pork industry.

Although research on the natural ventilation of single-sided buildings is progressing, research on the natural ventilation of the Mogao Grottoes, which have special shapes and structures, is relatively limited. The purpose of this paper is to develop a correlation for calculating the natural ventilation rates of such grottoes. Field experiments were carried out on two typical caves to measure their meteorological parameters and natural ventilation rates to verify the validity of the proposed correlation. The results show that our correlation has good reliability and stability when predicting the natural ventilation rates of the caves. First, the new correlation has a small average deviation of 16.35%. The average deviations in the natural ventilation rates predicted by seven established correlations are as low as 17.85% and as high as 59.39%, revealing a large gap compared with the correlation proposed herein. Second, the maximum deviation in the outputs of the proposed correlation is only 7.70% between each case. Finally, a comparison between the calculated results and the values measured in Cave 328 shows that the correlation is also suitable for large-volume caves. The developed correlation provides theoretical support and a scientific method for preventive protection and a quantitative analysis method for the study of natural ventilation in caves.

The influenza vaccine is not included in China’s national immunization program. Here, we assessed influenza vaccine coverage among Shanghai residents and estimated the impacts of the coronavirus disease 2019 (COVID-19) epidemic and a hypothetical free vaccine strategy on the willingness of participants to receive influenza vaccines. The coverage of influenza vaccines among Shanghai residents from 2015 to 2019 was 1.4% (range: 1%–2.4%). A total of 792 adult participants (aged 19–59 years) along with 821 children and 445 older individuals were included in the analysis. The willingness of participants to receive influenza vaccines reached 68.4% following the COVID-19 epidemic. Furthermore, if the vaccine was made available at no cost, 85.9% of participants were willing to be vaccinated. Our data indicated that influenza vaccine coverage is extremely low in Shanghai but that more than two-thirds of participants were willing to receive influenza vaccines following the COVID-19 epidemic. Making influenza vaccines available for free could further increase coverage.

Abstract Background Phytohormone abscisic acid (ABA) is involved in the regulation of a wide range of biological processes. In Arabidopsis, it has been well-known that SnRK2s are the central components of the ABA signaling pathway that control the balance between plant growth and stress response, but the functions of ZmSnRK2 in maize are rarely reported. Therefore, the study of ZmSnRK2 is of great importance to understand the ABA signaling pathways in maize. Results In this study, 14 ZmSnRK2 genes were identified in the latest version of maize genome database. Phylogenetic analysis revealed that ZmSnRK2s are divided into three subclasses based on their diversity of C-terminal domains. The exon-intron structures, phylogenetic, synteny and collinearity analysis indicated that SnRK2s, especially the subclass III of SnRK2, are evolutionally conserved in maize, rice and Arabidopsis. Subcellular localization showed that ZmSnRK2 proteins are localized in the nucleus and cytoplasm. The RNA-Seq datasets and qRT-PCR analysis showed that ZmSnRK2 genes exhibit spatial and temporal expression patterns during the growth and development of different maize tissues, and the transcript levels of some ZmSnRK2 genes in kernel are significantly induced by ABA and sucrose treatment. In addition, we found that ZmSnRK2.10, which belongs to subclass III, is highly expressed in kernel and activated by ABA. Overexpression of ZmSnRK2.10 partially rescued the ABA-insensitive phenotype of snrk2.2/2.3 double and snrk2.2/2.3/2.6 triple mutants and led to delaying plant flowering in Arabidopsis. Conclusion The SnRK2 gene family exhibits a high evolutionary conservation and has expanded with whole-genome duplication events in plants. The ZmSnRK2s expanded in maize with whole-genome and segmental duplication, not tandem duplication. The expression pattern analysis of ZmSnRK2s in maize offers important information to study their functions. Study of the functions of ZmSnRK.10 in Arabidopsis suggests that the ABA-dependent members of SnRK2s are evolutionarily conserved in plants. Our study elucidated the structure and evolution of SnRK2 genes in plants and provided a basis for the functional study of ZmSnRK2s protein in maize.

Abstract Background There are no pharmacological interventions currently available to prevent the transmission of SARS-CoV-2 or to treat COVID-19. The development of vaccines against COVID-19 is essential to contain the pandemic. we conducted a cross-sectional survey of Shanghai residents to understand residents’ willingness to be vaccinated with any future COVID-19 vaccines and take measures to further improve vaccination coverage. Methods We conducted a cross-sectional survey using self-administered anonymous questionnaires from 1 July to 8 September 2020. The main outcome was willingness of participants, and any children or older individuals living with them, to receive future COVID-19 vaccines. Logistic regression analyses were used to explore potential factors associated with vaccination willingness. Results A total of 1071 participants were asked about their willingness to receive future COVID-19 vaccines, for themselves and at least 747 children and 375 older individuals (≥60 years old) living with them. The highest proportion of expected willingness to vaccinate was among participants (88.6%), followed by children (85.3%) and older individuals (84.0%). The main reasons for reluctance to vaccinate among 119 participants were doubts regarding vaccine safety (60.0%) and efficacy (28.8%). Participants with a self-reported history of influenza vaccination were more likely to accept COVID-19 vaccines for themselves [adjusted odds ratio (OR) = 1.83; 95% confidence interval (CI): 1.19–2.82], their children (adjusted OR = 2.08; 95%CI: 1.30–3.33), and older individuals in their household (adjusted OR = 2.12; 95%CI: 1.14–3.99). Participants with older individuals in their families were less willing to vaccinate themselves (adjusted OR = 0.59; 95%CI: 0.40–0.87) and their children (adjusted OR = 0.58; 95%CI: 0.38–0.89). Conclusions Participants were more reluctant to accept COVID-19 vaccines for older individuals living with them. The presence of older individuals in the home also affected willingness of participants and their children to be vaccinated.

The ocean supports many livelihoods, but this is currently not sustainable with pressures on the climate and ecosystems. Here, in this perspective, the authors outline the barriers and solutions for financing a sustainable ocean economy.

The process of starch biosynthesis is a major developmental event that affects the final grain yield and quality in maize (Zea mays L.), and transcriptional regulation plays a key role in modulating the expression of the main players in the pathway. ZmBt2, which encodes the small subunits of AGPase, is a rate-controlling gene of the pathway; however, much remains unknown about its transcriptional regulation. Our earlier study identifies a short functional fragment of ZmBt2 promoter (394-bp), and further shows it contains multiple putative cis-acting regulatory elements, demonstrating that several transcription factors may govern ZmBt2 expression. Here, we identified a novel TCP transcription factor (TF), ZmTCP7, that interacted with the functional fragment of the ZmBt2 promoter in a yeast one hybrid screening system. We further showed that ZmTCP7 is a non-autonomous TF targeted to the nucleus and predominantly expressed in maize endosperm. Using promoter deletion analyzes by transient expression in maize endosperm protoplasts combined with electrophoretic mobility shift assays, we found that ZmTCP7 bound to GAACCCCAC elements on the ZmBt2 promoter to suppress its expression. Transgenic overexpression of ZmTCP7 in maize caused a significant repression of ZmBt2 transcription by ~77.58%, resulting in a 21.51% decrease in AGPase activity and a 9.58% reduction in the endosperm starch content of transgenic maize. Moreover, the expressions of ZmBt1, ZmSSI, ZmSSIIa, and ZmSSIIIa were increased, while those of ZmSh2 and ZmSSIV reduced significantly in the endosperm of the transgenic maize. Overall, this study shows that ZmTCP7 functions as a transcriptional repressor of ZmBt2 and a negative regulator of endosperm starch accumulation, providing new insights into the regulatory networks that govern ZmBt2 expression and starch biosynthesis pathway in maize.

In contrast to the adult mammalian central nervous system (CNS), the neurons in the peripheral nervous system (PNS) can regenerate their axons. However, the underlying mechanism dictating the regeneration program after PNS injuries remains poorly understood. Combining chemical inhibitor screening with gain- and loss-of-function analyses, we identified p90 ribosomal S6 kinase 1 (RSK1) as a crucial regulator of axon regeneration in dorsal root ganglion (DRG) neurons after sciatic nerve injury (SNI). Mechanistically, RSK1 was found to preferentially regulate the synthesis of regeneration-related proteins using ribosomal profiling. Interestingly, RSK1 expression was up-regulated in injured DRG neurons, but not retinal ganglion cells (RGCs). Additionally, RSK1 overexpression enhanced phosphatase and tensin homolog (PTEN) deletion-induced axon regeneration in RGCs in the adult CNS. Our findings reveal a critical mechanism in inducing protein synthesis that promotes axon regeneration and further suggest RSK1 as a possible therapeutic target for neuronal injury repair. This study shows that p90 ribosomal S6 kinase 1 (RSK1) responds differentially to nerve injury in the peripheral and central nervous systems, and identifies it as a crucial regulator of axonal regeneration; mechanistically, RSK1 preferentially induces the synthesis of regeneration-related proteins via the RSK1-eEF2K-eEF2 axis.

Although fiber-rich diets have been positively associated with sperm quality, there have not been any studies that have examined the effects of dietary fiber and its metabolites on sperm quality in young or pre-pubescent animals. In this study, we aimed to explore the effect of dietary fiber supplementation on semen quality and the underlying mechanisms in a boar model. Sixty purebred Yorkshire weaning boars were randomly divided into the four groups (T1–T4). Groups T1, T2, and T3 boars were fed diets with different levels of fiber until reaching 160 days of age and were then fed the same diet, while group T4 boars were fed a basal diet supplemented with butyrate and probiotics. Compared with T1 boars, sperm motility and effective sperm number were significantly higher among T3 boars. Meanwhile, at 240 days of age, the acetic acid and total short-chain fatty acid (SCFA) contents in the sera of T3 and T4 boars were significantly higher than those in T1 boars. The abundance of microbiota in T2 and T3 boars was significantly higher than that in T1 boars (P < 0.01). Moreover, dietary fiber supplementation increased “beneficial gut microbes” such as UCG-005, Rumenococcus, Rikenellaceae_RC9_gut_group and Lactobacillus and decreased the relative abundance of “harmful microbes” such as Clostridium_sensu_stricto_1, Romboutsia and Turicibacter. Collectively, the findings of this study indicate that dietary fiber supplementation improves gut microbiota and promotes SCFA production, thereby enhancing spermatogenesis and semen quality. Moreover, the effects of dietary fiber are superior to those of derived metabolites.

Peracetic acid (PAA) is an oxidative disinfectant with a broad spectrum of antimicrobial activity and low environmental impact. In this study, we investigated the physiological impacts of PAA application in Atlantic salmon (Salmo salar) parr reared in freshwater recirculating aquaculture systems over a 4-week period. PAA at a target concentration of 1 mg/L was administered either in pulse (every 3 days) or continuous. The group that did not receive PAA served as a control. Fish tissue samples were collected for histology, gene expression, and biochemical analyses at day 0 and after 2 and 4 weeks of exposure. The expression of genes encoding for antioxidant defence in the olfactory organs, skin, and gills changed during the trial, but the temporal effects were more pronounced than inter-treatment impacts. The glutathione group of antioxidant genes was more responsive to PAA. In most cases, an upregulation was observed. Significantly lower levels of reactive oxygen species were identified in the plasma and skin mucus of the two PAA-exposed groups at week 4; nonetheless, significantly increased levels of total antioxidant capacity were only observed in the skin mucus of fish from the continuous treatment group. Additional markers of oxidative stress (i.e., 8-oxo-2′-deoxyguanosine and o,o'-dityrosine) were analysed in the skin, gills, liver, and dorsal fins. These markers were unaffected by the two PAA treatments. Sporadic reversible structural alterations were observed in the three mucosal organs; the changes were time-dependent, and the effects of PAA treatment were minimal. The number of mucous cells varied over time but not within treatments except in the skin of the pulse group at week 4 where a reduction was observed. The ratio of acidic and neutral mucous cells in the skin and gills were affected by PAA treatments especially in the pulse group. Overall, this study revealed that Atlantic salmon parr mobilised mucosal and systemic antioxidant defences against the oxidative disinfectant PAA, but it was evident that the mode of application did not impose a strong influence. The minimal effects of PAA application on the indicators of health and welfare underscore the potential use of PAA as a routine disinfectant in recirculating aquaculture systems.

Abstract Background Intrahepatic cholangiocarcinoma (iCCA) is the second most common malignant hepatic tumor and has a high postoperative recurrence rate and a poor prognosis. The key roles of most tumor recurrence-associated molecules in iCCA remain unclear. This study aimed to explore hub genes related to the postsurgical recurrence of iCCA. Method Differentially expressed genes (DEGs) between iCCA samples and normal liver samples were screened from The Cancer Genome Atlas (TCGA) database and used to construct a weighted gene coexpression network. Module-trait correlations were calculated to identify the key module related to recurrence in iCCA patients. Genes in the key module were subjected to functional enrichment analysis, and candidate hub genes were filtered through coexpression and protein–protein interaction (PPI) network analysis. Validation studies were conducted to detect the “real” hub gene. Furthermore, the biological functions and the underlying mechanism of the real hub gene in iCCA tumorigenesis and progression were determined via in vitro experiments. Results A total of 1019 DEGs were filtered and used to construct four coexpression modules. The red module, which showed the highest correlations with the recurrence status, family history, and day to death of patients, was identified as the key module. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses demonstrated that genes in the red module were enriched in genes and pathways related to tumorigenesis and tumor progression. We performed validation studies and identified estrogen receptor 1 (ESR1), which significantly impacted the prognosis of iCCA patients, as the real hub gene related to the recurrence of iCCA. The in vitro experiments demonstrated that ESR1 overexpression significantly suppressed cell proliferation, migration, and invasion, whereas ESR1 knockdown elicited opposite effects. Further investigation into the mechanism demonstrated that ESR1 acts as a tumor suppressor by inhibiting the JAK/STAT3 signaling pathway. Conclusions ESR1 was identified as the real hub gene related to the recurrence of iCCA that plays a critical tumor suppressor role in iCCA progression. ESR1 significantly impacts the prognosis of iCCA patients and markedly suppresses cholangiocarcinoma cell proliferation, migration and invasion by inhibiting JAK/STAT3 signaling pathway.

Abstract. Objective:. Coronavirus disease 2019 (COVID-19) is a global public health crisis. There are no specific antiviral agents for the treatment of SARS-CoV-2. Information regarding the effect of Abidol on in-hospital mortality is scarce. The present study aimed to evaluate the treatment effect of Abidol for patients with COVID-19 before and after propensity score matching (PSM). Methods:. This retrospective cohort study analyzed 1019 patients with confirmed COVID-19 in China from December 22, 2019 to March 13, 2020. Patients were divided to Abidol (200 mg, tid, 5–7 days, n = 788, 77.3%) and No-Abidol (n = 231, 22.7%) groups. The primary outcome was the mortality during hospitalization. Results:. Among 1019 COVID-19 patients, the age was (60.4 ± 14.5) years. Abidol-treated patients, compared with No-Abidol-treated patients, had a shorter duration from onset of symptoms to admission, less frequent renal dysfunction, lower white blood cell counts (lymphocytes

Maize (Zea mays L.) is one of the most important food crops in the world, and starch is the main component of its endosperm. Transcriptional regulation plays a vital role in starch biosynthesis. However, it is not well understood in maize. We report the identification of the transcription factor ZmNAC126 and its role in regulation of starch synthesis in maize. Transcriptional expression of ZmNAC126 was higher in maize endosperm and kernels than in roots or stems. ZmNAC126 shared a similar expression pattern with starch synthesis genes during seed development, and its expression pattern was also consistent with the accumulation of starch. ZmNAC126 is a typical transcription factor with a transactivation domain between positions 201 and 227 of the amino acid sequence, is located in the nucleus, and binds to CACG repeats in vitro. Yeast one-hybrid assay revealed that ZmNAC126 bound the promoters of ZmGBSSI, ZmSSIIa, ZmSSIV, ZmISA1, and ZmISA2. Transient overexpression of ZmNAC126 in maize endosperm increased the activities of promoters pZmSh2, pZmBt2, pZmGBSSI, pZmSSIIIa, and pZmBT1 but inhibited the activities of pZmISA1 and pZmISA2. ZmNAC126 thus acts in starch synthesis by transcriptionally regulating targeted starch synthesis-related genes in maize kernels.

Abstract Herein, a rigorous derivation of an isosceles right‐angled triangular (IRT) metallic cavity is analysed. Then, the transverse field components in the IRT substrate‐integrated waveguide (SIW) cavity are derived, and the expression of the resonant frequencies can also be obtained. Then, a novel perturbed IRT SIW cavity is proposed, which is based on the characteristics of resonant modes in IRT SIW cavity and the capacitive‐loading technique. Three prototypes were designed to verify the validity of the derivation and analysis in this study. First, a dual‐mode single passband filter was implemented using the perturbed modes TE102 and TE202. Next, two tri‐mode triple‐band bandpass filters (BPFs) using the perturbed modes TE101, TE102 and TE202 are proposed, synthesised, verified and measured for demonstration, including a second‐order direct‐coupled one which operates at 8.02, 11.44 and 12.52 GHz, and a fourth‐order direct‐coupled one which operates at 7.7, 11.0 and 12.1 GHZ. The measured curves agree well with the simulated ones. Very compact circuit sizes and excellent filtering performances have been achieved for the three prototypes.

Autotaxin (ATX), the key enzyme that generates lysophosphatidic acid (LPA) from lysophosphatidylcholine (LPC), is involved in tumorigenesis through the ATX-LPA axis and is regarded as a valuable target in tumor therapy. Hypoxia is a major feature of solid tumors and contributes to tumor development with striking alterations in the gene expression profile. Here, we show that hypoxia induces ATX expression in a hypoxia-inducible factor (HIF) 2α-dependent fashion in human colon cancer SW480 cells. HIF-2α is directly bound to specific hypoxia response elements (HREs) in the ATX promoter. Under hypoxic conditions, knockout or inhibition of ATX suppressed the migration of SW480 cells, which could be rescued by the addition of LPA, suggesting that the induction of ATX during hypoxia promotes cancer cell migration through the ATX-LPA axis. Further studies showed that ATX expression was induced by HIF-2α through recruiting p300/CBP, which led to crotonylation but not acetylation of histone H3 in the ATX promoter region during hypoxia. Moreover, elevation of cellular histone crotonylation levels could induce ATX expression under normoxic conditions. In conclusion, our findings reveal that ATX is induced in SW480 cells during hypoxia by histone crotonylation in a HIF-2α-dependent manner, while as a novel mechanism of ATX expression regulation, the upregulation of ATX expression by histone crotonylation is not confined to hypoxia.

Brassinosteroids are a recently discovered group of substances that promote plant growth and productivity. Photosynthesis, which is vital for plant growth and high productivity, is strongly influenced by brassinosteroid signaling. However, the molecular mechanism underlying the photosynthetic response to brassinosteroid signaling in maize remains obscure. Here, we performed integrated transcriptome, proteome, and phosphoproteomic analyses to identify the key photosynthesis pathway that responds to brassinosteroid signaling. Transcriptome analysis suggested that photosynthesis antenna proteins and carotenoid biosynthesis, plant hormone signal transduction, and MAPK signaling in CK VS EBR and CK VS Brz were significantly enriched in the list of differentially expressed genes upon brassinosteroids treatment. Consistently, proteome and phosphoproteomic analyses indicated that photosynthesis antenna and photosynthesis proteins were significantly enriched in the list of differentially expressed proteins. Thus, transcriptome, proteome, and phosphoproteome analyses showed that major genes and proteins related to photosynthesis antenna proteins were upregulated by brassinosteroids treatment in a dose-dependent manner. Meanwhile, 42 and 186 transcription factor (TF) responses to brassinosteroid signals in maize leaves were identified in the CK VS EBR and CK VS Brz groups, respectively. Our study provides valuable information for a better understanding of the molecular mechanism underlying the photosynthetic response to brassinosteroid signaling in maize.

Myocardial fibrosis progression and imbalanced redox state are closely associated with increased extracellular matrix (ECM) stiffness. Candesartan (CAN), an angiotensin II (Ang II) receptor inhibitor, has shown promising anti-fibrosis and antioxidant efficacy in previous cardiovascular disease studies. However, the effect of ECM stiffness on CAN efficacy remains elusive. In this study, we constructed rat models with three different degrees of myocardial fibrosis and treated them with CAN, and then characterized the stiffness, cardiac function, and NADPH oxidase-2 (NOX2) expression of the myocardial tissues. Based on the obtained stiffness of myocardial tissues, we used polyacrylamide (PA) gels with three different stiffness to mimic the ECM stiffness of cardiac fibroblasts (CFs) at the early, middle, and late stages of myocardial fibrosis as the cell culture substrates and then constructed CFs mechanical microenvironment models. We studied the effects of PA gel stiffness on the migration, proliferation, and activation of CFs without and with CAN treatment, and characterized the reactive oxygen species (ROS) and glutathione (GSH) levels of CFs using fluorometry and scanning electrochemical microscopy (SECM). We found that CAN has the best amelioration efficacy in the cardiac function and NOX2 levels in rats with medium-stiffness myocardial tissue, and the most obvious anti-fibrosis and antioxidant efficacy in CFs on the medium-stiffness PA gels. Our work proves the effect of ECM stiffness on CAN efficacy in myocardial anti-fibrosis and antioxidants for the first time, and the results demonstrate that the effect of ECM stiffness on drug efficacy should also be considered in the treatment of cardiovascular diseases.

Maize is a main food and feed crop with great production potential and high economic benefits. Improving its photosynthesis efficiency is crucial for increasing yield. Maize photosynthesis occurs mainly through the C4 pathway, and NADP-ME (NADP-malic enzyme) is a key enzyme in the photosynthetic carbon assimilation pathway of C4 plants. ZmC4-NADP-ME catalyzes the release of CO2 from oxaloacetate into the Calvin cycle in the maize bundle sheath. Brassinosteroid (BL) can improve photosynthesis; however, its molecular mechanism of action remains unclear. In this study, transcriptome sequencing of maize seedlings treated with epi-brassinolide (EBL) showed that differentially expressed genes (DEGs) were significantly enriched in photosynthetic antenna proteins, porphyrin and chlorophyll metabolism, and photosynthesis pathways. The DEGs of C4-NADP-ME and pyruvate phosphate dikinase in the C4 pathway were significantly enriched in EBL treatment. Co-expression analysis showed that the transcription level of ZmNF-YC2 and ZmbHLH157 transcription factors was increased under EBL treatment and moderately positively correlated with ZmC4-NADP-ME. Transient overexpression of protoplasts revealed that ZmNF-YC2 and ZmbHLH157 activate C4-NADP-ME promoters. Further experiments showed ZmNF-YC2 and ZmbHLH157 transcription factor binding sites on the −1616 bp and −1118 bp ZmC4 NADP-ME promoter. ZmNF-YC2 and ZmbHLH157 were screened as candidate transcription factors mediating brassinosteroid hormone regulation of the ZmC4 NADP-ME gene. The results provide a theoretical basis for improving maize yield using BR hormones.

Qigong is a meditative movement with therapeutic effects and is commonly practiced in Eastern medicine. A growing body of evidence validates its health benefits, leading to mechanistic questions about how it works. We propose a novel mechanism by which the “acid” caused by hypoxia affects metabolism, and the way it is neutralized through Qigong practice involves the body’s blood flow and vasculature modifications. Specifically, Qigong exercise generates an oxygen supply and acid-base balance against the hypoxic effects of underlying pathological conditions. We also propose that Qigong exercise mediated and focused on the local hypoxia environment of tissues might normalize the circulation of metabolic and inflammation accumulation in the tumor tissue and restore the normal metabolism of tissues and cells through calm, relaxation, and extreme Zen-style breathing that gravitates toward preemptive health and medicine. Thus, we propose the mechanisms of action related to Qigong, intending to unify Eastern and Western exercise theory.

Charge order is a central feature of the physics of cuprate superconductors and is known to arise from a modulation of holes with primarily oxygen character. Low-valence nickelate superconductors also host charge order, but the electronic character of this symmetry breaking is unsettled. Here, using resonant inelastic x-ray scattering at the Ni L_{2} edge, we identify intertwined involvements of Ni 3d_{x^{2}-y^{2}}, 3d_{3z^{2}-r^{2}}, and O 2p_{σ} orbitals in the formation of diagonal charge order in an overdoped low-valence nickelate La_{4}Ni_{3}O_{8}. The Ni 3d_{x^{2}-y^{2}} orbitals, strongly hybridized with planar O 2p_{σ}, largely shape the spatial charge distribution and lead to Ni site-centered charge order. The 3d_{3z^{2}-r^{2}} orbitals play a small, but non-negligible role in the charge order as they hybridize with the rare-earth 5d orbitals. Our results reveal that the low-energy physics and ground-state character of these nickelates are more complex than those in cuprates.