Sodium leak channels in the central amygdala modulate the analgesic potency of volatile anaesthetics in mice.

BACKGROUND: Analgesia is an important effect of volatile anaesthetics, for which the spinal cord is a critical neural target. However, how supraspinal mechanisms modulate analgesic potency of volatile anaesthetics is not clear. We investigated the contribution of the central amygdala (CeA) to the analgesic effects of isoflurane and sevoflurane. METHODS: Analgesic potencies of volatile anaesthetics were tested during optogenetic and chemogenetic inhibition of CeA neurones. In vivo calcium imaging was used to measure neuronal activities of CeA neuronal subtypes under volatile anaesthesia. Contributions of the sodium leak channel (NALCN) in GABAergic CeA (CeAGABA) neurones to analgesic effects of volatile anaesthetics were explored by specific NALCN knockdown. Electrophysiological recordings on acute brain slices were applied to measure volatile anaesthetic modulation of CeA neuronal activity by NALCN. RESULTS: Optogenetic or chemogenetic silencing CeA neurones reduced the analgesic effects of isoflurane or sevoflurane in vivo. The calcium signals of CeAGABA neurones increased during exposure to isoflurane or sevoflurane at analgesic concentrations. Knockdown of NALCN in CeAGABA neurones attenuated antinociceptive effects of isoflurane, sevoflurane, or both. For example, mean concentrations of isoflurane, sevoflurane, or both that induced immobility to tail-flick stimuli were significantly increased (isoflurane: 1.17 [0.05] vol% vs 1.24 [0.04] vol%, P=0.01; sevoflurane: 2.65 [0.07] vol% vs 2.81 [0.07] vol%; P<0.001). In brain slices, isoflurane, sevoflurane, or both at clinical concentrations increased NALCN-mediated holding currents and conductance in CeAGABA neurones, which increased excitability of CeAGABA neurones in an NALCN-dependent manner. CONCLUSIONS: The analgesic potencies of volatile anaesthetics are partially mediated by modulation of NALCN in CeAGABA neurones.

Engineering Nannochloropsis oceanica for concurrent production of canthaxanthin and eicosapentaenoic acid.

The marine alga Nannochloropsis oceanica can synthesize the high-value ketocarotenoid canthaxanthin yet at an extremely low level. Introducing a ß-carotenoid ketolase from Chlamydomonas reinhardtii into the chloroplast for expression, enabled N. oceanica to synthesize substantial amounts of canthaxanthin and grow better under high light. Compared to wild type, the engineered strain had higher levels of primary carotenoids and chlorophyll a as well, and synthesized more eicosapentaenoic acid (EPA, an ω3 polyunsaturated fatty acids). Further metabolic engineering by enhancing the flux to carotenoids or suppressing competing pathways allowed for a considerable increase of canthaxanthin, reaching 4.7 mg g-1 dry weight. A fed-batch culture strategy with nitrate and phosphate replenishment was developed for the co-production of canthaxanthin and EPA, which within a 10-day period reached 37.6 and 268.8 mg/L, respectively. This study sheds light on manipulating the industrially relevant alga for efficient co-production of high-value biochemicals from CO2.

Automatic Segmentation of Ultrasound-Guided Quadratus Lumborum Blocks Based on Artificial Intelligence.

Ultrasound-guided quadratus lumborum block (QLB) technology has become a widely used perioperative analgesia method during abdominal and pelvic surgeries. Due to the anatomical complexity and individual variability of the quadratus lumborum muscle (QLM) on ultrasound images, nerve blocks heavily rely on anesthesiologist experience. Therefore, using artificial intelligence (AI) to identify different tissue regions in ultrasound images is crucial. In our study, we retrospectively collected 112 patients (3162 images) and developed a deep learning model named Q-VUM, which is a U-shaped network based on the Visual Geometry Group 16 (VGG16) network. Q-VUM precisely segments various tissues, including the QLM, the external oblique muscle, the internal oblique muscle, the transversus abdominis muscle (collectively referred to as the EIT), and the bones. Furthermore, we evaluated Q-VUM. Our model demonstrated robust performance, achieving mean intersection over union (mIoU), mean pixel accuracy, dice coefficient, and accuracy values of 0.734, 0.829, 0.841, and 0.944, respectively. The IoU, recall, precision, and dice coefficient achieved for the QLM were 0.711, 0.813, 0.850, and 0.831, respectively. Additionally, the Q-VUM predictions showed that 85% of the pixels in the blocked area fell within the actual blocked area. Finally, our model exhibited stronger segmentation performance than did the common deep learning segmentation networks (0.734 vs. 0.720 and 0.720, respectively). In summary, we proposed a model named Q-VUM that can accurately identify the anatomical structure of the quadratus lumborum in real time. This model aids anesthesiologists in precisely locating the nerve block site, thereby reducing potential complications and enhancing the effectiveness of nerve block procedures.

Evaluation and Validation on Sensitivity of Near-Infrared Diffuse Reflectance in Non-Invasive Human Blood Glucose Measurement.

In non-invasive blood glucose measurement, the sensitivity of glucose-induced optical signals within human tissue is a crucial reference point. This study evaluates the sensitivity of glucose-induced diffuse reflectance in the 1000-1700 nm range. A key factor in understanding this sensitivity is the rate at which the scattering coefficient changes due to glucose, as it is significantly higher than in non-living media and predominantly influences the diffuse light signal level when blood glucose levels change. The study measured and calculated the changes in the scattering coefficient at 1314 nm, a wavelength chosen for its minimal interference from glucose absorption and other bodily constituents. Based on the Mie scattering theory and the results at 1314 nm, the changes in the scattering coefficient within the 1000-1700 nm range were estimated. Subsequently, the sensitivity of the glucose signal across this range was determined through Monte Carlo (MC) simulations. The findings from 25 human trials indicate that the measured sensitivities at five other typical wavelengths within this band generally align with the sensitivities calculated using the aforementioned method. This research can guide the identification of blood glucose signals and the selection of wavelengths for non-invasive blood glucose measurements.

Apoptotic vesicles rescue impaired mesenchymal stem cells and their therapeutic capacity for osteoporosis by restoring miR-145a-5p deficiency.

Apoptotic vesicles (apoVs) play a vital role in various physiological and pathological conditions. However, we have yet to fully understand their precise biological effects in rescuing impaired mesenchymal stem cells (MSCs). Here, we proved that systemic infusion of MSCs derived from wild-type (WT) mice rather than from ovariectomized (OVX) mice effectively improved the osteopenia phenotype and rescued the impaired recipient MSCs in osteoporotic mice. Meanwhile, apoVs derived from WT MSCs (WT apoVs) instead of OVX apoVs efficiently restored the impaired biological function of OVX MSCs and their ability to improve osteoporosis. Mechanistically, the reduced miR-145a-5p expression hindered the osteogenic differentiation and immunomodulatory capacity of OVX MSCs by affecting the TGF-ß/Smad 2/3-Wnt/ß-catenin signaling axis, resulting in the development of osteoporosis. WT apoVs directly transferred miR-145a-5p to OVX MSCs, which were then reused to restore their impaired biological functions. The differential expression of miR-145a-5p is responsible for the distinct efficacy between the two types of apoVs. Overall, our findings unveil the remarkable potential of apoVs, as a novel nongenetic engineering approach, in rescuing the biological function and therapeutic capability of MSCs derived from patients. This discovery offers a new avenue for exploring apoVs-based stem cell engineering and expands the application scope of stem cell therapy, contributing to the maintenance of bone homeostasis through a previously unrecognized mechanism.

Enhancing Spatial Domain Identification in Spatially Resolved Transcriptomics Using Graph Convolutional Networks with Adaptively Feature-Spatial Balance and Contrastive Learning.

Recent advancements in spatially transcriptomics (ST) technologies have enabled the comprehensive measurement of gene expression profiles while preserving the spatial information of cells. Combining gene expression profiles and spatial information has been the most commonly used method to identify spatial functional domains and genes. However, most existing spatial domain decipherer methods are more focused on spatially neighboring structures and fail to take into account balancing the self-characteristics and the spatial structure dependency of spots. Therefore, we propose a novel model called SpaGCAC, which recognizes spatial domains with the help of an adaptive feature-spatial balanced graph convolutional network named AFSBGCN. The AFSBGCN can dynamically learn the relationship between spatial local topology structures and the self-characteristics of spots by adaptively increasing or declining the weight on the self-characteristics during message aggregation. Moreover, to better capture the local structures of spots, SpaGCAC exploits a local topology structure contrastive learning strategy. Meanwhile, SpaGCAC utilizes a probability distribution contrastive learning strategy to increase the similarity of probability distributions for points belonging to the same category. We validate the performance of SpaGCAC for spatial domain identification on four spatial transcriptomic datasets. In comparison with seven spatial domain recognition methods, SpaGCAC achieved the highest NMI median of 0.683 and the second highest ARI median of 0.559 on the multi-slice DLPFC dataset. SpaGCAC achieved the best results on all three other single-slice datasets. The above-mentioned results show that SpaGCAC outperforms most existing methods, providing enhanced insights into tissue heterogeneity.

Association of ACEI/ARB therapy with total and cardiovascular death in coronary artery disease patients with advanced chronic kidney disease: a large multi-center longitudinal study.

INTRODUCTION: Advanced chronic kidney disease (CKD) is common among patients with coronary artery disease (CAD), and angiotensin­converting enzyme inhibitors (ACEI) or angiotensin­receptor blockers (ARB) can improve cardiac and renal function, but whether ACEI/ARB therapy improves long-term prognosis remains unclear among these high-risk patients. Therefore, this research aimed to investigate the relationship between ACEI/ARB therapy and long-term prognosis among CAD patients with advanced CKD. METHODS: CAD patients with advanced CKD were included in five hospitals. Advanced CKD was defined as estimated glomerular filtration rate (eGFR)<30 ml/min per 1.73 m2. Cox regression models and competing risk Fine and Gray models were used to examine the relationship between ACEI/ARB therapy and all-cause and cardiovascular death, respectively. RESULTS: Of 2527 patients, 47.6% population of our cohort was discharged on ACEI/ARB. The overall all-cause and cardiovascular mortality were 38.6% and 24.7%, respectively. Multivariate Cox regression analyses indicated that ACEI/ARB therapy was found to be associated with lower rates of both all-cause mortality (hazard ratio (HR)=0.836, 95% confidence interval (CI): 0.738-0.948, p = 0.005) and cardiovascular mortality (HR = 0.817, 95%CI: 0.699-0.956, p = 0.011). In the propensity-matched cohort, the survival benefit was consistent, and significantly better survival was observed for all-cause mortality (HR = 0.856, 95%CI: 0.752-0.974, p = 0.019) and cardiovascular mortality (HR = 0.830, 95%CI: 0.707-0.974, p = 0.023) among patients treated with ACEI/ARB. CONCLUSION: ACEI/ARB therapy showed a better survival benefit among high-risk CAD patients with advanced CKD at long-term follow-up, which manifested that strategies to maintain ACEI/ARB treatment may improve clinical outcomes among these high-risk populations.

What is the current knowledge on the topic? Advanced CKD is highly prevalent and strongly associated with higher mortality risk and worse outcomes among CAD patients, and patients with advanced CKD have often been excluded from randomized controlled trials, creating an evidence gap for these high-risk CAD patients. ACEI/ARB are beneficial for greater survival among CAD patients, but the effect of ACEI/ARB therapy on long-term prognosis is unclear among CAD patients with advanced CKD.What does this study add to our knowledge? ACEI/ARB treatment showed a better survival benefit among high-risk CAD patients with advanced CKD at long-term follow-up.How might this change clinical pharmacology or translational science? CAD patients with advanced CKD are not only have worse outcomes but also limited in their choice of therapy strategies. Our study may prompt an important reference for the subsequent improvement of long-term prognosis among these high-risk populations.

Natural Linoleic Acid from Marine Fungus Eutypella sp. F0219 Blocks KEAP1/NRF2 Interaction and Ameliorates MASLD by Targeting FABP4.

Ectopic lipid accumulation induced lipotoxicity plays a crucial role in exacerbating the development of metabolic dysfunction-associated steatotic liver disease (MASLD), which affects over 30% of the worldwide population and 85% of the obese population. The growing demand for effective therapeutic agents highlights the need for high-efficacy lipotoxicity ameliorators and relevant therapeutic targets in the fight against MASLD. This study aimed to discover natural anti-lipotoxic and anti-MASLD candidates and elucidate the underlying mechanism and therapeutic targets. Utilizing palmitic acid (PA)-induced HepG-2 and primary mouse hepatocyte models, we identified linoleic acid (HN-002), a ligand of fatty acid binding protein 4 (FABP4), from the marine fungus Eutypella sp. F0219. HN-002 dose-dependently prevented lipid overload-induced hepatocyte damage and lipid accumulation, inhibited fatty acid esterification, and ameliorated oxidative stress. These beneficial effects were associated with improvements in mitochondrial adaptive oxidation. HN-002 treatment enhanced lipid transport into mitochondria and oxidation, inhibited mitochondrial depolarization, and reduced mitochondrial ROS (mtROS) level in PA-treated hepatocytes. Mechanistically, HN-002 treatment disrupted the interaction between KEAP1 and NRF2, leading to NRF2 deubiquitylation and nuclear translocation, which activated beneficial metabolic regulation. In vivo, HN-002 treatment (20 mg/kg/per 2 days, i. p.) for 25 days effectively reversed hepatic steatosis and liver injury in the fast/refeeding plus high-fat/high-cholesterol diet induced MASLD mice. These therapeutic effects were associated with enhanced mitochondrial adaptive oxidation and activation of NRF2 signaling in the liver. These data suggest that HN-002 would be an interesting candidate for MASLD by improving mitochondrial oxidation via the FABP4/KEAP1/NRF2 axis. The discovery offers new insights into developing novel anti- MASLD agents derived from marine sources.

PROTAC based STING degrader attenuates acute colitis by inhibiting macrophage M1 polarization and intestinal epithelial cells pyroptosis mediated by STING-NLRP3 axis.

Inflammatory bowel diseases (IBDs) are chronic, relapsing, and inflammatory disorders of the gastrointestinal tract characterized by abnormal immune responses. Recently, STING has emerged as a promising therapeutic target for various autoinflammatory diseases. However, few STING-selective small molecules have been investigated as novel strategies for IBD. In this study, we sought to examine the effects of PROTAC-based STING degrader SP23 on acute colitis and explore its underlying mechanism. SP23 treatment notably alleviates dextran sulfate sodium (DSS)-induced colitis. Pharmacological degradation of STING significantly reduced the production of inflammatory cytokines, such as TNF-α, IL-1ß, and IL-6, and inhibited macrophage polarization towards the M1 type. Furthermore, SP23 administration decreased the loss of tight junction proteins, including ZO-1, occludin, and claudin-1, and downregulated STING and NLRP3 signaling pathways in intestinal inflammation. In vitro, STING activated NLRP3 inflammasome-mediated pyroptosis in intestinal epithelial cells, which could be abrogated by SP23 and STING siRNA intervention. In conclusion, these findings provide new evidence for STING as a novel therapeutic target for IBD, and reveal that hyperactivation of STING could exaggerate colitis by inducing NLRP3/Caspase-1/GSDMD axis mediated intestinal epithelial cells pyroptosis.

pscAdapt: pre-trained domain adaptation network based on structural similarity for cell type annotation in single cell RNA-seq data.

Cell type annotation refers to the process of categorizing and labeling cells to identify their specific cell types, which is crucial for understanding cell functions and biological processes. Although many methods have been developed for automated cell type annotation, they often encounter challenges such as batch effects due to variations in data distribution across platforms and species, thereby compromising their performance. To address batch effects, in this study, a pre-trained domain adaptation model based on structural similarity, named pscAdapt, is proposed for cell type annotation. Specifically, a pre-trained strategy is employed to initialize model parameters to learn the data distribution of source domain. This strategy is also combined with an adversarial learning strategy to train the domain adaptation network for achieving domain level alignment and reducing domain discrepancy. Furthermore, to better distinguish different types of cells, a structural similarity loss is designed, aiming to shorten distances between cells of the same type and increase distances between cells of different types in feature space, thus achieving cell level alignment and enhancing the discriminability of cell types. Comprehensive experiments were conducted on simulated datasets, cross-platforms datasets and cross-species datasets to validate the effectiveness of pscAdapt, results of which demonstrate that pscAdapt outperforms several popular cell type annotation methods. The source code of pscAdapt is available online at https://github.com/CDMBlab/pscAdapt.

[A comprehensive undergraduate experiment: preparation and chromatographic evaluation of a core-shell stationary phase based on a covalent organic framework].

Continuously promoting new curriculum standards is a key aim of the Ministry of Education of China. With this in mind, this paper introduces a comprehensive teaching experiment for undergraduate instrumental analysis courses that aims to improve students' material-preparation and instrumental-analysis skills through practice. Herein, a covalent organic framework-based core-shell stationary phase material (SiO2@COFTTA-DHTA) is prepared via a one-pot method and characterized in detail, after which its chromatographic properties are evaluated by high performance liquid chromatography (HPLC). The experimental process includes material synthesis and characterization, as well as studying the chromatographic-retention behavior and chromatographic-separation performance of the material. By the combining theoretical science and experimental teaching, this experiment not only deepens students' understanding of the properties of functional materials and their applications, but also improves their experimental-design and critical-thinking skills. This experiment not only cultivates students' interests in scientific research, but also exercises their experimental, operational, innovative-thinking, and practical abilities, while concurrently enhancing their sense of social responsibility and historical mission, thereby delivering the all-round educational goals of experimental teaching.

Chromosome-level genome assemblies of two littorinid marine snails indicate genetic basis of intertidal adaptation and ancient karyotype evolved from bilaterian ancestors.

Living in the intertidal environment, littorinid snails are excellent models for understanding genetic mechanisms underlying adaptation to harsh fluctuating environments. Furthermore, the karyotypes of littorinid snails, with the same chromosome number as the presumed bilaterian ancestor, make them valuable for investigating karyotype evolution from the bilaterian ancestor to mollusks. Here, we generated high-quality, chromosome-scale genome assemblies for 2 littorinid marine snails, Littorina brevicula (927.94 Mb) and Littoraria sinensis (882.51 Mb), with contig N50 of 3.43 Mb and 2.31 Mb, respectively. Comparative genomic analyses identified 92 expanded gene families and 85 positively selected genes as potential candidates possibly associated with intertidal adaptation in the littorinid lineage, which were functionally enriched in stimulus responses, innate immunity, and apoptosis process regulation and might be involved in cellular homeostasis maintenance in stressful intertidal environments. Genome macrosynteny analyses indicated that 4 fissions and 4 fusions led to the evolution from the 17 presumed bilaterian ancestral chromosomes to the 17 littorinid chromosomes, implying that the littorinid snails have a highly conserved karyotype with the bilaterian ancestor. Based on the most parsimonious reconstruction of the common ancestral karyotype of scallops and littorinid snails, 3 chromosomal fissions and 1 chromosomal fusion from the bilaterian ancient linkage groups were shared by the bivalve scallop and gastropoda littorinid snails, indicating that the chromosome-scale ancient gene linkages were generally preserved in the mollusk genomes for over 500 million years. The highly conserved karyotype makes the littorinid snail genomes valuable resources for understanding early bilaterian evolution and biology.

[Hydrochemical Characteristics and Variation in Karst Groundwater in the Baiquan Spring Area of Xingtai Over the Last 30 Years].

To elucidate the variation patterns in the hydrochemical characteristics of karst groundwater in the Baiquan Spring area of Xingtai over the past 30 years, an integrated approach utilizing mathematical statistics, Piper trilinear diagrams, Gibbs diagrams, and ion ratio analyses was employed. Comparative analysis was conducted on 62 sets of karst water samples collected during the dry seasons of 1991 and 2020. The findings indicated that the groundwater in the spring area was generally weakly alkaline with a low salinization degree, predominantly characterized by Ca2+ and HCO3- as the dominant ions. Compared to that in 1991, the alkalinity of groundwater in 2020 had intensified, with a general increase in the concentration of various indicators. The hydrochemical types had shifted from the relatively concentrated HCO3-Ca and HCO3-Ca·Mg types to a broader spectrum of types, gradually exhibiting a salinization trend. The distribution characteristics of exceeding components such as TDS, Na++K+, SO42-, and F- showed significant spatial differences. Rock weathering played a pivotal role in the changes observed in the hydrochemical components of groundwater, with enhanced cation exchange and evaporation processes further influencing the hydrochemical characteristics and their spatial distribution.

[Stabilization of Cd-contaminated Soil with Thiol-modified Biochar and Response of Soil Microorganisms].

To explore the stabilization effect of livestock manure biochar on Cd-contaminated soil and its impact on the soil environment, a pot experiment was conducted to investigate the stabilization efficiency of cattle manure-biochar （BC） and thiol-modified biochar （SBC） on Cd in soil and their effect on the soil properties and microbial community. The structural equation model （SEM） was used to analyze the effect pathways of BC and SBC on the soil microbial community. The results showed that BC and SBC increased soil pH, available potassium, available phosphorus, and organic matter content but decreased soil available nitrogen content compared with those in CK. The stabilization efficiency of BC for Cd in soil was 14.97%, which was much lower than that of SBC （85.71%）. Moreover, SBC increased the abundance of dominant bacterial phyla in soil, with Proteobacteria, Bacteroidota, and Cyanobacteria increasing most significantly. SBC decreased the diversity of soil microorganisms, but the decrease was insignificant （P≥0.05） compared with that in CK and BC. SEM analysis indicated that the available phosphorus, available potassium, organic matter, and soil pH were the key factors influencing Cd availability in soil, whereas organic matter and Cd availability were the key factors affecting the soil microbial community. Overall, SBC could stabilize Cd effectively and increase the abundance of dominant bacteria and has great potential in the remediation of Cd-contaminated soil.

Delirium in the ICU: how much do we know? A narrative review.

Delirium in critical ill patients is a complex and common neurological syndrome in the intensive care unit (ICU) that is caused by a range of structural or functional abnormalities. ICU Delirium is associated with reduced compliance, prolonged hospital stays, greater use or delayed withdrawal of sedatives, higher rates and durations of mechanical ventilation, and higher rates of mortality. The aetiology and pathogenesis of ICU delirium are unclear, and the lack of better prediction, prevention, and treatment measures leads to a non-standardized control of delirium. By searching the relevant literature, we aim in this narrative review to describe progress in the pathogenesis, predictive biomarkers, diagnosis, and treatment of ICU delirium.

The regulatory effect and mechanism of traditional Chinese medicine on the renal inflammatory signal transduction pathways in diabetic kidney disease: A review.

Inflammatory injury is a critical factor in the occurrence and development of diabetic kidney disease (DKD). Signal transduction pathways such as the nuclear factor kappa beta (NF-κB), mitogen-activated protein kinase (MAPK), NOD-like receptor protein 3, and Smads are important mechanisms of inflammatory kidney injury in DKD, and the NF-κB pathway plays a key role. The inflammatory factor network formed after activation of the NF-κB pathway connects different signaling pathways and exacerbates renal inflammatory damage. Many traditional Chinese medicine compounds, single agents, effective components and active ingredients can regulate the expression of key molecules in the signaling pathways associated with inflammatory injury, such as transforming growth factor-ß activated kinase 1, NF-κB, p38MAPK, NOD-like receptor protein 3, and Smad7. These treatments have the characteristics of multiple targets and have multiple and overlapping effects, which can treat DKD kidney inflammation and injury through multiple mechanisms and apply the "holistic concept" of traditional Chinese medicine.

The association between the number of food kinds and risk of depression in U.S. adults.

BACKGROUND: The association between the number of food kinds and the risk of depression in adults was examined. METHODS: According to the inclusion and exclusion criteria, a total of 4593 adults were included in the study. The number of food kinds was collected via 24‒hour dietary recalls. Depression was assessed using the Patient Health Questionnaire‒9. Logistic regression and restricted cubic spline models were applied to assess the association between the number of food kinds and the risk of depression. RESULTS: This study included 4593 study participants, 451 of whom were diagnosed with depression. The revised advantage ratios (with corresponding confidence intervals) for the prevalence of depression among individuals in the fourth quartiles of the number of food kinds (Q4) in comparison to the lowest quartile (Q1) were determined to be 0.59 (0.36‒0.96), respectively. According to our subgroup analyses, the number of food kinds was negatively associated with the risk of depression in females, participants aged 18‒45 and 45‒65 years, and participants with a body mass index (BMI) of 25 to 24.9 kg/m2. According to our dose‒response analysis, the number of food kinds was linearly associated with the risk of depression (Pfor nonlinear=0.5896). CONCLUSION: The risk of depression exhibited a linear and negative correlation with the number of food kinds. The results indicated that a diversified diet was an effective nonpharmacological approach that deserved further generalization.

AmTPS6 promotes trehalose biosynthesis to enhance the Cd tolerance in mangrove Avicennia marina.

Cadmium (Cd) pollution poses a significant ecological risk to mangrove ecosystems. Trehalose has excellent potential to mitigate the adverse effects of heavy metals. Unfortunately, the mechanisms related to trehalose-mediated heavy metal tolerance in plants remain elusive. In the present study, we firstly found that Cd induced the accumulation of trehalose and the differential expression of trehalose biosynthesis genes in the roots of mangrove plant Avicennia marina. Then, we found that the application of exogenous trehalose could alleviate the negative effects of Cd on A. marina by phenotypic observation. In addition, photosynthetic parameters and cellular ultrastructure analyses demonstrated that exogenous trehalose could improve the photosynthesis and stabilize the chloroplast and nuclear structure of the leaves of A. marina. Besides, exogenous trehalose could inhibit the Cd2+ influx from the root to reduce the Cd2+ content in A. marina. Subsequently, substrate sensitivity assay combined with ion uptake analysis using yeast cells showed that several trehalose biosynthesis genes may have a regulatory function for Cd2+ transport. Finally, we further identified a positive regulatory factor, AmTPS6, which enhances the Cd tolerance in transgenic Arabidopsis thaliana. Taken together, these findings provide new understanding to the mechanism of Cd tolerance in mangrove A. marina at trehalose aspect and a theoretical basis for the conservation of mangroves in coastal wetlands.