Multi-omics analysis reveals spatiotemporal regulation and function of heteromorphic leaves in Populus.

Despite the high economic and ecological importance of forests, our knowledge of the adaptive evolution of leaf traits remains very limited. Euphrates poplar (Populus euphratica), which has high tolerance to arid environment, has evolved four heteromorphic leaf forms, including narrow (linear and lanceolate) and broad (ovate and broad-ovate) leaves on different crowns. Here, we revealed the significant functional divergence of four P. euphratica heteromorphic leaves at physiological and cytological levels. Through global analysis of transcriptome and DNA methylation across tree and leaf developmental stages, we revealed that gene expression and DNA epigenetics differentially regulated key processes involving development and functional adaptation of heteromorphic leaves, such as hormone signaling pathways, cell division, and photosynthesis. Combined analysis of gene expression, methylation, ATAC-seq, and Hi-C-seq revealed longer interaction of 3D genome, hypomethylation, and open chromatin state upregulates IAA-related genes (such as PIN-FORMED1 and ANGUSTIFOLIA3) and promotes the occurrence of broad leaves while narrow leaves were associated with highly concentrated heterochromatin, hypermethylation, and upregulated abscisic acid pathway genes (such as Pyrabactin Resistance1-like10). Therefore, development of P. euphratica heteromorphic leaves along with functional divergence was regulated by differentially expressed genes, DNA methylation, chromatin accessibility, and 3D genome remodeling to adapt to the arid desert. This study advances our understanding of differential regulation on development and functional divergence of heteromorphic leaves in P. euphratica at the multi-omics level and provides a valuable resource for investigating the adaptive evolution of heteromorphic leaves in Populus.

Metabolic adaptations in pressure overload hypertrophic heart.

This review article offers a detailed examination of metabolic adaptations in pressure overload hypertrophic hearts, a condition that plays a pivotal role in the progression of heart failure with preserved ejection fraction (HFpEF) to heart failure with reduced ejection fraction (HFrEF). The paper delves into the complex interplay between various metabolic pathways, including glucose metabolism, fatty acid metabolism, branched-chain amino acid metabolism, and ketone body metabolism. In-depth insights into the shifts in substrate utilization, the role of different transporter proteins, and the potential impact of hypoxia-induced injuries are discussed. Furthermore, potential therapeutic targets and strategies that could minimize myocardial injury and promote cardiac recovery in the context of pressure overload hypertrophy (POH) are examined. This work aims to contribute to a better understanding of metabolic adaptations in POH, highlighting the need for further research on potential therapeutic applications.

The adsorption and its mechanism of venlafaxine by original and aged polypropylene microplastic and the changes of joint toxicity.

Conjugation with the increment of consumption of polypropylene (PP) masks and antidepressants during pandemic, PP microplastics (MPs) and Venlafaxine (VEN) widely co-existed in surface waters. However, their environmental fate and the combined toxicity were unclear. Hence, we investigated the adsorption behaviors, and associated mechanisms of PP MPs for VEN. The impact factors including pH, salinity, and MPs aging were estimated. The results indicated PP MPs could adsorb amount of VEN within 24 h. The pseudo second-order kinetic model (R2 = 0.97) and Dubinin-Radushkevich model (R2 = 0.89) fitted well with the adsorption capacity of PP MPs for VEN, implying that chemical adsorption accompanied by electrostatic interaction might be the predominant mode for the interactions between PP MPs and VEN. Meanwhile, the adsorption capacity of PP MPs declined from pH of 2.5-4.5 and then increased from 4.5 to 9.5. The increased salinity (5-35 ppt) significantly suppressed the adsorption capacity. Aging by sunlight and UV triggered the formation of new functional group (carbonyl) on MPs, and then enhanced the adsorption capacity for VEN. Gaussian Model analysis further evidenced the electrostatic adsorption occurring in PP MPs and VEN. The combined exposure to PP MPs and VEN showed significantly antagonistic toxicity on Daphnia magna. The adsorption of VEN by PP MPs mitigated the lethal effects and behavioral function impairment posed by VEN on animals, implying the potential protective effects on zooplankton by PP MPs. This study for the first time provides perspective for assessing the environmental fate of MPs and antidepressants in aquatic system.

Identification of genes associated with fatty acid biosynthesis based on 214 safflower core germplasm.

BACKGROUND: Safflower (Carthamus tinctorius L.) is an oilseed crop with substantial medicinal and economic value. However, the methods for constructing safflower core germplasm resources are limited, and the molecular mechanisms of lipid biosynthesis in safflower seeds are not well understood. RESULTS: In this study, 11 oil-related quantitative traits and 50 pairs of InDel markers were used to assess the diversity of a collection of 605 safflower germplasms. The original safflower germplasm exhibited rich phenotypic diversity, with high variation for most of the phenotypic traits under investigation. Similarly, high genetic diversity was evaluated in the original germplasm, in which the mean Shannon's information index (I), observed heterozygosity (H0), and expected heterozygosity (He) were 0.553, 0.182, and 0.374, respectively. Four subgroups with strong genetic structures were identified and a core germplasm of 214 cultivars was constructed, which is well represented in the original germplasm. Meanwhile, differential expression analysis of the transcriptomes of high and low linoleic acid safflower varieties at two stages of seed development identified a total of 47 genes associated with lipid biosynthesis. High expression of the genes KAS II and SAD enhanced the synthesis and accumulation of oleic acid, while FAD genes like FAD2 (Chr8G0104100), FAD3, FAD7 and FAD8 promoted the consumption of oleic acid conversion. The coordinated regulation of these multiple genes ensures the high accumulation of oleic acid in safflower seed oil. CONCLUSIONS: Based on these findings, a core germplasm of 214 cultivars was constructed and 47 candidate genes related to unsaturated fatty acid biosynthesis and lipid accumulation were identified. These results not only provide guidance for further studies to elucidate the molecular basis of oil lipid accumulation in safflower seeds, but also contribute to safflower cultivar improvements.

A Neuroligin Isoform Translated by circNlgn Contributes to Cardiac Remodeling.

[Figure: see text].

Combined transcriptomic and metabolomic analysis reveals the potential mechanism of seed germination and young seedling growth in Tamarix hispida.

BACKGROUND: Seed germination is a series of ordered physiological and morphogenetic processes and a critical stage in plant life cycle. Tamarix hispida is one of the most salt-tolerant plant species; however, its seed germination has not been analysed using combined transcriptomics and metabolomics. RESULTS: Transcriptomic sequencing and widely targeted metabolomics were used to detect the transcriptional metabolic profiles of T. hispida at different stages of seed germination and young seedling growth. Transcriptomics showed that 46,538 genes were significantly altered throughout the studied development period. Enrichment study revealed that plant hormones, such as auxin, ABA, JA and SA played differential roles at varying stages of seed germination and post-germination. Metabolomics detected 1022 metabolites, with flavonoids accounting for the highest proportion of differential metabolites. Combined analysis indicated that flavonoid biosynthesis in young seedling growth, such as rhoifolin and quercetin, may improve the plant's adaptative ability to extreme desert environments. CONCLUSIONS: The differential regulation of plant hormones and the accumulation of flavonoids may be important for the seed germination survival of T. hispida in response to salt or arid deserts. This study enhanced the understanding of the overall mechanism in seed germination and post-germination. The results provide guidance for the ecological value and young seedling growth of T. hispida.

Propofol maintains Th17/Treg cell balance in elderly patients undergoing lung cancer surgery through GABAA receptor.

Propofol is widely used in clinical anesthesia due to its advantages of rapid onset and less adverse reactions. This study focused on the role of propofol in the balance of Th17/Treg in elderly patients with lung cancer during perioperative period. Patients undergoing lung cancer surgery were anesthetized by propofol or sevoflurane. Veinal blood was collected at different time points to evaluate the changes of Th17/Treg cell. Propofol better maintained the balance of Th17/Treg in vivo. The peripheral blood of patients with lung cancer was collected in vitro before surgery. Cluster of differentiation (CD)4+ T cells were obtained and then treated with propofol at different concentrations and γ-aminobutyric acid A (GABAA) receptor antagonists. Propofol affected Th17/Treg cell balance by increasing Th17 cells, decreasing Treg cells, thus elevating Th17/Treg ratio, and inhibited invasion and migration of lung cancer cells through GABAA receptor, which was counteracted by GABAA receptor inhibitors. Subsequently, tumor in situ model of lung cancer in aged mice was established. Propofol anesthetized mice had lower change of Th17/Treg ratio, higher survival rate and less metastasis. In brief, propofol regulated balance of Th17/Treg in elderly patients undergoing lung cancer surgery through GABAA receptor. Additionally, propofol could inhibit metastasis of lung cancer.

YAP Circular RNA, circYap, Attenuates Cardiac Fibrosis via Binding with Tropomyosin-4 and Gamma-Actin Decreasing Actin Polymerization.

Cardiac fibrosis is a common pathological feature of cardiac hypertrophy. This study was designed to investigate a novel function of Yes-associated protein (YAP) circular RNA, circYap, in modulating cardiac fibrosis and the underlying mechanisms. By circular RNA sequencing, we found that three out of fifteen reported circYap isoforms were expressed in nine human heart tissues, with the isoform hsa_circ_0002320 being the highest. The levels of this isoform in the hearts of patients with cardiac hypertrophy were found to be significantly decreased. In the pressure overload mouse model, the levels of circYap were reduced in mouse hearts with transverse aortic constriction (TAC). Upon circYap plasmid injection, the cardiac fibrosis was attenuated, and the heart function was improved along with the elevation of cardiac circYap levels in TAC mice. Tropomyosin-4 (TMP4) and gamma-actin (ACTG) were identified to bind with circYap in cardiac cells and mouse heart tissues. Such bindings led to an increased TPM4 interaction with ACTG, resulting in the inhibition of actin polymerization and the following fibrosis. Collectively, our study uncovered a novel molecule that could regulate cardiac remodeling during cardiac fibrosis and implicated a new function of circular RNA. This process may be targeted for future cardio-therapy.

MicroRNA-338-3p as a therapeutic target in cardiac fibrosis through FGFR2 suppression.

BACKGROUND: The development of cardiac fibrosis involves the activation of cardiac fibroblasts (CFs) and their differentiation into myofibroblasts, which leads to the disruption of the extracellular matrix network. In the past few years, microRNAs (miRNA) have been described as potential targets for treating cardiac diseases. Although miR-338-3p has been shown to participate in the development of carcinoma, whether it affects cardiac fibrosis is unclear. METHODS: We examined the expression profiles of microRNAs in left ventricular samples of heart failure mice established by thoracic aortic constriction (TAC). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-338-3p. CCK-8 assay/Transwell migration assay was used to measure the proliferation rate/migration of CFs. Luciferase reporter gene assay was used to test the binding between miR-338-3p and FGFR2. RESULTS: This study demonstrated that miR-338-3p was significantly decreased in thoracic aortic constriction mice. Cardiac miR-338-3p amounts were also reduced in patients with dilated cardiomyopathy (DCM). Interestingly, miR-338-3p overexpression inhibited α-SMA, COL1A1, and COL3A1 expression, as well as cell proliferation and migration in CFs. Bioinformatics analysis and dual-luciferase reporter assays revealed FGFR2 was targeted by miR-338-3p, whose antifibrotic effect could be alleviated by overexpression of FGFR2. Moreover, in DCM cases, serum miR-338-3p levels were markedly elevated in individuals with worse outcomes. CONCLUSIONS: The present study provides evidence that miR-338-3p suppresses cardiac fibroblast activation, proliferation, and migration by directly targeting FGFR2 in mice. Besides, serum miR-338-3p might constitute a potential prognostic biomarker of dilated cardiomyopathy.

Remote Sensing Image Fusion Based on Morphological Convolutional Neural Networks with Information Entropy for Optimal Scale.

Remote sensing image fusion is a fundamental issue in the field of remote sensing. In this paper, we propose a remote sensing image fusion method based on optimal scale morphological convolutional neural networks (CNN) using the principle of entropy from information theory. We use an attentional CNN to fuse the optimal cartoon and texture components of the original images to obtain a high-resolution multispectral image. We obtain the cartoon and texture components using sparse decomposition-morphological component analysis (MCA) with an optimal threshold value determined by calculating the information entropy of the fused image. In the sparse decomposition process, the local discrete cosine transform dictionary and the curvelet transform dictionary compose the MCA dictionary. We sparsely decompose the original remote sensing images into a texture component and a cartoon component at an optimal scale using the information entropy to control the dictionary parameter. Experimental results show that the remote sensing image fusion method proposed in this paper can effectively retain the information of the original image, improve the spatial resolution and spectral fidelity, and provide a new idea for image fusion from the perspective of multi-morphological deep learning.

End-to-End Network for Pedestrian Detection, Tracking and Re-Identification in Real-Time Surveillance System.

Surveillance video has been widely used in business, security, search, and other fields. Identifying and locating specific pedestrians in surveillance video has an important application value in criminal investigation, search and rescue, etc. However, the requirements for real-time capturing and accuracy are high for these applications. It is essential to build a complete and smooth system to combine pedestrian detection, tracking and re-identification to achieve the goal of maximizing efficiency by balancing real-time capture and accuracy. This paper combined the detector and Re-ID models into a single end-to-end network by introducing a new track branch to YOLOv5 architecture for tracking. For pedestrian detection, we employed the weighted bi-directional feature pyramid network (BiFPN) to enhance the network structure based on the YOLOv5-Lite, which is able to further improve the ability of feature extraction. For tracking, based on Deepsort, this paper enhanced the tracker, which uses the Noise Scale Adaptive (NSA) Kalman filter to track, and adds adaptive noise to strengthen the anti-interference of the tracking model. In addition, the matching strategy is further updated. For pedestrian re-identification, the network structure of Fastreid was modified, which can increase the feature extraction speed of the improved algorithm by leaps and bounds. Using the proposed unified network, the parameters of the entire model can be trained in an end-to-end method with the multi-loss function, which has been demonstrated to be quite valuable in some other recent works. Experimental results demonstrate that pedestrians detection can obtain a 97% mean Average Precision (mAP) and that it can track the pedestrians well with a 98.3% MOTA and a 99.8% MOTP on the MOT16 dataset; furthermore, high pedestrian re-identification performance can be achieved on the VERI-Wild dataset with a 77.3% mAP. The overall framework proposed in this paper has remarkable performance in terms of the precise localization and real-time detection of specific pedestrians across time, regions, and cameras.

Real-Time and Efficient Multi-Scale Traffic Sign Detection Method for Driverless Cars.

Traffic signs detection and recognition is an essential and challenging task for driverless cars. However, the detection of traffic signs in most scenarios belongs to small target detection, and most existing object detection methods show poor performance in these cases, which increases the difficulty of detection. To further improve the accuracy of small object detection for traffic signs, this paper proposed an optimization strategy based on the YOLOv4 network. Firstly, an improved triplet attention mechanism was added to the backbone network. It was combined with optimized weights to make the network focus more on the acquisition of channel and spatial features. Secondly, a bidirectional feature pyramid network (BiFPN) was used in the neck network to enhance feature fusion, which can effectively improve the feature perception field of small objects. The improved model and some state-of-the-art (SOTA) methods were compared on the joint dataset TT100K-COCO. Experimental results show that the enhanced network can achieve 60.4% mAP(Mean Average Precision), surpassing the YOLOv4 by 8% with the same input size. With a larger input size, it can achieve a best performance capability of 66.4% mAP. This work provides a reference for research on obtaining higher accuracy for traffic sign detection in autonomous driving.

Long-Lasting Somatic Modifications of Convergent Dendritic Inputs in Hippocampal Neurons.

Integrated neural inputs from different dendrites converge at the soma for action potential generation. However, it is unclear how the convergent dendritic inputs interact at the soma and whether they can be further modified there. We report here an entirely new plasticity rule in hippocampal neurons in which repetitive pairing of subthreshold excitatory inputs from proximal apical and basal dendrites at a precise interval induces persistent bidirectional modifications of the two dendritic inputs. Strikingly, the modification of the dendritic inputs specially occurs at soma in the absence of somatic action potential and requires activation of somatic N-methyl-D-aspartate receptors (NMDARs). Once induced, the somatic modification can also be observed in other unpaired dendritic inputs upon their arrival at the soma. We further reveal that the soma can employ an active mechanism to potentiate the dendritic inputs by promoting sustained activation of somatic NMDARs and subsequent down-regulating of the fast inactivating A-type potassium current (IA) at the soma. Thus, the input-timing-dependent somatic plasticity we uncovered here is in sharp contrast to conventional forms of synaptic plasticity that occur at the dendrites and is important to somatic action potential generation.

Predictors of atrial fibrillation detection and features of recurrent strokes in patients after cryptogenic stroke.

BACKGROUND AND PURPOSE: Use of implantable cardiac monitors (ICMs) has increased diagnosis of atrial fibrillation (AF) in cryptogenic stroke (CS) patients. Identifying AF predictors may enhance the yield of AF detection. Recurrent strokes after CS are not well described. We aimed to assess the predictors for AF detection and the characteristics of recurrent strokes in patients after CS. METHODS: We reviewed electronic medical records of CS patients who were admitted between February 2014 and September 2017 and underwent ICM placement with minimum one-year follow-up. Patient demographics, stroke characteristics, pre-defined risk factors as well as recurrent strokes were compared between patients with and without AF detection. RESULTS: 389 patients with median follow-up of 548 days were studied. AF was detected in 102 patients (26.2%). Age (per decade increase, OR 2.10, CI 1.64-2.68, with vs. without AF) and left atrium diameter (per 5 mm increase, OR 1.91, CI 1.33-2.74) were identified as AF predictors. Intracranial large vessel stenosis >50% irrelevant to the index strokes was associated with AF detection within 30 days (OR 0.24, CI 0.09-0.69, >30 vs. <30 days). Recurrent strokes occurred in 14% patients with median follow-up about 2.5 years. Topography of these strokes resembled embolic pattern and was comparable between patients with and without AF. Among recurrent strokes in patients with AF, the median time to AF detection was much shorter (90 vs. 251 days), and the median time to first stroke recurrence was much longer (422 vs. 76 days) in patients whose strokes recurred after AF detection than those before AF detection. CONCLUSIONS: Older age and enlarged left atrium are predictors for AF detection in CS patients. Intracranial atherosclerosis is more prevalent in patients with early AF detection within 30 days. Recurrent strokes follow the embolic pattern, and early AF detection could delay the stroke recurrence.

Damage Detection of Concrete-Filled Square Steel Tube (CFSST) Column Joints under Cyclic Loading Using Piezoceramic Transducers.

Concrete-filled square steel tube column (CFSSTC) joints are the most important parts of concrete-filled steel tube frame structures. It is of great significance to study the damage of CFSSTC joints under the seismic loads. In this paper, embedded piezoceramic transducers are used to monitor the damage of core concrete of CFSSTC joints under cyclic loading and surface-bonded piezoceramic disks are used to monitor the debonding damage of the steel tube and core concrete of two specimens. The damages of the joints under different loading levels and different loading cycles are evaluated by the received signal of the piezoceramic transducers. The experimental results show that the amplitude of the signal attenuates obviously with the appearance of damage in the joints, and the degree of attenuation increases with the development of the damage. The monitoring results from piezoceramic transducers are basically consistent with the hysteresis loops and skeleton curves of the CFSSTC joints during the cyclic loading. The effectiveness of the piezoceramic transducers are verified by the experimental results in structural health monitoring of the CFSSTC joint under cyclic loading.

Presenilin-1/γ-secretase controls glutamate release, tyrosine phosphorylation, and surface expression of N-methyl-D-aspartate receptor (NMDAR) subunit GluN2B.

Abnormally high concentrations of extracellular glutamate in the brain may cause neuronal damage via excitotoxicity. Thus, tight regulation of glutamate release is critical to neuronal function and survival. Excitotoxicity is caused mainly by overactivation of the extrasynaptic NMDA receptor (NMDAR) and results in specific cellular changes, including calcium-induced activation of calpain proteases. Here, we report that presenilin-1 (PS1) null mouse cortical neuronal cultures have increased amounts of calpain-dependent spectrin breakdown products (SBDPs) compared with WT cultures. NMDAR antagonists blocked accumulation of SBDPs, suggesting abnormal activation of this receptor in PS1 null cultures. Importantly, an increase in SBDPs was detected in cultures of at least 7 days in vitro but not in younger cultures. Conditioned medium from PS1 null neuronal cultures at 8 days in vitro contained higher levels of glutamate than medium from WT cultures and stimulated production of SBDPs when added to WT cultures. Use of glutamate reuptake inhibitors indicated that accumulation of this neurotransmitter in the media of PS1 null cultures was due to increased rates of release. PS1 null neurons showed decreased cell surface expression and phosphorylation of the GluN2B subunit of NMDAR, indicating decreased amounts of extrasynaptic NMDAR in the absence of PS1. Inhibition of γ-secretase activity in WT neurons caused changes similar to those observed in PS1 null neurons. Together, these data indicate that the PS1/γ-secretase system regulates release of glutamate, tyrosine phosphorylation, and surface expression of GluN2B-containing NMDARs.

Comment on "neurotoxicity of 4-nonylphenol in adult zebrafish: Evaluation of behaviour, oxidative stress parameters and histopathology of brain"by Jay K. Desai. et al. [Environmental Pollution 334 (2023): 122206].

In a recent study by Jay K. Desai et al., (Desai et al., 2023) the authors extensively documented the effects of long-term exposure to 4-nonylphenol neurotoxicity in zebrafish, including oxidative stress markers, behavioral changes, and neuropathology results. The results indicate that, although Neurotoxicity of 4-nonylphenol did not cause evident changes in zebrafish brain tissue pathology, it significantly induced oxidative stress reactions in the zebrafish brain and altered their exploratory behaviors in response to light and dark stimuli.However, upon reviewing the results of this study, we have identified several questionable outcomes and errors in image usage, leading to some concerns.

Antagonistic interaction between caffeine and ketamine in zebrafish: Implications for aquatic toxicity.

The coexistence of caffeine (CF) and ketamine (KET) in surface waters across Asia has been widely reported. Previous studies have implied that CF and KET may share a mechanism of action. However, the combined toxicity of these two chemicals on aquatic organisms remains unclear at environmental levels, and the underlying mechanisms are not well understood. Here we demonstrate that KET antagonizes the adverse effects of CF on zebrafish larvae by modulating the gamma-aminobutyric acid (GABA)ergic synapse pathway. Specifically, KET (10-250 ng L-1) ameliorates the locomotor hyperactivity and impaired circadian rhythms in zebrafish larvae induced by 2 mg L-1 of CF, showing a dose-dependent relationship. Additionally, the developmental abnormalities in zebrafish larvae exposed to CF are mitigated by KET, with an incidence rate reduced from 26.7% to 6.7%. The competition between CF and KET for binding sites on the GABA-A receptor (in situ and in silico) elucidates the antagonistic interactions between the two chemicals. Following a seven-day recovery period, the adverse outcomes of CF exposure persist in the fish, whereas the changes observed in the CF + KET groups are significantly alleviated, especially with KET at 10 ng L-1. Based on these results, it is imperative to further assess the environmental risks associated with CF and KET co-pollution. This pilot study underscores the utility of systems toxicology approaches in estimating the combined toxicity of environmental chemicals on aquatic organisms. Moreover, the nighttime behavioral functions of fish could serve as a sensitive biomarker for evaluating the toxicity of psychoactive substances.

Concurrent Cardio-Cerebral Infarction - A Case Report and Literature Review.

Concurrent cardio-cerebral infarction (CCI) describes the simultaneous occurrence of an acute myocardial infarction and an acute ischemic stroke. It is a rare phenomenon, and no consensus yet exists on how to best treat it. CCI patients present with variable clinical scenarios and complications which makes the establishment of a treatment guideline difficult. We present here a case of a 67-year-old male with concurrent acute ST-elevation myocardial infarction and acute ischemic stroke due to right middle cerebral artery occlusion who was successfully treated with Tenecteplase and mechanical thrombectomy. A literature review was also conducted in search of potential reasonable management strategies of CCI.

The Exploration of Joint Toxicity and Associated Mechanisms of Primary Microplastics and Methamphetamine in Zebrafish Larvae.

The co-existence of microplastics (MPs) and methamphetamine (METH) in aquatic ecosystems has been widely reported; however, the joint toxicity and associated mechanisms remain unclear. Here, zebrafish larvae were exposed individually or jointly to polystyrene (PS) and polyvinyl chloride (PVC) MPs (20 mg/L) and METH (1 and 5 mg/L) for 10 days. The mortality, behavioral functions, and histopathology of fish from different groups were determined. PS MPs posed a stronger lethal risk to fish than PVC MPs, while the addition of METH at 5 mg/L significantly increased mortality. Obvious deposition of MPs was observed in the larvae's intestinal tract in the exposure groups. Meanwhile, treatment with MPs induced intestinal deposits and intestinal hydrops in the fish, and this effect was enhanced with the addition of METH. Furthermore, MPs significantly suppressed the locomotor activation of zebrafish larvae, showing extended immobility duration and lower velocity. METH stimulated the outcome of PS but had no effect on the fish exposed to PVC. However, combined exposure to MPs and METH significantly increased the turn angle, which declined in individual MP exposure groups. RNA sequencing and gene quantitative analysis demonstrated that exposure to PS MPs and METH activated the MAPK signaling pathway and the C-type lectin signaling pathway of fish, while joint exposure to PVC MPs and METH stimulated steroid hormone synthesis pathways and the C-type lectin signaling pathway in zebrafish, contributing to cellular apoptosis and immune responses. This study contributes to the understanding of the joint toxicity of microplastics and pharmaceuticals to zebrafish, highlighting the significance of mitigating microplastic pollution to preserve the health of aquatic organisms and human beings.