Impaired motor-to-sensory transformation mediates auditory hallucinations.

Distinguishing reality from hallucinations requires efficient monitoring of agency. It has been hypothesized that a copy of motor signals, termed efference copy (EC) or corollary discharge (CD), suppresses sensory responses to yield a sense of agency; impairment of the inhibitory function leads to hallucinations. However, how can the sole absence of inhibition yield positive symptoms of hallucinations? We hypothesize that selective impairments in functionally distinct signals of CD and EC during motor-to-sensory transformation cause the positive symptoms of hallucinations. In an electroencephalography (EEG) experiment with a delayed articulation paradigm in schizophrenic patients with (AVHs) and without auditory verbal hallucinations (non-AVHs), we found that preparing to speak without knowing the contents (general preparation) did not suppress auditory responses in both patient groups, suggesting the absent of inhibitory function of CD. Whereas, preparing to speak a syllable (specific preparation) enhanced the auditory responses to the prepared syllable in non-AVHs, whereas AVHs showed enhancement in responses to unprepared syllables, opposite to the observations in the normal population, suggesting that the enhancement function of EC is not precise in AVHs. A computational model with a virtual lesion of an inhibitory inter-neuron and disproportional sensitization of auditory cortices fitted the empirical data and further quantified the distinct impairments in motor-to-sensory transformation in AVHs. These results suggest that "broken" CD plus "noisy" EC causes erroneous monitoring of the imprecise generation of internal auditory representation and yields auditory hallucinations. Specific impairments in functional granularity of motor-to-sensory transformation mediate positivity symptoms of agency abnormality in mental disorders.

Genotype diversity enhances invasion resistance of native plants via soil biotic feedbacks.

Although native species diversity is frequently reported to enhance invasion resistance, within-species diversity of native plants can also moderate invasions. While the positive diversity-invasion resistance relationship is often attributed to competition, indirect effects mediated through plant-soil feedbacks can also influence the relationship. We manipulated the genotypic diversity of an endemic species, Scirpus mariqueter, and evaluated the effects of abiotic versus biotic feedbacks on the performance of a global invader, Spartina alterniflora. We found that invader performance on live soils decreased non-additively with genotypic diversity of the native plant that trained the soils, but this reversed when soils were sterilized to eliminate feedbacks through soil biota. The influence of soil biota on the feedback was primarily associated with increased levels of microbial biomass and fungal diversity in soils trained by multiple-genotype populations. Our findings highlight the importance of plant-soil feedbacks mediating the positive relationship between genotypic diversity and invasion resistance.

Segregation and integration of sensory features by flexible temporal characteristics of independent neural representations.

Segregation and integration are two fundamental yet competing computations in cognition. For example, in serial speech processing, stable perception necessitates the sequential establishment of perceptual representations to remove irrelevant features for achieving invariance. Whereas multiple features need to combine to create a coherent percept. How to simultaneously achieve seemingly contradicted computations of segregation and integration in a serial process is unclear. To investigate their neural mechanisms, we used loudness and lexical tones as a research model and employed a novel multilevel oddball paradigm with Electroencephalogram (EEG) recordings to explore the dynamics of mismatch negativity (MMN) responses to their deviants. When two types of deviants were presented separately, distinct topographies of MMNs to loudness and tones were observed at different latencies (loudness earlier), supporting the sequential dynamics of independent representations for two features. When they changed simultaneously, the latency of responses to tones became shorter and aligned with that to loudness, while the topographies remained independent, yielding the combined MMN as a linear additive of single MMNs of loudness and tones. These results suggest that neural dynamics can be temporally synchronized to distinct sensory features and balance the computational demands of segregation and integration, grounding for invariance and feature binding in serial processing.

Dual-stream cortical pathways mediate sensory prediction.

Predictions are constantly generated from diverse sources to optimize cognitive functions in the ever-changing environment. However, the neural origin and generation process of top-down induced prediction remain elusive. We hypothesized that motor-based and memory-based predictions are mediated by distinct descending networks from motor and memory systems to the sensory cortices. Using functional magnetic resonance imaging (fMRI) and a dual imagery paradigm, we found that motor and memory upstream systems activated the auditory cortex in a content-specific manner. Moreover, the inferior and posterior parts of the parietal lobe differentially relayed predictive signals in motor-to-sensory and memory-to-sensory networks. Dynamic causal modeling of directed connectivity revealed selective enabling and modulation of connections that mediate top-down sensory prediction and ground the distinctive neurocognitive basis of predictive processing.

Delta-band neural tracking primarily reflects rule-based chunking instead of semantic relatedness between words.

It is debated whether cortical responses matching the time scales of phrases and sentences mediate the mental construction of the syntactic chunks or are simply caused by the semantic properties of words. Here, we investigate to what extent delta-band neural responses to speech can be explained by semantic relatedness between words. To dissociate the contribution of semantic relatedness from sentential structures, participants listened to sentence sequences and paired-word sequences in which semantically related words repeated at 1 Hz. Semantic relatedness in the 2 types of sequences was quantified using a word2vec model that captured the semantic relation between words without considering sentential structure. The word2vec model predicted comparable 1-Hz responses with paired-word sequences and sentence sequences. However, empirical neural activity, recorded using magnetoencephalography, showed a weaker 1-Hz response to paired-word sequences than sentence sequences in a word-level task that did not require sentential processing. Furthermore, when listeners applied a task-related rule to parse paired-word sequences into multi-word chunks, 1-Hz response was stronger than that in word-level task on the same sequences. Our results suggest that cortical activity tracks multi-word chunks constructed by either syntactic rules or task-related rules, whereas the semantic relatedness between words contributes only in a minor way.

Management of anastomotic biliary stricture through utilizing percutaneous transhepatic cholangioscopy.

AIM: Occurrence of anastomotic biliary stricture (AS) remains an essential issue following hepatobiliary surgeries, and percutaneous transhepatic cholangioscopy (PTCS) has great therapeutic significance in handling refractory AS for patients with altered gastrointestinal anatomy after cholangio-jejunostomy. This present study aimed to investigate feasibility of PTCS procedures in AS patients for therapeutic indications. MATERIALS AND METHODS: This study was a single-center, retrospective cohort study with a total number of 124 consecutive patients who received therapeutic PTCS due to AS. Clinical success rate, required number, and adverse events of therapeutic PTCS procedures as well as patients survival state were reviewed. RESULTS: These 124 patients previously underwent choledochojejunostomy or hepatico-jejunostomy, and there was post-surgical altered gastrointestinal anatomy. Overall, 366 therapeutic PTCS procedures were performed for these patients through applying rigid choledochoscope, and the median time of PTCS procedures was 3 (1-11). Among these patients, there were 34 cases (27.32%) accompanied by biliary strictures and 100 cases (80.65%) were also combined with biliary calculi. After therapeutic PTCS, most patients presented with relieved clinical manifestations and improved liver functions. The median time of follow-up was 26 months (2-86 months), and AS was successfully managed through PTCS procedures in 104 patients (83.87%). During the follow-up period, adverse events occurred in 81 cases (65.32%), most of which were tackled through supportive treatment. CONCLUSION: PTCS was a feasible, safe and effective therapeutic modality for refractory AS, which may be a promising alternative approach in clinical cases where the gastrointestinal anatomy was changed after cholangio-jejunostomy.

Advancements in employing two-dimensional nanomaterials for enhancing skin wound healing: a review of current practice.

The two-dimensional nanomaterials are characterized by their ultra-thin structure, diverse chemical functional groups, and remarkable anisotropic properties. Since its discovery in 2004, graphene has attracted significant scientific interest due to its potential applications in various fields, including electronics, energy systems, and biomedicine. In medicine, graphene is used for designing smart drug delivery systems, especially for antibiotics, and biosensing. Skin trauma is a prevalent dermatological condition that increasingly contributes to morbidities and mortalities, thus representing a significant health burden. During tissue damage, rapid skin repair is crucial to prevent blood loss and infection. Therefore, drugs used for skin trauma must possess antimicrobial and anti-inflammatory properties. Two-dimensional (2D) nanomaterials possess remarkable physical, chemical, optical, and biological characteristics due to their uniform shape, increased surface area, and surface charge. Graphene and its derivatives, transition-metal dichalcogenides (TMDs), black phosphorous (BP), hexagonal boron nitride (h-BN), MXene, and metal-organic frameworks (MOFs) are among the commonly used 2D nanomaterials. Moreover, they exhibit antibacterial and anti-inflammatory properties. This review presents a comprehensive discussion of the clinical approaches employed for wound healing treatment and explores the applications of commonly used 2D nanomaterials to enhance wound healing outcomes.

A Protective Role of Canonical Wnt/ß-Catenin Pathway in Pathogenic Bacteria-Induced Inflammatory Responses.

Inflammation is a complex host defensive response against various disease-associated pathogens. A baseline extent of inflammation is supposed to be tightly associated with a sequence of immune-modulated processes, resulting in the protection of the host organism against pathogen invasion; however, as a matter of fact is that an uncontrolled inflammatory cascade is the main factor responsible for the host damage, accordingly suggesting a significant and indispensable involvement of negative feedback mechanism in modulation of inflammation. Evidence accumulated so far has supported a repressive effect of the canonical Wnt/ß-catenin pathway on microbial-triggered inflammation via diverse mechanisms, although that consequence is dependent on the cellular context, types of stimuli, and cytokine environment. It is of particular interest and importance to comprehend the precise way in which the Wnt/ß-catenin pathway is activated, due to its essential anti-inflammatory properties. It is assumed that an inflammatory milieu is necessary for initiating and activating this signaling, implying that Wnt activity is responsible for shielding tissues from overwhelming inflammation, thus sustaining a balanced physiological condition against bacterial infection. This review gathers the recent efforts to elucidate the mechanistic details through how Wnt/ß-catenin signaling modulates anti-inflammatory responses in response to bacterial infection and its interactions with other inflammatory signals, which warrants further study for the development of specific interventions for the treatment of inflammatory diseases. Further clinical trials from different disease settings are required.

Prevalence and genotype/subtype distribution of Enterocytozoon bieneusi and Blastocystis in donkeys in Shanxi Province, north China.

Enterocytozoon bieneusi and Blastocystis may cause diarrhea in humans and various animals. However, little information is available regarding the prevalence and genetic diversity of E. bieneusi and Blastocystis in donkeys. To fill this gap, we molecularly assessed E. bieneusi and Blastocystis in fecal samples from donkeys (n = 815) in Shanxi Province, north China. The overall prevalence of E. bieneusi and Blastocystis in donkeys was 8.1% and 0.2%, respectively. Region and age were risk factors associated with E. bieneusi infection in donkeys. Three internal transcribed spacer (ITS) genotypes of E. bieneusi were identified in the current study, including two previously described genotypes (D and Henan-IV) and one novel genotype (named SXD1). Of which, genotype D was found to be the most prevalent. Phylogenetic analysis demonstrated that the three genotypes belonged to group 1, implying a potential of zoonotic transmission. Multilocus sequence typing showed that 19, 15, 13, and 22 types were identified at the loci MS1, MS3, MS4, and MS7, respectively, forming six multilocus genotypes (MLGs) distributed in the genotype D. One Blastocystis subtype (ST33) was identified, which has previously been reported only in horses. This is the first molecular-based description of E. bieneusi and Blastocystis infections in donkeys in Shanxi Province, north China, contributing to a better understanding of transmission dynamics and molecular epidemiological characteristics of the two intestinal protozoa.

Synthesis and Antitumor Activity Evaluation of Novel Echinatin Derivatives with a 1,3,4-Oxadiazole Moiety.

A series of novel echinatin derivatives with 1,3,4-oxadiazole moieties were designed and synthesized. Most of the newly synthesized compounds exhibited moderate antiproliferative activity against the four cancer cell lines. Notably, Compound T4 demonstrated the most potent activity, with IC50 values ranging from 1.71 µM to 8.60 µM against the four cancer cell lines. Cell colony formation and wound healing assays demonstrated that T4 significantly inhibited cell proliferation and inhibited migration. We discovered that T4 exhibited moderate binding affinity with the c-KIT protein through reverse docking. The results were effectively validated through subsequent molecular docking and c-KIT enzyme activity assays. In addition, Western blot analysis revealed that T4 inhibits the phosphorylation of downstream proteins of c-KIT. The results provide valuable inspiration for exploring novel insights into the design of echinatin-related hybrids as well as their potential application as c-KIT inhibitors to enhance the efficacy of candidates.

IL6 and WNK2 Polymorphisms and Prognosis in Patients With Intracerebral Hemorrhage Receiving Edaravone.

OBJECTIVE: Edaravone is utilized in intra-cerebral hemorrhage (ICH) patients for years, while personalized variances were observed in clinic. To explore the precision medicine strategy for Edaravone, this study investigated the association between genetic polymorphisms and Edaravone efficacy in ICH patients. METHODS: We genotyped 7 SNPs in 4 potential genes, including COL4A2, TNF, WNK2 and IL6, from the peripheral blood of 217 ICH patients with or without Edaravone utilizations. PLINK and SPSS were utilized for association tests, Student's t tests, Mann-Whitney U tests and Chi-square tests. RESULTS: Rs1800796 (C>G) in IL6 (OR: 0.41, 95% CI: 0.18-0.94, p-value = 0.03) and rs16936752 (G>T) in WNK2 (OR: 0.28, 95% CI: 0.09-0.88, p-value = 0.02) were found to be significantly associated with Edaravone efficacy. The association of rs1800796 and rs16936752 were found to be different in patients with or without smoking habit, alcohol drinking habit, hypertension history and hyperlipemia history were found to be different. Both of these two SNPs were found to be associated with the concentration of high-density lipoprotein cholesterol (HDL) in ICH patients. CONCLUSIONS: The IL6 rs1800796 and the WNK2 rs16936752 could be useful biomarkers for prognosis prediction during Edaravone treatment. These SNPs should be considered in the personalized medicine strategy for Edaravone in the future.

[Exploration of mechanism of total triterpenoids from fruits of Chaenomeles speciosa against senescent GES-1 cells induced by D-galactose based on Gln/GLS1/α-KG metabolic axis and mitochondrial apoptosis signaling pathway].

Total triterpenoids from the fruits of Chaenomeles speciosa(TCS) are active components in the prevention and treatment of gastric mucosal damage, which have potential anti-aging effects. However, it is still unclear whether TCS can improve gastric aging, especially its molecular mechanism against gastric aging. On this basis, this study explored the effect and mechanism of TCS on senescent GES-1 cells induced by D-galactose(D-gal) to provide scientific data for the clinical use of TCS to prevent gastric aging. GES-1 cells cultured in vitro and those transfected with overexpression GLS1(GLS1-OE) plasmid of glutaminase 1(GLS1) were induced to aging by D-gal, and then TCS and or GLS1 inhibitor bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl) ethyl sulfide(BPTES) were given. Cell survival rate, positive rate of ß-galactosidase(SA-ß-gal) staining, mitochondrial membrane potential(MMP), and apoptosis were investigated. GLS1 activity, levels of glutamine(Gln), glutamate(Glu), α-ketoglutarate(α-KG), urea, and ammonia in supernatant and cells were detected by enzyme-linked immunosorbent assay(ELISA) and colorimetric methods. The mRNA and protein expressions of GLS1 and the related genes of the mitochondrial apoptosis signaling pathway were measured by real-time fluorescence quantitative PCR and Western blot. The results manifested that compared with the D-gal model group and GLS1-OE D-gal model group, TCS significantly decreased the SA-ß-gal staining positive cell rate and MMP of D-gal-induced senescent GES-1 cells and GLS1-OE senescent GES-1 cells, inhibited the survival of senescent cells, and promoted their apoptosis(P<0.01). It decreased the activity of GLS1 and the content of Gln, Glu, α-KG, urea, and ammonia in supernatant and cell(P<0.01), reduced the concentration of cytochrome C(Cyto C) in mitochondria and the mRNA and protein expressions of GLS1 and proliferating nuclear antigen in cells(P<0.01). The mRNA expression of Bcl-2 and Bcl-xl, the protein expression of pro-caspase-9 and pro-caspase-3, and the ratio of Bcl-2/Bax and Bcl-xl/Bad in cells were decreased(P<0.01). Cyto C concentration in the cytoplasm, the mRNA expressions of Bax, Bad, apoptosis protease activating factor 1(Apaf-1), and protein expressions of cleaved-caspase-9, cleaved-caspase-3, cleaved-PARP-1 were increased(P<0.01). The aforementioned results indicate that TCS can counteract the senescent GES-1 cells induced by D-gal, and its mechanism may be closely related to suppressing the Gln/GLS1/α-KG metabolic axis, activating the mitochondrial apoptosis pathway, and thereby accelerating the apoptosis of the senescent cells and eliminating senescent cells.

Nf1 in heart development: a potential causative gene for congenital heart disease: a narrative review.

Congenital heart disease is the most frequent congenital disorder, affecting a significant number of live births. Gaining insights into its genetic etiology could lead to a deeper understanding of this condition. Although the Nf1 gene has been identified as a potential causative gene, its role in congenital heart disease has not been thoroughly clarified. We searched and summarized evidence from cohort-based and experimental studies on the issue of Nf1 and heart development in congenital heart diseases from various databases. Available evidence demonstrates a correlation between Nf1 and congenital heart diseases, mainly pulmonary valvar stenosis. The mechanism underlying this correlation may involve dysregulation of epithelial-mesenchymal transition (EMT). The Nf1 gene affects the EMT process via multiple pathways, including directly regulating the expression of EMT-related transcription factors and indirectly regulating the EMT process by regulating the MAPK pathway. This narrative review provides a comprehensive account of the Nf1 involvement in heart development and congenital cardiovascular diseases in terms of epidemiology and potential mechanisms. RAS signaling may contribute to congenital heart disease independently or in cooperation with other signaling pathways. Efficient management of both NF1 and cardiovascular disease patients would benefit from further research into these issues.

Mental operations in rhythm: Motor-to-sensory transformation mediates imagined singing.

What enables the mental activities of thinking verbally or humming in our mind? We hypothesized that the interaction between motor and sensory systems induces speech and melodic mental representations, and this motor-to-sensory transformation forms the neural basis that enables our verbal thinking and covert singing. Analogous with the neural entrainment to auditory stimuli, participants imagined singing lyrics of well-known songs rhythmically while their neural electromagnetic signals were recorded using magnetoencephalography (MEG). We found that when participants imagined singing the same song in similar durations across trials, the delta frequency band (1-3 Hz, similar to the rhythm of the songs) showed more consistent phase coherence across trials. This neural phase tracking of imagined singing was observed in a frontal-parietal-temporal network: the proposed motor-to-sensory transformation pathway, including the inferior frontal gyrus (IFG), insula (INS), premotor area, intra-parietal sulcus (IPS), temporal-parietal junction (TPJ), primary auditory cortex (Heschl's gyrus [HG]), and superior temporal gyrus (STG) and sulcus (STS). These results suggest that neural responses can entrain the rhythm of mental activity. Moreover, the theta-band (4-8 Hz) phase coherence was localized in the auditory cortices. The mu (9-12 Hz) and beta (17-20 Hz) bands were observed in the right-lateralized sensorimotor systems that were consistent with the singing context. The gamma band was broadly manifested in the observed network. The coherent and frequency-specific activations in the motor-to-sensory transformation network mediate the internal construction of perceptual representations and form the foundation of neural computations for mental operations.

Peptide YY inhibits transcription and replication of hepatitis B virus by suppressing promoter/enhancer activity.

Hepatitis B virus (HBV) infection is a noteworthy cause of liver diseases, especially cirrhosis and hepatocellular carcinomas. However, the interaction between the host and HBV has not been fully elucidated. Peptide YY (PYY) is a 36-amino-acid gastrointestinal hormone that is mainly involved in the regulation of the human digestive system. This study found that PYY expression was reduced in HBV-expressing hepatocytes and HBV patients. Overexpression of PYY could significantly inhibit HBV RNA, DNA levels, and the secretion of HBsAg. In addition, PYY inhibits HBV RNA dependent on transcription through reducing the activities of CP/Enh I/II, SP1 and SP2. Meanwhile, PYY blocks HBV replication independent on core, polymerase protein and ε structure of pregenomic RNA. These results suggest that PYY can impair HBV replication by suppressing viral promoters/enhancers in hepatocytes. Our data shed light on a novel role for PYY as anti-HBV restriction factor.

Novel Ziyuglycoside II derivatives inhibit MCF-7 cell proliferation via inducing apoptosis and autophagy.

A series of novel ziyuglycoside II derivatives were synthesized based on the classical 1,2,3-triazole moiety. Among the tested derivatives (Z-1 - Z-15), the compound Z-15 demonstrated the most potent antiproliferative effect on K562, MCF-7 and MV411 cell lines. Moreover, Z-15 did not show obvious cytotoxicity on MCF-10A cell, a human normal mammary epithelial cell. The cell colony formation assay showed that, compared to ziyuglycoside II and 5-fluorouracil, Z-15 could inhibit cell proliferation more robustly. Wound healing assays indicated that Z-15 could significantly inhibit MCF-7 cell migration. Further mechanistic research revealed that Z-15 induced mitochondrial-mediated apoptosis and autophagy in MCF-7 cell line in a dose-dependent manner.

Carbonized polyaniline-activated peracetic acid advanced oxidation process for organic removal: Efficiency and mechanisms.

Recently, advanced oxidation processes (AOPs) based upon peracetic acid (PAA) with high efficiency for degrading aqueous organic contaminants have attracted extensive attention. Herein, a novel metal-free N-doped carbonaceous catalyst, namely, carbonized polyaniline (CPANI), was applied to activate PAA to degrade phenolic and pharmaceutical pollutants. The results showed that the CPANI/PAA system could effectively degrade 10 µM phenol in 60 min with low concentrations of PAA (0.1 mM) and catalyst (25 mg L-1). This system also performed well within a wide pH range of 5-9 and displayed high tolerance to Cl-, HCO3- and humic acid. The nonradical pathway [singlet oxygen (1O2)] was found to be the dominant pathway for degrading organic contaminants in the CPNAI/PAA system. Systematic characterization revealed that the graphitic N, pyridinic N, carbonyl groups (CO) and defects played the role of active sites on CPANI during the activation of PAA. The catalytic capacity of spent CPANI could be conveniently recovered by thermal treatment. The findings will be helpful for the application of metal-free carbonaceous catalyst/PAA processes in decontaminating water.

Thermosensitive black phosphorus hydrogel loaded with silver sulfadiazine promotes skin wound healing.

Wounds can lead to skin and soft tissue damage and their improper management may lead to the growth of pathogenic bacteria at the site of injury. Identifying better ways to promote wound healing is a major unmet need and biomedical materials with the ability to promote wound healing are urgently needed. Here, we report a thermosensitive black phosphorus hydrogel composed of black phosphorus nano-loaded drug silver sulfadiazine (SSD) and chitosan thermosensitive hydrogel for wound healing. The hydrogel has temperature-sensitive properties and enables the continuous release of SSD under near-infrared irradiation to achieve synergistic photothermal and antibacterial treatment. Additionally, it exerts antibacterial effects on Staphylococcus aureus. In a rat skin injury model, it promotes collagen deposition, boosts neovascularization, and suppresses inflammatory markers. In summary, the excellent thermosensitivity, biocompatibility, and wound-healing-promoting qualities of the reported thermosensitive hydrogel make it suitable as an ideal wound dressing in the clinic.

Recent advances in exosomal non-coding RNA-based therapeutic approaches for photoaging.

BACKGROUND: Photoaging is a degenerative biological process that affects the quality of life. It is caused by environmental factors including ultraviolet radiation (UVR), deep skin burns, smoking, active oxygen, chemical substances, and trauma. Among them, UVR plays a vital role in the aging process. AIM: With the continuous development of modern medicine, clinical researchers have investigated novel approaches to treat aging. In particular, mesenchymal stem cells (MSCs), non-coding RNAs are involved in various physiological processes have broad clinical application as they have the advantages of convenient samples, abundant sources, and avoidable ethical issues. METHODS: This article reviews research progress on five types of stem cell, exosomes, non-coding RNA in the context of photoaging treatment: adipose-derived stem cell, human umbilical cord MSCs, epidermal progenitor cells, keratinocyte stem cells, and hair follicle stem cells (HFSCs). It also includes stem cell related exosomes and their non-coding RNA research. RESULTS: The results have clinical guiding significance for prevention and control of the onset and development of photoaging. It is found that stem cells secrete cytokines, cell growth factors, non-coding RNA, exosomes and proteins to repair aging skin tissues and achieve skin rejuvenation. In particular, stem cell exosomes and non-coding RNA are found to have significant research potential, as they possess the benefits of their source cells without the disadvantages which include immune rejection and granuloma formation.

Niclosamide exposure disrupts antioxidant defense, histology, and the liver and gut transcriptome of Chinese soft-shelled turtle (Pelodiscus sinensis).

Niclosamide (NIC) is the only commercially available molluscicide for controlling schistosomiasis, and its negative effects on aquatic animals had been frequently reported in recent years. However, the toxicity mechanism of NIC on the Chinese soft-shelled turtle (Pelodiscus sinensis) have not yet been investigated. Therefore, juvenile turtles were exposed to 0 (control group), 10 (low NIC, L), and 50 (high NIC, H) µg/L NIC for 120 h and our results demonstrated that NIC exposure induced severe pathological changes in the liver of P. sinensis. And the typical symptom included edema, nuclear migration and deformation, and vacuolization. Compared with the liver, the NIC exposure did not cause significant damage in the gut tissue. In addition, the DHE staining demonstrated that the ROS production of liver and gut increased with the increase in concentration of NIC. The activities of antioxidant enzymes including superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) was inhibited with increased malondialdehyde (MDA) content, indicating that the antioxidant defense was significantly perturbed. Further, the transcriptome sequencing and was applied to evaluate the underlying toxicity mechanisms of NIC exposure in liver and gut of P. sinensis. Pathway enrichment showed that the disorder of lipid metabolism and innate immune regulation, including Toll-like receptors (TLRs), tumor necrosis factor (TNF), lectins, and complement and coagulation cascades, were toxicological properties of NIC on P. sinensis. Overall, the current study provides valuable information to understand the toxic effect of NIC on Chinese soft-shelled turtle.