Mid-Pleistocene climate transition triggered by Antarctic Ice Sheet growth.

Despite extensive investigation, the nature and causes of the Mid-Pleistocene Transition remain enigmatic. In this work, we assess its linkage to asynchronous development of bipolar ice sheets by synthesizing Pleistocene mid- to high-latitude proxy records linked to hemispheric ice sheet evolution. Our results indicate substantial growth of the Antarctic Ice Sheets (AISs) at 2.0 to 1.25 million years ago, preceding the rapid expansion of Northern Hemisphere Ice Sheets after ~1.25 million years ago. Proxy-model comparisons suggest that AIS and associated Southern Ocean sea ice expansion can induce northern high-latitude cooling and enhanced moisture transport to the Northern Hemisphere, thus triggering the Mid-Pleistocene Transition. The dynamic processes involved are crucial for assessing modern global warming that is already inducing asynchronous bipolar melting of ice sheets.

The application of gradually expanding pedicle technology in the placement of screws in thinner pedicle of patients with idiopathic scoliosis.

Objective: To propose a technique of gradual expansion of pedicle diameter to place screws on the thinner pedicle that is difficult to place screws in scoliosis orthopedic surgery, in order to place thicker pedicle screws in the premise of good safety to achieve good stability and orthopaedic effect. Methods: The authors reviewed that 36 patients with Adolescent idiopathic scoliosis (AIS) (20 females, 16 males) in our department from June 2020 to March 2024 underwent posterior spinal correction and internal fixation were enrolled in the present study. 194 pedicles had narrower diameter ranging from 0 mm to 4.5 mm. After analysis, 155 pedicles (internal diameter: 2.5 mm-4.5 mm) were treated with gradually expanding pedicles technology. The angle between the inserted screws and the upper endplate of the vertebral body was measured 1 week after operation and 3 months after operation to evaluate the placement of the screws after pedicle expansion. Results: All operations were completed without dura mater rupture, nerve root injury, infection and poor incision healing. There was no screw breaking or screw pull-out in DR film at 3 months after operation compared with 1 week after operation. There was no significant difference in the angle between screw and upper endplate measured by the three observers at 3 months and 1 week after operation (Wilcoxon's signed rank test, p > 0.05). In the measurement at 1 week or 3 months after operation, there was no statistically significant difference among the three observers. There is a good consistency between the observers (Cronbach's alpha > 0.80). Conclusion: In AIS patients, the thinner pedicle with a diameter range of 2.5 mm to 4.5 mm can be safely inserted with relatively thicker pedicle screws after gradually expanding pedicle technology.

Development of a Sensitive High-throughput Enzymatic Assay Capable of Measuring Sub-nanomolar Inhibitors of SARS-CoV2 Mpro.

The SARS-CoV-2 main protease (Mpro) is essential for viral replication because it is responsible for the processing of most of the non-structural proteins encoded by the virus. Inhibition of Mpro prevents viral replication and therefore constitutes an attractive antiviral strategy. We set out to develop a high-throughput Mpro enzymatic activity assay using fluorescently labeled peptide substrates. A library of fluorogenic substrates of various lengths, sequences and dye/quencher positions was prepared and tested against full length SARS-CoV-2 Mpro enzyme for optimal activity. The addition of buffers containing strongly hydrated kosmotropic anion salts, such as citrate, from the Hofmeister series significantly boosted the enzyme activity and enhanced the assay detection limit, enabling the ranking of sub-nanomolar inhibitors without relying on the low-throughput Morrison equation method. By comparing cooperativity in citrate or non-citrate buffer while titrating the Mpro enzyme concentration, we found full positive cooperativity of Mpro with citrate buffer at less than one nanomolar (nM), but at a much higher enzyme concentration (∼320 nM) with non-citrate buffer. In addition, using a tight binding Mpro inhibitor, we confirmed there was only one active catalytical site in each Mpro monomer. Since cooperativity requires at least two binding sites, we hypothesized that citrate facilitates dimerization of Mpro at sub-nanomolar concentration as one of the mechanisms enhances Mpro catalytic efficiency. This assay has been used in high-throughput screening and structure activity relationship (SAR) studies to support medicinal chemistry efforts. IC50 values determined in this assay correlates well with EC50 values generated by a SARS-CoV-2 antiviral assay after adjusted for cell penetration.

Modeling gastric intestinal metaplasia in 3D organoids using nitrosoguanidine.

Gastric intestinal metaplasia (GIM) represents a precancerous stage characterized by morphological and pathophysiological changes in the gastric mucosa, where gastric epithelial cells transform into a phenotype resembling that of intestinal cells. Previous studies have demonstrated that the intragastric administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induces both gastric carcinoma and intestinal metaplasia in mice. Here, we show that MNNG induces GIM in three-dimensional (3D) mouse organoids. Our histological analyses reveal that MNNG-induced gastric organoids undergo classical morphological alterations, exhibiting a distinct up-regulation of CDX2 and MUC2, along with a down-regulation of ATP4B and MUC6. Importantly, metaplastic cells observed in MNNG-treated organoids originate from MIST1+ cells, indicating their gastric chief cell lineage. Functional analyses show that activation of the RAS signaling pathway drives MNNG-induced metaplasia in 3D organoids, mirroring the characteristics observed in human GIM. Consequently, modeling intestinal metaplasia using 3D organoids offers valuable insights into the molecular mechanisms and spatiotemporal dynamics of the gastric epithelial lineage during the development of intestinal metaplasia within the gastric mucosa. We conclude that the MNNG-induced metaplasia model utilizing 3D organoids provides a robust platform for developing preventive and therapeutic strategies to mitigate the risk of gastric cancer before precancerous lesions occur.

i-PI 3.0: A flexible and efficient framework for advanced atomistic simulations.

Atomic-scale simulations have progressed tremendously over the past decade, largely thanks to the availability of machine-learning interatomic potentials. These potentials combine the accuracy of electronic structure calculations with the ability to reach extensive length and time scales. The i-PI package facilitates integrating the latest developments in this field with advanced modeling techniques thanks to a modular software architecture based on inter-process communication through a socket interface. The choice of Python for implementation facilitates rapid prototyping but can add computational overhead. In this new release, we carefully benchmarked and optimized i-PI for several common simulation scenarios, making such overhead negligible when i-PI is used to model systems up to tens of thousands of atoms using widely adopted machine learning interatomic potentials, such as Behler-Parinello, DeePMD, and MACE neural networks. We also present the implementation of several new features, including an efficient algorithm to model bosonic and fermionic exchange, a framework for uncertainty quantification to be used in conjunction with machine-learning potentials, a communication infrastructure that allows for deeper integration with electronic-driven simulations, and an approach to simulate coupled photon-nuclear dynamics in optical or plasmonic cavities.

Efficient Biosynthesis of (+)-α-Pinene and de Novo Synthesis of (+)-cis-Verbenol in Escherichia coli.

Bark beetles, major pests that bore into forest stems, cause significant economic damage to forests globally. (+)-α-Pinene is the precursor to (+)-cis-verbenol, a crucial component of the aggregation pheromones produced by bark beetles. This paper describes the de novo synthesis of (+)-cis-verbenol in Escherichia coli. Initially, the truncation position of (+)-α-pinene synthase (PtPS30 from Pinus taeda) and monoterpene precursor (geranyl diphosphate/neryl diphosphate) synthases were evaluated. Neryl diphosphate synthase from Solanum lycopersicum (SlNPPS1) and truncated (+)-α-pinene synthase (PtPS30-39) were selected as promising candidates. Subsequently, the titer of (+)-α-pinene was significantly increased 8.9-fold by using the fusion tag CM29, which enhanced the solubility of PtPS30-39. In addition, by optimizing expression elements (ribosomal binding sites, linkers, and up elements) and overexpressing CM29*PtPS30-39, a yield of 134.12 mg/L (+)-α-pinene was achieved. Finally, the first de novo synthesis of enantiopure (+)-cis-verbenol was achieved by introducing a cytochrome P450 mutant from Pseudomonas putida (P450camF89W,Y98F,L246A), resulting in a yield of 11.13 mg/L. This study lays the groundwork for developing verbenol-based trapping technology for controlling bark beetles.

Integrating Molecular Motions in Ternary Cocrystals for NIR-II Photothermal Conversion.

Organic photothermal conversion materials hold immense promise for various applications owing to their structural flexibility. Recent research has focused on enhancing near-infrared (NIR) absorption and mitigating radiative transition processes. In this study, we have developed a viable approach to the design of photothermal conversion materials through the construction of ternary organic cocrystals, by introducing a third component as a molecular blocker and motion unit into a binary donor-acceptor system. Superstructural and photophysical properties of the ternary cocrystals were characterized using various spectroscopic techniques. The role of the molecular blocker in radical stabilization and photothermal conversion were demonstrated. Intriguingly, the motions of the entire pyrene molecules in the cocrystal have been observed by variable temperature single-crystal X-ray diffraction results. The excellent performance of ternary cocrystal as a photothermal material was validated through efficient NIR-II photothermal and solar-driven water evaporation experiments. The efficiency of water evaporation reached 88.7 %, with a corresponding evaporation rate of 1.29 kg m-2 h-1, representing excellent performance among pure organic small molecular photothermal conversion materials. Our research underscores the introduction of molecular blockers and motion units to stabilize radicals and produce outstanding photothermal conversion materials, offering new pathways for developing efficient and stable photothermal conversion materials.

Newborn concurrent hearing and genetic screening for hearing impairment: A systematic review and meta­analysis.

Hearing loss is the most prevalent neurosensory disorder in humans, with significant implications for language, social and cognitive development if not diagnosed and treated early. The present systematic review and meta-analysis aimed to determine the rate of hearing screening pass and genetic screening failure [universal newborn hearing screening (UNHS) pass/genetic failure] and to investigate the advantages of combining newborn hearing and genetic screening for newborn hearing impairment. The PubMed, Embase and Cochrane databases were searched from inception to September 2023 to identify studies reporting the combination of neonatal hearing screening with genetic screening. Duplicate literature, unpublished literature, studies with incomplete data, animal experiments, literature reviews and systematic studies were excluded. All the data were processed by STATA15.1 statistical software. A total of nine cross-sectional studies were included in this meta-analysis. The sample sizes ranged from 1,716 to 180,469, and there were a total of 377,688 participants. The pooled results revealed that the prevalence of passing the UNHS while failing genetic screening was 0.31% (95% CI, 0.22-0.41%). The prevalence of UNHS pass and gap junction protein beta 2 and solute carrier family 26 member 4 variant screen failure was 0.01% (95% CI, 0.00-0.02%) and 0.00% (95% CI, 0.00%), respectively, while the prevalence of mitochondrially encoded 12S RRNA variant screening failure and UNHS pass was 0.21% (95% CI, 0.18-0.26%). Combined screening has a significant advantage over pure hearing screening, especially in terms of identifying newborns with mitochondrial gene mutations that render them sensitive to certain medications. In clinical practice, decision-makers can consider practical circumstances and leverage the benefits of combined newborn hearing and genetic screening for early diagnosis, early counseling, and early intervention in patients with hearing loss.

Based on 3D-PDU and clinical characteristics nomogram for prediction of lymph node metastasis and lymph-vascular space invasion of early cervical cancer preoperatively.

PURPOSE: To develop and validate a nomogram based on 3D-PDU parameters and clinical characteristics to predict LNM and LVSI in early-stage cervical cancer preoperatively. MATERIALS AND METHODS: A total of first diagnosis 138 patients with cervical cancer who had undergone 3D-PDU examination before radical hysterectomy plus lymph dissection between 2014 and 2019 were enrolled for this study. Multivariate logistic regression analyses were performed to analyze the 3D-PDU parameters and selected clinicopathologic features and develop a nomogram to predict the probability of LNM and LVSI in the early stage. ROC curve was used to evaluate model differentiation, calibration curve and Hosmer-Lemeshow test were used to evaluate calibration, and DCA was used to evaluate clinical practicability. RESULTS: Menopause status, FIGO stage and VI were independent predictors of LNM. BMI and maximum tumor diameter were independent predictors of LVSI. The predicted AUC of the LNM and LSVI models were 0.845 (95%CI,0.765-0.926) and 0.714 (95%CI,0.615-0.813). Calibration curve and H-L test (LNM groups P = 0.478; LVSI P = 0.783) all showed that the predicted value of the model had a good fit with the actual observed value, and DCA indicated that the model had a good clinical net benefit. CONCLUSION: The proposed nomogram based on 3D-PDU parameters and clinical characteristics has been proposed to predict LNM and LVSI with high accuracy, demonstrating for the first time the potential of non-invasive prediction. The probability derived from this nomogram may have the potential to provide valuable guidance for physicians to develop clinical individualized treatment plans of FIGO patients with early cervical cancer.

Transcriptomic decoding of regional cortical vulnerability to major depressive disorder.

Previous studies in small samples have identified inconsistent cortical abnormalities in major depressive disorder (MDD). Despite genetic influences on MDD and the brain, it is unclear how genetic risk for MDD is translated into spatially patterned cortical vulnerability. Here, we initially examined voxel-wise differences in cortical function and structure using the largest multi-modal MRI data from 1660 MDD patients and 1341 controls. Combined with the Allen Human Brain Atlas, we then adopted transcription-neuroimaging spatial correlation and the newly developed ensemble-based gene category enrichment analysis to identify gene categories with expression related to cortical changes in MDD. Results showed that patients had relatively circumscribed impairments in local functional properties and broadly distributed disruptions in global functional connectivity, consistently characterized by hyper-function in associative areas and hypo-function in primary regions. Moreover, the local functional alterations were correlated with genes enriched for biological functions related to MDD in general (e.g., endoplasmic reticulum stress, mitogen-activated protein kinase, histone acetylation, and DNA methylation); and the global functional connectivity changes were associated with not only MDD-general, but also brain-relevant genes (e.g., neuron, synapse, axon, glial cell, and neurotransmitters). Our findings may provide important insights into the transcriptomic signatures of regional cortical vulnerability to MDD.

Knowledge and Attitudes About Screening and Preventive Treatment of Latent Tuberculosis Infection Among Patients with Rheumatic Diseases in Beijing, China.

Objective: Tuberculosis preventive treatment (TPT) is an important strategy for tuberculosis (TB) control. Rheumatic diseases (RD) patients are at high risk for active TB development. More researches are needed in terms of patient compliance in clinical practice. This study aims to explore the potential difficulties and obstacles in latent tuberculosis infection (LTBI) screening and TPT in RD patients. Methods: Convenience sampling was used to recruit RD outpatients who had indications for LTBI screening and TPT. All participants were given questionnaires on knowledge and attitudes regarding screening and preventive treatment of LTBI. Results: Of the 200 RD patients, most people were aware that they were at increased risk of ATB due to their rheumatic disease and knew that TB was curable. The main association with willingness to have screening for LTBI was tertiary education (P = 0.013). The main association with willingness to take treatment for LTBI was a sense of personal risk and belief that the treatment would reduce risk of ATB (P < 0.001). More than half of the people surveyed could not accept taking 6 or more pills per day, while more than half of the patients could tolerate a treatment course of 9 months or longer. Most (65.4%) preferred their own rheumatologists to initiate treatment. Conclusion: Educating RD patients about their individual risks of TB and the side effects of treatment, and educating/empowering rheumatologists to discuss these aspects with their patients and to offer LTBI screening and treatment, may help improve patients' compliance with LTBI screening and TPT.

PM2.5 triggers tau aggregation in a mouse model of tauopathy.

The aggregation and prion-like propagation of tau are the hallmarks of Alzheimer's disease (AD) and other tauopathies. However, the molecular mechanisms underlying the assembly and spread of tau pathology remain elusive. Epidemiological data show that exposure to fine particulate matter (PM2.5) is associated with an increased risk of AD. However, the molecular mechanisms remain unknown. Here, we showed that PM2.5 triggered the aggregation of tau and promoted the formation of tau fibrils. Injection of PM2.5-induced tau preformed fibrils (PFFs) into the hippocampus of tau P301S transgenic mice promoted the aggregation of tau and induced cognitive deficits and synaptic dysfunction. Furthermore, intranasal administration of PM2.5 exacerbated tau pathology and induced cognitive impairment in tau P301S mice. In conclusion, our results indicated that PM2.5 exposure promoted tau pathology and induced cognitive impairments. These results provide mechanistic insight into how PM2.5 increases the risk of AD.

Separation and purification of bovine nasal cartilage-derived chondroitin sulfate and evaluation of its binding to bovine serum albumin.

This study employs an optimized and environmentally friendly method to extract and purify chondroitin sulfate (CS) from bovine nasal cartilage using enzymatic hydrolysis, ethanol precipitation, and DEAE Sepharose Fast Flow column chromatography. The extracted CS, representing 44.67 % ± 0.0016 of the cartilage, has a molecular weight of 7.62 kDa. Characterization through UV, FT-IR, NMR spectroscopy, and 2-aminoacridone derivatization HPLC revealed a high content of sulfated disaccharides, particularly ΔDi4S (73.59 %) and ΔDi6S (20.61 %). Interaction studies with bovine serum albumin (BSA) using fluorescence spectroscopy and molecular docking confirmed a high-affinity, static quenching interaction with a single binding site, primarily mediated by van der Waals forces and hydrogen bonding. The interaction did not significantly alter the polarity or hydrophobicity of BSA aromatic amino acids. These findings provide a strong foundation for exploring the application of CS in tissue engineering and drug delivery systems, leveraging its unique interaction with BSA for targeted delivery and enhanced efficacy.

Lipids, lipid-modified drug target genes, and the risk of male infertility: a Mendelian randomization study.

Background: Previous observational studies have reported a possible association between circulating lipids and lipid-lowering drugs and male infertility (MIF), as well as the mediating role of circulating vitamin D. Then, due to issues such as bias, reverse causality, and residual confounding, inferring causal relationships from these studies may be challenging. Therefore, this study aims to explore the effects of circulating lipids and lipid-lowering drugs on MIF through Mendelian randomization (MR) analysis and evaluate the mediating role of vitamin D. Method: Genetic variations related to lipid traits and the lipid-lowering effect of lipid modification targets are extracted from the Global Alliance for Lipid Genetics Genome-Wide Association Study. The summary statistics for MIF are from the FinnGen 9th edition. Using quantitative expression feature loci data from relevant organizations to obtain genetic variations related to gene expression level, further to explore the relationship between these target gene expression levels and MIF risk. Two-step MR analysis is used to explore the mediating role of vitamin D. Multiple sensitivity analysis methods (co-localization analysis, Egger intercept test, Cochrane's Q test, pleiotropy residuals and outliers (MR-PRESSO), and the leave-one-out method) are used to demonstrate the reliability of our results. Result: In our study, we observed that lipid modification of four lipid-lowering drug targets was associated with MIF risk, the LDLR activator (equivalent to a 1-SD decrease in LDL-C) (OR=1.94, 95% CI 1.14-3.28, FDR=0.040), LPL activator (equivalent to a 1-SD decrease in TG) (OR=1.86, 95% CI 1.25-2.76, FDR=0.022), and CETP inhibitor (equivalent to a 1-SD increase in HDL-C) (OR=1.28, 95% CI 1.07-1.53, FDR=0.035) were associated with a higher risk of MIF. The HMGCR inhibitor (equivalent to a 1-SD decrease in LDL-C) was associated with a lower risk of MIF (OR=0.38, 95% CI 0.17-0.83, FDR=0.39). Lipid-modifying effects of three targets were partially mediated by serum vitamin D levels. Mediation was 0.035 (LDLR activator), 0.012 (LPL activator), and 0.030 (CETP inhibitor), with mediation ratios of 5.34% (LDLR activator), 1.94% (LPL activator), and 12.2% (CETP inhibitor), respectively. In addition, there was no evidence that lipid properties and lipid modification effects of six other lipid-lowering drug targets were associated with MIF risk. Multiple sensitivity analysis methods revealed insignificant evidence of bias arising from pleiotropy or genetic confounding. Conclusion: This study did not support lipid traits (LDL-C, HDL-C, TG, Apo-A1, and Apo-B) as pathogenic risk factors for MIF. It emphasized that LPL, LDLR, CETP, and HMGCR were promising drug targets for improving male fertility.

Photosynthesis and photoprotection in top leaves respond faster to irradiance fluctuations than bottom leaves in a tomato canopy.

Accounting for the dynamic responses of photosynthesis and photoprotection to naturally fluctuating irradiance can improve predictions of plant performance in the field, but the variation of these dynamics within crop canopies is poorly understood. We conducted a detailed study of dynamic and steady-state photosynthesis, photoprotection, leaf pigmentation, and stomatal anatomy in four leaf layers (100, 150, 200 and 250 cm from the floor) of a fully-grown tomato canopy in the greenhouse. We found that leaves at the top of the canopy exhibited higher photosynthetic capacity and slightly faster photosynthetic induction compared to lower-canopy leaves, accompanied by higher stomatal conductance and a faster activation of carboxylation and linear electron transport capacities. In upper-canopy leaves, non-photochemical quenching showed faster induction and relaxation after in- and decreases in irradiance, allowing for more effective photoprotection in these leaves. Despite these observed differences in transient responses between leaf layers, steady-state rather than dynamic photosynthesis traits were more influential for predicting photosynthesis under fluctuating irradiance. Also, a model analysis revealed that time-averaged photosynthesis under fluctuating irradiance could be accurately predicted by one set of Rubisco activation/deactivation parameters across all four leaf layers, thereby greatly simplifying future modelling efforts of whole-canopy photosynthesis.

Toripalimab plus chemotherapy and radiotherapy for treatment-naive advanced esophageal squamous cell carcinoma: a single-arm phase 2 trial.

This single-arm phase 2 trial (ChiCTR2100046715) examined previously untreated patients with advanced esophageal squamous cell carcinoma (ESCC) who received four cycles of paclitaxel with carboplatin every 3 weeks. Toripalimab was infused intravenously every 3 weeks for 12 months, or until disease progression or intolerable toxicity. Radiotherapy that encompassed the primary lesions and metastases commenced in the third cycle. The median progression-free survival time was 9.8 months (95% confidence interval [CI]: 6.8-not estimable) in the intent-to-treat population, failing to meet the pre-specified primary endpoints. Secondary endpoints included an objective response rate of 45.5%, a disease control rate of 57.6%, and a median duration of response of 11.5 months (interquartile range, 6.4-15.0). The 1-year progression-free survival and overall survival rates were 41.9% (95% CI: 27.7-63.5) and 69.7% (95% CI: 55.7-87.3), respectively. Lymphopenia was the most frequent grade ≥3 adverse event (82%), and an esophageal fistula developed in three patients (9.1%). No treatment-related deaths occurred. In prespecified exploratory biomarker analysis, higher densities of CD8 + T cells, CD11c+ dendritic cells, and CD68+ macrophages correlated with improved tumor response and prognosis. Radiotherapy supplementation to first-line chemo-immunotherapy for treatment-naive advanced ESCC demonstrated some antitumor activity and manageable safety profiles, warranting further randomized controlled trials.

Clinical significance of modified unilateral puncture percutaneous vertebroplasty guided by 3D- printed guides in the treatment of osteoporotic vertebral compression fractures: a retrospective study.

OBJECTIVE: To investigate the clinical significance of using 3D printing guides in modified unilateral puncture percutaneous vertebroplasty (PVP) for the treatment of osteoporotic vertebral compression fractures (OVCF), and to explore a new method for preventing paravertebral vein leakage during PVP in conjunction with a previous study of the optimal puncture-side bone cement/vertebral volume ratio(PSBCV/VV%). METHODS: This retrospective study analyzed 99 patients who underwent unilateral puncture PVP between January 2023 and December 2023. Patients were divided into a guide plate group (46 patients) and a conventional group (53 patients). The guide plate group underwent modified unilateral puncture PVP with the guidance of 3D printing guides, while the conventional group underwent unilateral puncture PVP using the conventional pedicle approach. The distribution of bone cement, surgical outcomes, and the occurrence of cement leakage into paravertebral veins were observed in both groups. RESULTS: The guide plate group had significantly shorter operating time and required fewer fluoroscopies compared to the conventional group. The amount of bone cement volume (BCV) used in the guide plate group was higher, but the amount of bone cement volume on the puncture side(PSBCV), the PSBCV/VV%, and the rate of paravertebral vein leakage were lower in the guide plate group compared to the conventional group (P < 0.05). Within each group, significant improvements in anterior vertebral margin height, Cobb angle, visual analog scale (VAS) score, and Oswestry Disability Index (ODI) were observed at 1 day and 1 month postoperatively compared to preoperative values (P < 0.05). CONCLUSION: Using 3D printing guides in modified unilateral puncture PVP is a safe and effective method for treating OVCF. And it has the advantages of short operation time, less fluoroscopy, even distribution of bone cement, and a low rate of paravertebral vein leakage.

Dysfunction of thalamocortical circuits in early-onset schizophrenia.

Previous studies have demonstrated that the thalamus is involved in multiple functional circuits in participants with schizophrenia. However, less is known about the thalamocortical circuit in the rare subtype of early-onset schizophrenia. A total of 110 participants with early-onset schizophrenia (47 antipsychotic-naive patients) and 70 matched healthy controls were recruited and underwent resting-state functional and diffusion-weighted magnetic resonance imaging scans. A data-driven parcellation method that combined the high spatial resolution of diffusion magnetic resonance imaging and the high sensitivity of functional magnetic resonance imaging was used to divide the thalamus. Next, the functional connectivity between each thalamic subdivision and the cortex/cerebellum was investigated. Compared to healthy controls, individuals with early-onset schizophrenia exhibited hypoconnectivity between subdivisions of the thalamus and the frontoparietal network, visual network, ventral attention network, somatomotor network and cerebellum, and hyperconnectivity between subdivisions of thalamus and the parahippocampal and temporal gyrus, which were included in limbic network. The functional connectivity between the right posterior cingulate cortex and 1 subdivision of the thalamus (region of interest 1) was positively correlated with the general psychopathology scale score. This study showed that the specific thalamocortical dysconnection in individuals with early-onset schizophrenia involves the prefrontal, auditory and visual cortices, and cerebellum. This study identified thalamocortical connectivity as a potential biomarker and treatment target for early-onset schizophrenia.