Inhibiting DNA methyltransferase DNMT3B confers protection against ferroptosis in nucleus pulposus and ameliorates intervertebral disc degeneration via upregulating SLC40A1.

Epigenetic changes are important considerations for degenerative diseases. DNA methylation regulates crucial genes by epigenetic mechanism, impacting cell function and fate. DNA presents hypermethylation in degenerated nucleus pulposus (NP) tissue, but its role in intervertebral disc degeneration (IVDD) remains elusive. This study aimed to demonstrate that methyltransferase mediated hypermethylation was responsible for IVDD by integrative bioinformatics and experimental verification. Methyltransferase DNMT3B was highly expressed in severely degenerated NP tissue (involving human and rats) and in-vitro degenerated human NP cells (NPCs). Bioinformatics elucidated that hypermethylated genes were enriched in oxidative stress and ferroptosis, and the ferroptosis suppressor gene SLC40A1 was identified with lower expression and higher methylation in severely degenerated human NP tissue. Cell culture using human NPCs showed that DNMT3B induced ferroptosis and oxidative stress in NPCs by downregulating SLC40A1, promoting a degenerative cell phenotype. An in-vivo rat IVDD model showed that DNA methyltransferase inhibitor 5-AZA alleviated puncture-induced IVDD. Taken together, DNA methyltransferase DNMT3B aggravates ferroptosis and oxidative stress in NPCs via regulating SLC40A1. Epigenetic mechanism within DNA methylation is a promising therapeutic biomarker for IVDD.

Multi-domain wavelet boundary element method for calculating two-dimensional stress intensity factors.

In order to improve the accuracy of stress intensity factors (SIFs) calculated by traditional boundary element methods (BEM), the multi-domain wavelet boundary element method (WBEM) is proposed. Firstly, by adjusting the nodes of the B-spline wavelet element on the interval, crack-tip elements are constructed. Since B-spline wavelet on the interval (BSWI) has excellent compact support characteristics and is particularly suitable for describing solution domains with large gradient changes, the constructed crack-tip can reduce the numerical oscillation effect near the crack tip. Secondly, the crack-tip elements are implemented into WBEM. And the combination of WBEM and multi-domain technology can effectively handle interface cracks. Thirdly, the crack problem solving strategy based on multi-domain WBEM can directly evaluate the SIFs of cracks. Finally, several numerical examples involving homogeneous media and bi-material models are given to verify that the proposed method is simple and highly accurate.

Exploring the causal relationship between antihypertensive drugs and glioblastoma by combining drug target Mendelian randomization study, eQTL colocalization, and single-cell RNA sequencing.

Recent reports indicate a potential oncogenic role of antihypertensive drugs in common cancers. However, it remains uncertain whether this phenomenon influences the risk of glioblastoma multiforme (GBM). This study aimed to assess the potential causal effects of blood pressure (BP) and antihypertensive drugs on GBM. Genome-wide association study (GWAS) summary statistics for systolic blood pressure (SBP), diastolic blood pressure (DBP), and GBM in Europeans were downloaded. To represent the effects of antihypertensive drugs, we utilized single nucleotide polymorphisms (SNPs) associated with SBP/DBP adjacent to the coding regions of different antihypertensive drugs as instrumental variables to model five antihypertensive drugs, including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, ß-receptor blockers (BBs), and thiazide diuretics. Positive control studies were performed using GWAS data in chronic heart failure. The primary method for causality estimation was the inverse-variance-weighted method. Mendelian randomization analysis showed that BBs with the ß1-adrenergic receptor (ADRB1) as a therapeutic target could significantly reduce the risk of GBM by mediating DBP (OR = 0.431, 95% CI: 0.267-0.697, p < .001) and that they could also significantly reduce the risk of GBM by mediating SBP (OR = 0.595, 95% CI: 0.422-0.837, p = .003). Sensitivity analysis and colocalization analysis reinforced the robustness of these findings. Finally, the low expression of the ADRB1 gene in malignant gliomas was found by GBM data from TCGA and single-cell RNA sequencing, which most likely contributed to the poor prognosis of GBM patients. In summary, our study provides preliminary evidence of some causal relationship between ADRB1-targeted BBs and glioblastoma development. However, more studies are needed to validate these findings and further reveal the complex relationship between BP and GBM.

TENET: Triple-enhancement based graph neural network for cell-cell interaction network reconstruction from spatial transcriptomics.

Cellular communication relies on the intricate interplay of signaling molecules, forming the Cell-cell Interaction network (CCI) that coordinates tissue behavior. Researchers have shown the capability of shallow neural networks in reconstructing CCI, given molecules' abundance in the Spatial Transcriptomics (ST) data. When encountering situations such as sparse connections in CCI and excessive noise, the susceptibility of shallow networks to these factors significantly impacts the accuracy of CCI reconstruction, resulting in subpar results. To reconstruct a more comprehensive and accurate CCI, we propose a novel method named Triple-Enhancement based Graph Neural Network (TENET). In TENET, three progressive enhancement mechanisms build upon each other, creating a cumulative effect. This approach can ensure the ability to capture valuable features in limited data and amplify the noise signal to facilitate the denoising effect. Additionally, the whole architecture guides the decoding reconstruction phase with integrated knowledge, which leverages the accumulated insights from each stage of enhancement to ensure a refined and comprehensive CCI reconstruction. The presented TENET has been implemented and tested on both real and synthetic ST datasets. Averagely, the CCI reconstruction using TENET achieves a 9.61% improvement in Average Precision (AP) and a 7.32% improvement in Area Under the Receiver Operating Characteristic (AUROC) compared to the existing state-of-the-art (SOTA) method. The source code and data are available at https://github.com/Yujian-Lee/TENET.

RARRES2 is involved in the "lock-and-key" interactions between osteosarcoma stem cells and tumor-associated macrophages.

Osteosarcoma (OS) is a type of tumor. Osteosarcoma stem cells (OSCs) are responsible for drug resistance, recurrence, and immunosuppression in OS. We aimed to determine the heterogeneity of OSCs and the immunosuppression mechanisms underlying the interactions between OSCs and tumor-associated macrophages (TAMs). The cell components, trajectory changes, and cell communication profiles of OS cells were analyzed by transcriptomics at the single-cell level. The intercellular communication patterns of OSCs were verified, and the role of the cell hub genes was revealed. Hub geneS are genes that play important roles in regulating certain biological processes; they are often defined as the genes with the strongest regulatory effect on differentially expressed gene sets. Moreover, various cellular components of the OS microenvironment were identified. Malignant cells were grouped, and OSCs were identified. Further regrouping and communication analysis revealed that the genes in the stemness maintenance and differentiation subgroups were involved in communication with macrophages. Key receptor-ligand pairs and target gene sets for cell communication were obtained. Transcriptome data analysis revealed the key gene RARRES2, which is involved in intercellular communication between OSCs and TAMs. In vitro studies confirmed that macrophages promote RARRES2-mediated stemness maintenance in OSCs via the TAM-secreted cytokine insulin-like growth factor 1. Patient studies confirmed that RARRES2 could be a biomarker of OS. OSCs are highly heterogeneous, and different subgroups are responsible for proliferation and communication with other cells. The IGF-RARRES2 axis plays a key role in maintaining OSC stemness through communication with TAMs.

A polarization-sensitive, high on/off ratio and self-powered photodetector based on Nb2CTxand Nd2CTx@MoS2.

MXene two-dimensional materials have been widely used in energy storage, catalysis, sensing and other fields, Nb2C as a typical two-dimensional MXene material, its exploration in the field of optoelectronics is still in its infancy, especially Nb2C-based photodetectors are still to be developed. This paper demonstrates that two-dimensional films based on few-layer Nb2C have a photoelectric response in the wavelength range from visible to near-infrared. We have found that the light response performance can be easily adjusted by controlling the thickness of the spin-coated film, and that Nb2C photodetectors show great advantages in terms of wide bandwidth, polarization response, high switching ratio, etc. By adjusting the material concentration and sample thickness, the photocurrent can reach up to 330 nA, the switching ratio can reach 410, and the responsivity can reach 8.3 × 10-4A W-1. In the polarization characteristic test, an extinction ratio of 7.6 can be obtained. By adjusting the content of that doped MoS2quantum dot, the dark current can reach 7.6 × 10-13A, and the switching ratio can reach 3 × 105, which can be increased by 700 times. The above results show that the few-layer Nb2C nanosheets can be used as optoelectronic detectors in the visible to near-infrared bands, which further broadens the application prospects of two-dimensional MXene.

Regioselective Synthesis of Unsymmetrical Vicinal Diamines via Azidoimination of Alkenes with TMSN3 and Ketimines.

2-Azidoimines are versatile precursors to value-added vicinal unsymmetrical diamines, which are among the most common motifs in biologically active compounds. Herein, we report their operationally simple synthesis through a highly regioselective intermolecular azidoamination of olefins under metal-free conditions. The approach proceeded through azide and iminyl, two differentiated N-centered radicals. The synthetic potential of the protocols was further established via the condensation/amination sequential cascade and chemoselective, orthogonal transformations to access vicinal primary diamines.

Lateral trochlear inclination measured by the transepicondylar axis holds potential for evaluating trochlear dysplasia in patients with lateral patellar dislocation.

PURPOSE: To verify that lateral trochlear inclination (LTI) measured by the transepicondylar axis can reliably be used to evaluate trochlear dysplasia (TD) on MRI and can serve as an objective indication of trochleoplasty for patients with lateral patellar dislocation (LPD). METHODS: Eighty patients with recurrent LPD and eighty healthy subjects were included. TD, posterior condylar angle (PCA), and LTI measured by the posterior condylar reference line (LTIp), surgical transepicondylar axis (LTIs), and anatomical transepicondylar axis (LTIa) were assessed on MRI. The intraclass correlation coefficient (ICC) and Bland-Altman analysis were performed, the correlations and differences amongst the parameters were identified, and a binary logistic regression model was established. RESULTS: Each measurement had excellent inter- and intra-observer agreement. The LTIp, LTIs and LTIa were smaller in the study group than in the control group, with mean differences of 9.0°, 7.2° and 7.0°, respectively (P < 0.001). The PCA was larger in patients with LPD than in the control group (P < 0.001). LTIp was associated with PCA in the study group (r = - 0.41, P < 0.001). The pathological values of LTIp, LTIs and LTIa were 11.7°, 15.3° and 17.4°, respectively. LTIs and LTIa were independent risk factors for LPD, with ORs of 7.33 (95% CI [1.06-52.90], P = 0.048) and 10.29 (95% CI [1.38-76.96], P = 0.023), respectively. CONCLUSION: The LTI can be reliably measured by MRI, but LTIp could potentially decrease the recorded value from the actual inclination angle. LTIs and LTIa are more appropriate to serve as trochleoplasty indications for patients with LPD, which could help orthopedists with surgical decision-making. LEVEL OF EVIDENCE: Level III.

AIFM2 promotes hepatocellular carcinoma metastasis by enhancing mitochondrial biogenesis through activation of SIRT1/PGC-1α signaling.

AIFM2 is a crucial NADH oxidase involved in the regulation of cytosolic NAD+. However, the role of AIFM2 in the progression of human cancers remains largely unexplored. Here, we elucidated the clinical implications, biological functions, and molecular mechanisms of AIFM2 in hepatocellular carcinoma (HCC). We found that AIFM2 is significantly upregulated in HCC, which is most probably caused by DNA hypomethylation and downregulation of miR-150-5p. High expression of AIFM2 is markedly associated with poor survival in patients with HCC. Knockdown of AIFM2 significantly impaired, while forced expression of AIFM2 enhanced the metastasis of HCC both in vitro and in vivo. Mechanistically, increased mitochondrial biogenesis and oxidative phosphorylation by activation of SIRT1/PGC-1α signaling contributed to the promotion of metastasis by AIFM2 in HCC. In conclusion, AIFM2 upregulation plays a crucial role in the promotion of HCC metastasis by activating SIRT1/PGC-1α signaling, which strongly suggests that AIFM2 could be targeted for the treatment of HCC.

Tenofovir disoproxil fumarate mediates neuronal injury by inducing neurotoxicity.

PURPOSE: Highly active antiretroviral therapy (HAART) is an accepted treatment option for patients with virus infection. Mounting evidence indicated that persistent HAART treatment is implicated with increased morbidity of HIV-associated neurocognitive disorders (HAND) in patients. Tenofovir disoproxil fumarate (TDF), a novel nucleotide reverse transcriptase inhibitor (NRTI), was used in patients with HIV co-infected with HBV. And it is still a vital first-line antiretroviral compounds in HAART. However, whether persistent treatment with TDF is involved in HAND development remains to be further elucidated. In this study, we aimed to discuss the neurotoxicity of TDF. METHODS: We used SH-SY5Y cells and primary neuronal cells to evaluate the neurotoxicity of TDF in vitro. The cytotoxicity of TDF on SH-SY5Y cells and primary neuronal cells was evaluated by the cell viability and LDH levels by MTT assay and LDH kit, respectively. Hoechst 33342 staining, TUNEL assay and flow cytometry were performed to evaluate the cells apoptosis. The intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) production were measured by commercial kits. In addition, the activation level of caspase-3 was evaluated using spectrophotometry and western blotting. RESULTS: Our results showed that TDF treatment significantly induced cell viability and induced apoptosis of SH-SY5Y cells and primary neuronal cells. Furthermore, the ROS levels and MDA productions were significantly up-regulated in nerve cells treated with TDF.  CONCLUSION: Our findings indicated that TDF may induce neuronal cell apoptosis through increasing the intracellular ROS and the expression level of caspase-3, which may be related to the increasing prevalence of HAND.

Review on Wood Deformation and Cracking during Moisture Loss.

Wood, being a natural hygroscopic material, the interaction between wood and moisture plays a crucial role in wood processing and utilization. Moisture affects the physical and mechanical properties of wood, and is also one of the main external factors that cause wood deformation and cracking. Drying shrinkage is a common phenomenon during the processing and utilization of wood induced by moisture loss. Drying stress is the main cause of wood deformation and cracking. The shrinkage differential between tangential and radial direction and moisture content gradient of wood are two reasons induced the generation of drying stresses. In this review, the existing states of moisture in wood and the interaction between water molecules and wood components were systematically summarized. The current research progress and deficiencies in three aspects including the factors resulted in deformation and cracking in wood caused by moisture loss, the correlation between wood mechanical properties and moisture, as well as the development of deformation and cracking in wood under moisture loss were discussed. This review aims to facilitate further research on the deformation and cracking of wood under moisture loss by providing valuable insights and assistance, ultimately reducing the occurrence of wood deformation and cracking. And thus, it will enhance the overall utilization of wood resources, making wood better serve human life.

Immunology and immunotherapy in gastric cancer.

Gastric cancer is the fifth leading cause of cancer-related deaths worldwide. As the diagnosis of early gastric cancer is difficult, most patients are at a late stage of cancer progression when diagnosed. The current therapeutic approaches based on surgical or endoscopic resection and chemotherapy indeed improve patients' outcomes. Immunotherapy based on immune checkpoint inhibitors has opened a new era for cancer treatment, and the immune system of the host is reshaped to combat tumor cells and the strategy differs according to the patient's immune system. Thus, an in-depth understanding of the roles of various immune cells in the progression of gastric cancer is beneficial to application for immunotherapy and the discovery of new therapeutic targets. This review describes the functions of different immune cells in gastric cancer development, mainly focusing on T cells, B cells, macrophages, natural killer cells, dendritic cells, neutrophils as well as chemokines or cytokines secreted by tumor cells. And this review also discusses the latest advances in immune-related therapeutic approaches such as immune checkpoint inhibitors, CAR-T or vaccine, to reveal potential and promising strategies for gastric cancer treatment.

Big versus small: The impact of aggregate size in disease.

Protein aggregation results in an array of different size soluble oligomers and larger insoluble fibrils. Insoluble fibrils were originally thought to cause neuronal cell deaths in neurodegenerative diseases due to their prevalence in tissue samples and disease models. Despite recent studies demonstrating the toxicity associated with soluble oligomers, many therapeutic strategies still focus on fibrils or consider all types of aggregates as one group. Oligomers and fibrils require different modeling and therapeutic strategies, targeting the toxic species is crucial for successful study and therapeutic development. Here, we review the role of different-size aggregates in disease, and how factors contributing to aggregation (mutations, metals, post-translational modifications, and lipid interactions) may promote oligomers opposed to fibrils. We review two different computational modeling strategies (molecular dynamics and kinetic modeling) and how they are used to model both oligomers and fibrils. Finally, we outline the current therapeutic strategies targeting aggregating proteins and their strengths and weaknesses for targeting oligomers versus fibrils. Altogether, we aim to highlight the importance of distinguishing the difference between oligomers and fibrils and determining which species is toxic when modeling and creating therapeutics for protein aggregation in disease.

A noncommutative combinatorial protein logic circuit controls cell orientation in nanoenvironments.

Single-protein-based devices that integrate signal sensing with logical operations to generate functional outputs offer exceptional promise for monitoring and modulating biological systems. Engineering such intelligent nanoscale computing agents is challenging, as it requires the integration of sensor domains into a functional protein via intricate allosteric networks. We incorporate a rapamycin-sensitive sensor (uniRapR) and a blue light-responsive LOV2 domain into human Src kinase, creating a protein device that functions as a noncommutative combinatorial logic circuit. In our design, rapamycin activates Src kinase, causing protein localization to focal adhesions, whereas blue light exerts the reverse effect that inactivates Src translocation. Focal adhesion maturation induced by Src activation reduces cell migration dynamics and shifts cell orientation to align along collagen nanolane fibers. Using this protein device, we reversibly control cell orientation by applying the appropriate input signals, a framework that may be useful in tissue engineering and regenerative medicine.

Contrasting effects of experiencing temporally heterogeneous light availability versus homogenous shading on plant subsequent responses to light conditions.

Temporally heterogeneous environments is hypothesized to correlate with greater plasticity of plants, which has rarely been supported by direct evidence. To address this issue, we subjected three species from different ranges of habitats to a first round of alternating full light and heavy shading (temporally heterogeneous light experience), constant moderate shading and full light conditions (temporally homogeneous light experiences, control) and a second round of light-gradient treatments. We measured plant performance in a series of morphological, biomass, physiological and biochemical traits at the end of each round. Compared to constant full light experience, temporally heterogeneous light conditions induced immediate active biochemical responses (in the first round) with improved late growth in biomass (during the second round); constant moderate shading experience increased photosynthetic physiological and biomass performances of plants in early response, and decreased their late growth in biomass. The karst endemic species of Kmeria septentrionalis showed greater improvement in late growth of biomass and lower decrease in biochemical performance, due to early heterogeneous experience, compared to the non-karst species of Lithocarpus glaber and the karst adaptable species of Celtis sinensis. Results suggested plants will prefer to produce morphological and physiological responses that are less reversible and more costly in the face of more reliable environmental cues at early stage in spite of decreased future growth potential, but to produce immediate biochemical responses for higher late growth potential when early environmental cues are less reliable, to avoid the loss of high costs and low profits. Typical karst species should be more able to benefit from early temporally heterogeneous experience, due to long-term adaptation to karst habitats of high environmental heterogeneity and low resource availability.

Integrating machine learning and bioinformatics analysis to m6A regulator-mediated methylation modification models for predicting glioblastoma patients' prognosis and immunotherapy response.

BACKGROUND: Epigenetic regulations of immune responses are essential for cancer development and growth. As a critical step, comprehensive and rigorous explorations of m6A methylation are important to determine its prognostic significance, tumor microenvironment (TME) infiltration characteristics and underlying relationship with glioblastoma (GBM). METHODS: To evaluate m6A modification patterns in GBM, we conducted unsupervised clustering to determine the expression levels of GBM-related m6A regulatory factors and performed differential analysis to obtain m6A-related genes. Consistent clustering was used to generate m6A regulators cluster A and B. Machine learning algorithms were implemented for identifying TME features and predicting the response of GBM patients receiving immunotherapy. RESULTS: It is found that the m6A regulatory factor significantly regulates the mutation of GBM and TME. Based on Europe, America, and China data, we established m6Ascore through the m6A model. The model accurately predicted the results of 1206 GBM patients from the discovery cohort. Additionally, a high m6A score was associated with poor prognoses. Significant TME features were found among the different m6A score groups, which demonstrated positive correlations with biological functions (i.e., EMT2) and immune checkpoints. CONCLUSIONS: m6A modification was important to characterize the tumorigenesis and TME infiltration in GBM. The m6Ascore provided GBM patients with valuable and accurate prognosis and prediction of clinical response to various treatment modalities, which could be useful to guide patient treatments.

Causal association of cardiovascular disease with erectile dysfunction: a two-sample bidirectional Mendelian randomization analysis.

BACKGROUND: The association between cardiovascular diseases (CVD), including ischemic stroke (IS), heart failure (HF), myocardial infarction (MI), and coronary heart disease (CHD), and erectile dysfunction (ED) remains unclear from observational studies. OBJECTIVES: We explored the potential bidirectional association between CVD and ED by Mendelian randomization (MR). METHODS: Data from genome-wide association studies for CVD in individuals with European ancestry were obtained from several databases, with 1,711,875-977,323 participants, while that for ED included 223,805 participants. We conducted univariate MR (UVMR), inverse variance-weighting (IVW), weighted median, MR-Egger, and multivariate MR (MVMR) analyses to explore the bidirectional causal effects between CVD and ED. RESULTS: UVMR indicated that IS (odds ratios [OR] = 1.34, 95% confidence interval [CI]: 1.08-1.21, P = 0.007), HF (OR = 1.36, 95% CI 1.07-1.74, P = 0.013), and CHD (OR = 1.15, 95% CI 1.09-1.18, P = 0.022) were associated with ED. By MVMR, IS estimates remained significant after accounting for combining single nucleotide polymorphisms from CVDs (OR = 1.42, 95%CI: 1.13-1.79, P = 0.002). Moreover, the effect of a genetic susceptibility to IS on ED was not mediated by type 2 diabetes or triglycerides; that of HF was not mediated by type 2 diabetes, and that of CHD was not mediated by body mass index. Bidirectional analyses showed that genetic susceptibility to ED did not confer any increased CVD risk. CONCLUSIONS: Our results, based on MR, indicated that genetic susceptibility to IS, HF, and CHD was causally associated with ED. These findings can inform prevention and intervention strategies for ED in IS, HF, and CHD patients.

Experimental study on tilting deformation and a new method for landslide prediction with retaining-wall locked segment.

The destruction of the locked-segment type landslide is often accompanied by the destruction of the locked segment with cumulative effects. Investigating the failure mode and instability mechanism of locked-segment type landslides is crucial. The study uses physical models to examine the evolution of locked-segment type landslides with retaining-walls. It utilizes a variety of instruments (tilt sensors, micro earth pressure sensors, pore water pressure sensors, strain gauges, and others) to conduct physical model tests of locked-segment type landslide with retaining-wall and to reveal the tilting deformation and evolution mechanism of retaining-wall locked landslide under the condition of rainfall. The results showed that the regularity of tilting rate, tilting acceleration, strain, and stress change in the retaining-wall locked segment is consistent with the landslide evolution process, indicating that tilting deformation can be used as the criterion of landslide instability and that the locked segment plays a vital role in controlling the landslide stability. The tertiary creep stages of tilting deformation are divided into initial, medium, and high tertiary creep stages using an improved angle tangent method. This establishes the failure criterion for locked-segment type landslides with tilting angles of 0.34°, 1.89°, and 4.38°. In addition, the tilting deformation curve of a locked-segment type landslide with a retaining-wall is utilized to predict the landslide instability by the reciprocal velocity method.

Femoral Anteversion Measured by the Surgical Transepicondylar Axis Is Correlated with the Tibial Tubercle-Roman Arch Distance in Patients with Lateral Patellar Dislocation.

Background and Objectives: Various predisposing factors for lateral patellar dislocation (LPD) have been identified, but the relation between femoral rotational deformity and the tibial tubercle-Roman arch (TT-RA) distance remains elusive. Materials and Methods: We conducted this study including 72 consecutive patients with unilateral LPD. Femoral anteversion was measured by the surgical transepicondylar axis (S-tAV), and the posterior condylar reference line (P-tAV), TT-RA distance, trochlear dysplasia, knee joint rotation, patellar height, and hip-knee-ankle angle were measured by CT images or by radiographs. The correlations among these parameters were analyzed, and the parameters were compared between patients with and without a pathological TT-RA distance. Binary regression analysis was performed, and receiver operating characteristic curves were obtained. Results: The TT-RA distance was correlated with S-tAV (r = 0.360, p = 0.002), but the correlation between P-tAV and the TT-RA distance was not significant. S-tAV had an AUC of 0.711 for predicting a pathological TT-RA, with a value of >18.6° indicating 54.8% sensitivity and 82.9% specificity. S-tAV revealed an OR of 1.13 (95% CI [1.04, 1.22], p = 0.003) with regard to the pathological TT-RA distance by an adjusted regression model. Conclusions: S-tAV was significantly correlated with the TT-RA distance, with a correlation coefficient of 0.360, and was identified as an independent risk factor for a pathological TT-RA distance. However, the TT-RA distance was found to be independent of P-tAV.