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Exaggerated airway constriction triggered by repeated exposure to allergen, also called hyperreactivity, is a hallmark of asthma. Whereas vagal sensory neurons are known to function in allergen-induced hyperreactivity1-3, the identity of downstream nodes remains poorly understood. Here we mapped a full allergen circuit from the lung to the brainstem and back to the lung. Repeated exposure of mice to inhaled allergen activated the nuclei of solitary tract (nTS) neurons in a mast cell-, interleukin-4 (IL-4)- and vagal nerve-dependent manner. Single-nucleus RNA sequencing, followed by RNAscope assay at baseline and allergen challenges, showed that a Dbh+ nTS population is preferentially activated. Ablation or chemogenetic inactivation of Dbh+ nTS neurons blunted hyperreactivity whereas chemogenetic activation promoted it. Viral tracing indicated that Dbh+ nTS neurons project to the nucleus ambiguus (NA) and that NA neurons are necessary and sufficient to relay allergen signals to postganglionic neurons that directly drive airway constriction. Delivery of noradrenaline antagonists to the NA blunted hyperreactivity, suggesting noradrenaline as the transmitter between Dbh+ nTS and NA. Together, these findings provide molecular, anatomical and functional definitions of key nodes of a canonical allergen response circuit. This knowledge informs how neural modulation could be used to control allergen-induced airway hyperreactivity.

Plastic pollution is widely present in terrestrial and aquatic ecosystems, and microplastics (MPs) can be detected in organisms. In situ detection methods for MPs in organisms have attracted widespread attention. Traditional imaging characterization methods of MPs, including stereo microscopes and fluorescence microscopy, are typically used to image artificially added microsphere standards under laboratory conditions. However, they cannot specifically identify MPs in biological samples. Thus, there is a need for a detection technique that can provide spatial distribution information of MPs in biological samples as well as measure their quality and quantity. In this perspective, to obtain high-resolution images with chemical composition analysis, we compared ion sources for ionizing plastic macromolecules and mass analyzers for analyzing macromolecules. Matrix-assisted laser desorption/ionization (MALDI) is suitable for imaging characterization, while time-of-flight (TOF) and Orbitrap mass spectrometry are suitable for polymer mass spectrometry analysis. Furthermore, we propose a technique that combines MALDI with TOF or Orbitrap, which holds promise for the in situ imaging of MPs in biological samples.

The advent of single cell transposase-accessible chromatin sequencing (scATAC-seq) technology enables us to explore the genomic characteristics and chromatin accessibility of blood cells at the single-cell level. To fully make sense of the roles and regulatory complexities of blood cells, it is critical to collect and analyze these rapidly accumulating scATAC-seq datasets at a system level. Here, we present scBlood (https://bio.liclab.net/scBlood/), a comprehensive single-cell accessible chromatin database of blood cells. The current version of scBlood catalogs 770,907 blood cells and 452,247 non-blood cells from ∼400 high-quality scATAC-seq samples covering 30 tissues and 21 disease types. All data hosted on scBlood have undergone preprocessing from raw fastq files and multiple standards of quality control. Furthermore, we conducted comprehensive downstream analyses, including multi-sample integration analysis, cell clustering and annotation, differential chromatin accessibility analysis, functional enrichment analysis, co-accessibility analysis, gene activity score calculation, and transcription factor (TF) enrichment analysis. In summary, scBlood provides a user-friendly interface for searching, browsing, analyzing, visualizing, and downloading scATAC-seq data of interest. This platform facilitates insights into the functions and regulatory mechanisms of blood cells, as well as their involvement in blood-related diseases.

Background: A decrease in the number and activity of thymic epithelial cells (TECs) is an important factor in thymic degeneration. Mesenchymal stem cells (MSCs) treating thymic ageing is a promising strategy, but the DNA methylation modification mechanism in TECs remains unclear. Methods: Aged rhesus monkeys were treated with MSCs to establish a thymic senescence model, and hematoxylin-eosin (HE) staining, immunofluorescence staining, and ELISA were performed to observe the structure and function of the thymus. TEC aging model and MSCs co-culture system were established to detect DNA methylation modification and transcriptomic changes, correlation analysis between transcription factor methylation and mRNA expression, and q-PCR, immunofluorescence staining, and Western blot were used to identified key genes. Results: MSCs improved the structure and function of thymus in elderly macaque monkeys; reduced the expression levels of β-Gal, P16, and P21; and increased the activity of aging TECs. There were 501 genes with increased methylation in the promoter region in the treated group compared with the untreated group, among which 23 genes were involved in the negative regulation of cell growth, proliferation and apoptosis, while 591 genes had decreased methylation, among which 37 genes were associated with promoting cell growth and proliferation and inhibiting apoptosis. Furthermore, 66 genes showed a negative correlation between promoter methylation levels and gene transcription; specifically, PDE5A, DUOX2, LAMP1 and SVIL were downregulated with increased methylation, inhibiting growth and development, while POLR3G, PGF, CHTF18, KRT17, FOXJ1, NGF, DYRK3, LRP8, CDT1, PRELID1, F2R, KNTC1 and TRIM3 were upregulated with decreased methylation, promoting cell growth. Conclusion: MSCs improve the structure and function of aged thymus, which involves the regulation of DNA methylation profiles and a decrease in the methylation level of the transcription factor NGF to specifically upregulate KRT17 and FOXJ1 to promote the proliferation of TECs.

In cardiac ablation procedures, the accuracy of catheter positioning determines the authenticity of the cardiac model and the accuracy of the ablation target. This article reviews the literature on catheter positioning in electrophysiology and summarizes the key technologies for catheter positioning, such as magnetic-electric fusion and interference suppression. Addressing the limitations of electric and magnetic positioning individually, the paper elaborates on the rationale for catheter positioning technology based on magnetic-electric fusion. It also outlines the framework of a complex catheter positioning system. Specifically, the magnetoelectric conversion matrix is established first, followed by the optimization of the catheter shape. The interference factors such as magnetic field interference, body movement, respiration, and heartbeat in catheter positioning and their suppression methods are analyzed and discussed in detail. Finally, the development trend of three-dimensional electrophysiology catheter positioning technology is prospected, offering feasible insights for the research on catheter positioning technology based on magnetic-electric fusion.

Objective To systematically evaluate the impact of chronic kidney disease (CKD) on pregnancy outcomes in pregnant patients. Methods Computer searching was conducted within the databases of MEDLINE, EMBASE, WANFANG DATA, China National Knowledge Infrastructure (CNKI) and China Biomedical Literature Database (CBM) from the establishment to July 2023 to identify the relevant literature items on the impact of CKD on pregnancy outcomes in pregnant patients. Two researchers independently screened the literature, extracted data and evaluated the quality of the included studies. Meta-analysis was performed with Review Manager 5.3 and STATA 17.0 software. ResultsA total of 15 case-control and cohort studies, including 2,785,115 subjects, were included for final analysis. The results of Meta-analysis demonstrated the following adverse pregnancy outcomes: CKD elevated the risk of adverse pregnancy outcomes, including preeclampsia (OR=2.68, 95%CI:1.47-4.89), gestational hypertension (OR=6.29, 95%CI:2.58-15.32), preterm birth (OR=4.62, 95%CI:2.78-7.67), small for gestational age (OR=1.54, 95%CI:1.24-1.91) and low birth weight (OR=2.44, 95%CI:1.78-3.35). CKD stage 3-5 patients were more prone to severe preeclampsia (OR=2.31, 95%CI:1.35-3.94), preterm birth (OR=5.06, 95%CI:3.28-7.79), small for gestational age (OR=3.85, 95%CI:1.91-7.76), low birth weight (OR=2.90, 95%CI:1.37-6.13) and fetal mortality (OR=3.41, 95%CI:1.33-8.73) as compared with CKD stage 1-2 counterparts. Pregnant patients with massive proteinuria were more prone to severe preeclampsia (OR=2.76, 95%CI:1.89-4.04), gestational hypertension (OR=2.38, 95%CI:1.62-3.50), preterm birth (OR=3.84, 95%CI:2.69-5.47), low birth weight (OR=2.38, 95%CI:1.62-3.50) and fetal mortality (OR=2.45, 95%CI:1.44-4.17) as compared with those with mild proteinuria. Conclusion CKD elevates the risk of adverse pregnancy outcomes, including preeclampsia, gestational hypertension, preterm birth, small for gestational age and low birth weight. Pregnant patients with CKD stage 3-5 or massive proteinuria (≥1 g) are more prone to adverse pregnancy outcomes as compared with those with CKD stage 1-2 or mild proteinuria (

Abstract CT is crucial for diagnosing chest diseases, with image quality affected by spatial resolution. Thick-slice CT remains prevalent in practice due to cost considerations, yet its coarse spatial resolution may hinder accurate diagnoses. Our multicenter study develops a deep learning synthetic model with Convolutional-Transformer hybrid encoder-decoder architecture for generating thin-slice CT from thick-slice CT on a single center (1576 participants) and access the synthetic CT on three cross-regional centers (1228 participants). The qualitative image quality of synthetic and real thin-slice CT is comparable (p = 0.16). Four radiologists’ accuracy in diagnosing community-acquired pneumonia using synthetic thin-slice CT surpasses thick-slice CT (p 0.99). For lung nodule detection, sensitivity with thin-slice CT outperforms thick-slice CT (p 0.05). These findings indicate the potential of our model to generate high-quality synthetic thin-slice CT as a practical alternative when real thin-slice CT is preferred but unavailable.

Abstract The utilization of visible-near infrared (Vis–NIR) spectroscopy presents a nondestructive, fast, reliable and cost-effective approach to predicting total nitrogen (TN) and organic carbon (OC) levels. This study employed a combination of Vis–NIR spectroscopy, partial least-squares regression (PLSR), and support vector machine (SVM) models to investigate the effects of mining on TN and OC stocks in both the topsoil (0–10 cm) and subsoil (10–40 cm). 105 soil samples were collected from agricultural areas near an iron mine, polluted, moderately-polluted, and non-polluted sites. Results indicated that soils at the non-polluted site had the highest of soil OC stocks (7.5 kg m–2) and total nitrogen (2.5 kg m–2), followed by the moderately-polluted site. Furthermore, it was observed that soils from the polluted site displayed the highest spectral reflectance. The spectral bands in the range of 500–700 nm showed the strongest correlation with soil organic carbon content. Notably, the SVM method utilizing Vis–NIR spectroscopy provided superior predictions for both subsoil and topsoil organic carbon and total nitrogen compared to the PLSR methods. Additionally, SVM demonstrated better performance in predicting topsoil soil organic carbon (R2 = 0.87, RMSE = 0.13%, and RPD = 2.8) and total nitrogen (R2 = 0.91, RMSE = 0.13%, and RPD = 2.4) compared to the subsoil, owing to the larger OM content in the topsoils.

Connected automated vehicles (CAVs) rely heavily on intelligent algorithms and remote sensors. If the control center or on-board sensors are under cyber-attack due to the security vulnerability of wireless communication, it can cause significant damage to CAVs or passengers. The primary objective of this study is to model cyber-attacked traffic flow and evaluate the impacts of cyber-attack on the traffic system filled with CAVs in a connected environment. Based on the analysis on environmental perception system and possible cyber-attacks on sensors, a novel lane-changing model for CAVs is proposed and multiple traffic scenarios for cyber-attacks are designed. The impact of the proportion of cyber-attacked vehicles and the severity of the cyber-attack on the lane-changing process is then quantitatively analyzed. The evaluation indexes include spatio-temporal evolution of average speed, spatial distribution of selected lane-changing gaps, lane-changing rate distribution, lane-changing preparation search time, efficiency and safety. Finally, the numerical simulation results show that the freeway traffic near an off-ramp is more sensitive to the proportion of cyber-attacked vehicles than to the severity of the cyber-attack. Also, when the traffic system is under cyber-attack, more unsafe back gaps are chosen for lane-changing, especially in the center lane. Therefore, more lane-changing maneuvers are concentrated on approaching the off-ramp, causing severe congestions and potential rear-end collisions. In addition, as the number of cyber-attacked vehicles and the severity of cyber-attacks increase, the road capacity and safety level will rapidly decrease. The results of this study can provide a theoretical basis for accident avoidance and efficiency improvement for the design of CAVs and management of automated highway systems.

Abstract Introduction Artificial cervical disc replacement (ACDR) is a widely accepted surgical procedure in the treatment of cervical radiculopathy and myelopathy. However, some research suggests that ACDR may redistribute more load onto the facet joints, potentially leading to postoperative axial pain in certain patients. Earlier studies have indicated that facet tropism is prevalent in the lower cervical spine and can significantly increase facet joint pressure. The present study aims to investigate the changes in the biomechanical environment of the cervical spine after ACDR using different prosthese when facet tropism is present. Methods A C2-C7 cervical spine finite element model was created. Symmetrical, moderate asymmetrical (7 degrees tropism), and severe asymmetrical (14 degrees tropism) models were created at the C5/C6 level by adjusting the left-side facet. C5/C6 ACDR with Prestige LP, Prodisc-C vivo, and Mobi-C were simulated in all models. A 75 N follower load and 1 N⋅m moment was applied to initiate flexion, extension, lateral bending, and axial rotation, and the range of motions (ROMs), facet contact forces(FCFs), and facet capsule stress were recorded. Results In the presence of facet tropism, all ACDR models exhibited significantly higher FCFs and facet capsule stress compared to the intact model. In the asymmetric model, FCFs on the right side were significantly increased in neutral position, extension, left bending and right rotation, and on both sides in right bending and left rotation compared to the symmetric model. All ACDR model in the presence of facet tropism, exhibited significantly higher facet capsule stresses at all positions compared to the symmetric model. The stress distribution on the facet surface and the capsule ligament in the asymmetrical models was different from that in the symmetrical model. Conclusions The existence of facet tropism could considerably increase FCFs and facet capsule stress after ACDR with Prestige-LP, Prodisc-C Vivo, and Mobi-C. None of the three different designs of implants were able to effectively protect the facet joints in the presence of facet tropism. Research into designing new implants may be needed to improve this situation. Clinical trials are needed to validate the impact of facet tropism.

Abstract Dental diseases such as caries and periodontitis have been common public health problems. Dental disease treatment can be achieved through stem cell-based dental regeneration. Biophysical cues determine the fate of stem cells and govern the success of dental regeneration. Some studies have manifested exosomes derived from stem cells could not only inherit biophysical signals in microenvironment but also evade some issues in the treatment with stem cells. Nowadays, biophysical cue-regulated exosomes become another promising therapy in dental regenerative medicine. However, methods to improve the efficacy of exosome therapy and the underlying mechanisms are still unresolved. In this review, the association between biophysical cues and dental diseases was summarized. We retrospected the role of exosomes regulated by biophysical cues in curing dental diseases and promoting dental regeneration. Our research also delved into the mechanisms by which biophysical cues control the biogenesis, release, and uptake of exosomes, as well as potential methods to enhance the effectiveness of exosomes. The aim of this review was to underscore the important place biophysical cue-regulated exosomes occupy in the realm of dentistry, and to explore novel targets for dental diseases.

Abstract Tryptophol (IET) is a metabolite derived from L-tryptophan that can be isolated from plants, bacteria, and fungi and has a wide range of biological activities in living systems. Despite the fact that IET biosynthesis pathways exist naturally in living organisms, industrial-scale production of IET and its derivatives is solely based on environmentally unfriendly chemical conversion. With diminishing petroleum reserves and a significant increase in global demand in all major commercial segments, it becomes essential to develop new technologies to produce chemicals from renewable resources and under mild conditions, such as microbial fermentation. Here we characterized and engineered the less-studied L-tryptophan pathway and IET biosynthesis in the baker’s yeast Saccharomyces cerevisiae, with the goal of investigating microbial fermentation as an alternative/green strategy to produce IET. In detail, we divided the aromatic amino acids (AAAs) metabolism related to IET synthesis into the shikimate pathway, the L-tryptophan pathway, the competing L-tyrosine/L-phenylalanine pathways, and the Ehrlich pathway based on a modular engineering concept. Through stepwise engineering of these modules, we obtained a yeast mutant capable of producing IET up to 1.04 g/L through fed-batch fermentation, a ~ 650-fold improvement over the wild-type strain. Besides, our engineering process also revealed many insights about the regulation of AAAs metabolism in S. cerevisiae. Finally, during our engineering process, we also discovered yeast mutants that accumulate anthranilate and L-tryptophan, both of which are precursors of various valuable secondary metabolites from fungi and plants. These strains could be developed to the chassis for natural product biosynthesis upon introducing heterologous pathways.