Dominant activities of fear engram cells in the dorsal dentate gyrus underlie fear generalization in mice.

Over-generalized fear is a maladaptive response to harmless stimuli or situations characteristic of posttraumatic stress disorder (PTSD) and other anxiety disorders. The dorsal dentate gyrus (dDG) contains engram cells that play a crucial role in accurate memory retrieval. However, the coordination mechanism of neuronal subpopulations within the dDG network during fear generalization is not well understood. Here, with the Tet-off system combined with immunostaining and two-photon calcium imaging, we report that dDG fear engram cells labeled in the conditioned context constitutes a significantly higher proportion of dDG neurons activated in a similar context where mice show generalized fear. The activation of these dDG fear engram cells encoding the conditioned context is both sufficient and necessary for inducing fear generalization in the similar context. Activities of mossy cells in the ventral dentate gyrus (vMCs) are significantly suppressed in mice showing fear generalization in a similar context, and activating the vMCs-dDG pathway suppresses generalized but not conditioned fear. Finally, modifying fear memory engrams in the dDG with "safety" signals effectively rescues fear generalization. These findings reveal that the competitive advantage of dDG engram cells underlies fear generalization, which can be rescued by activating the vMCs-dDG pathway or modifying fear memory engrams, and provide novel insights into the dDG network as the neuronal basis of fear generalization.

Rescue of cardiac dysfunction during chemotherapy in acute myeloid leukaemia by blocking IL-1α.

BACKGROUND AND AIMS: Patients with acute myeloid leukaemia (AML) suffer from severe myocardial injury during daunorubicin (DNR)-based chemotherapy and are at high risk of cardiac mortality. The crosstalk between tumour cells and cardiomyocytes might play an important role in chemotherapy-related cardiotoxicity, but this has yet to be demonstrated. This study aimed to identify its underlying mechanism and explore potential therapeutic targets. METHODS: Cardiac tissues were harvested from an AML patient after DNR-based chemotherapy and were subjected to single-nucleus RNA sequencing. Cardiac metabolism and function were evaluated in AML mice after DNR treatment by using positron emission tomography, magnetic resonance imaging, and stable-isotope tracing metabolomics. Plasma cytokines were screened in AML mice after DNR treatment. Genetically modified mice and cell lines were used to validate the central role of the identified cytokine and explore its downstream effectors. RESULTS: In the AML patient, disruption of cardiac metabolic homeostasis was associated with heart dysfunction after DNR-based chemotherapy. In AML mice, cardiac fatty acid utilization was attenuated, resulting in cardiac dysfunction after DNR treatment, but these phenotypes were not observed in similarly treated tumour-free mice. Furthermore, tumour cell-derived interleukin (IL)-1α was identified as a primary factor leading to DNR-induced cardiac dysfunction and administration of an anti-IL-1α neutralizing antibody could improve cardiac functions in AML mice after DNR treatment. CONCLUSIONS: This study revealed that crosstalk between tumour cells and cardiomyocytes during chemotherapy could disturb cardiac energy metabolism and impair heart function. IL-1α neutralizing antibody treatment is a promising strategy for alleviating chemotherapy-induced cardiotoxicity in AML patients.

Ferroptosis: a promising candidate for exosome-mediated regulation in different diseases.

Ferroptosis is a newly discovered form of cell death that is featured in a wide range of diseases. Exosome therapy is a promising therapeutic option that has attracted much attention due to its low immunogenicity, low toxicity, and ability to penetrate biological barriers. In addition, emerging evidence indicates that exosomes possess the ability to modulate the progression of diverse diseases by regulating ferroptosis in damaged cells. Hence, the mechanism by which cell-derived and noncellular-derived exosomes target ferroptosis in different diseases through the system Xc-/GSH/GPX4 axis, NAD(P)H/FSP1/CoQ10 axis, iron metabolism pathway and lipid metabolism pathway associated with ferroptosis, as well as its applications in liver disease, neurological diseases, lung injury, heart injury, cancer and other diseases, are summarized here. Additionally, the role of exosome-regulated ferroptosis as an emerging repair mechanism for damaged tissues and cells is also discussed, and this is expected to be a promising treatment direction for various diseases in the future. Video Abstract.

Noninvasive Evaluation of Tumoral PD-L1 Using a Novel 99mTc-Labeled Nanobody Tracer with Rapid Renal Clearance.

The expression level of PD-L1 in tumor tissue is considered one of the effective biomarkers to guide PD-1/PD-L1 therapy. Quantifying whole-body PD-L1 expression by SPECT imaging may help in selecting patients that potentially respond to PD-1/PD-L1 therapy. Nanobody is the smallest antibody fragment with antigen-binding ability that is well suited for radionuclide imaging. Nevertheless, high retention of radioactivity in the kidney may limit its clinical translation. The present study aimed to screen, design, and prepare a nanobody-based SPECT probe with rapid renal clearance to evaluate the PD-L1 expression level in vivo noninvasively. A phage library was constructed by immunizing alpaca with recombinant human PD-L1 protein, and 17 anti-PD-L1 nanobodies were screened by the phage display technique. After sequence alignment and flow cytometry analysis, APN09 was selected as the candidate nanobody, and a GGGC chelator was attached to its C-terminus for 99mTc labeling to prepare a SPECT imaging probe. The affinity and specificity of 99mTc-APN09 were evaluated by protein and cell-binding experiments, and SPECT imaging and biodistribution were performed in a mouse model with bilateral transplantation of A549 and A549PD-L1 tumors. The ability of 99mTc-APN09 to quantify the PD-L1 expression level in vivo was validated in tumor models with different PD-L1 expression levels. 99mTc-APN09 had a radiochemical purity higher than 99% and a binding equilibrium dissociation constant of 21.44 ± 1.65 nM with hPD-L1, showing high affinity. SPECT imaging results showed that 99mTc-APN09 could efficiently detect PD-L1-positive tumors within 0.5 h, and the quantitative results of SPECT were well correlated with the expression level of PD-L1 in cell lines. SPECT imaging and biodistribution results also showed that 99mTc-APN09 was rapidly cleared from the kidney in 2 h postinjection. 99mTc-APN09 was a simple and stable tool for visualizing PD-L1 expression in the whole body. In addition, due to its significant reduction in renal retention, it has better prospects for clinical translation.

The CSF1-CSF1R pathway in the trigeminal ganglion mediates trigeminal neuralgia via inflammatory responses in mice.

BACKGROUND: Trigeminal neuralgia (TN) is the most severe type of neuropathic pain. The trigeminal ganglion (TG) is a crucial target for the pathogenesis and treatment of TN. The colony-stimulating factor 1 (CSF1) - colony-stimulating factor 1 receptor (CSF1R) pathway regulates lower limb pain development. However, the effect and mechanism of the CSF1-CSF1R pathway in TG on TN are unclear. METHODS: Partial transection of the infraorbital nerve (pT-ION) model was used to generate a mouse TN model. Mechanical and cold allodynia were used to measure pain behaviors. Pro-inflammatory factors (IL-6, TNF-a) were used to measure inflammatory responses in TG. PLX3397, an inhibitor of CSF1R, was applied to inhibit the CSF1-CSF1R pathway in TG. This pathway was activated in naïve mice by stereotactic injection of CSF1 into the TG. RESULTS: The TN model activated the CSF1-CSF1R pathway in the TG, leading to exacerbated mechanical and cold allodynia. TN activated inflammatory responses in the TG manifested as a significant increase in IL-6 and TNF-a levels. After using PLX3397 to inhibit CSF1R, CSF1R expression in the TG declined significantly. Inhibiting the CSF1-CSF1R pathway in the TG downregulated the expression of IL-6 and TNF-α to reduce allodynia-related behaviors. Finally, mechanical allodynia behaviors were exacerbated in naïve mice after activating the CSF1-CSF1R pathway in the TG. CONCLUSIONS: The CSF1-CSF1R pathway in the TG modulates TN by regulating neuroimmune responses. Our findings provide a theoretical basis for the development of treatments for TN in the TG.

Effect of chewing gum of different weights before surgery on sore throat after total thyroidectomy: A randomized controlled trial.

BACKGROUND: Postoperative sore throat (POST) is a common postoperative complication. COMPLICATION: Chewing gum can inhibit the growth of oral bacteria, cleanse, and lubricate the oral cavity, which can help reduce postoperative sore throat. We hypothesize that chewing gum before surgery could relieve POST. METHODS: Patients planned to undergo total thyroidectomy under general anesthesia with tracheal intubation were randomized to swallow saliva twice or chew 1.4 g/2.8 g of gum for 2 minutes before surgery. A standard anesthesia protocol was performed. The numerical rating scale scores of POST at 1, 24, and 48 h after surgery were collected. The primary outcome was the incidence of moderate/severe POST (numerical rating scale score >3) within 48 h. RESULTS: Data from 148 patients (control group, n = 50; 1.4 g group, n = 48; and 2.8 g group, n = 50) were included in the analysis. Within 48 h, there was a significant difference among the three groups in the incidence of moderate/severe POST (control group: 74% vs. 1.4 g group: 65% vs. 2.8 g group: 50%. P = 0.04). The 2.8 g group had less incidence of moderate/severe POST than the control group (Odds Ratio = 0.351 95% Confidence Interval: (0.152 and 0.814) P = 0.02). CONCLUSION: Chewing 2.8 g gum before total thyroidectomy can reduce the incidence of moderate/severe POST within 48 h after surgery.

FACTORS ASSOCIATED WITH OUTCOMES OF SUPRACHOROIDAL HEMORRHAGE: An Individual Participant Data Systematic Review.

PURPOSE: To determine factors associated with visual and anatomic outcomes of suprachoroidal hemorrhage in studies published between 1990 and 2022. METHODS: Individual participant data systematic review. The protocol was prospectively registered on Open Science Framework ( https://osf.io/69v3q/ ). PubMed, EMBASE, Web of Science, and Google Scholar were searched for peer-reviewed studies of suprachoroidal hemorrhage with ≥3 patients published between January 1, 1990, and September 1, 2022. The primary outcome was the change in logarithm of the minimum angle of resolution visual acuity from the time of suprachoroidal hemorrhage diagnosis to last follow-up. RESULTS: Four hundred thirteen eyes from 49 studies were included, with mean (SD) age 60.8 (22.4) years and mean (SD) follow-up of 13.8 (12.6) months. Among 145 eyes with at least 6 months of follow-up, the mean (SD) gain in visual acuity was -0.98 (0.89) logarithm of the minimum angle of resolution. In multivariable regression, treatment with systemic steroids was associated with greater improvement in logarithm of the minimum angle of resolution visual acuity (adjusted mean [SE] -1.29 [0.09] vs. -0.16 [0.30] for no systemic steroids; P < 0.001) and greater odds of achieving anatomic success (adjusted OR 10.59, 95% confidence interval 2.59-43.3; P = 0.001). CONCLUSION: The use of systemic steroids was associated with better visual and anatomic outcomes for suprachoroidal hemorrhage.

Air pollution and upper respiratory diseases: an examination among medically insured populations in Wuhan, China.

Multiple evidence has supported that air pollution exposure has detrimental effects on the cardiovascular and respiratory systems. However, most investigations focus on the general population, with limited research conducted on medically insured populations. To address this gap, the current research was designed to examine the acute effects of inhalable particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2), ground-level ozone (O3), and sulfur dioxide (SO2) on the incidence of upper respiratory tract infections (URTI), utilizing medical insurance data in Wuhan, China. Data on URTI were collected from the China Medical Insurance Basic Database for Wuhan covering the period from 2014 to 2018, while air pollutant data was gathered from ten national monitoring stations situated in Wuhan city. Statistical analysis was performed using generalized additive models for quasi-Poisson distribution with a log link function. The analysis indicated that except for ozone, higher exposure to four other pollutants (NO2, SO2, PM2.5, and PM10) were significantly linked to an elevated risk of URTI, particularly during the previous 0-3 days and previous 0-4 days. Additionally, NO2 and SO2 were found to be positively linked with laryngitis. Furthermore, the effects of air pollutants on the risk of URTI were more pronounced during cold seasons than hot seasons. Notably, females and the employed population were more susceptible to infection than males and non-employed individuals. Our findings gave solid proof of the link between ambient air pollution exposure and the risk of URTI in medically insured populations.

Research on the Soft-Sensing Method of Indicator Diagram of Beam Pumping Unit.

An accurate calculation of the indicator diagram of a pumping unit is the key factor in analyzing the performance of an oilfield production and operation and in preparing and optimizing an oilfield development plan. Aiming at the problems of the poor stability of the conventional load-displacement sensor method and the wave equation method, owing to the influence of an alternating load on the force sensor and the difficulty in measuring the crank angle using the electrical parameter method, a new soft sensing method employing the input electrical parameters of the motor and the beam inclination has been proposed to obtain the indicator diagram. At first, this method is established based on the beam angle of the pumping unit, which is easily measured using the suspension point displacement mathematics calculation model and the torque factor. Subsequently, the electric motor input parameters, the parameters of the four-bar linkage, and the relationship between the polished rod load have been established. Finally, the motor and the beam angle of the measured electrical parameters have been substituted into the calculation of the suspension point displacement and load value and pull in accordance with the guidelines to eliminate the singularity mutation values. After processing the measured data through a Butterworth filter, the indicator diagram is obtained. The results of the engineering experiment and application show that the average relative error of the method is less than 3.95%, and the maximum relative error remains within 2% for 6 months, which verifies the stability of the soft sensing method.

Whole Blood Transcriptome Analysis in Patients with Trigeminal Neuralgia: a Prospective Clinical Study.

Trigeminal neuralgia (TN) brings a huge burden to patients, without long-term effective treatment. This study aimed to explore the differentially expressed genes (DEGs) and related enrichment pathways in patients with TN. This was a study of transcriptome sequencing and bioinformatics analysis of human samples. Whole blood samples were collected from the TN patients and pain-free controls. RNA was extracted to conduct the RNA-sequencing and the subsequent bioinformatics analysis. DEGs between the two groups were derived. Kyoto encyclopedia of genes and genomes (KEGG) and Gene ontology (GO) was used to find the enrichment pathways of DEGs. Protein protein interaction (PPI) network was used to depict the interaction between DEGs and find the most important gene, hub gene. Compared with the control group, there were 117 up-regulated DEGs and 103 down-regulated DEGs in the whole blood of patients in the TN group. Pathway enrichment analysis showed that DEGs were mainly enriched in the neuroimmune and metabolic pathways. The PPI network demonstrated that colony stimulating factor 2 (CSF2) was the most important hub gene in the whole blood of TN patients. This study shows the expression of the transcriptome in the whole blood samples of TN patients. The neuroimmune responses and key hub gene CSF2 in the whole blood cells play a vital role in the occurrence of TN. Our research provides a theoretical basis for the diagnosis and treatments of TN. This study was registered at clinicaltrials.gov in June 2021 (No. NCT04923399).

Evaluating the Utilities of Foundation Models in Single-cell Data Analysis.

Foundation Models (FMs) have made significant strides in both industrial and scientific domains. In this paper, we evaluate the performance of FMs in single-cell sequencing data analysis through comprehensive experiments across eight downstream tasks pertinent to single-cell data. By comparing ten different single-cell FMs with task-specific methods, we found that single-cell FMs may not consistently excel in all tasks than task-specific methods. However, the emergent abilities and the successful applications of cross-species/cross-modality transfer learning of FMs are promising. In addition, we present a systematic evaluation of the effects of hyper-parameters, initial settings, and stability for training single-cell FMs based on a proposed scEval framework, and provide guidelines for pre-training and fine-tuning. Our work summarizes the current state of single-cell FMs and points to their constraints and avenues for future development.

Two-stage sparse multi-objective evolutionary algorithm for channel selection optimization in BCIs.

Background: Channel selection has become the pivotal issue affecting the widespread application of non-invasive brain-computer interface systems in the real world. However, constructing suitable multi-objective problem models alongside effective search strategies stands out as a critical factor that impacts the performance of multi-objective channel selection algorithms. This paper presents a two-stage sparse multi-objective evolutionary algorithm (TS-MOEA) to address channel selection problems in brain-computer interface systems. Methods: In TS-MOEA, a two-stage framework, which consists of the early and late stages, is adopted to prevent the algorithm from stagnating. Furthermore, The two stages concentrate on different multi-objective problem models, thereby balancing convergence and population diversity in TS-MOEA. Inspired by the sparsity of the correlation matrix of channels, a sparse initialization operator, which uses a domain-knowledge-based score assignment strategy for decision variables, is introduced to generate the initial population. Moreover, a Score-based mutation operator is utilized to enhance the search efficiency of TS-MOEA. Results: The performance of TS-MOEA and five other state-of-the-art multi-objective algorithms has been evaluated using a 62-channel EEG-based brain-computer interface system for fatigue detection tasks, and the results demonstrated the effectiveness of TS-MOEA. Conclusion: The proposed two-stage framework can help TS-MOEA escape stagnation and facilitate a balance between diversity and convergence. Integrating the sparsity of the correlation matrix of channels and the problem-domain knowledge can effectively reduce the computational complexity of TS-MOEA while enhancing its optimization efficiency.

Vascular Bundle for Exceptional Water Confinement, Transport, and Evaporation.

Nature, through billions of years of evolution, has constructed extremely efficient biosystems for transporting, confining, and vaporizing water. Mankind's ability to master water, however, is far from impeccable, and a sustainable supply of clean fresh water remains a global challenge. Here, we learn from Nature and prepare papyrus carbon (PC) from Egyptian papyrus paper as a sustainable solar desalination material. By taking advantage of the capillary pores from vascular bundles that are inherently built for transporting water in plants, PC achieves an evaporation rate of 4.1 kg m-2 h-1 in a passive single-stage device. Raman spectroscopy and thermal calorimetry show that the capillary pores pose a confinement effect to generate loosely hydrogen-bonded intermediate water, which substantially reduces the enthalpy of vaporization, allowing for exceptionally high energy efficiencies. The understanding is applicable to all nature-designed vascular plants and man-made separation and purification systems.

Progress on the antiferromagnetic topological insulator MnBi2Te4.

Topological materials, which feature robust surface and/or edge states, have now been a research focus in condensed matter physics. They represent a new class of materials exhibiting nontrivial topological phases, and provide a platform for exploring exotic transport phenomena, such as the quantum anomalous Hall effect and the quantum spin Hall effect. Recently, magnetic topological materials have attracted considerable interests due to the possibility to study the interplay between topological and magnetic orders. In particular, the quantum anomalous Hall and axion insulator phases can be realized in topological insulators with magnetic order. MnBi2Te4, as the first intrinsic antiferromagnetic topological insulator discovered, allows the examination of existing theoretical predictions; it has been extensively studied, and many new discoveries have been made. Here we review the progress made on MnBi2Te4 from both experimental and theoretical aspects. The bulk crystal and magnetic structures are surveyed first, followed by a review of theoretical calculations and experimental probes on the band structure and surface states, and a discussion of various exotic phases that can be realized in MnBi2Te4. The properties of MnBi2Te4 thin films and the corresponding transport studies are then reviewed, with an emphasis on the edge state transport. Possible future research directions in this field are also discussed.

Field cabbage detection and positioning system based on improved YOLOv8n.

BACKGROUND: Pesticide efficacy directly affects crop yield and quality, making targeted spraying a more environmentally friendly and effective method of pesticide application. Common targeted cabbage spraying methods often involve object detection networks. However, complex natural and lighting conditions pose challenges in the accurate detection and positioning of cabbage. RESULTS: In this study, a cabbage detection algorithm based on the YOLOv8n neural network (YOLOv8-cabbage) combined with a positioning system constructed using a Realsense depth camera is proposed. Initially, four of the currently available high-performance object detection models were compared, and YOLOv8n was selected as the transfer learning model for field cabbage detection. Data augmentation and expansion methods were applied to extensively train the model, a large kernel convolution method was proposed to improve the bottleneck section, the Swin transformer module was combined with the convolutional neural network (CNN) to expand the perceptual field of feature extraction and improve edge detection effectiveness, and a nonlocal attention mechanism was added to enhance feature extraction. Ablation experiments were conducted on the same dataset under the same experimental conditions, and the improved model increased the mean average precision (mAP) from 88.8% to 93.9%. Subsequently, depth maps and colour maps were aligned pixelwise to obtain the three-dimensional coordinates of the cabbages via coordinate system conversion. The positioning error of the three-dimensional coordinate cabbage identification and positioning system was (11.2 mm, 10.225 mm, 25.3 mm), which meets the usage requirements. CONCLUSIONS: We have achieved accurate cabbage positioning. The object detection system proposed here can detect cabbage in real time in complex field environments, providing technical support for targeted spraying applications and positioning.

Super-resolution reconstruction of ultrasound image using a modified diffusion model.

Objective. This study aims to perform super-resolution (SR) reconstruction of ultrasound images using a modified diffusion model, designated as the diffusion model for ultrasound image super-resolution (DMUISR). SR involves converting low-resolution images to high-resolution ones, and the proposed model is designed to enhance the suitability of diffusion models for this task in the context of ultrasound imaging.Approach. DMUISR incorporates a multi-layer self-attention (MLSA) mechanism and a wavelet-transform based low-resolution image (WTLR) encoder to enhance its suitability for ultrasound image SR tasks. The model takes interpolated and magnified images as input and outputs high-quality, detailed SR images. The study utilized 1,334 ultrasound images from the public fetal head-circumference dataset (HC18) for evaluation.Main results. Experiments were conducted at 2× , 4× , and 8×  magnification factors. DMUISR outperformed mainstream ultrasound SR methods (Bicubic, VDSR, DECUSR, DRCN, REDNet, SRGAN) across all scales, providing high-quality images with clear structures and rich detailed textures in both hard and soft tissue regions. DMUISR successfully accomplished multiscale SR reconstruction while suppressing over-smoothing and mode collapse problems. Quantitative results showed that DMUISR achieved the best performance in terms of learned perceptual image patch similarity, with a significant decrease of over 50% at all three magnification factors (2× , 4× , and 8× ), as well as improvements in peak signal-to-noise ratio and structural similarity index measure. Ablation experiments validated the effectiveness of the MLSA mechanism and WTLR encoder in improving DMUISR's SR performance. Furthermore, by reducing the number of diffusion steps, the computational time of DMUISR was shortened to nearly one-tenth of its original while maintaining image quality without significant degradation.Significance. This study demonstrates that the modified diffusion model, DMUISR, provides superior performance for SR reconstruction of ultrasound images and has potential in improving imaging quality in the medical ultrasound field.

Unveiling the muscle-brain axis: A bidirectional mendelian randomization study investigating the causal relationship between sarcopenia-related traits and brain aging.

BACKGROUND: Observational studies suggest an association between sarcopenia-related traits and brain aging, but whether this association reflects a causal relationship remains unclear. This study aims to employ Mendelian randomization (MR) methods to investigate the causal impact of sarcopenia-related traits on brain aging. METHODS: This study presents a comprehensive analysis of genome-wide association study (GWAS) summary data associated with sarcopenia-related traits. The data were derived from a large-scale cohort, encompassing measures such as grip strength, lean body mass, and walking pace. Measurements of brain aging were obtained from neuroimaging genetics, utilizing meta-analysis (ENIGMA) to combine magnetic resonance imaging (MRI) data from 33,992 participants. The primary methodology employed in this analysis was the inverse-variance-weighted method (IVW). Additionally, sensitivity analyses were conducted, to assess heterogeneity and pleiotropy. RESULT: Appendicular lean mass(ALM) is negatively correlated with Pallidum aging; Whole body fat-free mass shows a negative correlation with Amygdala aging; Leg fat-free mass (left) and Leg fat-free mass (right) are negatively correlated with Pallidum aging; Usual walking pace is positively correlated with Nucleus Accumbens aging. Cerebellum WM aging is negatively correlated with Leg fat-free mass (left) and Leg fat-free mass (right); Hippocampus aging is negatively correlated with Hand grip strength (left) and Hand grip strength (right). Ventricles aging is positively correlated with Usual walking pace; Nucleus Accumbens aging is positively correlated with Leg fat-free mass (left) and Leg fat-free mass (right); Putamen aging is positively correlated with ALM. CONCLUSION: Our study confirms that reduced muscle mass speeds up brain aging. Walking too fast raises the risk of brain aging, while maintaining or increasing appendicular lean mass, overall muscle mass, and muscle mass in both legs lowers the risk of brain aging.