Machine Learning-Assisted High-Throughput Identification and Quantification of Protein Biomarkers with Printed Heterochains.

Advanced in vitro diagnosis technologies are highly desirable in early detection, prognosis, and progression monitoring of diseases. Here, we engineer a multiplex protein biosensing strategy based on the tunable liquid confinement self-assembly of multi-material heterochains, which show improved sensitivity, throughput, and accuracy compared to standard ELISA kits. By controlling the material combination and the number of ligand nanoparticles (NPs), we observe robust near-field enhancement as well as both strong electromagnetic resonance in polymer-semiconductor heterochains. In particular, their optical signals show a linear response to the coordination number of the semiconductor NPs in a wide range. Accordingly, a visible nanophotonic biosensor is developed by functionalizing antibodies on central polymer chains that can identify target proteins attached to semiconductor NPs. This allows for the specific detection of multiple protein biomarkers from healthy people and pancreatic cancer patients in one step with an ultralow detection limit (1 pg/mL). Furthermore, rapid and high-throughput quantification of protein expression levels in diverse clinical samples such as buffer, urine, and serum is achieved by combining a neural network algorithm, with an average accuracy of 97.3%. This work demonstrates that the heterochain-based biosensor is an exemplary candidate for constructing next-generation diagnostic tools and suitable for many clinical settings.

The Coexistence of Superconductivity and Topological Order in Van der Waals InNbS2.

The research on systems with coexistence of superconductivity and nontrivial band topology has attracted widespread attention. However, the limited availability of material platforms severely hinders the research progress. Here, it reports the first experimental synthesis and measurement of high-quality single crystal van der Waals transition-metal dichalcogenide InNbS2 , revealing it as a topological nodal line semimetal with coexisting superconductivity. The temperature-dependent measurements of magnetization susceptibility and electrical transport show that InNbS2 is a type-II superconductor with a transition temperature Tc of 6 K. First-principles calculations predict multiple topological nodal ring states close to the Fermi level in the presence of spin-orbit coupling. Similar features are also observed in the as-synthesized BiNbS2 and PbNbS2 samples. This work provides new material platforms ANbS2 (A = In, Bi, and Pb) and uncovers their intriguing potential for exploring the interplay between superconductivity and band topology.

Human periodontal ligament stem cell sheets activated by graphene oxide quantum dots repair periodontal bone defects by promoting mitochondrial dynamics dependent osteogenic differentiation.

BACKGROUND: Bone defects in the maxillofacial region restrict the integrity of dental function, posing challenges in clinical treatment. Bone tissue engineering (BTE) with stem cell implants is an effective method. Nanobiomaterials can effectively enhance the resistance of implanted stem cells to the harsh microenvironment of bone defect areas by promoting cell differentiation. Graphene oxide quantum dots (GOQDs) are zero-dimensional nanoscale derivatives of graphene oxide with excellent biological activity. In the present study, we aimed to explore the effects of GOQDs prepared by two methods (Y-GOQDs and B-GOQDs) on the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs), as well as the effect of gelatin methacryloyl (GelMA)-encapsulated GOQD-induced hPDLSC sheets on the repair of mandibular periodontal defects in rats. We also explored the molecular biological mechanism through which GOQD promotes bone differentiation. RESULTS: There were significant differences in oxygen-containing functional groups, particle size and morphology between Y-GOQDs and B-GOQDs. Y-GOQDs promoted the osteogenic differentiation of hPDLSCs more effectively than did B-GOQDs. In addition, GelMA hydrogel-encapsulated Y-GOQD-induced hPDLSC cell sheet fragments not only exhibited good growth and osteogenic differentiation in vitro but also promoted the repair of mandibular periodontal bone defects in vivo. Furthermore, the greater effectiveness of Y-GOQDs than B-GOQDs in promoting osteogenic differentiation is due to the regulation of hPDLSC mitochondrial dynamics, namely, the promotion of fusion and inhibition of fission. CONCLUSIONS: Overall, Y-GOQDs are more effective than B-GOQDs at promoting the osteogenic differentiation of hPDLSCs by regulating mitochondrial dynamics, which ultimately contributes to bone regeneration via the aid of the GelMA hydrogels in vivo.

The ATF4-regulated LncRNA MALAT1 promotes odontoblastic differentiation of human dental pulp stem cells via histone demethylase JMJD3: An in vitro study.

AIM: This study aimed to investigate the upstream regulators and specific mechanisms of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in the odontoblastic differentiation of human dental pulp stem cells (hDPSCs). METHODOLOGY: Human dental pulp stem cells were isolated and cultured, followed by conducting loss- or gain-of-function experiments on ATF4 and loss experiments on MALAT1 to elucidate their respective biological functions in odontoblastic differentiation. Chromatin immunoprecipitation assays and RNA immunoprecipitation were performed to uncover the interaction between ATF4-MALAT1 and MALAT1-JMJD3, respectively. The odontoblastic differentiation was estimated by the mRNA and protein of DSPP and DMP1, as well as alkaline phosphatase staining. RESULTS: Expression of MALAT1 was upregulated in the hDPSCs cultured in an odontoblastic medium, and MALAT1 downregulation suppressed the odontoblastic differentiation of the hDPSCs. Subsequent experiments confirmed that ATF4 promoted odontoblastic differentiation and induced MALAT1 expression by binding to the MALAT1 promoter region. Further experiments revealed that nuclear MALAT1 interacted with JMJD3. MALAT1 knockdown decreased the JMJD3 protein level and demethylase activity, and it enhanced H3K27me3 occupancy of the promoter region of DSPP and DMP1, resulting in the inhibition of DSPP and DMP1 transcription. Importantly, JMJD3 overexpression significantly attenuated the inhibition of odontoblastic differentiation induced by MALAT1 knockdown. CONCLUSIONS: ATF4-regulated MALAT1 plays a positive regulatory role in odontoblastic differentiation of hDPSCs through JMJD3-mediated H3K27me3 modifications of the DSPP and DMP1 promoters.

[Research progress on bioinformatics in pulmonary arterial hypertension]. / ç”Ÿç‰©ä¿¡æ¯å­¦åœ¨è‚ºåŠ¨è„‰é«˜åŽ‹ä¸­çš„ç ”ç©¶è¿›å±•.

Pulmonary arterial hypertension (PAH) is a severe disease characterized by abnormal pulmonary vascular remodeling and increased right ventricular pressure load, posing a significant threat to patient health. While some pathological mechanisms of PAH have been revealed, the deeper mechanisms of pathogenesis remain to be elucidated. In recent years, bioinformatics has provided a powerful tool for a deeper understanding of the complex mechanisms of PAH through the integration of techniques such as multi-omics analysis, artificial intelligence, and Mendelian randomization. This review focuses on the bioinformatics methods and technologies used in PAH research, summarizing their current applications in the study of disease mechanisms, diagnosis, and prognosis assessment. Additionally, it analyzes the existing challenges faced by bioinformatics and its potential applications in the clinical and basic research fields of PAH in the future.

Orientation-Controlled Ultralong Assembly of Janus Particles Induced by Bubble-Driven Instant Quasi-1D Interfaces.

Constructing precisely oriented assemblies and exploring their orientation-dependent properties remain a challenge for Janus nanoparticles (JNPs) due to their asymmetric characteristics. Herein, we propose a bubble-driven instant quasi-1D interfacial strategy for the oriented assembly of JNP chains in a highly controllable manner. It is found that the rapid formation of templated bubbles can promote the interfacial orientation of JNPs kinetically, while the confined quasi-1D interface in the curved liquid bridge can constrain the disordered rotation of the particles, yielding well-oriented JNP chains in a long range. During the evaporation process, the interfacial orientation of the JNPs can be transferred to the assembled chains. By regulating the amphiphilicity of the JNPs, both heteraxial and coaxial JNP assemblies are obtained, which show different polarization dependences on light scattering, and the related colorimetric logic behaviors are demonstrated. This work demonstrates the great potential of patterned interfacial assembly with a manageable orientation and shows the broad prospect of asymmetric JNP assembly in constructing novel optoelectronic devices.

Molecular Recognition-Modulated Hetero-Assembly of Nanostructures for Visualizable and Portable Detection of Circulating miRNAs.

Biomolecular markers, particularly circulating microRNAs (miRNAs) play an important role in diagnosis, monitoring, and therapeutic intervention of cancers. However, existing detection strategies remain intricate, laborious, and far from being developed for point-of-care testing. Here, we report a portable colorimetric sensor that utilizes the hetero-assembly of nanostructures driven by base pairing and recognition for direct detection of miRNAs. Following hybridization, two sizes of nanoparticles modified with single-strand DNA can be robustly assembled into heterostructures with strong optical resonance, exhibiting distinct structure colors. Particularly, the large nanoparticles are first arranged into nanochains to enhance scattering signals of small nanoparticles, which allows for sensitive detection and quantification of miRNAs without the requirement of target extraction, amplification, and fluorescent labels. Furthermore, we demonstrate the high specificity and single-base selectivity of testing different miRNA samples, which shows great potential in the diagnosis, staging, and monitoring of cancers. These heterogeneous assembled nanostructures provide an opportunity to develop simple, fast, and convenient tools for miRNAs detection, which is suitable for many scenarios, especially in low-resource setting.

Melatonin attenuates dental pulp stem cells senescence due to vitro expansion via inhibiting MMP3.

OBJECTIVE: We aimed to identify the crucial genes involved in dental pulp stem cell (DPSC) senescence and evaluate the impact of melatonin on DPSC senescence. METHODS: Western blotting, SA-ß-Gal staining and ALP staining were used to evaluate the senescence and differentiation potential of DPSCs. The optimal concentration of melatonin was determined using the CCK-8 assay. Differentially expressed genes (DEGs) involved in DPSC senescence were obtained via bioinformatics analysis, followed by RT-qPCR. Gain- and loss-of-function studies were conducted to explore the role of MMP3 in DPSC in vitro expansion and in response to melatonin. GSEA was employed to analyse MMP3-related pathways in cellular senescence. RESULTS: Treatment with 0.1 µM melatonin attenuated cellular senescence and differentiation potential suppression in DPSCs due to long-term in vitro expansion. MMP3 was a crucial gene in senescence, as confirmed by bioinformatics analysis, RT-qPCR and Western blotting. Furthermore, gain- and loss-of-function studies revealed that MMP3 played a regulatory role in cellular senescence. Rescue assays showed that overexpression of MMP3 reversed the effect of melatonin on senescence. GSEA revealed that the MMP3-dependent anti-senescence effect of melatonin was associated with the IL6-JAK-STAT3, TNF-α-Signalling-VIA-NF-κB, COMPLEMENT, NOTCH Signalling and PI3K-AKT-mTOR pathways. CONCLUSION: Melatonin attenuated DPSC senescence caused by long-term expansion by inhibiting MMP3.

Efficacy of cognitive therapy and behavior therapy for menopausal symptoms: a systematic review and meta-analysis.

BACKGROUND: T long-term effects of cognitive therapy and behavior therapy (CTBT) for menopausal symptoms are unknown, and whether the effects are different between natural menopause and treatment-induced menopause are currently unclear. Therefore, we sought to conduct an accurate estimate of the efficacy of CTBT for menopausal symptoms. METHODS: We conducted searches of Cochrane Library, EMBASE, PsycINFO, PubMed, and Web of Science databases for studies from 1 January 1977 to 1 November 2021. Randomized controlled trials (RCTs) comparing intervention groups to control groups for menopausal symptoms were included. Hedge's g was used as the standardized between-group effect size with a random-effects model. RESULTS: We included 14 RCTs comprising 1618 patients with a mean sample size of 116. CTBT significantly outperformed control groups in terms of reducing hot flushes [g = 0.39, 95% confidence interval (CI) 0.23-0.55, I2 = 45], night sweats, depression (g = 0.50, 95% CI 0.34-0.66, I2 = 51), anxiety (g = 0.38, 95% CI 0.23-0.54, I2 = 49), fatigue, and quality of life. Egger's test indicated no publication bias. CONCLUSIONS: CTBT is an effective psychological treatment for menopausal symptoms, with predominantly small to moderate effects. The efficacy is sustained long-term, although it declines somewhat over time. The efficacy was stronger for natural menopause symptoms, such as vasomotor symptoms, than for treatment-induced menopause symptoms. These findings provide support for treatment guidelines recommending CTBT as a treatment option for menopausal symptoms.

Weyl Monoloop Semi-Half-Metal and Tunable Anomalous Hall Effect.

Nodal monoloop, enjoying the cleanest scenario with a single loop, is recognized as the basic building block of intricate linked loops including chains, nets, and knots. Here, we explore the interplay of magnetic ordering and band topology in one system by introducing a brand-new quantum state, referred to as Weyl monoloop semi-half-metal, which is characterized by a single loop at the Fermi level stemming from the same spin channel. Such a nodal line Fermion, yielding 100% spin polarization, is protected by mirror (Mz) symmetry. As a prominent example, a realistic rutile-type metal fluorides LiV2F6 achieves the hitherto unmaterialized state, featuring fully spin-polarized ultraflat surface states. More interestingly, LiV2F6 has a "soft" ferromagnetic property, which is one of the desired systems to control the anomalous Hall effect by rotating the magnetization direction. Our findings offer a promising candidate for exploring the topology and magnetism with intriguing effects.

DOCK8 Serves as a Prognostic Biomarker and Is Related to Immune Infiltration in Patients With HPV Positive Head and Neck Squamous Cell Carcinoma.

PURPOSE: Dedicator of cytokinesis 8 (DOCK8) was reported to have a vital link to immunoregulation. However, the mechanisms by which it drives immune infiltration in cancer remain uncertain. We tried to assess the role of DOCK8 in patients with cancer, especially human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC). METHODS: Data on the expression and survival of DOCK8 in patients with various cancers were analyzed using the Oncomine and TIMER databases. The TIMER database assessed the relationship of DOCK8 with immune infiltration levels and various markers of multiple immune cells. Gene set enrichment analysis revealed tumor-associated biological processes related to DOCK8. ENCODE database was used to explore relevant transcription factors of DOCK8, and a PPI network was constructed using GENEMINIA. The expression and survival role of DOCK8 was confirmed in patients from independent GEO datasets. RESULTS: We determined that DOCK8 expression was upregulated or downregulated in various cancers unlike in healthy tissues. A high expression of DOCK8 was significantly correlated with a favorable prognosis in HPV-positive HNSCC and lung adenocarcinoma (LUAD). Furthermore, multivariate Cox regression analysis revealed that DOCK8 was an independent prognostic factor of HPV-positive HNSCC. Additionally, elevated DOCK8 expression was positively correlated with multiple immune cell infiltration levels and immune marker expression associated with particular immune cell subsets. Also, 14 pathways involved in immune activities and carcinogenesis, 22 potential TFs, and co-expression proteins of DOCK8 indicated DOCK8 to be related to tumor-associated biological processes. Ultimately, we verified that DOCK8 is upregulated and confers a favorable overall survival and progression-free survival status in patients with HPV-positive HNSCC. CONCLUSION: These results elucidate that high expression of DOCK8 indicates a favorable prognosis in patients with HPV-positive HNSCC as well as increased microenvironmental immune infiltration levels. It would provide new insights into the prognosis predicting and clinical regimen decision making in patients with HPV-positive HNSCC.

Printed Nanochain-Based Colorimetric Assay for Quantitative Virus Detection.

Fast and ultrasensitive detection of pathogens is very important for efficient monitoring and prevention of viral infections. Here, we demonstrate a label-free optical detection approach that uses a printed nanochain assay for colorimetric quantitative testing of viruses. The antibody-modified nanochains have high activity and specificity which can rapidly identify target viruses directly from biofluids in 15 min, as well as differentiate their subtypes. Arising from the resonance induced near-field enhancement, the color of nanochains changes with the binding of viruses that are easily observed by a smartphone. We achieve the detection limit of 1 PFU µL-1 through optimizing the optical response of nanochains in visible region. Besides, it allows for real-time response to virus concentrations ranging from 0 to 1.0×105  PFU mL-1 . This low-cost and portable platform is also applicable to rapid detection of other biomarkers, making it attractive for many clinical applications.

Nodal Line Spin-Gapless Semimetals and High-Quality Candidate Materials.

Spin-gapless semimetals (SGSMs), which generate 100% spin polarization, are viewed as promising semi-half-metals in spintronics with high speed and low consumption. We propose and characterize a new Z_{2} class of topological nodal line (TNL) in SGSMs. The proposed TNLSGSMs are protected by space-time inversion symmetry or glide mirror symmetry with two-dimensional (2D) fully spin-polarized nearly flat surface states. Based on first-principles calculations and effective model analysis, a series of high-quality materials with R3[over ¯]c and R3c space groups are predicted to realize such TNLSGSMs (chainlike). The 2D fully spin-polarized nearly flat surface states may provide a route to achieving equal spin pairing topological superconductivity as well as topological catalysts.

Evaporation Induced Spontaneous Micro-Vortexes through Engineering of the Marangoni Flow.

Vortex flow fields are widely used to manipulate objects at the microscale in microfluidics. Previous approaches to produce the vortex flow field mainly focused on inertia flows. It remains a challenge to create vortexes in Stokes flow regime. Here we reported an evaporation induced spontaneous vortex flow system in Stokes flow regime by engineering Marangoni flow in a micro-structured microfluidic chip. The Marangoni flow is created by nonuniform evaporation of surfactant solution. Various vortexes are constructed by folding the air-water interface via microstructures. Patterns of vortexes are programmable by designing the geometry of the microstructures and are predictable using numerical simulations. Moreover, rotation of micro-objects and enrichment of micro-particles using vortex flow is demonstrated. This approach to create vortexes will provide a promising platform for various microfluidic applications such as biological analysis, chemical synthesis, and nanomaterial assembly.

Non-Lithography Hydrodynamic Printing of Micro/Nanostructures on Curved Surfaces.

A key issue of micro/nano devices is how to integrate micro/nanostructures with specified chemical components onto various curved surfaces. Hydrodynamic printing of micro/nanostructures on three-dimensional curved surfaces is achieved with a strategy that combines template-induced hydrodynamic printing and self-assembly of nanoparticles (NPs). Non-lithography flexible wall-shaped templates are replicated with microscale features by dicing a trench-shaped silicon wafer. Arising from the capillary pumped function between the template and curved substrates, NPs in the colloidal suspension self-assemble into close-packed micro/nanostructures without a gravity effect. Theoretical analysis with the lattice Boltzmann model reveals the fundamental principles of the hydrodynamic assembly process. Spiral linear structures achieved by two kinds of fluorescent NPs show non-interfering photoluminescence properties, while the waveguide and photoluminescence are confirmed in 3D curved space. The printed multiconstituent micro/nanostructures with single-NP resolution may serve as a general platform for optoelectronics beyond flat surfaces.

Crizotinib in patients with anaplastic lymphoma kinase-positive advanced non-small cell lung cancer versus chemotherapy as a first-line treatment.

BACKGROUND: To compare the efficacy of crizotinib, pemetrexed and other chemotherapy regimens as a first-line treatment in patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) in real world clinical use and to evaluate the +86-571-87,236,876 predictive clinical factors of the efficacy of crizotinib. METHODS: The 73 patients with ALK-positive advanced NSCLC were divided into three groups based on the first-line treatment: first-line crizotinib group (1-CRZ group, n = 32); first-line platinum-based pemetrexed treatment group (1-PP group, n = 28), and first-line chemotherapy platinum-based non-pemetrexed group (N1-PP, n = 12). Sixty eight of the 73 patients received crizotinib treatment and followed up in our hospital. Differences in the objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) were compared in the different groups. The clinical factors were evaluated to predict the efficacy of crizotinib by the Kaplan-Meier survival analysis and Cox proportional hazards model. RESULTS: The PFS, ORR, DCR were 16.1 months, 78.1% (25/32) and 100% (32/32) in the 1-CRZ group; were 6.0 months, 17.9% (5/28) and 57.2% (16/28) in the 1-PP group; and were 2.9 months, 15.4% (2/13) and 46.2% (6/13) in the N1-PP group. The PFS of the 1-CRZ group was significantly longer than that of the 1-PP group (P < 0.001) and the N1-PP group (P < 0.001). The ORR and DCR of the 1-CRZ group was significantly greater than that of the 1-PP group and the N1-PP group (all the P < 0.001). Higher Eastern Cooperative Oncology Group (ECOG) performance status score (> = 2) (HR 2.345, 95% CI 1.137-4.834, P = 0.021) and patients received crizotinib after N1-PP chemotherapy (HR 2.345, 95% CI 1.137-4.834, P = 0.021) were two factors associated with shorter PFS after crizotinib treatment. CONCLUSIONS: In patients with ALK-positive NSCLC who did not receive previous treatment, crizotinib was superior to standard chemotherapy for the longer PFS and greater ORR and DCR. Higher ECOG score (> = 2) and patients received crizotinib after N1-PP chemotherapy predict poor efficacy of crizotinib.

A high-resolution colorimetric immunoassay platform realized by coupling enzymatic multicolor generation with smartphone readout.

A high-resolution colorimetric immunoassay platform has been developed based on enzyme-catalyzed multicolor generation and smartphone-assisted signal readout. The multi-color generation is accomplished in this system through the urease-catalyzed urea hydrolysis-induced color change of the pH indicator phenol red, from yellow to orange to red over pH 6.6 to 8.0. The color change is easily tailored by controlling the urease activity via the inhibitor silver ion (Ag+), the amount of which is in turn adjusted by alkaline phosphatase (ALP)-catalyzed ascorbic acid (AA) production. An ALP-linked colorimetric immunoassay is readily realized based on the above urease catalyzed multicolor generation system. Under optimal conditions, a limit of detection (LOD) of 1.73 ng mL-1 and a dynamic range from 0 to 18 ng mL-1 are achieved with rabbit IgG as a model analyte. A colored picture for each test is directly taken using a smartphone and then quantitatively analyzed with the free software ImageJ, eliminating the use of expensive and desktop equipment. The dose-dependent multicolor display is easier to distinguish with the naked eye for qualitative or semiquantitative detection over the traditional one-color system. The developed immunoassay scheme provides a promising platform for on-site testing or applications in resource-poor areas.

High-level production of α-amylase by manipulating the expression of alanine racamase in Bacillus licheniformis.

OBJECTIVES: To improve target protein production by manipulating expression levels of alanine racemase in Bacillus licheniformis. RESULTS: The gene of dal was identified to be responsible for alanine racemase function. Based on the selection marker of dal, a food-grade expression system was constructed in B. licheniformis, and effects of different dal expression levels mediated by promoters on α-amylase production were investigated. The highest α-amylase activity (155 U/ml) was obtained in BL10D/pP43SAT-PtetDal, increased by 27% compared with that of the control strain BL10/pP43SAT in tetracycline-based system (123 U/ml). Moreover, the dal transcriptional level was not correlated positively with that of amyL. CONCLUSIONS: A food-grade system for high-level production of α-amylase was constructed in B. licheniformis, revealing that expression levels of selection marker significantly affected target protein production.

Exploring the Electronic Structure and Chemical Homogeneity of Individual Bi2Te3 Nanowires by Nano-Angle-Resolved Photoemission Spectroscopy.

Due to their high surface-to-volume ratio, cylindrical Bi2Te3 nanowires are employed as model systems to investigate the chemistry and the unique conductive surface states of topological insulator nanomaterials. We report on nanoangle-resolved photoemission spectroscopy (nano-ARPES) characterization of individual cylindrical Bi2Te3 nanowires with a diameter of 100 nm. The nanowires are synthesized by electrochemical deposition inside channels of ion-track etched polymer membranes. Core level spectra recorded with submicron resolution indicate a homogeneous chemical composition along individual nanowires, while nano-ARPES intensity maps reveal the valence band structure at the single nanowire level. First-principles electronic structure calculations for chosen crystallographic orientations are in good agreement with those revealed by nano-ARPES. The successful application of nano-ARPES on single one-dimensional nanostructures constitutes a new avenue to achieve a better understanding of the electronic structure of topological insulator nanomaterials.

Causal association of depression, anxiety, cognitive performance, the brain cortical structure with pulmonary arterial hypertension: A Mendelian randomization study.

BACKGROUND: Patients with pulmonary arterial hypertension (PAH) often present with anxiety, depression and cognitive deterioration. Structural changes in the cerebral cortex in PAH patients have also been reported in observational studies. METHODS: PAH genome-wide association (GWAS) including 162,962 European individuals was used to assess genetically determined PAH. GWAS summary statistics were obtained for cognitive performance, depression, anxiety and alterations in cortical thickness (TH) or surface area (SA) of the brain cortex, respectively. Two-sample Mendelian randomization (MR) was performed. Finally, sensitivity analyses including Cochran's Q test, MR-Egger intercept test, leave-one-out analyses, and funnel plot was performed. RESULTS: PAH had no causal relationship with depression, anxiety, and cognitive performance. At the global level, PAH was not associated with SA or TH of the brain cortex; at the functional regional level, PAH increased TH of insula (P = 0.015), pars triangularis (P = 0.037) and pars opercularis (P = 0.010) without global weighted. After global weighted, PAH increased TH of insula (P = 0.004), pars triangularis (P = 0.032), pars opercularis (P = 0.007) and rostral middle frontal gyrus (P = 0.022) while reducing TH of inferior parietal (P = 0.004), superior parietal (P = 0.031) and lateral occipital gyrus (P = 0.033). No heterogeneity and pleiotropy were detected. LIMITATIONS: The enrolled patients were all European and the causal relationship between PAH and the structure of the cerebral cortex in other populations remains unknown. CONCLUSION: Causal relationship between PAH and the brain cortical structure was implied, thus providing novel insights into the PAH associated neuropsychiatric symptoms.