Uncovering specific taxonomic and functional alteration of gut microbiota in chronic kidney disease through 16S rRNA data.

Introduction: Chronic kidney disease (CKD) is worldwide healthcare burden with growing incidence and death rate. Emerging evidence demonstrated the compositional and functional differences of gut microbiota in patients with CKD. As such, gut microbial features can be developed as diagnostic biomarkers and potential therapeutic target for CKD. Methods: To eliminate the outcome bias arising from factors such as geographical distribution, sequencing platform, and data analysis techniques, we conducted a comprehensive analysis of the microbial differences between patients with CKD and healthy individuals based on multiple samples worldwide. A total of 980 samples from six references across three nations were incorporated from the PubMed, Web of Science, and GMrepo databases. The obtained 16S rRNA microbiome data were subjected to DADA2 processing, QIIME2 and PICRUSt2 analyses. Results: The gut microbiota of patients with CKD differs significantly from that of healthy controls (HC), with a substantial decrease in the microbial diversity among the CKD group. Moreover, a significantly reduced abundance of bacteria Faecalibacterium prausnitzii (F. prausnitzii) was detected in the CKD group through linear discriminant analysis effect size (LEfSe) analysis, which may be associated with the alleviating effects against CKD. Notably, we identified CKD-depleted F. prausnitzii demonstrated a significant negative correlation with three pathways based on predictive functional analysis, suggesting its potential role in regulating systemic acidbase disturbance and pro-oxidant metabolism. Discussion: Our findings demonstrated notable alterations of gut microbiota in CKD patients. Specific gut-beneficial microbiota, especially F. prausnitzii, may be developed as a preventive and therapeutic tool for CKD clinical management.

Fabrication of NiCo Bimetallic MOF Films on 3D Foam with Assistance of Atomic Layer Deposition for Non-Invasive Lactic Acid Sensing.

Lactic acid (LA) is an important downstream product of glycolysis in living cells and is abundant in our body fluids, which are strongly associated with diseases. The development of enzyme-free LA sensors with high sensitivity and low consumption remains a challenge. 2D metal-organic frameworks (MOFs) are considered to be promising electrochemical sensing materials and have attracted much attention in recent years. Compared to monometallic MOFs, the construction of bimetallic MOFs (BMOFs) can obtain a larger specific surface area, thereby increasing the exposed active site. 3D petal-like NixCoy MOF films on nickel foams (NixCoy BMOF@Ni foams) are successfully prepared by combining atomic layer deposition-assisted technology and hydrothermal strategy. The established NixCoy BMOF@Ni foams demonstrate noticeable LA sensing activity, and the study is carried out on behalf of the Ni1Co5 BMOF@Ni foam, which has a sensitivity of up to 9030 µA mM-1 cm-2 with a linear range of 0.01-2.2 mM and the detection limit is as low as 0.16 µM. Additionally, the composite has excellent stability and repeatability for the detection of LA under a natural air environment with high accuracy and reliability. Density functional theory calculation is applied to study the reaction process between composites and LA, and the result suggests that the active site in the NiCo BMOF film favors the adsorption of LA relative to the active site of monometallic MOF film, resulting in improved performance. The developed composite has a great potential for the application of noninvasive LA biosensors.

Design and Synthesis of Transferrable Macro-Sized Continuous Free-Standing Metal-Organic Framework Films for Biosensor Device.

Metal organic framework (MOF) films have attracted abundant attention due to their unique characters compared with MOF particles. But the high-temperature reaction and solvent corrosion limit the preparation of MOF films on fragile substrates, hindering further applications. Fabricating macro-sized continuous free-standing MOF films and transferring them onto fragile substrates are a promising alternative but still challenging. Here, a universal strategy to prepare transferrable macro-sized continuous free-standing MOF films with the assistance of oxide nanomembranes prepared by atomic layer deposition and studied the growth mechanism is developed. The oxide nanomembranes serve not only as reactant, but also as interfacial layer to maintain the integrality of the free-standing structure as the stacked MOF particles are supported by the oxide nanomembrane. The centimeter-scale free-standing MOF films can be transferred onto fragile substrates, and all in one device for glucose sensing is assembled. Due to the strong adsorption toward glucose molecules, the obtained devices exhibit outstanding performance in terms of high sensitivity, low limit of detection, and long durability. This work opens a new window toward the preparation of MOF films and MOF film-based biosensor chip for advantageous applications in post-Moore law period.

Rivastigmine nasal spray for the treatment of Alzheimer's Disease: Olfactory deposition and brain delivery.

Alzheimer's disease (AD) is characterized by a gradual decline in cognitive function and memory impairment, significantly impacting the daily lives of patients. Rivastigmine (RHT), a cholinesterase inhibitor, is used to treat mild to moderate AD via oral administration. However, oral administration is associated with slow absorption rate and severe systemic side effects. RHT nasal spray (RHT-ns), as a nose-to-brain delivery system, is more promising for AD management due to its efficient brain delivery and reduced peripheral exposure. This study constructed RHT-ns for enhancing AD treatment efficacy, and meanwhile the correlation between drug olfactory deposition and drug entering into the brain was explored. A 3D-printed nasal cast was employed to quantify the drug olfactory deposition. Brain delivery of RHT-ns was quantified using fluorescence tracking and Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) analysis, which showed a good correlation to the olfactory deposition. F2 (containing 1% (w/v) viscosity modifier Avicel® RC-591) with high olfactory deposition and drug brain delivery was further investigated for pharmacodynamics study. F2 exhibited superiority in AD treatment over the commercially available oral formulation. In summary, the present study showed the successful development of RHT-ns with improved olfactory deposition and enhanced brain delivery. It might provide new insight into the design and development of nose-to-brain systems for the treatment of AD.

Polymyxin B sulfate inhalable microparticles with high-lectin-affinity sugar carriers for efficient treatment of biofilm-associated pulmonary infections.

Pulmonary infections caused by multidrug-resistant bacteria have become a significant threat to human health. Bacterial biofilms exacerbate the persistence and recurrence of pulmonary infections, hindering the accessibility and effectiveness of antibiotics. In this study, a dry powder inhalation (DPI) consisting of polymyxin B sulfate (PMBS) inhalable microparticles and high-lectin-affinity (HLA) sugar (i.e., raffinose) carriers was developed for treating pulmonary infections and targeting bacterial lectins essential for biofilm growth. The formulated PMBS-HLA DPIs exhibited particle sizes of approximately 3 µm, and surface roughness varied according to the drug-to-carrier ratio. Formulation F5 (PMBS: raffinose = 10:90) demonstrated the highest fine particle fraction (FPF) value (64.86%), signifying its substantially enhanced aerosol performance, potentially attributable to moderate roughness and smallest mass median aerodynamic particle size. The efficacy of PMBS-HLA DPIs in inhibiting biofilm formation and eradicating mature biofilms was significantly improved with the addition of raffinose, suggesting the effectiveness of lectin-binding strategy for combating bacterial biofilm-associated infections. In rat models with acute and chronic pulmonary infections, F5 demonstrated superior bacterial killing and amelioration of inflammatory responses compared to spray-dried PMBS (F0). In conclusion, our HLA carrier-based formulation presents considerable potential for the efficient treatment of multidrug-resistant bacterial biofilm-associated pulmonary infections.

Corrigendum: Discriminative analysis of schizophrenia patients using graph convolutional networks: a combined multimodal MRI and connectomics analysis.

[This corrects the article DOI: 10.3389/fnins.2023.1140801.].

PDE4D/cAMP/IL-23 axis determines the immunotherapy efficacy of lung adenocarcinoma via activating the IL-9 autocrine loop of cytotoxic T lymphocytes.

Although immunotherapy has changed the prognosis of many advanced malignancies including lung adenocarcinoma (LUAD), many patients are insensitive to the drugs, with the mechanisms yet to be elucidated. Herein, we identified PDE4D as an immunotherapy efficacy-related gene through bioinformatics screening. By using a co-culture system of LUAD cells and tumor-cell-specific CD8+ T cells, a functional PDE4D/cAMP/IL-23 axis was further revealed in LUAD cells. Fluorescent multiplex immunohistochemistry analysis of patient-derived samples and the in vivo mouse LUAD xenograft tumors revealed not only the colocalization of IL-23 and CD8+ T cells but also the immune potentiating effect of IL-23 on cytotoxic T lymphocytes (CTLs) in LUAD tissues. Through transcriptome sequencing and functional validations, IL-23 was proven to up-regulate IL-9 expression in CTLs via activating the NF-κB signaling, leading to elevated productions of immune effector molecules and enhanced efficacy of antitumor immunotherapy. Interestingly, an autocrine loop of IL-9 was also uncovered during this process. In conclusion, PDE4D/cAMP/IL-23 axis determines the immunotherapy efficacy of human LUAD. This effect is mediated by the activation of an NF-κB-dependent IL-9 autocrine loop in CTLs.

Transformation of ALK-positive NSCLC to SCLC after alectinib resistance and response to combined atezolizumab: a case report.

Background: The genotypic and histological evolution of non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) has been described as a mechanism of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (TKIs). However, it was extremely rare in anaplastic lymphoma kinase (ALK) positive NSCLC, and the follow-up care and outcomes of patients with this rare condition were unclear. This case was the first described the effectiveness of combined chemo-immunotherapy in a patient, with a transformed ALK positive NSCLC into SCLC after the administration of an ALK-TKIs. Case Description: We described a unique case in which a patient with ALK-positive NSCLC underwent SCLC transformation at a metastatic site and remained ALK positive after TKI treatment. In July 2019, a 77-year-old man was diagnosed with ALK-positive stage IVB NSCLC, received alectinib and responded to alectinib. It was not until more than 7 months later that a cranial MRI showed brain metastases. And whole-brain radiotherapy was administered, and secondary epilepsy and metastatic progression occurred. One year later, computed tomography showed a left submandibular mass with multiple lymph node metastases, a left lower lung mass, and right pleura thickening. A left submandibular biopsy revealed SCLC. Echinoderm microtubule-associated protein-like 4-ALK (EML4-ALK) fusion and low tumor mutation burden (2.23 muts/Mb) were identified by next generation sequencing. The patient was administered atezolizumab (1,200 mg, d1) in combination with etoposide (0.13 g, d1-d3) and carboplatin (350 mg, d1). The left neck mass was reduced significantly, showing a partial response. Serum NSE (from 106 to 15 ng/mL), CA19-9 (from 49.4 to 34.6 U/mL) and CEA (from 4.18 to 3.09 ng/mL) returned to normal. Only mild myelosuppression (Grade 1), fatigue (Grade 1), and anorexia (Grade 1) were present. The patient had an overall survival time of 21 months. Conclusions: This case highlighted the importance of re-biopsies to reveal pathological SCLC transformation after ALK-TKI resistance, and suggested the treatment of atezolizumab in combination with etoposide and carboplatin were potentially helpful for this phenotype.

Discriminative analysis of schizophrenia patients using graph convolutional networks: A combined multimodal MRI and connectomics analysis.

Introduction: Recent studies in human brain connectomics with multimodal magnetic resonance imaging (MRI) data have widely reported abnormalities in brain structure, function and connectivity associated with schizophrenia (SZ). However, most previous discriminative studies of SZ patients were based on MRI features of brain regions, ignoring the complex relationships within brain networks. Methods: We applied a graph convolutional network (GCN) to discriminating SZ patients using the features of brain region and connectivity derived from a combined multimodal MRI and connectomics analysis. Structural magnetic resonance imaging (sMRI) and resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 140 SZ patients and 205 normal controls. Eighteen types of brain graphs were constructed for each subject using 3 types of node features, 3 types of edge features, and 2 brain atlases. We investigated the performance of 18 brain graphs and used the TopK pooling layers to highlight salient brain regions (nodes in the graph). Results: The GCN model, which used functional connectivity as edge features and multimodal features (sMRI + fMRI) of brain regions as node features, obtained the highest average accuracy of 95.8%, and outperformed other existing classification studies in SZ patients. In the explainability analysis, we reported that the top 10 salient brain regions, predominantly distributed in the prefrontal and occipital cortices, were mainly involved in the systems of emotion and visual processing. Discussion: Our findings demonstrated that GCN with a combined multimodal MRI and connectomics analysis can effectively improve the classification of SZ at an individual level, indicating a promising direction for the diagnosis of SZ patients. The code is available at https://github.com/CXY-scut/GCN-SZ.git.

Growth Control of Metal-Organic Framework Films on Marine Biological Carbon and Their Potential-Dependent Dopamine Sensing.

Ever-evolving advancements in films have fueled many of the developments in the field of electrochemical sensors. For biosensor application platforms, the fabrication of metal-organic framework (MOF) films on microscopically structured substrates is of tremendous importance. However, fabrication of MOF film-based electrodes always exhibits unsatisfactory performance, and the mechanisms of the fabrication and sensing application of the corresponding composites also need to be explored. Here, we report the fabrication of conformal MIL-53 (Fe) films on carbonized natural seaweed with the assistance of an oxide nanomembrane and a potential-dependent electrochemical dopamine (DA) sensor. The geometry and structure of the composite can be conveniently tuned by the experimental parameters, while the sensing performance is significantly influenced by the applied potential. The obtained sensor demonstrates ultrahigh sensitivity, a wide linear range, a low limit of detection, and a good distinction between DA and ascorbic acid at an optimized potential of 0.3 V. The underneath mechanism is investigated in detail with the help of theoretical calculations. This work bridges the natural material and MOF films and is promising for future biosensing applications.

Doxycycline-dependent Cas9-expressing pig resources for conditional in vivo gene nullification and activation.

BACKGROUND: CRISPR-based toolkits have dramatically increased the ease of genome and epigenome editing. SpCas9 is the most widely used nuclease. However, the difficulty of delivering SpCas9 and inability to modulate its expression in vivo hinder its widespread adoption in large animals. RESULTS: Here, to circumvent these obstacles, a doxycycline-inducible SpCas9-expressing (DIC) pig model was generated by precise knock-in of the binary tetracycline-inducible expression elements into the Rosa26 and Hipp11 loci, respectively. With this pig model, in vivo and/or in vitro genome and epigenome editing could be easily realized. On the basis of the DIC system, a convenient Cas9-based conditional knockout strategy was devised through controlling the expression of rtTA component by tissue-specific promoter, which allows the one-step generation of germline-inherited pigs enabling in vivo spatiotemporal control of gene function under simple chemical induction. To validate the feasibility of in vivo gene mutation with DIC pigs, primary and metastatic pancreatic ductal adenocarcinoma was developed by delivering a single AAV6 vector containing TP53-sgRNA, LKB1-sgRNA, and mutant human KRAS gene into the adult pancreases. CONCLUSIONS: Together, these results suggest that DIC pig resources will provide a powerful tool for conditional in vivo genome and epigenome modification for fundamental and applied research.

TAK1 Activation by NLRP3 Deficiency Confers Cardioprotection Against Pressure Overload-Induced Cardiomyocyte Pyroptosis and Hypertrophy.

A comprehensive view of the role of NLRP3/caspase-1/GSDMD-mediated pyroptosis in pressure overload cardiac hypertrophy is presented in this study. Furthermore, mitigation of NLRP3 deficiency-induced pyroptosis confers cardioprotection against pressure overload through activation of TAK1, whereas this salutary effect is abolished by inhibition of TAK1 activity, highlighting a previously unrecognized reciprocally regulatory role of NLRP3-TAK1 governing inflammation-induced cell death and hypertrophic growth. Translationally, this study advocates strategies based on inflammation-induced cell death might be exploited therapeutically in other inflammatory and mechanical overload disorders, such as myocardial infarction and mitral regurgitation.

Nanomembrane-assembled nanophotonics and optoelectronics: from materials to applications.

Nanophotonics and optoelectronics are the keys to the information transmission technology field. The performance of the devices crucially depends on the light-matter interaction, and it is found that three-dimensional (3D) structures may be associated with strong light field regulation for advantageous application. Recently, 3D assembly of flexible nanomembranes has attracted increasing attention in optical field, and novel optoelectronic device applications have been demonstrated with fantastic 3D design. In this review, we first introduce the fabrication of various materials in the form of nanomembranes. On the basis of the deformability of nanomembranes, 3D structures can be built by patterning and release steps. Specifically, assembly methods to build 3D nanomembrane are summarized as rolling, folding, buckling and pick-place methods. Incorporating functional materials and constructing fine structures are two important development directions in 3D nanophotonics and optoelectronics, and we settle previous researches on these two aspects. The extraordinary performance and applicability of 3D devices show the potential of nanomembrane assembly for future optoelectronic applications in multiple areas.

Association of serum klotho levels with different-staged vascular calcification status in patients with maintenance hemodialysis.

BACKGROUND: Vascular calcification (VC) is suggested to be associated with serum klotho levels in patients with maintenance hemodialysis (MHD), whereas there is a lack of reports on the associations of VC status in whole arteries with serum klotho contents. METHODS: One hundred forty eligible patients with MHD and a total of age-and gender-matched normal controls (NCs) were recruited. We analyzed the VC statuses of large arteries and peripheral muscular arteries by calculating the sum of scores from each artery. The levels of serum klotho were determined by ELISA. In addition, the relationship between serum klotho and VC status was evaluated using correlation analysis and regression analysis. RESULTS: The VC severity in MHD patients tended to be worse in comparison with NCs. Serum klotho level in patients with MHD was lower than that in the NC subjects (​P < 0.0001), which was correlated with VC scores as reflected by correlation analysis and regression analysis. Serum klotho concentrations exhibited a dynamic decline along with increased VC status stages. Subjects with higher levels of serum klotho had a higher prevalence of cardiovascular events. CONCLUSION: Our study indicates serum klotho is strongly associated with VC status in a stage-dependent manner.

MADET: a Manually Curated Knowledge Base for Microbiomic Effects on Efficacy and Toxicity of Anticancer Treatments.

A plethora of studies have reported the associations between microbiota and multiple diseases, leading to the development of at least four databases to demonstrate microbiota-disease associations, i.e., gutMDisorder, mBodyMap, Gmrepo, and Amadis. Moreover, gut microbiota mediates drug efficacy and toxicity, whereas a comprehensive database to elucidate the microbiota-drug associations is lacking. Here, we report an open-access knowledge base, MADET (Microbiomics of Anticancer Drug Efficacy and Toxicity), which harbors 483 manually annotated microbiota-drug associations from 26 studies. MADET provides user-friendly functions allowing users to freely browse, search, and download data conveniently from the database. Users can customize their search filters in MADET using different types of keywords, including bacterial name (e.g., Akkermansia muciniphila), anticancer treatment (e.g., anti-PD-1 therapy), and cancer type (e.g., lung cancer) with different types of experimental evidence of microbiota-drug association and causation. We have also enabled user submission to further enrich the data documented in MADET. The MADET database is freely available at https://www.madet.info. We anticipate that MADET will serve as a useful resource for a better understanding of microbiota-drug associations and facilitate the future development of novel biomarkers and live biotherapeutic products for anticancer therapies. IMPORTANCE Human microbiota plays an important role in mediating drug efficacy and toxicity in anticancer treatment. In this work, we developed a comprehensive online database, which documents over 480 microbiota-drug associations manually curated from 26 research articles. Users can conveniently browse, search, and download the data from the database. Search filters can be customized using different types of keywords, including bacterial name (e.g., Akkermansia muciniphila), anticancer treatment (e.g., anti-PD-1 therapy), and cancer type (e.g., lung cancer), with different types of experimental evidence of microbiota-drug association. We anticipate that this database will serve as a convenient platform for facilitating research on microbiota-drug associations, including the development of novel biomarkers for predicting drug outcomes as well as novel live biotherapeutic products for improving the outcomes of anticancer drugs.

Metagenomic and metabolomic analyses reveal synergistic effects of fecal microbiota transplantation and anti-PD-1 therapy on treating colorectal cancer.

Anti-PD-1 immunotherapy has saved numerous lives of cancer patients; however, it only exerts efficacy in 10-15% of patients with colorectal cancer. Fecal microbiota transplantation (FMT) is a potential approach to improving the efficacy of anti-PD-1 therapy, whereas the detailed mechanisms and the applicability of this combination therapy remain unclear. In this study, we evaluated the synergistic effect of FMT with anti-PD-1 in curing colorectal tumor-bearing mice using a multi-omics approach. Mice treated with the combination therapy showed superior survival rate and tumor control, compared to the mice received anti-PD-1 therapy or FMT alone. Metagenomic analysis showed that composition of gut microbiota in tumor-bearing mice treated with anti-PD-1 therapy was remarkably altered through receiving FMT. Particularly, Bacteroides genus, including FMT-increased B. thetaiotaomicron, B. fragilis, and FMT-decreased B. ovatus might contribute to the enhanced efficacy of anti-PD-1 therapy. Furthermore, metabolomic analysis upon mouse plasma revealed several potential metabolites that upregulated after FMT, including punicic acid and aspirin, might promote the response to anti-PD-1 therapy via their immunomodulatory functions. This work broadens our understanding of the mechanism by which FMT improves the efficacy of anti-PD-1 therapy, which may contribute to the development of novel microbiota-based anti-cancer therapies.

Effects of microbiota on anticancer drugs: Current knowledge and potential applications.

Over the last decade, mounting evidence has revealed the key roles of gut microbiota in modulating the efficacy and toxicity of anticancer drugs, via mechanisms such as immunomodulation and microbial enzymatic degradation. As such, human microbiota presents as an exciting prospect for developing biomarkers for predicting treatment outcomes and interventional approaches for improving therapeutic effects. In this review, we analyze the current knowledge of the interplays among gut microorganisms, host responses and anticancer therapies (including cytotoxic chemotherapy and targeted therapy), with an emphasis on the immunomodulation function of microbiota which facilitates the efficacy of immune checkpoint inhibitors. Moreover, we propose several microbiota-modulating strategies including fecal microbiota transplantation and probiotics, which can be pursued to optimize the use and development of anticancer treatments. We anticipate that future clinical and preclinical studies will highlight the significance of human microbiome as a promising target towards precision medicine in cancer therapies. FUNDING: National Key Research and Development Program of China (2020YFA0907800), Shenzhen Science and Technology Innovation Program (KQTD20200820145822023) and National Natural Science Foundation of China (31900056 and 32000096).

Double knock-in pig models with elements of binary Tet-On and phiC31 integrase systems for controllable and switchable gene expression.

Inducible expression systems are indispensable for precise regulation and in-depth analysis of biological process. Binary Tet-On system has been widely employed to regulate transgenic expression by doxycycline. Previous pig models with tetracycline regulatory elements were generated through random integration. This process often resulted in uncertain expression and unpredictable phenotypes, thus hindering their applications. Here, by precise knock-in of binary Tet-On 3G elements into Rosa26 and Hipp11 locus, respectively, a double knock-in reporter pig model was generated. We characterized excellent properties of this system for controllable transgenic expression both in vitro and in vivo. Two attP sites were arranged to flank the tdTomato to switch reporter gene. Single or multiple gene replacement was efficiently and faithfully achieved in fetal fibroblasts and nuclear transfer embryos. To display the flexible application of this system, we generated a pig strain with Dox-inducing hKRASG12D expression through phiC31 integrase-mediated cassette exchange. After eight months of Dox administration, squamous cell carcinoma developed in the nose, mouth, and scrotum, which indicated this pig strain could serve as an ideal large animal model to study tumorigenesis. Overall, the established pig models with controllable and switchable transgene expression system will provide a facilitating platform for transgenic and biomedical research.

Pulmonary delivery nanomedicines towards circumventing physiological barriers: Strategies and characterization approaches.

Pulmonary delivery of nanomedicines is very promising in lung local disease treatments whereas several physiological barriers limit its application via the interaction with inhaled nanomedicines, namely bio-nano interactions. These bio-nano interactions may affect the pulmonary fate of nanomedicines and impede the distribution of nanomedicines in its targeted region, and subsequently undermine the therapeutic efficacy. Pulmonary diseases are under worse scenarios as the altered physiological barriers generally induce stronger bio-nano interactions. To mitigate the bio-nano interactions and regulate the pulmonary fate of nanomedicines, a number of manipulating strategies were established based on size control, surface modification, charge tuning and co-delivery of mucolytic agents. Visualized and non-visualized characterizations can be employed to validate the robustness of the proposed strategies. This review provides a guiding overview of the physiological barriers affecting the in vivo fate of inhaled nanomedicines, the manipulating strategies, and the validation methods, which will assist with the rational design and application of pulmonary nanomedicine.

Multimodal Magnetic Resonance Imaging Reveals Aberrant Brain Age Trajectory During Youth in Schizophrenia Patients.

Accelerated brain aging had been widely reported in patients with schizophrenia (SZ). However, brain aging trajectories in SZ patients have not been well-documented using three-modal magnetic resonance imaging (MRI) data. In this study, 138 schizophrenia patients and 205 normal controls aged 20-60 were included and multimodal MRI data were acquired for each individual, including structural MRI, resting state-functional MRI and diffusion tensor imaging. The brain age of each participant was estimated by features extracted from multimodal MRI data using linear multiple regression. The correlation between the brain age gap and chronological age in SZ patients was best fitted by a positive quadratic curve with a peak chronological age of 47.33 years. We used the peak to divide the subjects into a youth group and a middle age group. In the normal controls, brain age matched chronological age well for both the youth and middle age groups, but this was not the case for schizophrenia patients. More importantly, schizophrenia patients exhibited increased brain age in the youth group but not in the middle age group. In this study, we aimed to investigate brain aging trajectories in SZ patients using multimodal MRI data and revealed an aberrant brain age trajectory in young schizophrenia patients, providing new insights into the pathophysiological mechanisms of schizophrenia.