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AbstractIn graphene electronics applications, in order to obtain the size and pattern required for the device, it is often necessary to photolithography the graphene after growth, resulting in contamination of graphene by the photoresist which have doping effect. Therefore, in order to avoid this effect, this article focused on directly grown patterned graphene. Based on atmospheric pressure chemical vapour deposition (APCVD) technology, patterned graphene was successfully grown on SiO2/Si by metal proximity catalytic effect. The patterned graphene was characterized by Raman spectroscopy and optical microscope. The effects of parameters such as gas flow, growth temperature, and growth time on the growth of patterned graphene were explored, and the best results were obtained. Metal copper and cobalt thin films were used for assisted catalysis, respectively, and the mechanism of metal proximity catalysis was explored. The experimental results showed that proximity catalysis is a catalytic growth mechanism based on surface diffusion. The growth method avoids using photolithography to make patterns, and can grow patterned graphene on insulating substrates or semiconductors in one step, which is of great significance for making patterned graphene and applying them to semiconductor devices.

Summary: Nanoparticle vaccines displaying mosaic receptor-binding domains (RBDs) or spike (S) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or other sarbecoviruses are used in preparedness against potential zoonotic outbreaks. Here, we describe a self-assembling nanoparticle using lumazine synthase (LuS) as the scaffold to display RBDs from different sarbecoviruses. Mosaic nanoparticles induce sarbecovirus cross-neutralizing antibodies comparable to a nanoparticle cocktail. We find mosaic nanoparticles elicit a B cell receptor repertoire using an immunodominant germline gene pair of IGHV14-3:IGKV14-111. Most of the tested IGHV14-3:IGKV14-111 monoclonal antibodies (mAbs) are broadly cross-reactive to clade 1a, 1b, and 3 sarbecoviruses. Using mAb competition and cryo-electron microscopy, we determine that a representative IGHV14-3:IGKV14-111 mAb, M2-7, binds to a conserved epitope on the RBD, largely overlapping with the pan-sarbecovirus mAb S2H97. This suggests mosaic nanoparticles expand B cell recognition of the common epitopes shared by different clades of sarbecoviruses. These results provide immunological insights into the cross-reactive responses elicited by mosaic nanoparticles against sarbecoviruses.

07Cr16Ni6 alloy is a kind of martensitic-austenitic duplex stainless steel that is widely used in aviation and aerospace. Electrochemical machining (ECM) is an ideal manufacturing process for 07Cr16Ni6 alloy because of its high machining accuracy and good final surface quality. Studying the electrochemical dissolution behavior is pre-requisite and key to optimizing the ECM process; however, few studies have focused on the electrochemical dissolution behavior of 07Cr16Ni6 alloy. In this work, the corrosion behavior, passivation characteristics, efficiency curves, and material-removal process of 07Cr16Ni6 alloy in NaNO3 solution were comprehensively investigated. Based on the curves of potentiodynamic polarization and conductivity curve, it was found that both of them have significant passive and transpassive characteristics. The results of X-ray photoelectron spectroscopy and electrochemical impedance spectroscopy indicated that the passive film was mainly composed of Fe3O4, α-Fe2O3, γ-Fe2O3, Cr2O3, NiO, SiO, and SiO2, and its structure was composed of a dense inner-layer film and a loose outer-layer film. A schematic model was proposed to characterize the interface structure between the 07Cr16Ni6 alloy, the passive film and electrolyte. ECM tests were performed at different current densities and for different corrosion times. The current-efficiency results indicate that the material-removal rate can be divided into three regions. The current efficiency first rises gently, then rises steeply once the current density exceeds 26 A cm−2; it finally remains stable at current densities greater than 45 A cm−2. The corrosion morphology exhibits loose, blocky bulges at low current density, while the surface exhibits lath-type martensite structures when the current density j > 15 A cm−2. The material-dissolution process of the 07Cr16Ni6 alloy in NaNO3 solution at 20 A cm−2 was presented. Finally, a model of dissolution was established to characterize the electrochemical dissolution of the 07Cr16Ni6 alloy in NaNO3 solution.

Abstract Diamond, with ultrahigh hardness, high wear resistance, high thermal conductivity, and so forth, has attracted worldwide attention. However, researchers found emergent reactions at the interfaces between diamond and ferrous materials, which significantly affects the performance of diamond‐based devices. Herein, combing experiments and theoretical calculations, taking diamond–iron (Fe) interface as a prototype, the counter‐diffusion mechanism of Fe/carbon atoms has been established. Surprisingly, it is identified that Fe and diamond first form a coherent interface, and then Fe atoms diffuse into diamond and prefer the carbon vacancies sites. Meanwhile, the relaxed carbon atoms diffuse into the Fe lattice, forming Fe3C. Moreover, graphite is observed at the Fe3C surface when Fe3C is over‐saturated by carbon atoms. The present findings are expected to offer new insights into the atomic mechanism for diamond‐ferrous material's interfacial reactions, benefiting diamond‐based device applications.

Abstract Engineering lattice defects have emerged as a promising approach to effectively modulate the functionality of devices. Particularly, antiphase boundaries (APBs) as planar defects have been considered major obstacles to optimizing the ionic conductivity of mixed ionic-electronic conductors (MIECs) in solid oxide fuel applications. Here our study identifies topotactically transformable APBs (tt-APBs) at the atomic level and demonstrates that they exhibit higher ionic conductivity at elevated temperatures as compared to perfect domains. In-situ observation at the atomic scale tracks dynamic oxygen migration across these tt-APBs, where the abundant interstitial sites between tetrahedrons facilitate the ionic migration. Furthermore, annealing in an oxidized atmosphere can lead to the formation of interstitial oxygen at these APBs. These pieces of evidence clearly clarify that the tt-APBs can contribute to oxygen conductivity as anion diffusion channels, while the topotactically non-transformable APBs cannot. The topotactic transformability opens the way of defect engineering strategies for improving ionic transportation in MIECs.

Abstract Fully convolutional neural network has shown advantages in the salient object detection by using the RGB or RGB-D images. However, there is an object-part dilemma since most fully convolutional neural network inevitably leads to an incomplete segmentation of the salient object. Although the capsule network is capable of recognizing a complete object, it is highly computational demand and time consuming. In this paper, we propose a novel convolutional capsule network based on feature extraction and integration for dealing with the object-part relationship, with less computation demand. First and foremost, RGB features are extracted and integrated by using the VGG backbone and feature extraction module. Then, these features, integrating with depth images by using feature depth module, are upsampled progressively to produce a feature map. In the next step, the feature map is fed into the feature-integrated convolutional capsule network to explore the object-part relationship. The proposed capsule network extracts object-part information by using convolutional capsules with locally-connected routing and predicts the final salient map based on the deconvolutional capsules. Experimental results on four RGB-D benchmark datasets show that our proposed method outperforms 23 state-of-the-art algorithms.

Abstract With wave-particle decomposition, a unified gas-kinetic wave-particle (UGKWP) method has been developed for multiscale flow simulations. With the variation of the cell Knudsen number, the UGKWP method captures the transport process in all flow regimes without the kinetic solver’s constraint on the numerical mesh size and time step being determined by the kinetic particle mean free path and particle collision time. In the current UGKWP method, the cell Knudsen number, which is defined as the ratio of particle collision time to numerical time step, is used to distribute the components in the wave-particle decomposition. The adaptation of particles in the UGKWP method is mainly for the capturing of the non-equilibrium transport. In this aspect, the cell Knudsen number alone is not enough to identify the non-equilibrium state. For example, in the equilibrium flow regime with a Maxwellian distribution function, even at a large cell Knudsen number, the flow evolution can be still modelled by the Navier-Stokes solver. More specifically, in the near space environment both the hypersonic flow around a space vehicle and the plume flow from a satellite nozzle will encounter a far field rarefied equilibrium flow in a large computational domain. In the background dilute equilibrium region, the large particle collision time and a uniform small numerical time step can result in a large local cell Knudsen number and make the UGKWP method track a huge number of particles for the far field background flow in the original approach. But, in this region the analytical wave representation can be legitimately used in the UGKWP method to capture the nearly equilibrium flow evolution. Therefore, to further improve the efficiency of the UGKWP method for multiscale flow simulations, an adaptive UGKWP (AUGKWP) method is developed with the introduction of an additional local flow variable gradient-dependent Knudsen number. As a result, the wave-particle decomposition in the UGKWP method is determined by both the cell and gradient Knudsen numbers, and the use of particles in the UGKWP method is solely to capture the non-equilibrium flow transport. The current AUGKWP method becomes much more efficient than the previous one with the cell Knudsen number only in the determination of wave-particle composition. Many numerical tests, including Sod shock tube, normal shock structure, hypersonic flow around cylinder, flow around reentry capsule, and an unsteady nozzle plume flow, have been conducted to validate the accuracy and efficiency of the AUGKWP method. Compared with the original UGKWP method, the AUGKWP method achieves the same accuracy, but has advantages in memory reduction and computational efficiency in the simulation for flows with the co-existing of multiple regimes.

Although many people have been vaccinated against COVID-19, infections with SARS-CoV-2 seem hard to avoid. There is a need to develop more effective vaccines and immunization strategies against emerging variants of infectious diseases. To understand whether different immunization strategies using variants sequence-based virus-like particles (VLPs) vaccines could offer superior immunity against future SARS-CoV-2 variants, our team constructed VLPs for the original Wuhan-Hu-1 strain (prototype), Delta (δ) variant, and Omicron (ο) variant of SARS-CoV-2, using baculovirus-insect expression system. Then we used these VLPs to assess the immune responses induced by homologous prime-boost, heterologous prime-boost, and sequential immunizations strategies in a mouse model. Our results showed that the pro+δ+ο sequential strategies elicited better neutralizing antibody responses. These sequential strategies also take advantage of inducing CD4+ T and CD8+ T lymphocytes proliferation and tendency to cytokine of Th1. Currently, our data suggest that sequential immunization with VLPs of encoding spike protein derived from SARS-CoV-2 variants of concern may be a potential vaccine strategy against emerging diseases, such as “Disease X”.

In China, saline–alkali lands constitute 5.01% of the total land area, having a significant impact on both domestic and international food production. Rapeseed (Brassica napus L.), as one of the most important oilseed crops in China, has garnered considerable attention due to its potential adaptability to saline conditions. Breeding and improving salt-tolerant varieties is a key strategy for the effective utilization of saline lands. Hence, it is important to conduct comprehensive research into the adaptability and salt tolerance mechanisms of Brassica napus in saline environments as well as to breed novel salt-tolerant varieties. This review summarizes the molecular mechanism of salt tolerance, physiological and phenotypic indexes, research strategies for the screening of salt-tolerant germplasm resources, and genetic engineering tools for salt stress in Brassica napus. It also introduces various agronomic strategies for applying exogenous substances to alleviate salt stress and provide technological tools and research directions for future research on salt tolerance in Brassica napus.

Reinforced concrete structures play a pivotal role in island and reef engineering projects. Given the resource constraints typical of island regions, substituting traditional manufactured sand aggregate with reef limestone not only reduces reliance on river sand but also addresses the issue of disposing of waste reef limestone slag generated during excavation. However, the performance characteristics of reef limestone concrete, particularly its bond strength with reinforcing steel, warrant further investigation. This is particularly true for the bond–slip behavior of the reinforcement. This study aims to elucidate the effects of various parameters on the bond performance between steel and reef limestone concrete through central pullout tests. These parameters include the type and diameter of the reinforcement, bond length, and loading rate. The investigation encompasses the analysis of load–slip curves, bond failure modes, and variations in bond stress. Additionally, using the Abaqus software, a numerical simulation was conducted to analyze the mesoscopic stress characteristics, thereby revealing the mechanisms of bond formation and failure modes between steel reinforcement and reef limestone concrete. The results indicate that the bond–slip curve for reef limestone concrete reinforced with ribbed rebars and Glass Fiber-Reinforced Polymer (GFRP) rebars can be broadly categorized into four phases: minor slip, slip, decline, and residual, with the residual phase exhibiting a wave-like pattern. The predominant failure modes in reef limestone concrete are either pulling out or splitting. The bond stress in reef limestone concrete decreases with an increase in rebar diameter and bond length; conversely, it increases with the loading rate, although the ultimate slip decreases. The mesoscopic failure characteristics of reinforced reef limestone concrete, as simulated in Abaqus, are consistent with the experimental outcomes.

Introduction The widespread popularity of e-cigarettes is considered an important public health concern. However, only some studies have investigated the prevalence of e-cigarette use in Shanghai, China. Research on the perceived harmfulness of e-cigarettes and public support for e-cigarette regulations in China is limited. This study aimed to estimate e-cigarette awareness, prevalence, and associated factors among adults in Shanghai, China. Methods This study used data from a representative survey conducted in Shanghai, China, in 2019. The survey was conducted at 64 surveillance points in Shanghai, China, using a multistage, stratified, cluster-randomized sampling design, recruiting community-based Chinese adults aged ≥15 years. Based on the principles outlined in the Global Adult Tobacco Survey (GATS) China Project, data were collected by conducting face-to-face interviews in households. Of the 3200 selected households, 3060 people completed the individual survey. The overall response rate was 97.4%. Results In all, 72.3% of the respondents had heard of e-cigarettes. The respondents who had used e-cigarettes at some point in their life, used them in the last 12 months, and used them currently were 5.8%, 2.6%, and 1.3%, respectively. Among adult residents who had heard of e-cigarettes, 38.2% thought they were less harmful than traditional cigarettes. The respondents who perceived e-cigarettes as more harmful than traditional cigarettes were less likely to have ever used e-cigarettes (AOR=0.2; 95% CI: 0.1–0.5, p=0.0015) and more likely to support incorporating e-cigarettes into the regulation of smoking control (AOR=3.9; 95% CI: 1.8–8.6, p=0.0008). Conclusions Our findings reveal that the awareness about e-cigarettes was high, and the prevalence of e-cigarette use was similar to the findings from previous studies in China. The harmful perception of e-cigarettes warrants further attention from public health practitioners.

Abstract Vaccination with different vaccines has been implemented globally to counter the continuous COVID-19 pandemic. However, the vaccine-elicited antibodies have reduced efficiency against the highly mutated Omicron sub-variants. Previously, we developed a protein subunit COVID-19 vaccine called ZF2001, based on the dimeric receptor-binding domain (RBD). This vaccine has been administered using different dosing intervals in real-world setting. Some individuals received three doses of ZF2001, with a one-month interval between each dose, due to urgent clinical requirements. Others had an extended dosing interval of up to five months between the second and third dose, a standard vaccination regimen for the protein subunit vaccine against hepatitis B. In this study, we profile B cell responses in individuals who received three doses of ZF2001, and compared those with long or short dosing intervals. We observed that the long-interval group exhibited higher and broader serologic antibody responses. These responses were associated with the increased size and evolution of vaccine-elicited B-cell receptor repertoires, characterized by the elevation of expanded clonotypes and somatic hypermutations. Both groups of individuals generated substantial amounts of broadly neutralizing antibodies (bnAbs) against various SARS-CoV-2 variants, including Omicron sub-variants such as XBB. These bnAbs target four antigenic sites within the RBD. To determine the vulnerable site of SARS-CoV-2, we employed cryo-electron microscopy to identify the epitopes of highly potent bnAbs that targeted two major sites. Our findings provide immunological insights into the B cell responses elicited by RBD-based vaccine, and suggest that a vaccination regimen of prolonging time interval should be used in practice.

Abstract Background Intra-tumoral heterogeneity (ITH) is a distinguished hallmark of cancer, and cancer stem cells (CSCs) contribute to this malignant characteristic. Therefore, it is of great significance to investigate and even target the regulatory factors driving intra-tumoral stemness. c-Myc is a vital oncogene frequently overexpressed or amplified in various cancer types, including breast cancer. Our previous study indicated its potential association with breast cancer stem cell (BCSC) biomarkers. Methods In this research, we performed immunohistochemical (IHC) staining on sixty breast cancer surgical specimens for c-Myc, CD44, CD24, CD133 and ALDH1A1. Then, we analyzed transcriptomic atlas of 1533 patients with breast cancer from public database. Results IHC staining indicated the positive correlation between c-Myc and BCSC phenotype. Then, we used bioinformatic analysis to interrogate transcriptomics data of 1533 breast cancer specimens and identified an intriguing link among c-Myc, cancer stemness and copper-induced cell death (also known as “cuproptosis”). We screened out cuproptosis-related characteristics that predicts poor clinical outcomes and found that the pro-tumoral cuproptosis-based features were putatively enriched in MYC-targets and showed a significantly positive correlation with cancer stemness. Conclusion In addition to previous reports on its oncogenic roles, c-Myc showed significant correlation to stemness phenotype and copper-induced cell toxicity in breast cancer tissues. Moreover, transcriptomics data demonstrated that pro-tumoral cuproptosis biomarkers had putative positive association with cancer stemness. This research combined clinical samples with large-scale bioinformatic analysis, covered description and deduction, bridged classic oncogenic mechanisms to innovative opportunities, and inspired the development of copper-based nanomaterials in targeting highly heterogeneous tumors.

MicroRNAs (miRNAs) are important regulatory elements involved in the regulation of various plant developmental and physiological processes by blocking the expression of target genes. MiR156 and miR529 are two combinatorial regulators, which cooperatively target the SQUAMOSA PROMOTER BINDING-LIKE (SPL) family genes. However, there has been no report about the functional conservation and divergence of miR156 and miR529 during plant development to date. In this study, the biological function and relationship of miR156, miR529 and their target OsSPL14 in rice were explored. Overexpression of miR156e or miR529a (miR156e-OE and miR529a-OE) increased the grain size and tiller number but decreased the plant height and panicle length, while an opposite phenotype was observed for their target mimicry (miR156-MIMIC and miR529a-MIMIC) transgenic plants. Stem-loop RT-PCR results revealed ubiquitous expression of miR156 in roots, axillary buds and leaves, while miR529 was preferentially expressed in the panicle. Accordingly, OsSPL14 could be preferentially and precisely cleaved by miR529a in young panicle but by miR156 in vegetative tissues. Transgenic plants generated by the target immune strategy exhibited obvious growth defects upon the blocking of miR156 and/or miR529 function in rice, confirming that both miR156 and miR529 play important roles in controlling rice growth and development. Moreover, the miR156/miR529-OsSPL14 module negatively controlled grain size by regulating the genes associated with grain size and cell cycling, and controlled plant height through a more complicated mechanism. Taken together, our results demonstrate that miR156 and miR529 respectively function dominantly in the vegetative stage and reproductive stage to control rice growth and development by regulating the accumulation of OsSPL14. These findings facilitate a better understanding of the functional conservation and divergence of miR156 and miR529 family in the miRNA combinatorial regulatory network of plants.

The spatial distribution of underground tunnels is significant to the stress redistribution in the surrounding rock masses and blast wave propagation. The field blasting tests were first carried out to study the propagation of blast-induced seismic waves through underground tunnels of the Xiluodu Hydropower Station in China. The results show that the peak horizontal particle vibration velocity can be used as a safety criterion for underground tunnels. The effects of in situ stresses and spatial distributions of the tunnel group on the vibration velocities distribution is afterward investigated by numerical simulation. The results show that there is a significant amplification of the blasting vibrations in the adjacent tunnels, which depends on their vertical positions during the excavation of a tunnel. The peak vibration velocity decreases as the lateral separation between tunnels increases. When the separation between the tunnels exceeds the width of three tunnels, the impact of the blast waves on each part of the adjacent tunnel tends to be stable on the whole. In terms of the size of the tunnel, the blasting vibration velocity in the upper part of the straight wall on the front-blast side increases as the width increases (and then levels off), while the blasting vibration velocity in the lower part decreases as the width increases (and then levels off). Finally, a generalized formula of blasting vibration velocity considering the spatial distribution is established, which can well predict the vibration velocity of particles in underground tunnels.

Alzheimer's disease (AD) is the leading cause of dementia and is rapidly becoming one of the most costly, fatal diseases, which is typically discovered in the late stage of molecular pathology, at which point medication intervention is irreversible. As a result, there is an urgent need for a low-cost, least-invasive way of screening cognitive impairment, with the goal of identifying persons at risk of AD. Mild cognitive impairment (MCI) has been described as a transitional state between normal cognitive aging and AD. Early detection and timely tracking of MCI can to some extent prevent the progression towards AD. We found a population in Northwestern China has a comparatively high prevalence of MCI. Continued education, consistent exercise, and a secure financial situation can all help older people maintain cognitive function. Due to the critical role of circulating microRNAs in intercellular signaling and the perturbations thereof, their investigation has assumed paramount significance in elucidating various pathological conditions. Numerous investigations have substantiated the significance of circulating miRNAs specifically in MCI. Here, we evaluated miR-483-5p (Area Under the Curve (AUC) is 0.901, sensitivity 79.2 % and specificity 100 %) and miR-502-5p (AUC is 0.872, sensitivity 79.2 % and specificity 83.3 %), which were derived from plasma exosomes and maintained at high levels in elderly people with MCI, could be employed as promising noninvasive biomarkers.

Shock wave therapy (SWT) is a new alternative therapy for patients with severe coronary artery disease that improves myocardial ischemic symptoms by delivering low-energy shock wave stimulation to ischaemic myocardium with low-energy pulsed waves. However, the specific mechanism of its protective effect is not fully understood, especially for the protective mechanism in cardiomyocytes after hypoxia/reoxygenation (H/R). We selected a rat H9c2 cardiomyocyte cell line to establish a stable H/R cardiomyocyte injury model by hypoxia/reoxygenation, and then used SWT for therapeutic intervention to explore its cardiomyocyte protective mechanisms. The results showed that SWT significantly increased cell viability and GSH levels while decreasing LDH levels, ROS levels, and MDA levels. SWT also improved mitochondrial morphology and function of cells after H/R. Meanwhile, we found that SWT could increase the expression of GPX4, xCT, and Bcl-2, while decreasing the expression of Bax and cleaved caspase-3, and inhibiting cardiomyocyte apoptosis and ferroptosis. Moreover, this protective effect of SWT on cardiomyocytes could be significantly reversed by knockdown of xCT, a key regulator protein of ferroptosis. In conclusion, our study shows that SWT can attenuate hypoxia–reoxygenation-induced myocardial injury and protect cardiomyocyte function by inhibiting H/R-induced apoptosis and ferroptosis, and this therapy may have important applications in the treatment of clinical myocardial ischemic diseases.

An improved understanding of biodiversity-productivity relationships (BPRs) along environmental gradients is crucial for effective ecosystem management and biodiversity conservation. The stress-gradient hypothesis suggests that BPRs are stronger in stressful environments compared to more favorable conditions. However, there is limited knowledge regarding the variation of BPRs along elevational gradients and their generality across different landscapes. To study how BPRs change with elevation, we harnessed inventory data on 6,431 trees from 152 plots surveyed twice in eight to ten year intervals in mountain forests of temperate Europe and subtropical Asia. We quantified the relationship between aboveground productivity and different biodiversity measures, including taxonomic, functional, and phylogenetic diversity. To elucidate the processes underlying BPRs, we studied the variation of different functional traits along elevation across landscapes. We found no general pattern of BPRs across landscapes and elevations. Relationships were neutral for all biodiversity measures in temperate forests, and negative for taxonomic and functional diversity in subtropical forests. BPRs were largely congruent between taxonomic, functional and phylogenetic diversity. We found only weak support for the stress-gradient hypothesis, with BPRs turning from negative to positive (effect not significant) close to the tree line in subtropical forests. In temperate forests, however, elevation patterns were strongly modulated by species identity effects as influenced by specific traits. The effect of traits such as community-weighted mean of maximum plant height and wood density on productivity was congruent across landscapes. Our study highlights the context-dependence of BPRs across elevation gradients and landscapes. Species traits are key modulating factors of BPRs and should be considered more explicitly in studies of the functional role of biodiversity. Furthermore, our findings highlight that potential trade-offs between conserving biodiversity and fostering ecosystem productivity exist, which require more attention in policy and management.

Abstract Mitochondrial base editing with DddA‐derived cytosine base editor (DdCBE) is limited in the accessible target sequences and modest activity. Here, the optimized DdCBE tools is presented with improved editing activity and expanded C‐to‐T targeting scope by fusing DddA11 variant with different cytosine deaminases with single‐strand DNA activity. Compared to previous DdCBE based on DddA11 variant alone, fusion of the activation‐induced cytidine deaminase (AID) from Xenopus laevis not only permits cytosine editing of 5′‐GC‐3′ sequence, but also elevates editing efficiency at 5′‐TC‐3′, 5′‐CC‐3′, and 5′‐GC‐3′ targets by up to 25‐, 10‐, and 6‐fold, respectively. Furthermore, the A‐to‐G editing efficiency is significantly improved by fusing the evolved DddA6 variant with TALE‐linked deoxyadenosine deaminase (TALED). Notably, the authors introduce the reported high‐fidelity mutations in DddA and add nuclear export signal (NES) sequences in DdCBE and TALED to reduce off‐target editing in the nuclear and mitochondrial genome while improving on‐target editing efficiency in mitochondrial DNA (mtDNA). Finally, these engineered mitochondrial base editors are shown to be efficient in installing mtDNA mutations in human cells or mouse embryos for disease modeling. Collectively, the study shows broad implications for the basic study and therapeutic applications of optimized DdCBE and TALED.

IntroductionAltered functional connectivity of resting-state functional magnetic resonance imaging (rs-fMRI) within default mode network (DMN) regions has been verified to be closely associated with cognitive decline in patients with Type 2 diabetes mellitus (T2DM), but most studies neglected the fluctuations of brain activities—the dynamic effective connectivity (DEC) within DMN of T2DM is still unknown.MethodsFor the current investigation, 40 healthy controls (HC) and 36 T2DM patients have been recruited as participants. To examine the variation of DEC between T2DM and HC, we utilized the methodologies of independent components analysis (ICA) and multivariate granger causality analysis (mGCA).ResultsWe found altered DEC within DMN only show decrease in state 1. In addition, the causal information flow of diabetic patients major affected areas which are closely associated with food craving and metabolic regulation, and T2DM patients stayed longer in low activity level and exhibited decreased transition rate between states. Moreover, these changes related negatively with the MoCA scores and positively with HbA1C level.ConclusionOur study may offer a fresh perspective on brain dynamic activities to understand the mechanisms underlying T2DM-related cognitive deficits.

Highly contagious respiratory illnesses like influenza and COVID-19 pose serious risks to public health. A two-in-one vaccine would be ideal to avoid multiple vaccinations for these diseases. Here, we generated a chimeric receptor binding domain of the spike protein (S-RBD) and hemagglutinin (HA)-stalk-based vaccine for both SARS-CoV-2 and influenza viruses. The S-RBD from SARS-CoV-2 Delta was fused to the headless HA from H1N1 (H1Delta), creating a chimera that forms trimers in solution. The cryo-electron microscopy structure of the chimeric protein complexed with the RBD-targeting CB6 and the HA-stalk-targeting CR9114 antibodies shows that the trimeric protein is stable and accessible for neutralizing antibody binding. Immunization with the vaccine elicited high and long-lasting neutralizing antibodies and effectively protected mice against the challenges of lethal H1N1 or heterosubtypic H5N8, as well as the SARS-CoV-2 Delta or Omicron BA.2 variants. Overall, this study offers a two-in-one universal vaccine design to combat infections caused by both SARS-CoV-2 variants of concern and influenza viruses.

ABSTRACTDietary fibers/probiotics may relieve constipation via optimizing gut microbiome, yet with limited trial-based evidences. We aimed to evaluate the effects of formulas with dietary fibers or probiotics on functional constipation symptoms, and to identify modulations of gut microbiota of relevance. We conducted a 4-week double-blinded randomized placebo-controlled trial in 250 adults with functional constipation. Intervention: A: polydextrose; B: psyllium husk; C: wheat bran + psyllium husk; D: Bifidobacterium animalis subsp. lactis HN019 + Lacticaseibacillus rhamnosus HN001; Placebo: maltodextrin. Oligosaccharides were also included in group A to D. 16S rRNA sequencing was used to assess the gut microbiota at weeks 0, 2, and 4. A total of 242 participants completed the study. No time-by-group effect was observed for bowel movement frequency (BMF), Bristol stool scale score (BSS), and degree of defecation straining (DDS), while BSS showed mean increases of 0.95–1.05 in group A to D (all P

ABSTRACTThe SARS-CoV-2 Omicron variants of concern (VOCs) showed severe resistance to the early-approved COVID-19 vaccines-induced immune responses. The breakthrough infections by the Omicron VOCs are currently the major challenge for pandemic control. Therefore, booster vaccination is crucial to enhance immune responses and protective efficacy. Previously, we developed a protein subunit COVID-19 vaccine ZF2001, based on the immunogen of receptor-binding domain (RBD) homodimer, which was approved in China and other countries. To adapt SARS-CoV-2 variants, we further developed chimeric Delta-Omicron BA.1 RBD-dimer immunogen which induced broad immune responses against SARS-CoV-2 variants. In this study, we tested the boosting effect of this chimeric RBD-dimer vaccine in mice after priming with two doses of inactivated vaccines, compared with a booster of inactivated vaccine or ZF2001. The results demonstrated that boosting with bivalent Delta-Omicron BA.1 vaccine greatly promoted the neutralizing activity of the sera to all tested SARS-CoV-2 variants. Therefore, the Delta-Omicron chimeric RBD-dimer vaccine is a feasible booster for those with prior vaccination of COVID-19 inactivated vaccines.

Abstract Current attempts in vaccine delivery systems concentrate on replicating the natural dissemination of live pathogens, but neglect that pathogens evolve to evade the immune system rather than to provoke it. In the case of enveloped RNA viruses, it is the natural dissemination of nucleocapsid protein (NP, core antigen) and surface antigen that delays NP exposure to immune surveillance. Here, we report a multi-layered aluminum hydroxide-stabilized emulsion (MASE) to dictate the delivery sequence of the antigens. In this manner, the receptor-binding domain (RBD, surface antigen) of the spike protein was trapped inside the nanocavity, while NP was absorbed on the outside of the droplets, enabling the burst release of NP before RBD. Compared with the natural packaging strategy, the inside-out strategy induced potent type I interferon-mediated innate immune responses and triggered an immune-potentiated environment in advance, which subsequently boosted CD40+ DC activations and the engagement of the lymph nodes. In both H1N1 influenza and SARS-CoV-2 vaccines, rMASE significantly increased antigen-specific antibody secretion, memory T cell engagement, and Th1-biased immune response, which diminished viral loads after lethal challenge. By simply reversing the delivery sequence of the surface antigen and core antigen, the inside-out strategy may offer major implications for enhanced vaccinations against the enveloped RNA virus.

Background The measurement of exhaled gas nitric oxide (FeNO) has safe, non-invasive, simple, repetitive characteristics which is widely used in the assessment of airway inflammation in asthmatic patients, but the determination of FeNO is affected by a variety of factors, among which living environment factors exposure may have a close relationship to FeNO level, whereas there are few studies on the impact of exposure of living environment factors on the level of FeNO. Objective To analyze the effect of exposure to living environment factors on the level of exhaled nitric oxide (FeNO) in patients with bronchial asthma in non acute attack period, so as to improve the efficacy of clinicians in using FeNO to manage asthma. Methods A total of 109 patients with bronchial asthma in non acute attack period who visited the Respiratory Department Outpatient of the Second Affiliated Hospital of Guangzhou Medical University from July 2018 to June 2020 were included as the study subjects, the data were collected through a questionnaire survey, and the questionnaire information mainly included general information (gender, age, height, body mass) , living environment factors (including smoking history, whether family members smoked at home, allergy history, location of residence, the distance between the residence and the main road with large traffic volume, whether there were factories around the residence, floors of residential buildings, length of residence building, frequency of washing and drying bed sheets, quilt covers/pillow cases, curtain materials at home, potted plants at home, whether the trash can in the home was cleaned regularly, whether kept pets at home, whether there were cockroaches at home and whether kitchen waste was disposed of the same day, whether there were plush toys at home) and the inspection data of FeNO collected. Patients with bronchial asthma were divided into 3 groups according to FeNO level: there were 47 cases in the FeNO low level group (FeNO50 ppb) . Ordinal multiple classification logistic regression analysis was used to explore the environmental factors affecting the FeNO value level measurement. Results There was no significant difference in gender, age, height and body mass among the three groups (P>0.05) . There was no significant difference among the three groups in floors of residential buildings, length of residence, frequency of washing and drying bed sheets, quilt covers/pillow cases, curtain materials at home, potted plants at home, whether the trash can in the home was cleaned regularly, whether there were cockroaches at home and whether kitchen waste was disposed of the same day, whether there were plush toys at home (P>0.05) ; There were statistically significant differences in smoking history, whether family members smoked at home, allergy history, location of residence, the distance between the residence and the main road with large traffic volume, whether there were factories around the residence, and whether there were pets at home (P

Allium vegetables attract attention for their flavor and aroma in Asia, especially in China and Japan. The aim of this experiment was to uncover the differences in the unique flavor compounds of two Welsh onions that are typical cultivars in China and Japan (‘Zhangqiu’ and ‘Tenko’). Chemical methods and solid-phase microextraction–gas chromatography-mass spectrometry were performed to determine the nutritional quality and quantity of volatile compounds of various organs of Welsh onions. The results show that a total of 30, 37, and 28 compounds were detected in the roots, pseudostem, and leaves of ‘Zhangqiu’, respectively, while 21, 27, and 20 compounds were detected in the corresponding organs of ‘Tenko’. The distribution of sulfur compounds in the roots, pseudostem, and leaves of ‘Zhangqiu’ accounted for 72%, 83%, and 26% of the total content, while those of ‘Tenko’ accounted for 55%, 84%, and 57%, respectively. Aldehydes are the second largest class of volatiles in Welsh onions. The distribution of aldehydes in the leaves was notably different: 52% and 27% in ‘Zhangqiu’ and ‘Tenko’, respectively. The contribution of S to the volatile substances was outstanding, and through forward selection, it was found that P, Ca, and Mg contribute to the volatile substances of Welsh onions. The above results indicate that the different genotypes of Welsh onions have various flavors, and mineral elements contribute variously to these flavors. Calcium could be a new topic of interest for our subsequent research on elements and volatiles.

The penetration of electric vehicles (EVs) in vehicle-to-grid (V2G) interaction can effectively assist the grid in achieving frequency regulation and peak load balancing. However, the customer perceives that participating in V2G services would result in the additional cycling of the battery and the accelerated aging of the EVs’ power battery, which has become a major obstacle to the widespread adoption of V2G services. Most existing methods require long-term cycling data and battery parameters to quantify battery aging, which is not suitable for the V2G scenario with large-scale and short-time intervals. Consequently, the real-time and accurate quantification of battery aging for optimization remains a challenge. This study proposes a charging scheduling method for EVs that can accurately and online quantify battery aging. Firstly, V2G scheduling is formulated as an optimization problem by defining an online sliding window to collect real-time vehicle information on the grid, enabling online optimization. Secondly, battery aging is more accurately quantified by proposing a novel amplitude-based rain-flow cycle counting (MRCC) method, which utilizes the charging information of the battery within a shorter time period. Lastly, an intelligent optimization algorithm is employed to optimize the charging and discharging power of EVs, aiming to minimize grid fluctuations and battery aging. The proposed method is validated using a V2G scenario with 50 EVs with randomly generated behaviors, and the results demonstrate that the proposed online scheduling method not only reduces the EFCC of the battery by 8.4%, but also achieves results close to global optimization.

We reported a highly efficient electrochemical immunosensor utilizing chitosan–graphene nanosheets (CS-GNs) nanocomposites for the detection of aflatoxin B1 (AFB1) in corn samples. The CS-GNs nanocomposites, serving as a modifying layer, provide a significant specific surface area and biocompatibility, thereby enhancing both the electron transfer rate and the efficiency of antibody immobilization. The electrochemical characterization was conducted utilizing both differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). Moreover, the antibody concentration, pH, antibody immobilization time, and immunoreaction time, were optimized. The results showed that the current change (ΔI) before and after the immunoreaction demonstrated a strong linear relationship (R2=0.990) with the AFB1 concentration, as well as good specificity and stability. The linear range extended from 0.05 to 25 ng/mL, with a detection limit of 0.021 ng/mL (S/N=3). The immunosensor exhibited a recovery rate ranging from 97.3% to 101.4% in corn samples, showing a promising performance using an efficient method, and indicating a remarkable prospect for the detection of fungal toxins in grains.

IntroductionAt present, machine learning and image processing technology are widely used in plant disease diagnosis. In order to address the challenges of subjectivity, cost, and timeliness associated with traditional methods of diagnosing potassium deficiency in apple tree leaves. MethodsThe study proposes a model that utilizes image processing technology and machine learning techniques to enhance the accuracy of detection during each growth period. Leaf images were collected at different growth stages and processed through denoising and segmentation. Color and shape features of the leaves were extracted and a multiple regression analysis model was used to screen for key features. Linear discriminant analysis was then employed to optimize the data and obtain the optimal shape and color feature factors of apple tree leaves during each growth period. Various machine-learning methods, including SVM, DT, and KNN, were used for the diagnosis of potassium deficiency. ResultsThe MLR-LDA-SVM model was found to be the optimal model based on comprehensive evaluation indicators. Field experiments were conducted to verify the accuracy of the diagnostic model, achieving high diagnostic accuracy during different growth periods. DiscussionThe model can accurately diagnose whether potassium deficiency exists in apple tree leaves during each growth period. This provides theoretical guidance for intelligent and precise water and fertilizer management in orchards.

To investigate the embryonic development of the mud crab Scylla paramamosain, we analyzed three critical parameters: egg color of, embryo morphology (through conventional and laser scanning confocal microscopy), and the distribution of cell divisions. During embryonic development, the egg color exhibited a progressive transition, shifting from orange to reddish-orange, then to brown, before ultimately darkening to black. Each embryo displayed a spherical shape, measuring approximately 280 μm in diameter, characterized by a smooth surface devoid of any depressions. The embryonic cell division was in the form of mixed oogenesis, comprised of complete division in the early stage, spiral oogenesis in the middle stage and surface division in the late stage. It is noteworthy that the blastopore appeared at the position where the transparent area and cell aggregation just appeared under the microscope, and the blastomere was a characteristic of the embryo entering the gastrulation stage. After entering the gastrulation stage, the cells aggregated towards the blastopore and formed two symmetrical cell clusters, which formed a V-shape with the void of the classic blastopore. When the transparent region occupied approximately 1/5 of the embryo’s volume, the embryo entered the nauplius stage, and the thoracic and abdominal armor, as well as the optic lobe and abdominal limb primordia, could be clearly distinguished. The appearance of the compound eye pigment band indicated the stage of compound eye pigment formation. At this time, the transparent area accounted for 1/4 of the embryo and a large number of ganglia appeared. The change of the compound eye pigment band from red to black was also one of the reasons for the blackening of the egg color of the crabs. The data obtained through this study have potential applications in the determination of embryonic development status and obtaining of high-quality seeds for S. paramamosain culture.

Co/Fe bimetallic spherical nanomaterials were synthesized by hydrothermal method as an efficient heterogeneous catalyst, which can catalyze the selective oxidation of benzyl alcohol to benzaldehyde by O2, thereby replacing stoichiometric oxidation reagents such as chromate and manganese oxide. CoFe2O4 has good oxidation activity and selectivity for benzyl alcohol. The catalyst catalyzes the preparation of formaldehyde from benzyl alcohol oxide by O2 at 150 °C, with a conversion rate of 95.3% and a yield of 96.7%. Furthermore, the catalyst is recycled for 5 consecutive uses without significant degradation of its catalytic performance.

SARS-CoV-2 variants with severe immune evasion are a major challenge for COVID-19 prevention, especially the circulating Omicron XBB/BQ.1.1/BF.7 strains. Thus, the next-generation of broad-spectrum vaccines are urgently needed. Previously, we developed a COVID-19 protein subunit vaccine, ZF2001, based on the RBD-homodimer as the immunogen. To adapt SARS-CoV-2 variants, we developed chimeric RBD-heterodimers to induce broad immune responses. In this study, we further explored the concept of tandem RBD homotrimer and heterotrimer. Prototype SARS-CoV-2 RBD-homotrimer, prototype-Delta-BA.1 (PDO) RBD-heterotrimer and Delta-BA.2-BA.5 (DBA2BA5) RBD-heterotrimer were designed. Biochemical and cryo-EM structural characterization demonstrated total epitope exposure of the RBD-trimers. In mouse experiments, PDO and DBA2BA5 elicited broad SARS-CoV-2 neutralization. Potent protection against SARS-CoV-2 variants was observed in challenge assays and was correlated with neutralizing antibody titer. This study validated the design strategy of tandem RBD-heterotrimers as multivalent immunogens and presented a promising vaccine candidate, DBA2BA5, eliciting broad-spectrum immune responses, including against the circulating XBB/BF.7/BQ.1.1.

BackgroundMycobacterium tuberculosis antigen (Mtb-Ag) is a polypeptide component with a molecular weight of 10-14 kDa that is obtained from the supernatant of the H37Ra strain after heat treatment. It stimulates the activation and proliferation of γδT cells in the blood to produce an immune response against tuberculosis. Mtb-Ag is therefore crucial for classifying and detecting the central genes and key pathways involved in TB initiation and progression.MethodsIn this study, we performed high-throughput RNA sequencing of peripheral blood mononuclear cells (PBMC) from Mtb-Ag-stimulated and control samples to identify differentially expressed genes and used them for gene ontology (GO) and a Kyoto Encyclopedia of Genomes (KEGG) enrichment analysis. Meanwhile, we used PPI protein interaction network and Cytoscape analysis to identify key genes and qRT-PCR to verify differential gene expression. Single-gene enrichment analysis (GSEA) was used further to elucidate the potential biological functions of key genes. Analysis of immune cell infiltration and correlation of key genes with immune cells after Mtb-Ag-stimulated using R language.ResultsWe identified 597 differentially expressed genes in Mtb-Ag stimulated PBMCs. KEGG and GSEA enrichment analyzed the cellular pathways related to immune function, and DEGs were found to be primarily involved in the TNF signaling pathway, the IL-17 signaling pathway, the JAK-STAT signaling pathway, cytokine-cytokine receptor interactions, and the NF-κB signaling pathway. Wayne analysis using GSEA, KEGG, and the protein-protein interaction (PPI) network showed that 34 genes, including PTGS2, IL-1β, IL-6, TNF and IFN-γ et al., were co-expressed in the five pathways and all were up-regulated by Mtb-Ag stimulation. Twenty-four DEGs were identified using qRT-PCR, including fourteen up-regulated genes (SERPINB7, IL20, IFNG, CSF2, PTGS2, TNF-α, IL36G, IL6, IL10, IL1A, CXCL1, CXCL8, IL4, and CXCL3) and ten down-regulated genes (RTN1, CSF1R CD14, C5AR1, CXCL16, PLXNB2, OLIG1, EEPD1, ENG, and CCR1). These findings were consistent with the RNA-Seq results.ConclusionThe transcriptomic features associated with Mtb-Ag provide the scientific basis for exploring the intracellular immune mechanisms against Mtb. However, more studies on these DEGs in pathways associated with Mtb-Ag stimulation are needed to elucidate the underlying pathologic mechanisms of Mtb-Ag during Mtb infection.

Summary: Type H vessels couple angiogenesis with osteogenesis, while sympathetic cues regulate vascular and skeletal function. The crosstalk between sympathetic nerves and type H vessels in bone remains unclear. Here, we first identify close spatial connections between sympathetic nerves and type H vessels in bone, particularly in metaphysis. Sympathoexcitation, mimicked by isoproterenol (ISO) injection, reduces type H vessels and bone mass. Conversely, beta-2-adrenergic receptor (ADRB2) deficiency maintains type H vessels and bone mass in the physiological condition. In vitro experiments reveal indirect sympathetic modulation of angiogenesis via paracrine effects of mesenchymal stem cells (MSCs), which alter the transcription of multiple angiogenic genes in endothelial cells (ECs). Furthermore, Notch signaling in ECs underlies sympathoexcitation-regulated type H vessel formation, impacting osteogenesis and bone mass. Finally, propranolol (PRO) inhibits beta-adrenergic activity and protects type H vessels and bone mass against estrogen deficiency. These findings unravel the specialized neurovascular coupling in bone homeostasis and regeneration.

Faced with increasingly complex industrial data, standard machine learning algorithms struggle to effectively extract both linear and nonlinear features. In this study, an improved residual network (ResNet) called Residual network with Independent Multi-Channel Weighting (RMCW) to tackle the nonlinear, temporally uncertain, and unevenly distributed fault. Firstly, a strategy for constructing the multi-channel vibration intrinsic mode function (IMF) images is designed to obtain the primary features by combing the empirical mode decomposition (EMD) and the gramian angular field (GAF). Secondly, a dynamic receptive field (DRF) with independent channel weighting is utilized to adaptively fuse the multi-channel features. This renders both initialization parameters for each individual channel and DRF parameters mutually independently adaptive to the fault features in the different batch. Thirdly, the RMCW model is built by inputting the fused features to the network of 9 residual building blocks. Two experimental cases verify that the propose method is effective for the machinery fault diagnosis and is superior to the comparing methods.

Patients with lung cancer may experience various symptoms as the disease progresses, which may reduce the benefits of cancer treatment, reduce treatment compliance, delay cancer treatment, reduce the quality of life (QoL), and impact survival. This review discusses comprehensive symptom assessment and management, which are crucial for high-quality lung cancer treatment. Traditional Chinese medicine (TCM) is important in relieving cancer-related symptoms in patients with lung cancer. Including patient-reported outcomes (PROs) in clinical trials and practice can provide a better assessment of symptom burden and the effectiveness of symptom management. Patient-centered care with TCM in lung cancer patients may include six steps: Symptom screening, etiology investigation, comprehensive assessment, integrative management, reassessment, and regular symptom follow-up monitoring. PRO measures can be used to evaluate symptom intensity, the degree to which symptoms interfere with activities of daily living, and the QoL. Clearly defined and reliable PRO measures can enhance patient satisfaction and improve symptom control. Quantitative PRO measures developed from the TCM perspective should be considered one of the important outcome measurements in TCM care. A multidisciplinary collaborative symptom management model, including TCM and conventional therapy, will be the future goal for treating patients with lung cancer.

Abstract The MYC oncogenic family is dysregulated in diverse tumors which is generally linked to the poor prognosis of tumors. The members in MYC family are transcription factors which are responsible for the regulation of various genes expression. Among them, c-MYC is closely related to the progression of tumors. Furthermore, c-MYC aberrations is tightly associated with the prevalence of breast cancer. Tumor microenvironment (TME) is composed of many different types of cellular and non-cellular factors, mainly including cancer-associated fibroblasts, tumor-associated macrophages, vascular endothelial cells, myeloid-derived suppressor cells and immune cells, all of which can affect the diagnosis, prognosis, and therapeutic efficacy of breast cancer. Importantly, the biological processes occurred in TME, such as angiogenesis, immune evasion, invasion, migration, and the recruition of stromal and tumor-infiltrating cells are under the modulation of c-MYC. These findings indicated that c-MYC serves as a critical regulator of TME. Here, we aimed to summarize and review the relevant research, thus to clarify c-MYC is a key mediator between breast cancer cells and TME. Video Abstract