Electro-optically tunable optical delay on a lithium niobate photonic chip.

An approach for continuous tuning of on-chip optical delay with a microring resonator is proposed and demonstrated. By introducing an electro-optically tunable waveguide coupler, the bus waveguide to the resonance coupling can be effectively tuned from the under-coupling regime to the over-coupling regime. The optical delay is experimentally characterized by measuring the relative phase shift between lasers and shows a large dynamic range of delay from -600 to 600 ps and an efficient tuning of delay from -430 to -180 ps and from 40 to 240 ps by only a 5 V voltage.

Assessment of opioid knowledge and attitudes among senior medical students in Taiwan's pain education curriculum: A cross-sectional questionnaire survey.

INTRODUCTION: While the opioid crisis has been a significant concern in North America, Taiwan has not encountered a similar crisis. This study investigated medical students' perceptions of opioid therapy for chronic pain management in Taiwan. METHODS: A cross-sectional questionnaire survey was conducted among third- and fourth-year medical students who had completed an 18-hour pain medicine curriculum, in comparison with those who did not take the course in Mar 2022 and May 2023. The survey assessed their knowledge, attitude, and perceptions of the opioid crisis in the United States and Taiwan. RESULTS: In total, 135 (88.2%) of 153 senior medical students who had completed the curriculum responded to the survey. They exhibited a better understanding of opioids (P < 0.001) and held a more negative attitude toward opioid use (P = 0.011) compared with 105 students who did not take the course. Additionally, out of 240 respondents, 177 (73.8%) acknowledged the ongoing opioid crisis in the United States, while only 70 (29.2%) disagreed with the notion of an ongoing opioid crisis in Taiwan. Furthermore, 90% of all students expressed agreement with the need for further education on chronic pain management after graduation. CONCLUSION: Among senior medical students in Taiwan, those who completed an elective pain medicine curriculum demonstrated enhanced knowledge of opioids, a more cautious attitude toward opioid use, and a willingness to receive further education on chronic pain management. Over 70% of students remained uncertain or incorrectly believed that there was an opioid crisis in Taiwan.

Experimental Demonstration of Fully Passive Quantum Key Distribution.

The passive approach to quantum key distribution (QKD) consists of removing all active modulation from the users' devices, a highly desirable countermeasure to get rid of modulator side channels. Nevertheless, active modulation has not been completely removed in QKD systems so far, due to both theoretical and practical limitations. In this Letter, we present a fully passive time-bin encoding QKD system and report on the successful implementation of a modulator-free QKD link. According to the latest theoretical analysis, our prototype is capable of delivering competitive secret key rates in the finite key regime.

Intrinsically Disordered Protein Condensate-Modified Surface for Mitigation of Biofouling and Foreign Body Response.

Mitigation of biofouling and the host's foreign body response (FBR) is a critical challenge with biomedical implants. The surface coating with various anti-fouling materials provides a solution to overcome it, but limited options in clinic and their potential immunogenicity drive the development of more alternative coating materials. Herein, inspired by liquid-liquid phase separation of intrinsically disordered proteins (IDPs) to form separated condensates in physiological conditions, we develop a new type of low-fouling biomaterial based on flexible IDP of FUS protein containing rich hydrophilic residues. A chemical structure-defined FUS IDP sequence tagged with a tetra-cysteine motif (IDPFUS) was engineered and applied for covalent immobilization on various surfaces to form a uniform layer of protein tangles, which boosted strong hydration on surfaces, as revealed by molecular dynamics simulation. The IDPFUS-coated surfaces displayed excellent performance in resisting adsorption of various proteins and adhesion of different cells, platelets, and bacteria. Moreover, the IDPFUS-coated implants largely mitigated the host's FBR compared with bare implants and particularly outperformed PEG-coated implants in reducing collagen encapsulation. Thus, this novel low-fouling and anti-FBR strategy provides a potential surface coating material for biomedical implants, which will also shed light on exploring similar applications of other IDP proteins.

Directing group strategies in rhodium-catalyzed C-H amination.

Construction of a carbon-nitrogen bond is one of the most prevalent operations in nature and organic synthesis. The resulting amino compounds are privileged structural fragments in natural products, pharmaceutical drugs, and functional materials. With the rapid advancement of C-H bond activation, directing-group strategies in C-H amination catalyzed by rhodium have emerged. This reaction approach considerably enhances the step economy and atom economy of the reaction, and it complies with green chemistry and atom economy. The reactivity and selectivity of chelation-assisted rhodium-catalyzed C-H amination are discussed in relation to the types of aminating reagent, as well as the challenges and future development prospects in this field.

Efficacy of a temporary CentriMag ventricular assist device in acute fulminant myocarditis patients revived with extracorporeal cardiopulmonary resuscitation.

BACKGROUND: Although extracorporeal life support (ECLS) can provide emergency systemic perfusion for acute fulminant myocarditis (AFM), the mortality rate remains extremely high, especially in those undergoing extracorporeal cardiopulmonary resuscitation (ECPR). Temporary ventricular assist device (VAD) can provide a more physiological blood flow direction and better subsequent organ perfusion than ECLS. We investigated temporary VAD efficacy in ECPR-revived AFM patients. METHODS: During January 2012-May 2019, we retrospectively recruited 22 AFM patients with hemodynamic collapse and ECPR; 11 underwent ECLS only and 11 underwent additional VAD support after ECLS. Systemic perfusion was compared via laboratory biochemistry at post-ECPR days 2 (D2) and 4 (D4). Consciousness and cardiac function were assessed through the Glasgow Coma Scale (GCS) and echocardiography, respectively. All major complications and causes of mortality were recorded; 30-day survival was analyzed and risk factors were predicted. RESULTS: The VAD group had significantly better hemodynamic improvement; more inotropes being tapered at D2 and D4; better data representative of systemic perfusion, including albumin, pH, bicarbonate, and lactate levels at D4; and better 30-day survival (72.7% vs. 27.2%, p = 0.033). The causes of mortality included central failure, multiple organ failure, and bacteremia with sepsis. The risk factors included lethal dysrhythmia before ECLS, GCS <5 at D2, and elevated cardiac enzymes at D4. CONCLUSION: For AFM patients, temporary VAD could provide better systemic perfusion and organ preservation than ECLS. VAD had better survival, including improved recovery and successful transplantation. Hence, temporary VAD should be considered if ECLS cannot revive the sustained cardiogenic shock.

Apoptosis, Proliferation, and Autophagy Are Involved in Local Anesthetic-Induced Cytotoxicity of Human Breast Cancer Cells.

Breast cancer accounts for almost one quarter of all female cancers worldwide, and more than 90% of those who are diagnosed with breast cancer undergo mastectomy or breast conservation surgery. Local anesthetics effectively inhibit the invasion of cancer cells at concentrations that are used in surgical procedures. The limited treatment options for triple-negative breast cancer (TNBC) demonstrate unmet clinical needs. In this study, four local anesthetics, lidocaine, levobupivacaine, bupivacaine, and ropivacaine, were applied to two breast tumor cell types, TNBC MDA-MB-231 cells and triple-positive breast cancer BT-474 cells. In addition to the induction of apoptosis and the suppression of the cellular proliferation rate, the four local anesthetics decreased the levels of reactive oxygen species and increased the autophagy elongation indicator in both cell types. Our combination index analysis with doxorubicin showed that ropivacaine had a synergistic effect on the two cell types, and lidocaine had a synergistic effect only in MDA-MB-231 cells; the others had no synergistic effects on doxorubicin. Lidocaine contributed significantly to the formation of autophagolysosomes in a dose-dependent manner in MDA-MB-231 cells but not in BT-474 cells. Our study demonstrated that the four local anesthetics can reduce tumor growth and proliferation and promote apoptosis and autophagy.

Mitochondrial Dysfunction Involved in the Cytotoxicity of Tramadol in Human Endometrial Carcinoma Cells.

Tramadol is a common anesthetic used to treat cancer pain, including endometrial cancer, but its function in endometrial cancer remains unclear. The purpose of this study was to elucidate the antitumor effects of tramadol on human endometrial cancer cells. Colony formation, BrdU, cell cycle profiles, apoptosis, ROS, and Western blot analyses were used to study the response of endometrial cancer cells to tramadol. JC-1 and seahorse metabolic flux assays were used to detect the effect of tramadol on mitochondria in endometrial cancer cells. Combination index was used to detect the interaction of tramadol with chemotherapy drugs in endometrial cancer cells. In this study, we found that tramadol was able to inhibit proliferation and induce cell cycle arrest, ROS generation, and apoptosis in two types of endometrial cancer cells. In addition, tramadol treatment also induced mitochondrial dysfunction in endometrial cancer cells by causing a loss of mitochondrial membrane potential and a decreased oxygen consumption rate. More importantly, the synergetic effect of tramadol with doxorubicin or cisplatin was further confirmed in endometrial cancer cells by the results of the combination index and apoptosis assay. In summary, our findings indicate that tramadol has an antitumor effect on endometrial cancer cells, which might serve as a potential adjuvant therapy strategy for endometrial cancer.

Effects of Levosimendan on Systemic Perfusion in Patients with Low Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Score: Experience from a Single Center in Taiwan.

BACKGROUND: Patients with cardiogenic shock have a high risk of mortality. Intravenous levosimendan can provide pharmacologic inotrope support. OBJECTIVES: We aimed to investigate the effect of levosimendan in patients with extremely severe cardiogenic shock and low Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) score with or without mechanical circulatory support. METHODS: From January 2017 to May 2019, 24 patients with INTERMACS 1-4 were enrolled in this retrospective study. All patients had systemic malperfusion and were treated with levosimendan. Biochemistry data related to systemic perfusion were recorded and compared before and at 24 and 72 hours after levosimendan administration. Echocardiography and Kansas City Cardiomyopathy Questionnaire (KCCQ) were completed 2 months later to assess left ventricular ejection fraction (LVEF) and quality of life (QoL), respectively. RESULTS: Arterial pressure and heart rate did not significantly differ before and after levosimendan administration. Atrial fibrillation and ventricular premature complex increased without significance. The dose of inotropes could be significantly tapered down. There were no significant differences in blood urea nitrogen, creatinine, and lactate levels. Urine output significantly increased (p = 0.018), and liver-related enzymes improved but without significance. B-type natriuretic peptide significantly decreased (p = 0.007) at 24 hours after levosimendan administration. Echocardiography showed significantly improved LVEF 2 months later (22.43 ± 8.13% to 35.87 ± 13.4%, p = 0.001). KCCQ showed significantly improved physical activity and greater relief of symptoms (p = 0.003). The survival-to-discharge rate was 75%. CONCLUSIONS: We observed a decrease in B-type natriuretic peptide, better urine output, and alleviated hepatic injury in the levosimendan group. Most patients who survived without transplantation had significantly improved LVEF and better QoL after levosimendan administration.

Purification, identification and characterization of an esterase with high enantioselectivity to (S)-ethyl indoline-2-carboxylate.

OBJECTIVE: To purify an esterase which can selectively hydrolyze (R,S)-ethyl indoline-2-carboxylate to produce (S)-indoline-2-carboxylic acid and characterize its enzymatic properties. RESULTS: An intracellular esterase from Bacillus aryabhattai B8W22 was isolated and the purified protein was identified as a carboxylesterase by MALDI-TOF mass spectrometry. The enzyme (named BaCE) was 59.03-fold purification determined to be of approximately 35 kDa. Its specific activity was 0.574 U/mL with 20% yield. The enzyme showed maximum activity at pH 8.5 and 30 °C and was stable at 20-30 °C using pNPB as the substrate. The Km, Vmax, kcat and kcat/Km of the esterase were 0.52 mM, 6.39 µM/min, 26.87 min-1 and 51.67 mM/min, respectively. The esterase demonstrated high enantioselectivity toward (S)-ethyl indoline-2-carboxylate with 96.55% e.e.p at 44.39% conversion, corresponding to an E value of 133.45. CONCLUSIONS: In this study, a new esterase BaCE with an apparent molecular mass of 35 kDa was purified to homogeneity for the first time. The esterase from Bacillus aryabhattai B8W22 was isolated with a purification more than 59-fold and a yield of 20% by anion exchange chromatography and hydrophobic interaction chromatography. And its biochemical characterization were described in detail with pNPB as substrate. It displayed high enantioselectivity toward (S)-ethyl indoline-2-carboxylate. We next plan to highly express esterase BaCE in Escherichia coli, and apply it to industrial production of (S)-indoline-2-carboxylic acid.

The implication of seniority of supervising attending surgeon on the reexploration rate following elective coronary artery bypass grafting.

BACKGROUND AND AIMS: During coronary artery bypass graft (CABG) surgery, the residual hemostasis procedures, from weaning cardiopulmonary bypass to closing sternotomy, are always completed by residents and supervised by attending surgeons. We want to evaluate the teaching effectiveness for residents under the supervision of attending surgeons with different levels of seniority. MATERIALS AND METHODS: Between January 1st 2001 and December 31st 2010, 2279 consecutive CABG surgeries were performed in our medical center. In total, 83 patients underwent a reexploration for postoperative bleeding. All causes of bleeding were identified and recorded. Competent attending surgeons were defined as having >3 years' experience and young attending surgeons with ≦3 years' experience. We compared the reexploration rate and aimed to identify the common sources of bleeding by the two groups. We also assessed the impact of attending experience on the outcomes and major complications after reexploration. RESULTS: There were 36 surgical bleeding and 17 non-surgical bleeding in the young group and 16 surgical bleeding and 14 non-surgical bleeding in the competent group. The young group experienced more mediastinal drainage before a reexploration and a longer time interval to a reexploration. However, both are without statistical significance. Furthermore, the young group has a significant longer hospital stay. The most common intra-pericardium surgical bleeding included two-stage cannulation, side branch of the left internal mammary artery (LIMA), and side branch of vein grafts. The most common extra-pericardium surgical bleeding included a puncture hole by sternal wires, LIMA bed, and fragile sternum. CONCLUSION: Young attending surgeons indeed had both higher incidence of reexploration and surgical bleeding after a CABG. However, the supervisor experience only impacted hospital stay, not major complications or mortality after a reexploration. This might imply the competent attending surgeons provide higher teaching effectiveness for the hemostasis procedure after CABG.

Physical regulation of stem cells differentiation into teno-lineage: current strategies and future direction.

Tendon injuries are commonly encountered in the clinic, disrupting the patient's normal work/life routine and damaging the career life of athletes. Currently, there is still no effective treatment for tendon injury. Tendon tissue engineering appears to be a promising route for tendon repair and regeneration. However, current strategies utilized in research are still far away from clinical applications due to unsuccessful cellular differentiation to tendon/tenocytes. In this review, we focus on the current physical strategies (mechanical stimulation and extracellular matrix topography) and evaluate their roles in precise and stepwise tendon differentiation. A systematic comprehension of normal tendon development process by structure, gene profile and physical microenvironment analysis is likely suggestive for stepwise tenocyte differentiation.

Prolonged Use of Levitronix Left Ventricular Assist Device as a Bridge to Heart Transplantation.

UNLABELLED: A 61-year-old male presented to our emergency room with chest tightness, dyspnea, and cold sweat. He underwent a 12-lead EKG which showed ST-elevation from leads V1-V4 and T wave inversion in leads II, III, and aVF. His troponin-I level was elevated to 70.3 ng/ml. He went into cardiogenic shock when he was in the catheter room. After advanced cardiac life support was administered for 30 min, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) cannulation was set up using 21-french arterial and 21-french venous cannula through the right femoral artery and right femoral vein by the puncture method for hemodynamic support. Subsequently, a coronary artery bypass graft (CABG) for acute myocardial infarction was performed. However, the patient was unable to be weaned from the VA-ECMO. Four days later, a CentriMag (Levitronix LLC, Waltham, MA, USA) left ventricular assist device (LVAD) was applied to avoid ECMO-related complications such as severe hemolysis, ischemic, deteriorated liver and renal function. The patient subsequently underwent a successful orthotopic heart transplant after 87 days on the CentriMag LVAD. The patient was extubated on the next postoperative day and was discharged 2 weeks later. KEY WORDS: Acute myocardial infarction; Extracorporeal membrane oxygenation; Heart transplantation; Ventricular assist device.

Acute pulmonary injury with refractory hypoxaemia after implantation of Levitronix CentriMag ventricular assist device: successful treatment with veno-venous extracorporeal membrane oxygenation.

Although acute pulmonary injury after cardiopulmonary bypass has been detailed in the literature, it was seldom mentioned in the context of following implantation of a ventricular assist device. We report on a 65-year-old male with end-stage ischemic cardiomyopathy who underwent implantation of Levitronix CentriMag (Levitronix, Waltham, MA) for cardiac support and was listed for heart transplantation. Acute pulmonary injury with profound hypoxaemia was noted 6 h after the implantation. Despite optimal medical treatment and maximal ventilator support, refractory hypoxaemia persisted, and veno-venous extracorporeal membrane oxygenation (oxygenator: Affinity-NT; centrifugal pump: BPX-80 Bio-Pump, Medtronic, Minneapolis, MN, USA) was applied for ventilation support. The patient was weaned from the extracorporeal membrane oxygenation 4 days later and from the ventilator on the next 2 days. He underwent a successful orthotopic heart transplant after a total of 77 days on Levitronix left ventricular device cardiac support.

Risk Factors of Mortality and Long-Term Survival in Burn Patients With/Without Extracorporeal Membrane Oxygenation: A 16 Year Real-World Study.

Burn patients face cardiopulmonary failure risks, with recent observational studies suggesting promising outcomes for extracorporeal membrane oxygenation (ECMO). However, the effectiveness and long-term survival remain unclear. Our study aims to assess mortality risk factors and long-term survival in burn patients with and without ECMO. This study used Taiwan's National Health Insurance Research Database and designed a case-control with onefold propensity score matching across variables including sex, age, total body surface area (TBSA) burned, and index date. We analyzed mortality and survival risk factors in each stratified group with/without ECMO. Finally, we analyze the mortality according to ECMO and TBSA burned, and the cause of death and long-term survival. From 2000 to 2015, 4,556 burn patients with ECMO compared to an equivalent number without ECMO. Primary mortality include male, age >65, TBSA ≥30%, escharotomy, hemodialysis, and bacteremia. The ECMO group showed lower survival across all stratified risk factors, with the primary cause of death being burn-related issues, followed by respiratory and heart failure. The overall mortality rate was 54.41% with ECMO and 40.94% without ECMO (p < 0.001). Additionally, long-term survival is lower in the group with ECMO. This research provides a valuable real-world gross report about ECMO efficacy and long-term survival among burn patients with/without ECMO.

CTSD upregulation as a key driver of spinal ligament abnormalities in spinal stenosis.

Spinal stenosis (SS) is frequently caused by spinal ligament abnormalities, such as ossification and hypertrophy, which narrow the spinal canal and compress the spinal cord or nerve roots, leading to myelopathy or sciatic symptoms; however, the underlying pathological mechanism is poorly understood, hampering the development of effective nonsurgical treatments. Our study aims to investigate the role of co-expression hub genes in patients with spinal ligament ossification and hypertrophy. To achieve this, we conducted an integrated analysis by combining RNA-seq data of ossification of the posterior longitudinal ligament (OPLL) and microarray profiles of hypertrophy of the ligamentum flavum (HLF), consistently pinpointing CTSD as an upregulated hub gene in both OPLL and HLF. Subsequent RT-qPCR and IHC assessments confirmed the heightened expression of CTSD in human OPLL, ossification of the ligamentum flavum (OLF), and HLF samples. We observed an increase in CTSD expression in human PLL and LF primary cells during osteogenic differentiation, as indicated by western blotting (WB). To assess CTSD's impact on osteogenic differentiation, we manipulated its expression levels in human PLL and LF primary cells using siRNAs and lentivirus, as demonstrated by WB, ALP staining, and ARS. Our findings showed that suppressing CTSD hindered the osteogenic differentiation potential of PLL and LF cells, while overexpressing CTSD activated osteogenic differentiation. These findings identify CTSD as a potential therapeutic target for treating spinal stenosis associated with spinal ligament abnormalities.

The synergistic mechanisms of propofol with cisplatin or doxorubicin in human ovarian cancer cells.

BACKGROUND: Most ovarian cancer cases are diagnosed at an advanced stage, leading to poor outcomes and a relatively low 5-year survival rate. While tumor resection in the early stages can be highly effective, recurrence following primary treatment remains a significant cause of mortality. Propofol is a commonly used intravenous anesthetic agent in cancer resection surgery. Previous research has shown that propofol anesthesia was associated with improved survival in patients undergoing elective surgery for epithelial ovarian cancer. However, the underlying antitumor mechanisms are not yet fully understood. METHODS: This study aimed to uncover the antitumor properties of propofol alone and combined with cisplatin or doxorubicin, in human SKOV3 and OVCAR3 ovarian cancer cells. We applied flowcytometry analysis for mitochondrial membrane potential, apoptosis, and autophagy, colony formation, migration, and western blotting analysis. RESULTS: Given that chemotherapy is a primary clinical approach for managing advanced and recurrent ovarian cancer, it is essential to address the limitations of current chemotherapy, particularly in the use of cisplatin and doxorubicin, which are often constrained by their side effects and the development of resistance. First of all, propofol acted synergistically with cisplatin and doxorubicin in SKOV3 cells. Moreover, our data further showed that propofol suppressed colony formation, disrupted mitochondrial membrane potential, and induced apoptosis and autophagy in SKOV3 and OVCAR3 cells. Finally, the effects of combined propofol with cisplatin or doxorubicin on mitochondrial membrane potential, apoptosis, autophagy, and epithelial-mesenchymal transition were different in SKOV3 and OVCAR3 cells, depending on the p53 status. CONCLUSION: In summary, repurposing propofol could provide novel insights into the existing chemotherapy strategies for ovarian cancer. It holds promise for overcoming resistance to cisplatin or doxorubicin and may potentially reduce the required chemotherapy dosages and associated side effects, thus improving treatment outcomes.

Neuroimaging Correlates with Clinical Severity in Wilson Disease: A Multiparametric Quantitative Brain MRI.

BACKGROUND AND PURPOSE: Previous studies have reported metal accumulation and microstructure changes in deep gray nuclei (DGN) in Wilson disease (WD). However, there are limited studies that investigate whether there is metal accumulation and microstructure changes in DGN of patients with WD with normal-appearing routine MRI. This study aimed to evaluate multiparametric changes in DGN of WD and whether the findings correlate with clinical severity in patients with WD. MATERIALS AND METHODS: The study enrolled 28 patients with WD (19 with neurologic symptoms) and 25 controls. Fractional anisotropy (FA), mean diffusivity (MD), and magnetic susceptibility in globus pallidus, pontine tegmentum, dentate nucleus, red nucleus, head of caudate nucleus, putamen, substantia nigra, and thalamus were extracted. Correlations between imaging data and the Unified Wilson's Disease Rating Scale (UWDRS) neurologic subitems were explored. RESULTS: FA, MD, and susceptibility values were higher in multiple DGN of patients with WD than controls (P < .05). Patients with WD without abnormal signals in DGN on routine MRI also had higher FA, MD, and susceptibility values than controls (P < .017). We found that UWDRS neurologic subscores correlated with FA and susceptibility values of DGN (P < .05). In addition, we also found that FA and susceptibility values in specific structures correlated with specific neurologic symptoms of WD (ie, tremor, parkinsonism, dysarthria, dystonia, and ataxia) (P < .05). CONCLUSIONS: Patients with WD have increased FA, MD, and susceptibility values even before the lesion is morphologically apparent on routine MRI. The increased FA and susceptibility values correlate with clinical severity of WD.

Integrated DNA methylation analysis reveals a potential role for PTPRN2 in Marfan syndrome scoliosis.

Background: Marfan syndrome (MFS) is a rare genetic disorder caused by mutations in the Fibrillin-1 gene (FBN1) with significant clinical features in the skeletal, cardiopulmonary, and ocular systems. To gain deeper insights into the contribution of epigenetics in the variability of phenotypes observed in MFS, we undertook the first analysis of integrating DNA methylation and gene expression profiles in whole blood from MFS and healthy controls (HCs). Methods: The Illumina 850K (EPIC) DNA methylation array was used to detect DNA methylation changes on peripheral blood samples of seven patients with MFS and five HCs. Associations between methylation levels and clinical features of MFS were analyzed. Subsequently, we conducted an integrated analysis of the outcomes of the transcriptome data to analyze the correlation between differentially methylated positions (DMPs) and differentially expressed genes (DEGs) and explore the potential role of methylation-regulated DEGs (MeDEGs) in MFS scoliosis. The weighted gene co-expression network analysis was used to find gene modules with the highest correlation coefficient with target MeDEGs to annotate their functions in MFS. Results: Our study identified 1253 DMPs annotated to 236 genes that were primarily associated with scoliosis, cardiomyopathy, and vital capacity. These conditions are typically associated with reduced lifespan in untreated MFS. We calculated correlations between DMPs and clinical features, such as cobb angle to evaluate scoliosis and FEV1% to assess pulmonary function. Notably, cg20223687 (PTPRN2) exhibited a positive correlation with cobb angle of scoliosis, potentially playing a role in ERKs inactivation. Conclusions: Taken together, our systems-level approach sheds light on the contribution of epigenetics to MFS and offers a plausible explanation for the complex phenotypes that are linked to reduced lifespan in untreated MFS patients.

Incorporating machine learning and PPI networks to identify mitochondrial fission-related immune markers in abdominal aortic aneurysms.

Purpose: The aim of this study is to investigate abdominal aortic aneurysm (AAA), a disease characterised by inflammation and progressive vasodilatation, for novel gene-targeted therapeutic loci. Methods: To do this, we used weighted co-expression network analysis (WGCNA) and differential gene analysis on samples from the GEO database. Additionally, we carried out enrichment analysis and determined that the blue module was of interest. Additionally, we performed an investigation of immune infiltration and discovered genes linked to immune evasion and mitochondrial fission. In order to screen for feature genes, we used two PPI network gene selection methods and five machine learning methods. This allowed us to identify the most featrue genes (MFGs). The expression of the MFGs in various cell subgroups was then evaluated by analysis of single cell samples from AAA. Additionally, we looked at the expression levels of the MFGs as well as the levels of inflammatory immune-related markers in cellular and animal models of AAA. Finally, we predicted potential drugs that could be targeted for the treatment of AAA. Results: Our research identified 1249 up-regulated differential genes and 3653 down-regulated differential genes. Through WGCNA, we also discovered 44 genes in the blue module. By taking the point where several strategies for gene selection overlap, the MFG (ITGAL and SELL) was produced. We discovered through single cell research that the MFG were specifically expressed in T regulatory cells, NK cells, B lineage, and lymphocytes. In both animal and cellular models of AAA, the MFGs' mRNA levels rose. Conclusion: We searched for the AAA novel targeted gene (ITGAL and SELL), which most likely function through lymphocytes of the B lineage, NK cells, T regulatory cells, and B lineage. This analysis gave AAA a brand-new goal to treat or prevent the disease.