Relationship between triglyceride-glucose index and carotid artery plaques in ischemic stroke patients: Based on blood pressure status, sex, and age.

BACKGROUND: Numerous studies have shown that the triglyceride-glucose (TyG) index is a reliable substitute marker for insulin resistance. Nevertheless, its correlation with carotid artery plaques (CAPs) among patients with ischemic stroke (IS) remains to be elucidated. METHODS: 9248 IS patients hospitalized at the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine were grouped according to the quartiles of TyG index. Patients were further stratified by blood pressure status, sex, age and hypertension control status. Employing logistic regression to examine the connection between the TyG index and CAPs.Additionally, analyzing the receiver operating characteristic (ROC) curve to evaluate the predictive value of the TyG index for CAPs. RESULTS: Participants with an elevated TyG index had an increased prevalence of CAPs. The TyG index was positively correlated with CAPs (OR: 1.26, CI: 1.14-1.40, P<0.001). Compared with normal blood pressure and prehypertensive patients, the TyG index was markedly correlated with CAPs among hypertensive patients (OR: 1.29, 95% CI: 1.15-1.44, P<0.001). Females had a higher OR value than males(OR: 1.31, 95% CI: 1.11-1.54, P=0.001 versus OR: 1.24, 95% CI: 1.09-1.41, P=0.001). Older patients (>60 years) had a higher OR value than their middle-aged counterparts (≤60 years) (OR: 1.35; 95% CI: 1.16-1.58, P<0.001 versus OR: 1.20; 95% CI: 1.05-1.37, P=0.007). Patients with poorly-controlled hypertension had a higher OR value than patients with well-controlled hypertension(OR: 1.36; 95% CI: 1.14-1.63, P=0.001 versus OR: 1.24; 95% CI: 1.07-1.44, P=0.003). After adjusting for potential confounding factors, the area under the ROC curve (AUC) value in the overall population, sex-stratified group, hypertensive patients and hypertension control status-stratified group were all above 0.7 (P<0.01), demonstrating good forecasting capability. CONCLUSIONS: In IS patients, the TyG index was significantly associated with CAPs. Additionally, this correlation was more pronounced in hypertensive patients, females, older individuals and patients with poorly-controlled hypertension.

Codon Usage Bias: A Potential Factor Affecting VGLUT Developmental Expression and Protein Evolution.

More and more attention has been paid to the role of synonymous substitution in evolution, in which codon usage preference can affect gene expression distribution and protein structure and function. Vesicular glutamate transporter (VGLUT) consists of three isoforms, among which VGLUT3 is significantly different from other VGLUTs in functional importance, expression level, and distribution range, whose reason is still unclear. This study sought to analyze the role of codon preference in VGLUT differentiation. To conduct an evolutionary analysis of the three VGLUTs, this paper uses bioinformatics research methods to analyze the coding sequences of the three VGLUTs in different species and compare the codon usage patterns. Furthermore, the differences among the three VGLUTs were analyzed by combining functional importance, expression level, distribution range, gene structure, protein relationship network, expression at specific developmental stages, and phylogenetic tree, and the influence of codon usage pattern was explored. The results showed that the VGLUT with greater codon preference had less functional importance, lower expression levels, more peripheral distribution away from the CNS, smaller exon density of gene, less conserved and farther away from the CDS region miRNA regulatory sites, simpler and less tight protein interaction networks, delayed developmental expression, and more distant evolutionary relationships. Codon usage preference is a potential factor affecting VGLUT developmental expression and protein evolution.

Design of a Novel Microlens Array and Imaging System for Light Fields.

Light field cameras are unsuitable for further acquisition of high-quality images due to their small depth of field, insufficient spatial resolution, and poor imaging quality. To address these issues, we proposed a novel four-focal-square microlens and light field system. A square aspheric microlens array with four orthogonal focal lengths was designed, in which the aperture of a single lens was 100 µm. The square arrangement improves pixel utilization, the four focal lengths increase the depth of field, and the aspheric improves image quality. The simulations demonstrate pixel utilization rates exceeding 90%, depth-of-field ranges 6.57 times that of a single focal length, and image quality is significantly improved. We have provided a potential solution for improving the depth of field and image quality of the light field imaging system.

Correlation Between Growth Differentiation Factor-15 and Peripheral Neuropathy in Patients with Type 2 Diabetes Mellitus.

Purpose: To inquire into the relationship between diabetic peripheral neuropathy (DPN) and serum levels of growth differentiation factor-15 (GDF-15) in individuals with type 2 diabetes mellitus (T2DM). Patients and Methods: Out of 162 T2DM patients classified according to the diagnostic criteria of DPN, 75 were allocated to the non-DPN group and 87 to the DPN group. In turn, based on serum GDF-15 quartiles, all patients were additionally divided (GDF-15 low to high) into group A (40 cases), group B (41 cases), group C (41 cases), and group D (40 cases). General data and laboratory indexes of patients were collected, and enzyme-linked immunosorbent assay (ELISA) was used to determine serum GDF-15 levels. Results: Compared to the non-DPN group, in the DPN group GDF-15 levels were noticeably greater (P < 0.001). Using serum GDF-15 as a grouping variable, DPN prevalence and body mass index were gradually increased, motor and sensory nerve latencies were gradually lengthened, and amplitude (Amp) and nerve conduction velocity (NCV) were gradually decreased with increasing GDF-15 levels (P < 0.05). Linear regression modeling revealed that GDF-15 levels correlated positively with the latencies of sensory and motor nerves, and negatively with their corresponding NCV (P < 0.05). Binary logistic regression results indicated GDF-15 as an independent predictor for DPN (P < 0.05), whereas restricted cubic spline analysis indicated a dose-response, nonlinear relationship between GDF-15 and DPN. Conclusion: Serum GDF-15 level strongly correlates with DPN, and may represent an independent predictor and a biological marker for the disease.

Comparison of lipidome profiles in serum from lactating dairy cows supplemented with Acremonium terrestris culture based on UPLC-QTRAP-MS/MS.

This study evaluated the effects of supplementing the diet of lactating cows with Acremonium terrestris culture (ATC) on milk production, serum antioxidant capacity, inflammatory indices, and serum lipid metabolomics. Over 90 days, 24 multiparous Chinese Holstein cows in mid-lactation (108 ± 10.4 days in milk, 637 ± 25 kg body weight, 30.23 ± 3.7 kg/d milk yield) were divided into either a control diet (CON) or a diet supplemented with 30 g of ATC daily. All the data were analyzed using Student's t test with SPSS 20.0 software. The results showed that compared with CON feeding, ATC feeding significantly increased milk yield, antioxidant capacity, and immune function. Lipidome screening identified 143 lipid metabolites that differed between the two groups. Further analysis using "random forest" machine learning revealed three glycerophospholipid serum metabolites that could serve as lipid markers with a predictive accuracy of 91.67%. This study suggests that ATC can be a useful dietary supplement for improving lactational performance in dairy cows and provides valuable insights into developing nutritional strategies to maintain metabolic homeostasis in ruminants.

MS-YOLOv8-Based Object Detection Method for Pavement Diseases.

Detection of pavement diseases is crucial for road maintenance. Traditional methods are costly, time-consuming, and less accurate. This paper introduces an enhanced pavement disease recognition algorithm, MS-YOLOv8, which modifies the YOLOv8 model by incorporating three novel mechanisms to improve detection accuracy and adaptability to varied pavement conditions. The Deformable Large Kernel Attention (DLKA) mechanism adjusts convolution kernels dynamically, adapting to multi-scale targets. The Large Separable Kernel Attention (LSKA) enhances the SPPF feature extractor, boosting multi-scale feature extraction capabilities. Additionally, Multi-Scale Dilated Attention in the network's neck performs Spatially Weighted Dilated Convolution (SWDA) across different dilatation rates, enhancing background distinction and detection precision. Experimental results show that MS-YOLOv8 increases background classification accuracy by 6%, overall precision by 1.9%, and mAP by 1.4%, with specific disease detection mAP up by 2.9%. Our model maintains comparable detection speeds. This method offers a significant reference for automatic road defect detection.

Early Warning of Systemic Risk in Commodity Markets Based on Transfer Entropy Networks: Evidence from China.

This study aims to employ a causal network model based on transfer entropy for the early warning of systemic risk in commodity markets. We analyzed the dynamic causal relationships of prices for 25 commodities related to China (including futures and spot prices of energy, industrial metals, precious metals, and agricultural products), validating the effect of the causal network structure among commodity markets on systemic risk. Our research results identified commodities and categories playing significant roles, revealing that industry and precious metal markets possess stronger market information transmission capabilities, with price fluctuations impacting a broader range and with greater force on other commodity markets. Under the influence of different types of crisis events, such as economic crises and the Russia-Ukraine conflict, the causal network structure among commodity markets exhibited distinct characteristics. The results of the effect of external shocks to the causal network structure of commodity markets on the entropy of systemic risk suggest that network structure indicators can warn of systemic risk. This article can assist investors and policymakers in managing systemic risk to avoid unexpected losses.

Proteomic Analysis of Lysine Acetylation and Succinylation to Investigate the Pathogenicity of Virulent Pseudomonas syringae pv. tomato DC3000 and Avirulent Line Pseudomonas syringae pv. tomato DC3000 avrRpm1 on Arabidopsis thaliana.

Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) is able to infect many economically important crops and thus causes substantial losses in the global agricultural economy. Pst DC3000 can be divided into virulent lines and avirulent lines. For instance, the pathogen effector avrRPM1 of avirulent line Pst-avrRpm1 (Pst DC3000 avrRpm1) can be recognized and detoxified by the plant. To further compare the pathogenicity mechanisms of virulent and avirulent Pst DC3000, a comprehensive analysis of the acetylome and succinylome in Arabidopsis thaliana was conducted following infection with virulent line Pst DC3000 and avirulent line Pst-avrRpm1. In this study, a total of 1625 acetylated proteins encompassing 3423 distinct acetylation sites were successfully identified. Additionally, 229 succinylated proteins with 527 unique succinylation sites were detected. A comparison of these modification profiles between plants infected with Pst DC3000 and Pst-avrRpm1 revealed significant differences. Specifically, modification sites demonstrated inconsistencies, with a variance of up to 10% compared to the control group. Moreover, lysine acetylation (Kac) and lysine succinylation (Ksu) displayed distinct preferences in their modification patterns. Lysine acetylation is observed to exhibit a tendency towards up-regulation in Arabidopsis infected with Pst-avrRpm1. Conversely, the disparity in the number of Ksu up-regulated and down-regulated sites was not as pronounced. Motif enrichment analysis disclosed that acetylation modification sequences are relatively conserved, and regions rich in polar acidic/basic and non-polar hydrophobic amino acids are hotspots for acetylation modifications. Functional enrichment analysis indicated that the differentially modified proteins are primarily enriched in the photosynthesis pathway, particularly in relation to light-capturing proteins. In conclusion, this study provides an insightful profile of the lysine acetylome and succinylome in A. thaliana infected with virulent and avirulent lines of Pst DC3000. Our findings revealed the potential impact of these post-translational modifications (PTMs) on the physiological functions of the host plant during pathogen infection. This study offers valuable insights into the complex interactions between plant pathogens and their hosts, laying the groundwork for future research on disease resistance and pathogenesis mechanisms.

Identification of a novel intronic variant of ATP6V0A2 in a Han-Chinese family with cutis laxa.

BACKGROUND: Cutis laxa is a connective tissue disease caused by abnormal synthesis or secretion of skin elastic fibers, leading to skin flabby and saggy in various body parts. It can be divided into congenital cutis laxa and acquired cutis laxa, and inherited cutis laxa syndromes is more common in clinic. METHODS: In this study, we reported a case of a Han-Chinese male newborn with ATP6V0A2 gene variant leading to cutis laxa. The proband was identified by whole-exome sequencing to determine the novel variant, and their parents were verified by Sanger sequencing. Bioinformatics analysis and minigene assay were used to verify the effect of this variant on splicing function. RESULTS: The main manifestations of the proband are skin laxity, abnormal facial features, and enlargement of the anterior fontanelle. Whole-exome sequencing showed that the newborn carried a non-canonical splicing-site variant c.117 + 5G > T, p. (?) in ATP6V0A2 gene. Sanger sequencing showed that both parents of the proband carried the heterozygous variant. The results of bioinformatics analysis and minigene assay displayed that the variant site affected the splicing function of pre-mRNA of the ATP6V0A2 gene. CONCLUSIONS: In this study, it was identified that ATP6V0A2 gene c. 117 + 5G > T may be the cause of the disease. The non-canonical splicing variants of ATP6V0A2 gene were rarely reported in the past, and this variant expanded the variants spectrum of the gene. The functional study of minigene assay plays a certain role in improving the level of evidence for the pathogenicity of splicing variants, which lays a foundation for prenatal counseling and follow-up gene therapy.

Comparative analysis of sipeimine content, metabolome and chloroplast genome in cultivated and wild varieties of Fritillaria taipaiensis.

BACKGROUND: The wild variety Fritillaria taipaiensis E.B (EB) is known for its superior therapeutic effects, but its limited production cannot meet demand. As a result, the cultivated variety F. taipaiensis P. Y. Li (PY) has been widely grown. In this study, we conducted a comprehensive analysis comparing EB and PY in terms of external features, sipeimine content, metabolome and chloroplast genome to differentiate these two varieties. RESULTS: Our research revealed that the petals and pods of EB are green, while those of PY have purple markings. The bulbs of EB contain significantly higher levels of sipeimine compared to those of PY. Metabolomic analysis identified 56 differentially expressed metabolites (DMs), with 23 upregulated and 33 downregulated in EB bulbs. Particularly, 3-hydroxycinnamic acid and secoxyloganin may serve as distinctive DMs. These DMs were associated with 17 KEGG pathways, including pyrimidine metabolism, alanine, aspartate and glutamate metabolism, and galactose metabolism. Differences in the length of the chloroplast genome were primarily observed in the large single-copy (LSC) region, with the largest variation in the trnH-GUC-psbA region. The placement of the trnH gene and the rps gene in proximity to the LSC/IRb boundary differs between EB and PY. CONCLUSION: The results of this study provide valuable insights for the introduction and comprehensive development of wild F. taipaiensis from a scientific perspective. © 2024 Society of Chemical Industry.

Analysis of the Immune Response by Standardized Whole-Blood Stimulation with Metabolism Modulation.

The immune system defends the body from infection and plays a vital role in a wide range of health conditions. Metabolism affects a series of physiological processes, including those linked to the function of human immune system. Cellular metabolism modulates immune cell activation and cytokine production. Understanding the relationship between metabolism and immune response has important implications for the development of immune-based therapeutics. However, the deployment of large-scale functional assays to investigate the metabolic regulation of immune response has been limited by the lack of standardized procedures. Here, we present a protocol for the analysis of immune response using standardized whole-blood stimulation with metabolism modulation. Diverse immune stimuli including pattern recognition receptor (PRR) ligands and microbial stimuli were incubated with fresh human whole blood. The metabolic inhibitors were used to modulate metabolic status in the immune cells. The variable immune responses after metabolic interventions were evaluated. We described in detail the main steps involved in the whole-blood stimulation and cytokines quantification, namely, collection and treatment of whole blood, preparation of samples and controls, cytokines detection, and stimulation with metabolic interventions. The metabolic inhibitors for anabolic pathways and catabolic pathways exert selective effects on the production of cytokines from immune cells. In addition to a robust and accurate assessment of immune response in cohort studies, the standardized whole-blood stimulation with metabolic regulation might provide new insights for modulating immunity. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-023-00114-0.

Time-Course Transcriptomic Analysis Reveals Molecular Insights into the Inflorescence and Flower Development of Cardiocrinum giganteum.

Cardiocrinum giganteum is an endemic species of east Asia which is famous for its showy inflorescence and medicinal bulbs. Its inflorescence is a determinate raceme and the flowers bloom synchronously. Morphological observation and time-course transcriptomic analysis were combined to study the process of inflorescence and flower development of C. giganteum. The results show that the autonomic pathway, GA pathway, and the vernalization pathway are involved in the flower formation pathway of C. giganteum. A varied ABCDE flowering model was deduced from the main development process. Moreover, it was found that the flowers in different parts of the raceme in C. giganteum gradually synchronized during development, which is highly important for both evolution and ecology. The results obtained in this work improve our understanding of the process and mechanism of inflorescence and flower development and could be useful for the flowering period regulation and breeding of C. giganteum.

Transcriptome Analysis Reveals Coexpression Networks and Hub Genes Involved in Papillae Development in Lilium auratum.

Lilium is a genus of important ornamental plants with many colouring pattern variations. Lilium auratum is the parent of Oriental hybrid lilies. A typical feature of L. auratum is the presence of red-orange special raised spots named papillae on the interior tepals. Unlike the usual raised spots, the papillae are slightly rounded or connected into sheets and usually have hairy tips. To elucidate the potential genes regulating papillae development in L. auratum, we performed high-throughput sequencing of its tepals at different stages. Genes involved in the flavonoid biosynthesis pathway were significantly enriched during the colouration of the papillae, and CHS, F3H, F3'H, FLS, DFR, ANS, and UFGT were significantly upregulated. To identify the key genes involved in the papillae development of L. auratum, we performed weighted gene coexpression network analysis (WGCNA) and further analysed four modules. In total, 51, 24, 1, and 6 hub genes were identified in four WGCNA modules, MEbrown, MEyellow, MEpurple, and MEred, respectively. Then, the coexpression networks were constructed, and important genes involved in trichome development and coexpressed with anthocyanin biosynthesis genes, such as TT8, TTG1, and GEM, were identified. These results indicated that the papillae are essentially trichomes that accumulate anthocyanins. Finally, we randomly selected 12 hub genes for qRT-PCR analysis to verify the accuracy of our RNA-Seq analysis. Our results provide new insights into the papillae development in L. auratum flowers.

Infrared photoinduced electrochemiluminescence microscopy of single cells.

Electrochemiluminescence (ECL) is evolving rapidly from a purely analytical technique into a powerful microscopy. Herein, we report the imaging of single cells by photoinduced ECL (PECL; λem = 620 nm) stimulated by an incident near-infrared light (λexc = 1050 nm). The cells were grown on a metal-insulator-semiconductor (MIS) n-Si/SiOx/Ir photoanode that exhibited stable and bright PECL emission. The large anti-Stokes shift allowed for the recording of well-resolved images of cells with high sensitivity. PECL microscopy is demonstrated at a remarkably low onset potential of 0.8 V; this contrasts with classic ECL, which is blind at this potential. Two imaging modes are reported: (i) photoinduced positive ECL (PECL+), showing the cell membranes labeled with the [Ru(bpy)3]2+ complex; and (ii) photoinduced shadow label-free ECL (PECL-) of cell morphology, with the luminophore in the solution. Finally, by adding a new dimension with the near-infrared light stimulus, PECL microscopy should find promising applications to image and study single photoactive nanoparticles and biological entities.

Near-IR Photoinduced Electrochemiluminescence Imaging with Structured Silicon Photoanodes.

Infrared (IR) imaging devices that convert IR irradiation (invisible to the human eye) to a visible signal are based on solid-state components. Here, we introduce an alternative concept based on light-addressable electrochemistry (i.e., electrochemistry spatially confined under the action of a light stimulus) that involves the use of a liquid electrolyte. In this method, the projection of a near-IR image (λexc = 850 or 840 nm) onto a photoactive Si-based photoanode, immersed into a liquid phase, triggers locally the photoinduced electrochemiluminescence (PECL) of the efficient [Ru(bpy)3]2+-TPrA system. This leads to the local conversion of near-IR light to visible (λPECL = 632 nm) light. We demonstrate that compared to planar Si photoanodes, the use of a micropillar Si array leads to a large enhancement of local light generation and considerably improves the resolution of the PECL image by preventing photogenerated minority carriers from diffusing laterally. These results are important for the design of original light conversion devices and can lead to important applications in photothermal imaging and analytical chemistry.

Off-Grid Electrogenerated Chemiluminescence with Customized p-i-n Photodiodes.

Electrochemiluminescence (ECL) is the generation of light induced by an electrochemical reaction, driven by electricity. Here, an all-optical ECL (AO-ECL) system is developped, which triggers ECL by the illumination of electrically autonomous "integrated" photoelectrochemical devices immersed in the electrolyte. Because these systems are made using small and cheap devices, they can be easily prepared and readily used by any laboratories. They are based on commercially available p-i-n Si photodiodes (≈1 € unit-1), coupled with well-established ECL-active and catalytic materials, directly coated onto the component leads by simple and fast wet processes. Here, a Pt coating (known for its high activity for reduction reactions) and carbon paint (known for its optimal ECL emission properties) are deposited at cathode and anode leads, respectively. In addition to its optimized light absorption properties, using the commercial p-i-n Si photodiode eliminates the need for a complicated manufacturing process. It is shown that the device can emit AO-ECL by illumination with polychromatic (simulated sunlight) or monochromatic (near IR) light sources to produce visible photons (425 nm) that can be easily observed by the naked eye or recorded with a smartphone camera. These low-cost off-grid AO-ECL devices open broad opportunities for remote photodetection and portable bioanalytical tools.

All-Optical Electrochemiluminescence at Metal-Insulator-Semiconductor Diodes.

Pt/InGa/n-Si/SiOx/Pt devices were prepared by using standard chemical and sputtering processes. These systems are diodes comprising a frontside photoactive metal-insulator-semiconductor (MIS) n-Si/SiOx/Pt junction and a backside Pt/InGa/n-Si Ohmic contact. Pt/InGa/n-Si/SiOx/Pt was first characterized by dark-solid-state electrical and impedance measurements. Then, each side of the device was investigated by electrochemical means in the dark and under near-IR illumination at 850 nm in the luminol-H2O2 electrochemiluminescence (ECL) electrolyte. The results suggested the possibility of triggering an all-optical ECL (AO-ECL) at Pt/InGa/n-Si/SiOx/Pt. This was confirmed by studying AO-ECL at the monolithic, all-integrated Pt/InGa/n-Si/SiOx/Pt device, immersed in the ECL electrolyte. The conversion process can occur with good stability and the intensity of the visible emission (440 nm) depends on tunable parameters such as the illumination power density, O2 concentration, or the concentration of added H2O2. These results are important for the next developments of AO-ECL in sensing and microscopy.

Maize ZmBES1/BZR1-1 transcription factor negatively regulates drought tolerance.

Drought stress is a common abiotic factor and restricts plant growth and development. Exploring maize stress-related genes and their regulatory mechanisms is crucial for ensuring agricultural productivity and food security. The BRI1-EMS1 suppressor (BES1)/brassinazole-resistant 1 (BZR1) transcription factors (TFs) play important roles in plant growth, development, and stress response. However, maize ZmBES1/BZR1s are rarely reported. In the present study, the ZmBES1/BZR1-1 gene was cloned from maize B73 and functionally characterized in transgenic Arabidopsis and rice in drought stress response. The ZmBES1/BZR1-1 protein possessed a conserved bHLH domain characterized by BES1/BZR1 TFs, localized in the nucleus, and showed transcription activation activity. The expression of ZmBES1/BZR1-1 exhibited no tissue specificity but drought-inhibitory expression in maize. Under drought stress, overexpression of ZmBES1/BZR1-1 resulted in the enhancement of drought sensitivity of transgenic Arabidopsis and rice with a lower survival rate, reactive oxygen species (ROS) level and relative water content (RWC) and a higher stomatal aperture and relative electrolyte leakage (REL). The RNA-seq results showed that 56 differentially expressed genes (DEGs) were regulated by ZmBES1/BZR1-1 by binding to E-box elements in their promoters. The GO analysis showed that the DEGs were significantly annotated with response to oxidative stress and oxygen level. The study suggests that the ZmBES1/BZR1-1 gene negatively regulates drought stress, which provides insights into further underlying molecular mechanisms in the drought stress response mediated by BZR1/BES1s.

Identification of region-specific splicing QTLs in human hippocampal tissue and its distinctive role in brain disorders.

Alternative splicing (AS) regulation has an essential role in complex diseases. However, the AS profiles in the hippocampal (HIPPO) region of human brain are underexplored. Here, we investigated cis-acting sQTLs of HIPPO region in 264 samples and identified thousands of significant sQTLs. By enrichment analysis and functional characterization of these sQTLs, we found that the HIPPO sQTLs were enriched among histone-marked regions, transcription factors binding sites, RNA binding proteins sites, and brain disorders-associated loci. Comparative analyses with the dorsolateral prefrontal cortex revealed the importance of AS regulation in HIPPO (rg = 0.87). Furthermore, we performed a transcriptome-wide association study of Alzheimer's disease and identified 16 significant genes whose genetically regulated splicing levels may have a causal role in Alzheimer. Overall, our study improves our knowledge of the transcriptome gene regulation in the HIPPO region and provides novel insights into elucidating the pathogenesis of potential genes associated with brain disorders.