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Abstract We report SARS-CoV-2 KP.1, KP.1.1, KP.2 and KP.3 neutralizing antibody titers. They displayed increased immune evasion compared to JN.1, especially KP.1 and KP.3, for participants who experienced BF.7/BA.5.2 breakthrough infection or received bivalent (delta/BA.5) vaccine boosting. Second XBB sub-variants breakthrough infection enhanced the neutralization responses. HK.3-JN.1 RBD-heterodimer induced balanced and potent neutralizing responses against recently-circulating SARS-CoV-2 sub-variants in mice, supporting to replace the COVID-19 antigen containing JN.1 or its sub-variants.

Abstract Face detection is a multidisciplinary research subject that employs fundamental computer algorithms, image processing, and patterning. Neural networks, on the other hand, have been widely developed to solve challenges in the domains of feature extraction, pattern detection, and the like in general. The presented study investigates the DNN (deep neural networks) use in the creation of facial detection operating systems. In this study, a novel optimized deep network has been presented to face detection. In this paper, after using some preprocessing stages for contrast enhancement and increasing the data number for the next deep tool, they fed to a bidirectional recurrent neural network (BRNN). The network is optimized via a novel enhanced version of Ebola optimization algorithm to provide far greater accuracy. The suggested procedure is examined on GTFD (Georgia Tech Face Database) and the results indicate that the proposed technique significantly outperforms other comparative methods, attaining an accuracy of 94.3%, a precision of 93.51%, a recall of 94.53%, and an F1-score of 92.47%. Furthermore, the method exhibits resilience against various challenges, achieving an accuracy of 95.6% under occlusions, 96.3% under lighting variations, 94.8% under pose variations, and 92.4% under low resolution conditions. Simulation results depict that the suggested technique gives far greater accuracy in comparison with the other comparative approaches.

Abstract In this research, we investigated whether secondhand smoking (SHS) increases the possibility of hypertension. We used data from the Shaanxi baseline survey of the Regional Ethnic Cohort Study in Northwest China (RECS). Active smoking and SHS were determined by questionnaires. Hypertension was defined as self-reported or objectively measured. Multivariable logistic regression model was performed to estimate the risk of hypertension under active smoking and SHS. Compared to never-smokers, exposure to SHS had a 9% (P = 0.005) higher possibility of hypertension. The adjusted OR for exposure time of ≤ 3 h/week, 3–12 h/week, and > 12 h/week were 1.03 (P = 0.545), 1.10 ( P = 0.040), and 1.15 (P = 0.015), respectively. The adjusted OR for frequency of SHS of 1–2 times/week, 3–5 times/week, and nearly every day were 0.94 (P = 0.421), 1.01 (P = 0.846), and 1.14 (P

An ion cyclotron resonance heating (ICRH) antenna will be installed in the equatorial port plug of the China Fusion Engineering Test Reactor (CFETR) for heating ions and electrons in plasma. This study reports the latest neutronic modeling and analyses of antenna for the subsequent optimization of the shielding design, with radiation damage, nuclear heating, gas generation of key components, and shutdown dose rate (SDDR) used as main indicators. Results showed that the nuclear heating of the BP was extremely high, thus posing a high risk to the structure, highlighting the necessity of further upgrading the shielding performance. In addition, the SDDR was more than 100 μSv/hr 12 days after the shutdown, rendering hands-on maintenance in the areas at a short time challenging. Meanwhile, key contributors to higher SDDR have been analyzed.

Abstract Ferroelectrics as emerging and attractive catalysts have shown tremendous potential for applications including wastewater treatment, hydrogen production, nitrogen fixation, and organic synthesis, etc. In this study, we demonstrate that molecular ferroelectric crystal TMCM-CdCl3 (TMCM = trimethylchloromethylammonium) with multiaxial ferroelectricity and superior piezoelectricity has an effective catalytic activity on the direct construction of the pharmacologically important substituted quinoline derivatives via one-pot [3 + 2 + 1] annulation of anilines and terminal alkynes by using N,N-dimethylformamide (DMF) as the carbon source. The recrystallized TMCM-CdCl3 crystals from DMF remain well ferroelectricity and piezoelectricity. Upon ultrasonic condition, periodic changes in polarization contribute to the release of free charges from the surface of the ferroelectric domains in nano size, which then quickly interacts with the substrates in the solution to trigger the pivotal redox process. Our work advances the molecular ferroelectric crystal as a catalytic route to organic synthesis, not only providing valuable direction for molecular ferroelectrics but also further enriching the executable range of ferroelectric catalysis.

Ion cyclotron resonance heating (ICRH) is an important auxiliary heating method applied to the China Fusion Engineering Test Reactor, which can effectively heat the ions and electrons in plasma. Owing to the harsh nuclear environment, neutronic analyses are required to verify tritium self-sufficiency and neutron-shielding requirements. In this study, a neutronics analysis of the ICRH antenna was conducted using the COre and System integrated engine for Reactor Monte Carlo (cosRMC) code to estimate the neutron flux, radiation damage, nuclear heating, gas generation rate of key components, and tritium breeding ratio (TBR), providing data support for the subsequent optimization of the shielding design. In addition, the neutron flux of the coils around the antenna was calculated to prevent the entry of neutrons that damage the magnetic field coils through the gaps between the port plugs and antenna, and the shielding effects of the port-plug antenna on the surrounding components were analyzed. Finally, the results obtained using the cosRMC and MCNP codes were compared, which and presented good agreement, thus verifying the reliability of the neutronic analysis using the cosRMC code.

Abstract To improve locomotion and operation integration, this paper presents an integrated leg-arm quadruped robot (ILQR) that has a reconfigurable joint. First, the reconfigurable joint is designed and assembled at the end of the leg-arm chain. When the robot performs a task, reconfigurable configuration and mode switching can be achieved using this joint. In contrast from traditional quadruped robots, this robot can stack in a designated area to optimize the occupied volume in a nonworking state. Kinematics modeling and dynamics modeling are established to evaluate the mechanical properties for multiple modes. All working modes of the robot are classified, which can be defined as deployable mode, locomotion mode and operation mode. Based on the stability margin and mechanical modeling, switching analysis and evaluation between each mode is carried out. Finally, the prototype experimental results verify the function realization and switching stability of multimode and provide a design method to integrate and perform multimode for quadruped robots with deployable characteristics.

Abstract Background In the context of increasing exposure to silica nanoparticles (SiNPs) and ensuing respiratory health risks, emerging evidence has suggested that SiNPs can cause a series of pathological lung injuries, including fibrotic lesions. However, the underlying mediators in the lung fibrogenesis caused by SiNPs have not yet been elucidated. Results The in vivo investigation verified that long-term inhalation exposure to SiNPs induced fibroblast activation and collagen deposition in the rat lungs. In vitro, the uptake of exosomes derived from SiNPs-stimulated lung epithelial cells (BEAS-2B) by fibroblasts (MRC-5) enhanced its proliferation, adhesion, and activation. In particular, the mechanistic investigation revealed SiNPs stimulated an increase of epithelium-secreted exosomal miR-494-3p and thereby disrupted the TGF-β/BMPR2/Smad pathway in fibroblasts via targeting bone morphogenetic protein receptor 2 (BMPR2), ultimately resulting in fibroblast activation and collagen deposition. Conversely, the inhibitor of exosomes, GW4869, can abolish the induction of upregulated miR-494-3p and fibroblast activation in MRC-5 cells by the SiNPs-treated supernatants of BEAS-2B. Besides, inhibiting miR-494-3p or overexpression of BMPR2 could ameliorate fibroblast activation by interfering with the TGF-β/BMPR2/Smad pathway. Conclusions Our data suggested pulmonary epithelium-derived exosomes serve an essential role in fibroblast activation and collagen deposition in the lungs upon SiNPs stimuli, in particular, attributing to exosomal miR-494-3p targeting BMPR2 to modulate TGF-β/BMPR2/Smad pathway. Hence, strategies targeting exosomes could be a new avenue in developing therapeutics against lung injury elicited by SiNPs. Graphical Abstract

Background: Coarse grains are rich in fiber, minerals, and other beneficial nutrients but are consumed at low levels in modern populations. The factors that influence coarse grain consumption in current living and dietary environments are not fully understood. Objectives: This study aimed to explore the knowledge and behavior related to coarse grain consumption and identify the influencing factors among Chinese citizens. Methods: Six focus group discussions were conducted with 39 participants aged 18–65 years from diverse social backgrounds in Xi'an, China. All discussions were transcribed verbatim and analyzed using inductive thematic analysis. Results: The majority of participants demonstrated insufficient knowledge about coarse grains, including their definitions, health benefits, and recommended intake. A small number of the participants reported regular consumption. The barriers to coarse grain consumption were poor sensory properties, insufficient cooking skills and time, limited availability of ready-to-eat foods, established dietary habits, and high prices. Additionally, new barriers included psychological burden, concerns about food safety, the impact of processing methods on health benefits, and special health conditions. Health benefits and family influence emerged as the 2 primary factors motivating coarse grain consumption. Most participants expressed a positive attitude toward partially replacing staple foods with coarse grains. Enhancing health education, innovating food processing methods, improving labeling systems, and strengthening safety supervision have been recommended for increasing coarse grain consumption. Conclusions: A gap exists between health awareness and healthy behaviors regarding coarse grain consumption; thus, collaborative efforts among government agencies, educational institutions, nutrition societies, the food industry, policymakers, and health professionals are essential to overcome these challenges.

Microplastics (MPs) pollution is emerging as a significant environmental concern, threatening human and animal health. Liver, as an important organ, plays an important role in the metabolism and detoxification of pollutants. Many studies have suggested that the liver is a potential target organ for MPs. However, the extent and consequences of the impacts of MPs on the liver reported in studies remain inconsistent. We categorized vertebrates into fish, mammals, and birds and performed a meta–analysis to comprehensively examine the effects of MPs on the liver. Hedges’ g values were calculated to evaluate effect sizes. To further explore the sources of heterogeneity among the studies, we conducted subgroup analyses focusing on life stage, MPs type, MPs size, and exposure duration. Additionally, we normalized the MPs concentrations and conducted meta-regression analyses to explore the relationship between MPs concentrations and their hepatotoxic effects. A total of 118 studies were included in this meta-analysis. By quantifying 19 indicators, the results showed that MPs could damage the liver by altering liver morphology, inducing oxidative stress, producing intracellular toxicity, altering biotransformation processes, and disturbing lipid metabolism. Intracellular toxicity, followed by oxidative stress, had the greatest impact. Organisms are more sensitive to MPs under the following conditions: longer exposure duration, smaller MPs sizes, and earlier life stages. As the concentration of MPs increases, the levels of several liver indicators, including catalase, glutathione S-transferase, reactive oxygen species, and alkaline phosphatase, progressively increase. This study provides a comprehensive understanding of the effects of MPs on the liver and suggests the underlying mechanisms of MPs hepatotoxicity.

Background Dengue, a mosquito-borne viral disease, has occurred in many cities in China, and it tends to spread to higher latitudes (Huang et al., 2023). Xi’an, situated in central-west China, has witnessed an increase imported cases in the past few years, raising concerns of local dengue transmission. It is crucial to investigate the population density of Aedes albopictus and its insecticides resistance to enhance early warning of dengue fever. Methods Eight sampling sites in eight counties (YT, BL, WY, CH, YL, LN, LT, ZZ) of Xi’an city were surveyed by larval dipping and human-baited double net trap biweekly from June 2021 to September 2022. The Breteau Index (BI, number of positive containers per 100 houses) and Container Index (CI, the percentage of containers containing larvae or pupae) were used to assess larval density, and the human-baited double net trap (HDN, the number of Ae. albopictus females collected per person per hour) to indicate human bating rate (HBR). Meanwhile, the association between the meteorological factors and mosquito density was analyzed. The Ae. albopictus adult insecticides resistance was evaluated by the World Health Organization (WHO) standard resistance bioassay. Adult females were exposed to insecticide-impregnated paper for 1 h, then transferred to the recovery tube, and mortality rate was calculated after 24 h. According to the Implementation Plan for National Vector Surveillance (2016), resistance status was classified into three levels based on mortality: 98% mortality as sensitive. Results From June 2021 to September 2022, a total of 1,065 houses were surveyed for water holding containers, and 99 of 430 water holding containers were checked to be positive for Ae. albopictus larvae and pupae. A total of 1,048 Ae. albopictus females were collected. The average BI, CI and HBR were 10.39, 21.41, and 11.20 female/man/hour in 2021 and 8.86, 20.86, and 11.63 f/m/h in 2022, respectively. The findings showed that the BI exceeded 5 in most months and reached above 20 in specific months. The CI varied in different months and monitoring sites, with the highest CI in August 2021 and July 2022. The discarded tires had the highest positivity rate, with up to 40.32% testing positive for Ae. albopictus larvae. The monthly average temperature showed a positive correlation with CI (r = 0.77), and the monthly BI was positively associated with CI (r = 0.93). The BI, CI, and HBR were significantly higher in the rainy season than other seasons. The bioassay results showed that the mortality rate of Ae. albopictus at the YT monitoring site was 76.92%, indicating resistance to deltamethrin. The mortality rate of Ae. Albopictus at BL, WY, CH, YL, LN, LT, and ZZ sampling sites were varying from 81.25%∼100%, suggesting possibly resistant or still sensitive to beta-cypermethrin, alpha-cypermethrin, malathion, chlorpyrifos, and propoxur.

Abstract Rock‐climbing robots have significant potential in fieldwork and planetary exploration. However, they currently face limitations such as a lack of stability and adaptability on extreme terrains, slow locomotion, and single functionality. This study introduces a novel multimodal and adaptive rock‐climbing robot (MARCBot), which addresses these limitations through spiny grippers that draw inspiration from morpho‐functionalities observed in beetles, arboreal birds, and hoofed animals. This hybrid bioinspired design enables high attachment strength, passive adaptability to different terrains, and quick attachment on rock surfaces. The multimodal functionality of the gripper allows for attachment during climbing and support during walking. A novel control strategy using dynamics and quadratic programming (QP) optimizes attachment wrench distribution, reducing cost‐of‐transport by 20.03% and 6.05% compared to closed‐loop inverse kinematic (CLIK) and virtual model control (VMC) methods, respectively. MARCBot achieved climbing speeds of 0.15 m min−1 on a vertical discrete rock surface under gravity and trotting speeds of up to 0.21 m s−1 on various complex terrains. It is the first robot capable of climbing on rock surfaces and trotting in complex terrains without the need for switching end‐effectors. This study highlights significant advancements in climbing and multimodal locomotion for robots in extreme environments.

IntroductionExtreme weather becomes increasingly frequent and severe under climate change, causing unexpected damage to trees. Among them, sleet damage is particularly harmful to evergreen trees in subtropical area. Camphor trees (Cinnamomum camphora), as dominant street trees in central China, are prone to sleet damage, resulting in loss of valuable ecosystem functions.MethodsBy measuring tree size characteristics of 118 camphor trees before and after a record-breaking sleet event in Wuhan, a mega-city in central China, we built allometric equations between size and volume of broken branches and used the random forest regression to model sleet damage to camphor trees.ResultsWe identified that larger trees with intermediate bole height suffered more than smaller trees with tall bole height from the sleet event. We estimated the volume of broken branches of a camphor tree with DBH at 35.0 cm as 106.4 dm3, equivalent to 55.3 kg biomass loss, from the sleet event.DiscussionWe suggest that pruning the branches instead of topping the main stems of small camphor trees would reduce the sleet hazard. To mitigate the negative impacts of climate change, regular pruning should be practiced on street camphor trees to protect them from future heavy sleet events.

IntroductionClean drinking water is a necessity for maintaining public health and livelihoods. Hard water containing excessive calcium and magnesium threatens urinary health with elevated risks of kidney stones at rural villages with tap water shortages. After entitled poverty alleviation in 2019, residents of Yangxin county of Hubei Province in central China unexpected suffered shortage of tap water and additional cost of water softening. However, the impact of lack of tap water on risks of kidney stones was not yet quantified for residents at rural villages in Yangxin.MethodsWe conducted a cross-sectional analysis by testing 216 water samples from 114 families at four villages and surveying urinary health and living conditions of each householder.ResultsLab tests showed that mean total hardness of well and tap water at each village was above 355 mg/L CaCO3, except tap water from the village with government support for industrial development. Mean softening depth was 309.3 mg/L at the families paying for filters or bottle water, and mean annual cost of water was 1,915 CNY (1 CNY = 0.14 USD) equivalent to 5.8% of mean annual household income. Mean tap water availability was only 34%, and the prevalence of kidney stones among the four villages was 33.9%, 25.0% higher than the rate of kidney stones in Hubei Province. About 60% of the families showed strong willingness to accept annual government compensation of 3,324 CNY for clean water supply, whereas only 2.6% of the families wanted to pay government for water treatment. Using logistic and random forest regression models, we identify factors associated with the prevalence of kidney stones as gender (males have 3.78 times the risks of females), age (2.42 times greater risks if 10 years older), body mass index (higher risks if overweight or obese), total hardness of drinking water (2.59 times for a 100 mg/L increase in total hardness), and tap water availability (2.42 times higher among those without tap water supply compared to those with constant supply).DiscussionOld and obese males are more likely to be diagnosed with kidney stones, but tap water shortages and high total hardness of drinking water increase the risks for all residents. To improve urinary health and meet support needs of residents, tap water supply of soft water is urgently needed at the rural villages in Yangxin.

BackgroundCervical cancer, a severe threat to women’s health, is experiencing a global increase in incidence, notably among younger demographics. With artificial intelligence (AI) making strides, its integration into medical research is expanding, particularly in cervical cancer studies. This bibliometric study aims to evaluate AI’s role, highlighting research trends and potential future directions in the field.MethodsThis study systematically retrieved literature from the Web of Science Core Collection (WoSCC), employing VOSviewer and CiteSpace for analysis. This included examining collaborations and keyword co-occurrences, with a focus on the relationship between citing and cited journals and authors. A burst ranking analysis identified research hotspots based on citation frequency.ResultsThe study analyzed 927 articles from 2008 to 2024 by 5,299 authors across 81 regions. China, the U.S., and India were the top contributors, with key institutions like the Chinese Academy of Sciences and the NIH leading in publications. Schiffman, Mark, featured among the top authors, while Jemal, A, was the most cited. ‘Diagnostics’ and ‘IEEE Access’ stood out for publication volume and citation impact, respectively. Keywords such as ‘cervical cancer,’ ‘deep learning,’ ‘classification,’ and ‘machine learning’ were dominant. The most cited article was by Berner, ES; et al., published in 2008.ConclusionsAI’s application in cervical cancer research is expanding, with a growing scholarly community. The study suggests that AI, especially deep learning and machine learning, will remain a key research area, focusing on improving diagnostics and treatment. There is a need for increased international collaboration to maximize AI’s potential in advancing cervical cancer research and patient care.

The distribution information of irrigated cultivated land is important to many studies, including grain yield estimation, water resources management, drought risk assessment, and so on. This study developed a feature variable, called the irrigation probability index (IPI), based on the principle that irrigation can slow down or inhibit the evolution from meteorological drought to agricultural drought. Nebraska, which has a good irrigation information database, was selected as the study area. Combining IPI with the irrigation statistical data and other selected feature variables, irrigated cultivated land in Nebraska was mapped in 2017 using both the spatialization method and remote sensing classification methods (random forest and support vector machine). We verified the effectiveness of IPI in identifying irrigated cultivated land, analyzed the importance of different feature variables for irrigated cultivated land identification, and compared the accuracy of different irrigation mapping methods. The results show that the IPI is significantly correlated with the actual irrigation area, the area of irrigation facilities, and the number of active irrigation wells. It has a better indicative ability of irrigation in areas with a suitable climate or arid areas, than in areas with a humid climate. The crop water stress index (CWSI), IPI, vegetation index (EVI and NDVI), and land surface temperature difference between day and night are the most important feature variables that are used to distinguish irrigated cultivated land from rain-fed cultivated land. There are differences between the recognition accuracies of the three mapping methods in different climatic regions. Overall, the spatialization method had the highest accuracy (overall accuracy = 86.92 %, kappa = 0.74) and the highest similarity with the existing high-resolution irrigation maps. This study provides a direct and useful reference for other researchers to select feature variables and mapping methods in irrigated cultivated land mapping research.

Abstract Orthopedic conditions have emerged as global health concerns, impacting approximately 1.7 billion individuals worldwide. However, the limited understanding of the underlying pathological processes at the cellular and molecular level has hindered the development of comprehensive treatment options for these disorders. The advent of single-cell RNA sequencing (scRNA-seq) technology has revolutionized biomedical research by enabling detailed examination of cellular and molecular diversity. Nevertheless, investigating mechanisms at the single-cell level in highly mineralized skeletal tissue poses technical challenges. In this comprehensive review, we present a streamlined approach to obtaining high-quality single cells from skeletal tissue and provide an overview of existing scRNA-seq technologies employed in skeletal studies along with practical bioinformatic analysis pipelines. By utilizing these methodologies, crucial insights into the developmental dynamics, maintenance of homeostasis, and pathological processes involved in spine, joint, bone, muscle, and tendon disorders have been uncovered. Specifically focusing on the joint diseases of degenerative disc disease, osteoarthritis, and rheumatoid arthritis using scRNA-seq has provided novel insights and a more nuanced comprehension. These findings have paved the way for discovering novel therapeutic targets that offer potential benefits to patients suffering from diverse skeletal disorders.

Abstract DEAD-box helicase 17 (DDX17) is a typical member of the DEAD-box family with transcriptional cofactor activity. Although DDX17 is abundantly expressed in the myocardium, its role in heart is not fully understood. We generated cardiomyocyte-specific Ddx17-knockout mice (Ddx17-cKO), cardiomyocyte-specific Ddx17 transgenic mice (Ddx17-Tg), and various models of cardiomyocyte injury and heart failure (HF). DDX17 is downregulated in the myocardium of mouse models of heart failure and cardiomyocyte injury. Cardiomyocyte-specific knockout of Ddx17 promotes autophagic flux blockage and cardiomyocyte apoptosis, leading to progressive cardiac dysfunction, maladaptive remodeling and progression to heart failure. Restoration of DDX17 expression in cardiomyocytes protects cardiac function under pathological conditions. Further studies showed that DDX17 can bind to the transcriptional repressor B-cell lymphoma 6 (BCL6) and inhibit the expression of dynamin-related protein 1 (DRP1). When DDX17 expression is reduced, transcriptional repression of BCL6 is attenuated, leading to increased DRP1 expression and mitochondrial fission, which in turn leads to impaired mitochondrial homeostasis and heart failure. We also investigated the correlation of DDX17 expression with cardiac function and DRP1 expression in myocardial biopsy samples from patients with heart failure. These findings suggest that DDX17 protects cardiac function by promoting mitochondrial homeostasis through the BCL6-DRP1 pathway in heart failure.

Abstract Background Mycobacterium tuberculosis heat-resistant antigen (Mtb-HAg) is a peptide antigen released from the mycobacterial cytoplasm into the supernatant of Mycobacterium tuberculosis (Mtb) attenuated H37Ra strain after autoclaving at 121 °C for 20 min. Mtb-HAg can specifically induce γδ T-cell proliferation in vitro. However, the exact composition of Mtb-HAg and the protein antigens that are responsible for its function are currently unknown. Methods Mtb-HAg extracted from the Mtb H37Ra strain was subjected to LC‒MS mass spectrometry. Twelve of the identified protein fractions were recombinantly expressed in Escherichia coli by genetic engineering technology using pET-28a as a plasmid and purified by Ni–NTA agarose resin to stimulate peripheral blood mononuclear cells (PBMCs) from different healthy individuals. The proliferation of γδ T cells and major γδ T-cell subset types as well as the production of TNF-α and IFN-γ were determined by flow cytometry. Their proliferating γδ T cells were isolated and purified using MACS separation columns, and Mtb H37Ra-infected THP-1 was co-cultured with isolated and purified γδ T cells to quantify Mycobacterium viability by counting CFUs. Results In this study, Mtb-HAg from the attenuated Mtb H37Ra strain was analysed by LC‒MS mass spectrometry, and a total of 564 proteins were identified. Analysis of the identified protein fractions revealed that the major protein components included heat shock proteins and Mtb-specific antigenic proteins. Recombinant expression of 10 of these proteins in by Escherichia coli genetic engineering technology was used to successfully stimulate PBMCs from different healthy individuals, but 2 of the proteins, EsxJ and EsxA, were not expressed. Flow cytometry results showed that, compared with the IL-2 control, HspX, GroEL1, and GroES specifically induced γδ T-cell expansion, with Vγ2δ2 T cells as the main subset, and the secretion of the antimicrobial cytokines TNF-α and IFN-γ. In contrast, HtpG, DnaK, GroEL2, HbhA, Mpt63, EsxB, and EsxN were unable to promote γδ T-cell proliferation and the secretion of TNF-α and IFN-γ. None of the above recombinant proteins were able to induce the secretion of TNF-α and IFN-γ by αβ T cells. In addition, TNF-α, IFN-γ-producing γδ T cells inhibit the growth of intracellular Mtb. Conclusion Activated γδ T cells induced by Mtb-HAg components HspX, GroES, GroEL1 to produce TNF-α, IFN-γ modulate macrophages to inhibit intracellular Mtb growth. These data lay the foundation for subsequent studies on the mechanism by which Mtb-HAg induces γδ T-cell proliferation in vitro, as well as the development of preventive and therapeutic vaccines and rapid diagnostic reagents.

Abstract Stabilization of topological spin textures in layered magnets has the potential to drive the development of advanced low-dimensional spintronics devices. However, achieving reliable and flexible manipulation of the topological spin textures beyond skyrmion in a two-dimensional magnet system remains challenging. Here, we demonstrate the introduction of magnetic iron atoms between the van der Waals gap of a layered magnet, Fe3GaTe2, to modify local anisotropic magnetic interactions. Consequently, we present direct observations of the order-disorder skyrmion lattices transition. In addition, non-trivial topological solitons, such as skyrmioniums and skyrmion bags, are realized at room temperature. Our work highlights the influence of random spin control of non-trivial topological spin textures.

Protective vaccines are crucial for preventing and controlling coronavirus disease 2019 (COVID-19). Updated vaccines are needed to confront the continuously evolving and circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. These vaccines should be safe, effective, amenable to easily scalable production, and affordable. Previously, we developed receptor binding domain (RBD) dimer-based protein subunit vaccines (ZF2001 and updated vaccines) in mammalian cells. In this study, we explored a strategy for producing RBD-dimer immunogens in Pichia pastoris. We found that wild-type P. pastoris produced hyperglycosylated RBD-dimer protein containing four N-glycosylation sites in P. pastoris. Therefore, we engineered the wild type P. pastoris (GS strain) into GSΔOCH1pAO by deleting the OCH1 gene (encoding α-1,6-mannosyltransferase enzyme) to decrease glycosylation, as well as by overexpressing the HIS4 gene (encoding histidine dehydrogenase) to increase histidine synthesis for better growth. In addition, RBD-dimer protein was truncated to remove the R328/F329 cleavage sites in P. pastoris. Several homogeneous RBD-dimer proteins were produced in the GSΔOCH1pAO strain, demonstrating the feasibility of using the P. pastoris expression system. We further resolved the cryo-EM structure of prototype-Beta RBD-dimer complexed with the neutralizing antibody CB6 to reveal the completely exposed immune epitopes of the RBDs. In a murine model, we demonstrated that the yeast-produced RBD-dimer induces robust and protective antibody responses, which is suitable for boosting immunization. This study developed the yeast system for producing SARS-CoV-2 RBD-dimer immunogens, providing a promising platform and pipeline for the future continuous updating and production of SARS-CoV-2 vaccines.

ABSTRACT It is critical to develop quick, accurate, and efficient sterilization for detecting Escherichia coli O157:H7 in order to prevent infections and outbreaks of foodborne illnesses. Herein, we established a colorimetric biosensor with sterilizing properties using copper selenide nanoparticles to detect E. coli O157:H7. The sample was mixed with magnetic nanoprobes and nanozyme probes to form a sandwich structure, and then the unbound nanozyme probes were collected by magnetic separation. Finally, the 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate)-hydrogen peroxide (H2O2) reporting system was added for signal amplification. The change from colorless to green can be seen with the naked eye. Under the optimal conditions, the detection range of E. coli O157:H7 was 102–106 CFU/mL, and the detection limit was 0.35 × 102 CFU/mL. The total detection time was 80 minutes, which can be successfully applied to milk and mineral water. In addition, the colorimetric sensor can kill the target bacteria by irradiating it under a 980-nm laser for 5 minutes. In conclusion, this sensor is a promising tool for rapidly detecting foodborne pathogens and promptly eliminating bacteria.IMPORTANCEEscherichia coli O157:H7 is a major threat to public health. At present, the detection methods for E. coli O157:H7 mainly include traditional bacterial culture, immunology (enzyme-linked immune-sorbent assay) and molecular biology techniques (polymerase chain reaction). These methods have the limitations of professional operation, waste of time and energy, and high cost. Therefore, we have developed a simple, fast, bactericidal colorimetric biosensor to detect E. coli. O157:H7. The entire process was completed in 80 minutes. The method has been successfully applied to milk and mineral water samples with satisfactory results, proving that the method is an effective method for real-time detection and inactivation of bacteria.

Abstract Acute asthma exacerbation refers to the progressive deterioration of asthma symptoms that is always triggered by virus infection represented by respiratory syncytial virus (RSV). After RSV infection, exaggerated Th2‐mediated pulmonary inflammation is the critical pathological response of asthmatic patients with acute exacerbation. Significantly, airway epithelial cells, being the primary targets of RSV infection, play a crucial role in controlling the pulmonary inflammatory response by releasing airway epithelial cell‐derived exosomes (AEC‐Exos), which potentially influence the development of asthma. However, the specific role of AEC‐Exos in acute asthma exacerbation after RSV infection remains obscure. The purpose of this study was to determine the distinct function of AEC‐Exos in exacerbating acute asthma following RSV infection. Blockade of exosomes by GW reduce the enhanced pulmonary inflammation significantly. Specifically, the enhanced Th2 inflammation was induced by AEC‐Exos thorough transportation of hsa‐miR‐155‐5p–Sirtuin 1 (SIRT1) pathway during acute asthma exacerbation. Targeted inhibition of hsa‐miR‐155‐5p blocks the exaggerated Th2 inflammation effectively in mice with acute asthma exacerbation. In summary, our study showed that during acute asthma exacerbation after RSV infection, AEC‐Exos promote the enhanced Th2 inflammation through transportation of increased hsa‐miR‐155‐5p, which was mediated partly through SIRT1‐mediated pathway. hsa‐miR‐155‐5p is a potential biomarker for early prediction of acute asthma exacerbation.

ObjectiveThis study investigates the efficacy of training methodologies aimed at mitigating asymmetries in lower limb strength and explosiveness among basketball players.MethodsThirty male university basketball athletes were enrolled in this research. Initial assessments were made regarding their physical attributes, strength, and explosiveness. Subsequently, the participants were randomly allocated into two groups: an experimental group (EG, n = 15) and a control group (CG, n = 15). Over 10 weeks, the EG engaged in a unilateral compound training regimen, incorporating resistance training exercises such as split squats, Bulgarian split squats, box step-ups, and single-leg calf raises (non-dominant leg: three sets of six repetitions; dominant leg: one set of six repetitions) and plyometric drills including lunge jumps, single-leg hops with back foot raise, single-leg lateral jumps, and single-leg continuous hopping (non-dominant leg: three sets of 12 repetitions; dominant leg: one set of 12 repetitions). The CG continued with their standard training routine. Assessments of limb asymmetry and athletic performance were conducted before and after the intervention to evaluate changes.Results1) Body morphology assessments showed limb length and circumference discrepancies of less than 3 cm. The initial average asymmetry percentages in the single-leg countermovement jump (SLCMJ) for jump height, power, and impulse were 15.56%, 12.4%, and 4.48%, respectively. 2) Post-intervention, the EG demonstrated a significant reduction in the asymmetry percentages of SLCMJ height and power (p < 0.01), along with improvements in the isometric mid-thigh pull (IMTP) test metrics (p < 0.05). 3) The EG also showed marked enhancements in the double-leg countermovement jump (CMJ) and standing long jump (SLJ) outcomes compared to the CG (p < 0.01), as well as in squat performance (p < 0.05).ConclusionThe 10-week unilateral compound training program effectively reduced the asymmetry in lower limb strength and explosiveness among elite male university basketball players, contributing to increased maximal strength and explosiveness.

The biological world serves as a vast reservoir of inspiration for human innovation, particularly in the realm of robotics designed to navigate intricate granular environments. Among these creatures adept at burrowing, the mole stands out due to its exceptional body structure and unparalleled efficiency, surpassing most engineering burrowing systems. Consequently, the mole serves as an ideal model for designing highly efficient burrowing robots. This study introduces a mole‐inspired robot burrowing with forelimbs, specifically designed for planetary soil exploration. By closely examining the distinctive body morphology of moles, a forelimb burrowing mechanism is devised through biomimetic mapping, and its kinematics is thoroughly analyzed. A robot prototype is developed and an experimental setup is constructed to evaluate its burrowing performance. A series of tests are conducted to assess the capabilities of the robot, including forelimb burrowing, robot crawling, and robot burrowing. The results demonstrate that the proposed mole‐inspired burrowing robot is capable of crawling and burrowing to a certain depth using its forelimbs. Although it exhibits some upward displacement, this issue can be mitigated by modifying the head configuration and adjusting the forelimb posture to effectively overcome the vertical stress and lift force exerted by granular soils due to intensity gradient.

Abstract Temozolomide (TMZ) resistance presents a significant challenge in the treatment of gliomas. Although lysine demethylase 4A (KDM4A) has been implicated in various cancer‐related processes, its role in TMZ resistance remains unclear. This study aims to elucidate the contribution of KDM4A to TMZ resistance in glioma cells and its potential implications for glioma prognosis. We assessed the expression of KDM4A in glioma cells (T98G and U251MG) using qRT‐PCR and Western blot assays. To explore the role of KDM4A in TMZ resistance, we transfected siRNA targeting KDM4A into drug‐resistant glioma cells. Cell viability was assessed using the CCK‐8 assay and the TMZ IC50 value was determined. ChIP assays were conducted to investigate KDM4A, H3K9me3, and H3K36me3 enrichment on the promoters of ROCK2 and HUWE1. Co‐immunoprecipitation confirmed the interaction between HUWE1 and ROCK2, and we examined the levels of ROCK2 ubiquitination following MG132 treatment. Notably, T98G cells exhibited greater resistance to TMZ than U251MG cells, and KDM4A displayed high expression in T98G cells. Inhibiting KDM4A resulted in decreased cell viability and a reduction in the TMZ IC50 value. Mechanistically, KDM4A promoted ROCK2 transcription by modulating H3K9me3 levels. Moreover, disruption of the interaction between HUWE1 and ROCK2 led to reduced ROCK2 ubiquitination. Inhibition of HUWE1 or overexpression of ROCK2 counteracted the sensitization effect of si‐KDM4A on TMZ responsiveness in T98G cells. Our findings highlight KDM4A's role in enhancing TMZ resistance in glioma cells by modulating ROCK2 and HUWE1 transcription and expression through H3K9me3 and H3K36me3 removal.

Abstract. Background:. Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer associated with poor prognosis and limited treatment options. The androgen receptor (AR) has emerged as a potential therapeutic target for luminal androgen receptor (LAR) TNBC. However, multiple studies have claimed that anti-androgen therapy for AR-positive TNBC only has limited clinical benefits. This study aimed to investigate the role of AR in TNBC and its detailed mechanism. Methods:. Immunohistochemistry and TNBC tissue sections were applied to investigate AR and nectin cell adhesion molecule 4 (NECTIN4) expression in TNBC tissues. Then, in vitro and in vivo assays were used to explore the function of AR and estrogen receptor beta (ERβ) in TNBC. Chromatin immunoprecipitation sequencing (ChIP-seq), co-immunoprecipitation (co-IP), molecular docking method, and luciferase reporter assay were performed to identify key molecules that affect the function of AR. Results:. Based on the TNBC tissue array analysis, we revealed that ERβ and AR were positive in 21.92% (32/146) and 24.66% (36/146) of 146 TNBC samples, respectively, and about 13.70% (20/146) of TNBC patients were ERβ positive and AR positive. We further demonstrated the pro-tumoral effects of AR on TNBC cells, however, the oncogenic biology was significantly suppressed when ERβ transfection in LAR TNBC cell lines but not in AR-negative TNBC. Mechanistically, we identified that NECTIN4 promoter –42 bp to –28 bp was an AR response element, and that ERβ interacted with AR thus impeding the AR-mediated NECTIN4 transcription which promoted epithelial–mesenchymal transition in tumor progression. Conclusions:. This study suggests that ERβ functions as a suppressor mediating the effect of AR in TNBC prognosis and cell proliferation. Therefore, our current research facilitates a better understanding of the role and mechanisms of AR in TNBC carcinogenesis.

This paper delves into what the application of authenticity to Human-Machine Communication (HMC) can teach us about authenticity and us as HMC researchers and as a com- munity. Inspired by the 2023 pre-conference “HMC: Authenticity in communicating with machines,” two central questions guide the discussion: How does HMC contribute to our understanding of authentic communication with machines? And how can the concept of authenticity contribute to our sense of self as researchers within the HMC field? Through the collaborative effort of 22 authors, the paper explores the re-conceptualization of authenticity and presents recent areas of tension that guide the HMC research and community. With this paper we aim at offering a gateway for scholars to connect and engage with the evolving HMC field.

We propose a distributed multi-objective optimization (DMO) method for designing chiral plasmonic metasurface that satisfies multiple objectives simultaneously. We aim to improve the refractive index sensitivity of the archetypical Born-Kuhn type chiral plasmonic metasurface while ensuring that circular dichroism (CD) is as pronounced as possible at a designated resonance wavelength. By leveraging distributed technology, the proposed method significantly improves the time efficiency of the optimization process. The simulation results demonstrate approximately 33% enhancement in sensitivity by DMO, as well as greater than 100% boost in time efficiency compared to stand-alone optimization approaches. These findings highlight the potential of the proposed method to guide the design of chiral plasmonic metasurface sensors, enabling the simultaneous optimization of multiple objectives and facilitating advancements in chiral optics and sensing applications.

Macrophages play a central role in immunological responses to metallic species associated with the localized corrosion of metallic implants, and mediating in peri-implant inflammations. Herein, the pathways of localized corrosion-macrophage interactions were systematically investigated on 316L stainless steel (SS) implant metals. Electrochemical monitoring under macrophage-mediated inflammatory conditions showed a decreased pitting corrosion resistance of 316L SSs in the presence of RAW264.7 cells as the cells would disrupt biomolecule adsorbed layer on the metal surface. The pitting potentials were furtherly decreased when the RAW264.7 cells were induced to the M1 pro-inflammatory phenotype by the addition of lipopolysaccharide (LPS), and pitting corrosion preferentially initiated at the peripheries of macrophages. The overproduction of aggressive ROS under inflammatory conditions would accelerate the localized corrosion of 316L SS around macrophages. Under pitting corrosion condition, the viability and pro-inflammatory polarization of RAW264.7 cells were region-dependent, lower viability and more remarkable morphology transformation of macrophages in the pitting corrosion region than the pitting-free region. The pitting corrosion of 316L SS induced high expression of CD86, TNF-α, IL-6 and high level of intracellular ROS in macrophages. Uneven release of metallic species (Fe2+, Cr3+, Ni2+, etc) and uneven distribution of surface overpotential stimulated macrophage inflammatory responses near the corrosion pits. A synergetic effect of localized corrosion and macrophages was revealed, which could furtherly promote localized corrosion of 316L SS and macrophage inflammatory reactions. Our results provided direct evidence of corrosion-macrophage interaction in metallic implants and disclosed the pathways of this mutual stimulation effect.