In-silico study of the impact of system design parameters on microcalcification detection in wide-angle digital breast tomosynthesis.

Purpose: Accurate detection of microcalcifications ( µ Calcs ) is crucial for the early detection of breast cancer. Some clinical studies have indicated that digital breast tomosynthesis (DBT) systems with a wide angular range have inferior µ Calc detectability compared with those with a narrow angular range. This study aims to (1) provide guidance for optimizing wide-angle (WA) DBT for improving µ Calcs detectability and (2) prioritize key optimization factors. Approach: An in-silico DBT pipeline was constructed to evaluate µ Calc detectability of a WA DBT system under various imaging conditions: focal spot motion (FSM), angular dose distribution (ADS), detector pixel pitch, and detector electronic noise (EN). Images were simulated using a digital anthropomorphic breast phantom inserted with 120 µ m µ Calc clusters. Evaluation metrics included the signal-to-noise ratio (SNR) of the filtered channel observer and the area under the receiver operator curve (AUC) of multiple-reader multiple-case analysis. Results: Results showed that FSM degraded µ Calcs sharpness and decreased the SNR and AUC by 5.2% and 1.8%, respectively. Non-uniform ADS increased the SNR by 62.8% and the AUC by 10.2% for filtered backprojection reconstruction with a typical clinical filter setting. When EN decreased from 2000 to 200 electrons, the SNR and AUC increased by 21.6% and 5.0%, respectively. Decreasing the detector pixel pitch from 85 to 50 µ m improved the SNR and AUC by 55.6% and 7.5%, respectively. The combined improvement of a 50 µ m pixel pitch and EN200 was 89.2% in the SNR and 12.8% in the AUC. Conclusions: Based on the magnitude of impact, the priority for enhancing µ Calc detectability in WA DBT is as follows: (1) utilizing detectors with a small pixel pitch and low EN level, (2) allocating a higher dose to central projections, and (3) reducing FSM. The results from this study can potentially provide guidance for DBT system optimization in the future.

The synergistic effects of anoikis-related genes and EMT-related genes in the prognostic prediction of Wilms tumor.

Wilms tumor (WT) is the most common type of malignant abdominal tumor in children; it exhibits a high degree of malignancy, grow rapidly, and is prone to metastasis. This study aimed to construct a prognosis model based on anoikis-related genes (ARGs) and epithelial-mesenchymal transition (EMT)-related genes (ERGs) for WT patients; we assessed the characteristics of the tumor microenvironment and treatment efficacy, as well as identifying potential therapeutic targets. To this end, we downloaded transcriptome sequencing data and clinical data for WT and normal renal cortices and used R to construct and validate the prognostic model based on ARGs and ERGs. Additionally, we performed clinical feature analysis, nomogram construction, mutation analysis, drug sensitivity analysis, Connectivity Map (cMAP) analysis, functional enrichment analysis, and immune infiltration analysis. Finally, we screened the hub gene using the STRING database and validated it via experiments. In this way, we constructed a model with good accuracy and robustness, which was composed of seven anoikis- and EMT-related genes. Paclitaxel and mesna were selected as potential chemotherapeutic drugs and adjuvant chemotherapeutic drugs for the WT high-risk group by using the Genomics of Drug Sensitivity in Cancer (GDSC) and cMAP compound libraries, respectively. We proved the existence of a strong correlation between invasive immune cells and prognostic genes and risk scores. Next, we selected NTRK2 as the hub gene, and in vitro experiments confirmed that its inhibition can significantly inhibit the proliferation and migration of tumor cells and promote late apoptosis. In summary, we screened out the potential biomarkers and chemotherapeutic drugs that can improve the prognosis of patients with WT.

High-efficiency microplastic removal in water treatment based on short flow control of hydrocyclone: Mechanism and performance.

Microplastics have been identified as a potentially emerging threat to water environment and human health. Therefore, there is a pressing demand for effective strategies to remove microplastics from water. Hydrocyclone offers a rapid separation and low energy consumption alternative but require reduction of microparticle entrainment by short flow, which limits the effectiveness for small density differentials and ultralow concentrations separation. We proposed an enhanced mini-hydrocyclone with overflow microchannels (0.72 mm width) based on the active control of short flow in hydrocyclone for microplastic removal from water. The overflow microchannels effectively redirect the particles that would typically be entrained by the short flow, leading to higher separation efficiency. Simulation results show overflow microchannels effectively reduced short flow to 0.7 %, a reduction of up to 94 % compared to conventional hydrocyclones. The hydrocyclone with overflow microchannel demonstrated a removal efficiency exceeding 98 % for 8 µm plastic microbeads at ultralow concentrations (10 ppm), which is a 33.7 % improvement over conventional hydrocyclone. Compared with other methods (e.g., filtration, adsorption, coagulation) for microplastic removal, this work achieves rapid separation capability and long period operation, highlighting hydrocyclone as a promising approach for microplastic removal in industry-scale water treatment.

GSDMB interacts with IGF2BP1 to suppress colorectal cancer progression by modulating DUSP6-ERK pathway.

There is growing evidence that the protein family of Gasdermins (GSDMs) play an essential role during the progression of colorectal cancer (CRC). However, it is not completely clear that how GSDMB, abundantly expressed in epithelial cells of gastrointestinal tract, regulates the tumorigenesis of CRC. A wealth of evidence linking GSDMB to the pathogenesis of cancer has come from genome-wide association studies. Here, we provide evidence that aberrantly upregulated GSDMB is responsible for suppressing the CRC progression by using in vitro cell and intestinal organoid, as well as in vivo GSDMB transgenic mice models. Mechanistically, GSDMB interacts with insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), which directly binds to and recognizes the 3'-UTR of dual specificity phosphatase 6 (DUSP6) mRNA, enhances the translation of DUSP6 protein and inhibits downstream ERK phosphorylation, thereby facilitating cell death and restraining cell proliferation. Our results suggest that GSDMB has potential as a novel therapeutic target for CRC treatment.

Epitope prime editing shields hematopoietic cells from CD123 immunotherapy for acute myeloid leukemia.

Acute myeloid leukemia (AML) is a malignant cancer characterized by abnormal differentiation of hematopoietic stem and progenitor cells (HSPCs). While chimeric antigen receptor T (CAR-T) cell immunotherapies target AML cells, they often induce severe on-target/off-tumor toxicity by attacking normal cells expressing the same antigen. Here, we used base editors (BEs) and a prime editor (PE) to modify the epitope of CD123 on HSPCs, protecting healthy cells from CAR-T-induced cytotoxicity while maintaining their normal function. Although BE effectively edits epitopes, complex bystander products are a concern. To enhance precision, we optimized prime editing, increasing the editing efficiency from 5.9% to 78.9% in HSPCs. Epitope-modified cells were resistant to CAR-T lysis while retaining normal differentiation and function. Furthermore, BE- or PE-edited HSPCs infused into humanized mice endowed myeloid lineages with selective resistance to CAR-T immunotherapy, demonstrating a proof-of-concept strategy for treating relapsed AML.

Lateral lymph node metastasis without mesenteric lymph node involvement in middle-low rectal cancer: Results of a multicentre lateral node collaborative group study in China.

BACKGROUND: Characteristics and prognoses of lateral lymph node (LLN) metastasis but not mesenteric lymph node (LN) metastasis are poorly understood. This study explored patterns of mesenteric and LLN metastases in rectal cancer patients. METHOD: This retrospective, multicentre study was conducted at three institutions and included patients who underwent total mesorectal excision (TME) with lateral lymph node dissection (LLND) for rectal cancer (n = 271). RESULTS: Among the patients with LLN metastases, 210 patients (77.5 %) with clinical stage T3-4 disease and 157 patients (57.9 %) with clinical stage N1-N2 disease underwent TME as well as LLND. The prognoses of patients with metastasis confined to LLNs were significantly better than those of patients with both mesenteric and LLN metastases (3-year overall survival: 85.0 % vs. 51.0 %, p = 0.005; 3-year disease-free survival: 75.0 % vs. 26.5 %, p = 0.003) and were similar to those of patients with metastasis confined to mesenteric LNs (3-year overall survival: 85.0 % vs. 83.8 %, p = 0.607; 3-year disease-free survival 75.0 % vs. 68.8 %, p = 0.717). Patients with metastases confined to LLN had a lower proportion of poor histological types (20.0 % vs. 65.3 %, p = 0.002), lymphatic invasion (20.0 % vs. 59.2 %, p = 0.036) and number of LLN metastases (1.6 vs 2.7, p = 0.004), and all metastases were confined to the internal iliac or obturator region (100.0 % vs. 77.6 %, p = 0.008) compared to patients with both mesenteric and LLN metastasis. CONCLUSIONS: Approximately a quarter of patients with rectal cancer have LLN metastases but no mesenteric LN metastases. These patients have favourable pathological features and prognoses and can be managed and treated for mesenteric LN metastasis.

Rhodium-Catalyzed Asymmetric Cyclopropanation of Indoles with N-Triftosylhydrazones.

Here we report a general rhodium-catalyzed asymmetric intermolecular dearomative cyclopropanation of indoles using trifluoromethyl N-triftosylhydrazones as carbene precursors. The reaction enables the rapid construction of diverse cyclopropane fused indolines bearing a trifluoromethylated quaternary stereocenter in high enantioselectivities (up to 99% ee). This mild method exhibits a broad substrate scope, is compatible with various functional groups, and can even be utilized for the late-stage diversification of complex bioactive molecules. DFT calculations suggest that the formation of a key zwitterionic intermediate is responsible for the chiral induction. Overall, this approach opens up new possibilities for asymmetric cyclopropanation of challenging aromatic heterocyclic compounds.

Evolution and functional divergence of glycosyltransferase genes shaped the quality and cold tolerance of tea plants.

Plant glycosyltransferases (UGTs) play a key role in plant growth and metabolism. Here, we examined the evolutionary landscape among UGTs in 28 fully sequenced species from early algae to angiosperms. Our findings revealed a distinctive expansion and contraction of UGTs in the G and H groups in tea (Camellia sinensis), respectively. Whole-genome duplication and tandem duplication events jointly drove the massive expansion of UGTs, and the interplay of natural and artificial selection has resulted in marked functional divergence within the G group of the sinensis-type tea population. In Cluster II of group G, differences in substrate selection (e.g., Abscisic Acid) of the enzymes encoded by UGT genes led to their functional diversification, and these genes influence tolerance to abiotic stresses such as low temperature and drought via different modes of positive and negative regulation, respectively. UGTs in Cluster III of the G group have diverse aroma substrate preferences, which contributes a diverse aroma spectrum of the sinensis-type tea population. All Cluster III genes respond to low-temperature stress, whereas UGTs within Cluster III-1, shaped by artificial selection, are unresponsive to drought. This suggests that artificial selection of tea plants focused on improving quality and cold tolerance as primary targets.

Construction and validation of a machine learning-based immune-related prognostic model for glioma.

BACKGROUND: Glioma stands as the most prevalent primary brain tumor found within the central nervous system, characterized by high invasiveness and treatment resistance. Although immunotherapy has shown potential in various tumors, it still faces challenges in gliomas. This study seeks to develop and validate a prognostic model for glioma based on immune-related genes, to provide new tools for precision medicine. METHODS: Glioma samples were obtained from a database that includes the ImmPort database. Additionally, we incorporated ten machine learning algorithms to assess the model's performance using evaluation metrics like the Harrell concordance index (C-index). The model genes were further studied using GSCA, TISCH2, and HPA databases to understand their role in glioma pathology at the genomic, molecular, and single-cell levels, and validate the biological function of IKBKE in vitro experiments. RESULTS: In this study, a total of 199 genes associated with prognosis were identified using univariate Cox analysis. Subsequently, a consensus prognostic model was developed through the application of machine learning algorithms. In which the Lasso + plsRcox algorithm demonstrated the best predictive performance. The model showed a good ability to distinguish two groups in both the training and test sets. Additionally, the model genes were closely related to immunity (oligodendrocytes and macrophages), and mutation burden. The results of in vitro experiments showed that the expression level of the IKBKE gene had a significant effect on the apoptosis and migration of GL261 glioma cells. Western blot analysis showed that down-regulation of IKBKE resulted in increased expression of pro-apoptotic protein Bax and decreased expression of anti-apoptotic protein Bcl-2, which was consistent with increased apoptosis rate. On the contrary, IKBKE overexpression caused a decrease in Bax expression an increase in Bcl-2 expression, and a decrease in apoptosis rate. Tunel results further confirmed that down-regulation of IKBKE promoted apoptosis, while overexpression of IKBKE reduced apoptosis. In addition, cells with down-regulated IKBKE had reduced migration in scratch experiments, while cells with overexpression of IKBKE had increased migration. CONCLUSION: This study successfully constructed a glioma prognosis model based on immune-related genes. These findings provide new perspectives for glioma prognosis assessment and immunotherapy.

Target-inhibited MCOF-Apt-AuNPs self-assembly for multicolor colorimetric detection of Salmonella Typhimurium.

Pathogens detection is a crucial measure in the prevention of foodborne diseases. This study developed a novel multicolor colorimetric assay to visually detect Salmonella Typhimurium (S. Typhimurium), by utilizing the etching process of gold nanorods (AuNRs) with TMB2+. The strategy involved the construction of nanozyme by assembling magnetic covalent organic framework (MCOF) with aptamer-conjugated AuNPs (Apt-AuNPs), exhibiting remarkable peroxidase-like activity to catalyze the oxidation of TMB/H2O2 and inducing the etching of AuNRs. The presence of S. Typhimurium could inhibit this process, resulting in the generation of vivid colors. The multicolor colorimetric assay could specifically determine S. Typhimurium from 102 to 108 CFU mL-1 in 60 min with visual detection limit of 102 CFU mL-1, and instrumental detection limit of 2.3 CFU mL-1. Moreover, detecting S. Typhimurium in chicken, milk, pork and lettuce samples has shown promise in practical applications.

The Value of Topological Radiomics Analysis in Predicting Malignant Risk of Pulmonary Ground-Glass Nodules: A Multi-Center Study.

BACKGROUND: Early detection and accurate differentiation of malignant ground-glass nodules (GGNs) in lung CT scans are crucial for the effective treatment of lung adenocarcinoma. However, existing imaging diagnostic methods often struggle to distinguish between benign and malignant GGNs in the early stages. This study aims to predict the malignancy risk of GGNs observed in lung CT scans by applying two radiomics methods: topological data analysis and texture analysis. METHODS: A retrospective analysis was conducted on 3223 patients from two centers between January 2018 and June2023. The dataset was divided into training, testing, and validation sets to ensure robust model development and validation. We developed topological features applied to GGNs using radiomics analysis based on homology. This innovative approach emphasizes the integration of topological information, capturing complex geometric and spatial relationships within GGNs. By combining machine learning and deep learning algorithms, we established a predictive model that integrates clinical parameters, previous radiomics features, and topological radiomics features. RESULTS: Incorporating topological radiomics into our model significantly enhanced the ability to distinguish between benign and malignant GGNs. The topological radiomics model achieved areas under the curve (AUC) of 0.85 and 0.862 in two independent validation sets, outperforming previous radiomics models. Furthermore, this model demonstrated higher sensitivity compared to models based solely on clinical parameters, with sensitivities of 80.7% in validation set 1 and 82.3% in validation set 2. The most comprehensive model, which combined clinical parameters, previous radiomics features, and topological radiomics features, achieved the highest AUC value of 0.879 across all datasets. CONCLUSION: This study validates the potential of topological radiomics in improving the predictive performance for distinguishing between benign and malignant GGNs. By integrating topological features with previous radiomics and clinical parameters, our comprehensive model provides a more accurate and reliable basis for developing treatment strategies for patients with GGNs.

Synergetic Enzyme-Incorporated Metal-Organic Framework and Polyoxometalate Nanozyme: Achieving Stable Tandem Catalysis for Organic Photoelectrochemical Transistor Bioanalysis.

Organic photoelectrochemical transistor (OPECT) has emerged as a promising technique for biomolecule detection, yet its operational rationale remains limited due to its short development time. This study introduces a stable tandem catalysis protocol by synergizing the enzyme-incorporated metal-organic frameworks (E-MOFs) with polyoxometalate (POM) nanozyme for sensitive OPECT bioanalysis. The zeolitic imidazolate framework-8 (ZIF-8) acts as the skeleton to protect the encapsulated glucose oxidase (GOx), allowing the stable catalytic generation of H2O2. With peroxidase-like activity, a phosphotungstic acid hydrate (PW12) is then able to utilize the H2O2 to induce the biomimetic precipitation on the photogate, ultimately resulting in the altered device characteristics for quantitative detection. This work reveals the potential and versatility of an engineered enzymatic system as a key enabler to achieve novel OPECT bioanalysis, which is believed to offer a feasible framework to explore new operational rationale in optoelectronic and bioelectronic detection.

A Dynamic H-Bonding Network Enables Stimuli-Responsive Color-Tunable Chiral Afterglow Polymer for 4D Encryption.

The development of stimuli-responsive and color-tunable chiral organic afterglow materials has attracted great attention but remains a daunting challenge. Here, a simple yet effective strategy through the construction of a dynamic H-bonding network is proposed to explore the multi-color stimuli-responsive chiral afterglow by doping a self-designed chiral phosphorescent chromophore into a polyvinyl alcohol matrix. A stimuli-responsive deep blue chiral afterglow system with a lifetime of up to 3.35 s, quantum yield of 25.0%, and luminescent dissymmetry factor of up to 0.05 is achieved through reversible formation and breakdown of the H-bonding network upon thermal-heating and water-fumigating. Moreover, multi-color stimuli-responsive chiral afterglow can be obtained by chiral and afterglow energy transfer, allowing the establishment of afterglow information displays and high-level 4D encryption. This work not only offers a facile platform to develop advanced stimuli-responsive materials but also opens a new avenue for developing next-generation optical information technology with enhanced functionality and responsiveness.

Treatment of acute pharyngitis in rats with season tea decoctions from traditional Chinese medicine through a synergistic and subtle regulation of ARNTL and BHLHE40.

ETHNOPHARMACOLOGICAL RELEVANCE: While the seasonal variations in the human immune function and many infectious diseases are well-known, to develop therapeutic strategies regarding such seasonality is quite challenging. However, some traditional medical practices have already taken the seasonality into account, such as the "Season Tea" (ST) decoctions investigated in the present study. AIM OF THE STUDY: We present a study of the ST decoctions from traditional Chinese medicine, which include four formulae designed for the four seasons, aiming to investigate their pharmacological commonality and distinction. MATERIALS AND METHODS: A rat model of acute pharyngitis was utilized for the pharmacological study, and the effects of the ST decoctions were evaluated through histology, biomedical assays, microarray analysis, real-time quantitative PCR and western blot. RESULTS: The experimental data show that all of the four ST formulae display good pharmaceutical effects on acute pharyngitis, and circadian rhythm appears to be a significant pathway for investigating their pharmacological commonality and distinction. Specifically, while all of the four ST decoctions can regulate the circadian-rhythm-related genes ARNTL and BHLHE40, the regulation is along different directions with the modification of the supplements and the substrates in each ST formula. CONCLUSION: These results indicate the correlation between the acute pharyngitis and circadian rhythm, and illustrate the possibility of synergistically and subtly regulating ARNTL and BHLHE40, which is significant for relevant drug development.

A global view on quantitative proteomic and metabolic analysis of rat livers under different hypoxia protocols.

Hypobaric hypoxia causes altitude sickness and significantly affects human health. As of now, focusing on rats different proteomic and metabolic changes exposed to different hypoxic times at extreme altitude is blank. Our study integrated in vivo experiments with tandem mass tag (TMT)- and gas chromatography time-of-flight (GC-TOF)-based proteomic and metabolomic assessments, respectively. Male Sprague-Dawley rats were exposed to long-term constant hypoxia for 40 days or short-term constant hypoxia for three days, and their responses were compared with those of a normal control group. Post-hypoxia, serum marker assays related to lipid metabolism revealed significant increases in the levels of low-density lipoprotein (LDL), triglycerides (TG), and total cholesterol (TC) in the liver. In contrast, high-density lipoprotein (HDL) levels were upregulated in the long-term constant hypoxia cohorts and were significantly reduced in the short-term constant hypoxia cohorts. Furthermore, metabolic pathway analysis indicated that glycerolipid and glycerophospholipid metabolisms were the most significantly affected pathways in long-term hypoxia group. Subsequently, RT-qPCR analyses were performed to corroborate the key regulatory elements, including macrophage galactose-type lectin (MGL) and Fatty Acid Desaturase 2 (FADS2). The results of this study provide new information for understanding the effects of different hypobaric hypoxia exposure protocols on protein expression and metabolism in low-altitude animals.

Knockout of neutrophil cytosolic factor 1 ameliorates neuroinflammation and motor deficit after traumatic brain injury.

Traumatic brain injury (TBI) is a predominant cause of long-term disability in adults, yet the molecular mechanisms underpinning the neuropathological processes associated with it remain inadequately understood. Neutrophil cytosolic factor 1 (NCF1, also known as p47phox) is one of the cytosolic components of NADPH oxidase NOX2. In this study, we observed a reduction in the volume of TBI-induced brain lesions in NCF1-knockout mice compared to controls. Correspondingly, the neuronal loss induced by TBI was mitigated in the NCF1-knockout mice. Behavioral analysis also demonstrated that the motor coordination deficit following TBI was mitigated by the depletion of NCF1. Mechanistically, our findings revealed that NCF1 deficiency attenuated TBI-induced inflammatory responses by inhibiting the release of proinflammatory factors and reducing neutrophil infiltration into the brain parenchyma. Additionally, our results indicated that NCF1 deficiency significantly decreased the levels of reactive oxygen species in neutrophils. Taken together, our findings indicate that NCF1 plays a crucial role in the regulation of brain injury and secondary inflammation post-TBI.

Productivity experienced a more rapid enhancement trend than greenness across the Tibetan Plateau.

Satellite-derived products and field measurements verify that Tibetan Plateau (TP) has been experiencing continuous vegetation greening and productivity increase; however, it remains unclear how this greening translates into productivity and how long-term productivity variations depend on greenness across the TP. Moreover, ignoring the accuracy evaluation of satellite-derived greenness and productivity products may mislead the understanding of TP vegetation changes. Thus, we initially assessed the accuracy of three widely used leaf area index (LAI, proxy of greenness) products (i.e., MODIS, GLASS and GEOV2 LAI) and three gross primary productivity (GPP, proxy of productivity) products (i.e., MODIS, GLASS and PML-V2 GPP) to selected robust products to represent greenness and productivity respectively. Then, we explored the dependence of spatiotemporal GPP dynamics on greenness variations during 2000-2020. Results indicated that PML-V2 GPP and MODIS LAI were more robust and reliable than other satellite-derived products when compared to the reference values. They revealed a prevailing increase in GPP over the past two decades, with a regional average of 71 % higher than that of LAI. Notably, the area proportion of significant productivity enhancement was 31.6 % higher than that of significant greening. About 24.7 % of the TP displayed significantly inconsistent trends. The dependency of GPP on LAI gradually decreased with the increasing water availability, the complexity of vegetation structures, and dense canopy community. By calculating leaf photosynthetic capacity, we found that this indicator greatly regulated the velocity discrepancy between GPP and LAI, and the contribution of only greening to productivity is limited, only occupying 11.9 % of the TP, which was helpful in understanding the inter-annual changes of vegetation dynamics under varying environment conditions. We therefore reveal an unexpected rapid increase in productivity than greening during 2000-2020 on the TP, as well as highlight the caution of only using satellite-derived greenness indicators for assessing long-term changes in vegetation productivity dynamics, especially over mesic ecosystems with complex vegetation structures and dense canopies of TP.

An Aquatic Autonomic Nervous System.

Reproducing human nervous systems with endogenous mechanisms has attracted increasing attention, driven by its great potential in streamlining the neuro-electronic interfaces with bilateral signaling. Here, an artificial aquatic autonomic nervous system (ANS) with switchable excitatory/inhibitory characteristics and acetylcholine (ACh)-mediated plasticity is reported based on the newly emerged organic photoelectrochemical transistor (OPECT). Under the modulation of spatial light and ACh, the system exhibits an immediate switch between excitation and inhibition, and many pulse patterns as well as advanced ANS functions are mimicked. To demonstrate its potential usage, the artificial ANS is then utilized to control artificial pupils and muscles to emulate real biological responses during an emergency. In contrast to previous solid-state attempts, this ANS is aqueous compatible just like biological nervous systems, which are capable of real neurotransmitter mediation.

Investigating the shared genetic links between hypothyroidism and psychiatric disorders: a large-scale genomewide cross-trait analysis.

BACKGROUND: Associations between thyroid diseases and psychiatric disorders have been mainly described before. However, the genetic mechanism behind hypothyroidism and psychiatric disorders remains unexplained. METHODS: We examined the genetic architecture of hypothyroidism and 8 psychiatric disorders. Firstly, the global and local genetic relationship between the paired traits was explored. Secondly, cross-trait analysis was performed to investigate the genomic loci and genes between psychiatric disorders and hypothyroidism. Thirdly, the significant expression of these genes and the causal relationships were investigated. Lastly, enrichment analysis was conducted on these genes to explore their biological mechanisms. RESULTS: We observed significant positive genetic correlations between psychiatric disorders and hypothyroidism. The cross-trait meta-analysis identified 62 shared genetic loci between hypothyroidism and psychiatric disorders. The colocalization analysis additionally revealed 15 potential pleiotropic loci with a posterior probabilities.H4 (PP·H4) value >0.7. We also found 2308 genes shared between both traits, which were highly enriched in biological pathways such as immune cell differentiation and autoimmune diseases, as well as in tissue structures like the frontal cortex and cerebral cortex. Especially, many pleiotropic genes were significantly expressed for multiple pairwise traits, such as BCL11B, RERE, and SUOX. Lastly, the Latent causal variable model (LCV) analysis did not find any causal components in the genetic structure between them. LIMITATIONS: The limitations of this study include that the conclusions were drawn from a European population. CONCLUSIONS: These findings not only deepens our understanding of their biological mechanisms but also has significant implications for the intervention and treatment of these diseases.