Light-Dependent Circadian Rhythm Governs O-GlcNAc Cycling to Influence Cognitive Function in Adult Zebrafish.

This study explores the 24-h rhythmic cycle of protein O-GlcNAcylation within the brain and highlights its crucial role in regulating the circadian cycle and neuronal function based on zebrafish as an animal model. In our experiments, disruption of the circadian rhythm, achieved through inversion of the light-dark cycle or daytime melatonin treatment, not only impaired the rhythmic changes of O-GlcNAcylation along with altering expression patterns of O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) in zebrafish brain but also significantly impeded learning and memory function. In particular, circadian disruption affected rhythmic expression of protein O-GlcNAcylation and OGT in the nuclear fraction. Notably, the circadian cycle induces rhythmic alterations in O-GlcNAcylation of H2B histone protein that correspond to changes in H3 trimethylation. Disruption of the cycle interfered with these periodic histone code alterations. Pharmacological inhibition of OGT with OSMI-1 disrupted the wake-sleep patterns of zebrafish without affecting expression of circadian rhythm-regulating genes. OSMI-1 inhibited the expression of c-fos, bdnf, and calm1, key genes associated with brain function and synaptic plasticity, and decreased the binding of O-GlcNAcylated H2B and OGT to promoter regions of these genes. The collective findings support the potential involvement of circadian cycling of the O-GlcNAc histone code in regulating synaptic plasticity and brain function. Overall, data from this study provide evidence that protein O-GlcNAcylation serves as a pivotal posttranslational mechanism integrating circadian signals and neuronal function to regulate rhythmic physiology.

Development of a toroidally resolved broadband ECE imaging system for measurement of turbulent fluctuations on the KSTAR.

The two electron cyclotron emission imaging (ECEI) systems installed at adjacent ports (G and H) on the KSTAR tokamak incorporate large-aperture mm-wave optics, broadband electronics, and high speed digitization (up to 1 MSa/s) for 2D and quasi-3D visualization of MHD-scale fluid dynamics. Recently, the ECEI systems have been proved to be capable of visualization of smaller scale fluctuations albeit with a limited spatiotemporal resolution and even capable of measurement of ion cyclotron harmonic waves by direct high-speed sampling of the ECE IF signals. A four-channel prototype subsystem with a higher sampling rate up to 16 GS/s has been integrated into the G-port ECEI system, enabling the measurement of plasma waves in the GHz range in the form of modulated ECE signals and characterization of high-frequency turbulence during the evolution of pedestal. To achieve higher toroidal resolution in the turbulence measurement, the H-port ECEI system is now being upgraded to have a toroidally dual detector array of 2(toroidal) × 12(vertical) × 8(radial) channel configuration and a high-speed subsystem of 2(toroidal) × 4 channel configuration. The new mm-wave optics has been designed via beam propagation simulation, and the measured performance of the fabricated lens indicates a toroidal resolution of 8-10 cm depending on the focus position and zoom factor, allowing for the measurement of parallel wavenumber up to k‖ ∼ 0.8 cm-1.

COVID-19 Vaccination-Related Pericarditis: A Korean Nationwide Study.

OBJECTIVE: To investigate the incidence, characteristics, and outcomes of COVID-19 vaccine-related pericarditis (VRP) without myocarditis, we analyzed nationwide Korean data. PATIENTS AND METHODS: This is a retrospective nationwide report including all vaccinated Koreans with COVID-19 vaccine of any platform (BNT162b2, mRNA-1273, ChAdOx1, or Ad26.COV2.S) from February 26 to December 31, 2021. We analyzed the confirmed cases of COVID-19 VRP by the Expert Adjudication Committee. The incidence, clinical characteristics, and outcomes of COVID-19 VRP were analyzed. RESULTS: Among 44,322,068 Koreans with least one dose of COVID-19 vaccination, COVID-19 VRP was confirmed in 179 cases, with 1.73 per million shots (95% CI, 1.48 to 2.00 per million shots). The incidence of VRP was significantly higher in males than females (2.01 per 1 million doses vs 1.45 per 1 million doses, respectively; P=.029), in mRNA vaccines than in other vaccines (2.09 per 1 million doses vs 0.36 per 1 million doses, respectively; P<.001), and in those younger than 40 years of age than those older than 40 years of age (3.52 per 1 million doses vs 0.89 per 1 million doses, respectively; P<.001). The incidence of VRP was highest in males between the ages of 12 and 17 years (7.38 per 1 million doses; 95% CI, 2.01 to 16.07). Although there was no case of mortality, hemodynamically significant pericardial effusion requiring pericardial drainage was noted in 10 cases (5.6%). CONCLUSION: COVID-19 VRP was very rare and developed mainly in association with mRNA vaccines, especially in males younger than 40 years of age. The clinical course of VRP was excellent, and there were no cases of mortality. However, the development of hemodynamically significant pericardial effusion should be carefully monitored.

Blood culture bottles meet the operating room: enhancing the diagnostic accuracy of infectious spondylitis through open microsurgical biopsy and intraoperative inoculation.

PURPOSE: Infectious spondylitis is caused by hematogenous seeding or adjacent soft tissue infection. No study has provided evidence that incubating biopsy specimens in blood culture bottles could enhance detection rates, nor has any study compared this method with conventional culture techniques. We aimed to assess the diagnostic yield of open microsurgical biopsies for infectious spondylitis and the efficacy of various culture media in the presence and absence of pre-biopsy antibiotic therapy. METHODS: This retrospective study, which was conducted at a university-affiliated teaching hospital in Korea, enrolled 165 adult patients with suspected infectious spondylitis between February 2014 and September 2020. The diagnostic yield of open biopsy was compared among three culture media, namely, blood culture bottles, swab culture using transport media, and tissue culture using plain tubes, while considering preoperative antibiotic exposure. RESULTS: Causative bacteria were identified in 84.2% of all cases. Blood culture bottles had the highest positivity rate (83.5%), followed by swab cultures (64.4%) and tissue cultures (44.9%). The differences in positivity rates were significant (P < 0.001). Preoperative antibiotic therapy reduced detection rates across all media, particularly in tissue cultures. CONCLUSIONS: We established the high diagnostic yield of open microsurgical biopsy using blood culture bottles, suggesting that pre-biopsy antibiotic therapy significantly affects bacterial detection, thereby underscoring the importance of culture medium selection in the diagnosis of infectious spondylitis.

Biomechanical and histological evaluation of aspirin in rotator cuff tear rat model.

Background: Aspirin is a representative non-steroidal anti-inflammatory drug (NSAIDs) and has been commonly used for the treatment of tendinopathy in clinical practice. In this study, we aimed to evaluate the biomechanical and histological healing effects of aspirin on the healing of the tendon-to-bone interface after rotator cuff tear repair. Methods: A total of 20 male Sprague-Dawley rats were randomly divided into two groups of 10 rats each. Group-C performed repaironly, and group-aspirin treated with aspirin after tendon repair. Group-aspirin rat were intraperitoneally injected with aspirin at 10 mg/kg every 24 h for 7 days. Eight weeks after surgery, the left shoulder of each rat was used for histological analysis and the right shoulder for biomechanical analysis. Results: In the biomechanical analysis, there was no significant difference in load-to-failure (group-C: 0.61 ± 0.32 N, group-aspirin: 0.74 ± 0.91 N; p = .697) and ultimate stress (group-C: 0.05 ± 0.01 MPa, group-aspirin: 0.29 ± 0.43 MPa; p = .095). For the elongation (group-C: 222.62 ± 57.98%, group-aspirin: 194.75 ± 75.16%; p = .028), group-aspirin confirmed a lower elongation level than group-C. In the histological evaluation, the Bonar score confirmed significant differences in collagen fiber density (group-C: 1.60 ± 0.52, group-aspirin: 2.60 ± 0.52, p = .001) and vascularity (group-C: 1.00 ± 0.47, group-aspirin: 2.20 ± 0.63, p = .001) between the groups. Conclusions: Aspirin injection after rotator cuff tear repair may enhance the healing effect during the early remodeling phase of tendon healing.

Integrating Deep Learning-Based Dose Distribution Prediction with Bayesian Networks for Decision Support in Radiotherapy for Upper Gastrointestinal cancer.

Purpose: Selecting the better techniques to harbor optimal motion management, either a stereotactic linear accelerator delivery using TrueBeam (TBX) or Magnetic Resonance (MR)-guided gated delivery using MRIdian (MRG), is time-consuming and costly. To address this challenge, we aimed to develop a decision-supporting algorithm based on a combination of deep learning-generated dose distributions and clinical data. Materials and Methods: We retrospectively analyzed 65 patients with liver or pancreatic cancer who underwent both TBX and MRG simulations and planning process. We trained three-dimensional U-Net deep learning models to predict dose distributions and generated dose volume histograms (DVHs) for each system. We integrated predicted DVH metrics into a Bayesian network (BN) model incorporating clinical data. Results: The MRG prediction model outperformed the TBX model, demonstrating statistically significant superiorities in predicting normalized dose to the PTV and liver. We developed a final BN prediction model integrating the predictive DVH metrics with patient factors like age, PTV size, and tumor location. This BN model an area under the receiver operating characteristic curve index of 83.56%. The decision tree derived from the BN model showed that the tumor location (abutting vs. apart of PTV to hollow viscus organs) was the most important factor to determine TBX or MRG. Conclusion: We demonstrated a decision-supporting algorithm for selecting optimal RT plans in upper gastrointestinal cancers, incorporating both deep learning-based dose prediction and BN-based treatment selection. This approach might streamline the decision-making process, saving resources and improving treatment outcomes for patients undergoing RT.

Ultrasonographic differential diagnosis of medial elbow pain.

Medial elbow pain is a common musculoskeletal problem among individuals engaging in repetitive activities. Medial epicondylitis is the predominant cause of this pain. However, other potential causes must be considered as part of the differential diagnosis. This article discusses several etiologies of medial elbow pain, including medial epicondylitis, ulnar neuropathy, snapping triceps syndrome, ulnar collateral ligament injury, medial antebrachial cutaneous neuropathy, and diseases of the elbow joint, with an emphasis on ultrasound (US) findings. Awareness of possible diagnoses and their US features can assist radiologists in establishing a comprehensive diagnosis for medial elbow pain.

Paenibacillus gyeongsangnamensis sp. nov., Isolated from Soil.

A Gram-stain-positive, aerobic, white-coloured, rod-shaped bacteria, designated as a strain dW9T , was isolated from soil. Strain dW9T was catalase-positive and oxidase-negative. Strain dW9T grew at temperature of 20-37°C and at pH of 5.0-7.0. Phylogenetic and 16S rRNA gene analysis indicated that strain dW9T belonged to the genus Paenibacillus with its closest relative being Paenibacillus filicis S4T (97.4% sequence similarity). The genome size of dW9T was 7,787,916 bp with DNA G+C content of 51.3%. The digital DNA-DNA hybridization (dDDH) and average nucleotide identity (ANI) values of dW9T with its closest relatives were found to be <22.0% and <74.0%, respectively. The only respiratory quinone was MK-7, and the major fatty acids were antiso-C15:0 and iso-C16:0. Overall, the comprehensive taxonomic analysis revealed that strain dW9T met all the fundamental criteria to be classified as a novel species within the genus Paenibacillus. Accordingly, we propose the name Paenibacillus gyeongsangnamensis sp. nov., with the type strain dW9T (=KCTC 43431T =NBRC 116022T ).

Femoral Neck Shaft Angle Measurement for Differentiating Femoral Head Stress Fracture from Avascular Necrosis.

OBJECTIVE: The study aimed to evaluate whether the measurement of Femoral Neck Shaft Angle (FNSA) can be helpful in differentiating femoral head Stress Fracture (SF) from Avascular Necrosis (AVN). METHODS: From September 2019 to April 2022, sixty-four patients [median age 32.0 years, interquartile range (IQR) 23.0-39.0 years] who underwent both hip radiograph and Magnetic Resonance Imaging (MRI) and diagnosed as femoral head SF or AVN were included in our retrospective study. Patients were divided into as having either femoral head SF (n = 34) or AVN (n = 30). The FNSA was measured in anteroposterior hip radiography. Continuous values were compared using the Mann-Whitney U test. The assessment of the predictive value of FNSA for femoral head SF was performed by Receiver Operating Characteristic (ROC) analysis. RESULTS: The FNSA was significantly higher in patients with SF (median 133.5°, IQR 128.0-136.7°) than those with AVN (median 127.5°, IQR 124.0-132.0°) (p = 0.001). In addition, the FNSA was significantly higher in SF femurs (median 134.8°, IQR 129.2-137.4°) than in contralateral normal femurs (median 127.1°, IQR 124.3-132.5°) in patients with unilateral femoral head SF (n = 30) (p < 0.001). In ROC analysis, the sensitivity, specificity, and Area Under the Curve (AUC) for predicting the femoral head SF were 77.3%, 63.3%, and 0.785 (95% confidence interval: 0.666-0.905), respectively, at a cutoff of 130.2°. CONCLUSION: Increased FNSA was associated with femoral head SF; thus, measurement of FNSA could be helpful for differentiating femoral head SF from AVN.

Solution-Processed Thick Hole-Transport Layer for Reliable Quantum-Dot Light-Emitting Diodes Based on an Alternatingly Doped Structure.

The operating lifetime of quantum-dot light-emitting diodes (QLED) is a bottleneck for commercial display applications. To enhance the operational stability of QLEDs, we developed a robust solution-processed highly conductive hole-transport-layer (HTL) structure, which enables a thick HTL structure to mitigate the electric field. An alternating doping strategy, which involves multiple alternating stacks of N4,N4'-di(naphthalen-1-yl)-N4,N4'-bis(4-vinylphenyl)biphenyl-4,4'-diamine and phosphomolybdic acid layers, could provide significantly improved conductivity; more specifically, the 90 nm-thick alternatingly doped HTL exhibited higher conductivity than the 45 nm-thick undoped HTL. Therefore, when applied to a QLED, the increase in the thickness of the alternatingly doped HTL increased device reliability. As a result, the lifetime of the QLED with a thick, alternatingly doped HTL was 48-fold higher than that of the QLED with a thin undoped HTL. This alternating doping strategy provides a new paradigm for increasing the stability of solution-based optoelectronic devices in addition to QLEDs.

The unfolded features on the synchronized fashion of gut microbiota and Drynaria rhizome against obesity via integrated pharmacology.

Drynaria rhizome (DR) is used as a natural remedy to ameliorate obesity (OB) in East Asia; in parallel, the gut microbiota (GM) might exert a positive impact on OB through their metabolites. This study elucidates the orchestrated effects of DR and GM on OB. DR-GM, - a key signaling pathway-target-metabolite (DGSTM) networks were used to unveil the relationship between DR and GM, and Molecular Docking Test (MDT) and Density Functional Theory (DFT) were adopted to underpin the uppermost molecules. The NR1H3 (target) - 3-Epicycloeucalenol (ligand), and PPARG (target) - Clionasterol (ligand) conjugates from DR, FABP3 (target) - Ursodeoxycholic acid, FABP4 (target) - Lithocholic acid (ligand) or Deoxycholic acid (ligand), PPARA (target) - Equol (ligand), and PPARD (target) - 2,3-Bis(3,4-dihydroxybenzyl)butyrolactone (ligand) conjugates from GM formed the most stable conformers via MDT and DFT. Overall, these findings suggest that DR-GM might be a promising ameliorator on PPAR signaling pathway against OB.

Effects of body mass index on mortality in elderly patients with hip fractures.

Hip fractures remain a substantial health concern, particularly among elderly individuals with osteoporosis, leading to high global mortality rates. This study aimed to analyze the association between body mass index (BMI) and postoperative mortality in patients who underwent surgery for hip fractures. A total of 680 patients treated at a single institution between January 2018 and December 2022 were included. Factors such as age, BMI, sex, Charlson Comorbidity Index (CCI), preoperative hemoglobin levels, American Society of Anesthesiologists score, anesthesia method, duration of surgery, and time from injury to surgery were assessed. Underweight status, male sex, higher CCI, and general anesthesia were significantly associated with 1-year and in-hospital mortality. Notably, underweight individuals exhibited a higher risk of mortality than normal-weight individuals, and female patients had lower mortality rates. This study underscores the importance of considering BMI, along with other demographic and clinical factors, in predicting postoperative mortality among patients with hip fractures, aiding the development of tailored management strategies to improve outcomes and reduce complications in this vulnerable patient population.

Adverse effects of meteorological factors and air pollutants on dry eye disease: a hospital-based retrospective cohort study.

Although previous studies have suggested that meteorological factors and air pollutants can cause dry eye disease (DED), few clinical cohort studies have determined the individual and combined effects of these factors on DED. We investigated the effects of meteorological factors (humidity and temperature) and air pollutants [particles with a diameter ≤ 2.5 µ m (PM2.5), ozone (O3), nitrogen dioxide (NO2), and carbon monoxide (CO)] on DED. A retrospective cohort study was conducted on 53 DED patients. DED was evaluated by Symptom Assessment in Dry Eye (SANDE), tear secretion, tear film break-up time (TBUT), ocular staining score (OSS), and tear osmolarity. To explore the individual, non-linear, and joint associations between meteorological factors, air pollutants, and DED parameters, we used generalized linear mixed model (GLMM) and Bayesian kernel machine regression (BKMR). After adjusting for all covariates, lower relative humidity or temperature was associated with a higher SANDE (p < 0.05). Higher PM2.5, O3, and NO2 levels were associated with higher SANDE and tear osmolarity (p < 0.05). Higher O3 levels were associated with lower tear secretion and TBUT, whereas higher NO2 levels were associated with higher OSS (p < 0.05). BKMR analyses indicated that a mixture of meteorological factors and air pollutants was significantly associated with increased SANDE, OSS, tear osmolarity, and decreased tear secretion.

Full-cycle study on developing a novel structured micromixer and evaluating the nanoparticle products as mRNA delivery carriers.

Achieving precise control of nanoparticle size while maintaining consistency and high uniformity is of paramount importance for improving the efficacy of nanoparticle-based therapies and minimizing potential side effects. Although microfluidic technologies are widely used for reliable nanoparticle synthesis, they face challenges in meeting critical homogeneity requirements, mainly due to imperfect mixing efficiency. Furthermore, channel clogging during continuous operation presents a significant obstacle in terms of quality control, as it progressively impedes the mixing behavior necessary for consistent nanoparticle production for therapeutic delivery and complicates the scaling-up process. This study entailed the development of a 3D-printed novel micromixer embedded with hemispherical baffle microstructures, a dual vortex mixer (DVM), which integrates Dean vortices to generate two symmetrical counter-rotating intensified secondary flows. The DVM with a relatively large mixer volume showed rapid mixing characteristics even at a flow rate of several mL min-1 and produced highly uniform lipids, liposomes, and polymer nanoparticles in a size range (50-130 nm) and polydispersity index (PDI) values below 0.15. For the evaluation of products, SARS-CoV-2 Spike mRNA-loaded lipid nanoparticles were examined to verify protein expression in vitro and in vivo using firefly luciferase (FLuc) mRNA. This showed that the performance of the system is comparable to that of a commercial toroidal mixer. Moreover, the vigorous in-situ dispersion of nanoparticles by harnessing the power of vortex physically minimizes the occurrence of aggregation, ensuring consistent production performance without internal clogging of a half-day operation and facilitating quality control of the nanoparticles at desired scales.

Quality Properties and Flavor-Related Components of Beef Longissimus Lumborum Muscle from Four Korean Native Cattle Breeds.

This study was carried out to assess the quality properties, components associated with taste and aroma of beef as a function of breed. For this purpose, steers from four Korean native cattle breeds: Hanwoo (n=10), Chikso (n=10), black Hanwoo (n=12, BHW) and Jeju black cattle (n=12, JBC) were used. The steers all were raised under identical conditions and finished at a similar age of around 30-months old. Following 24 h of slaughter, all longissimus lumborum muscles were collected and used for analysis of meat quality, fatty acids, and flavor-related components (metabolic compounds, free amino acids, and aroma volatiles). The Hanwoo presented a significantly higher intramuscular fat content (IMF, 22.85%) than the BHW (11.78%), Chikso (9.25%), and JBC (9.14%; p<0.05). The meat of Hanwoo breed showed lighter and redder color, and lower shear force value (p<0.05). The JBC presented a "healthier" fatty acid profiles as it had a higher total unsaturated fatty acids content (p<0.05). With regard to flavor-related components, Hanwoo also had higher total contents of free amino acids and metabolites associated with umami and sweet tastes, and fat-derived volatile compounds (aldehydes, alcohols, and ketones) associated with fatty aroma. It may be concluded that there was a considerable difference in the meat quality properties among breeds. The variations of IMF content and flavor-related components may be the main factors contributing to the typical flavors of beef among the four Korean native cattle breeds.

Gut microbiome and metabolome signatures in liver cirrhosis-related complications.

Background/Aims: Shifts in the gut microbiota and metabolites are interrelated with liver cirrhosis progression and complications. However, causal relationships have not been evaluated comprehensively. Here, we identified complication-dependent gut microbiota and metabolic signatures in patients with liver cirrhosis. Methods: Microbiome taxonomic profiling was performed on 194 stool samples (52 controls and 142 cirrhosis patients) via V3-V4 16S rRNA sequencing. Next, 51 samples (17 controls and 34 cirrhosis patients) were selected for fecal metabolite profiling via gas chromatography mass spectrometry and liquid chromatography coupled to time-of-flight-mass spectrometry. Correlation analyses were performed targeting the gut- microbiota, metabolites, clinical parameters, and presence of complications (varices, ascites, peritonitis, encephalopathy, hepatorenal syndrome, hepatocellular carcinoma, and deceased). Results: Veillonella bacteria, Ruminococcus gnavus, and Streptococcus pneumoniae are cirrhosis-related microbiotas compared with control group. Bacteroides ovatus, Clostridium symbiosum, Emergencia timonensis, Fusobacterium varium, and Hungatella_uc were associated with complications in the cirrhosis group. The areas under the receiver operating characteristic curve (AUROCs) for the diagnosis of cirrhosis, encephalopathy, hepatorenal syndrome, and deceased were 0.863, 0.733, 0.71, and 0.69, respectively. The AUROCs of mixed microbial species for the diagnosis of cirrhosis and complication were 0.808 and 0.847, respectively. According to the metabolic profile, 5 increased fecal metabolites in patients with cirrhosis were biomarkers (AUROC > 0.880) for the diagnosis of cirrhosis and complications. Clinical markers were significantly correlated with the gut microbiota and metabolites. Conclusion: Cirrhosis-dependent gut microbiota and metabolites present unique signatures that can be used as noninvasive biomarkers for the diagnosis of cirrhosis and its complications.

Blood culture-free ultra-rapid antimicrobial susceptibility testing.

Treatment assessment and patient outcome for sepsis depend predominantly on the timely administration of appropriate antibiotics1-3. However, the clinical protocols used to stratify and select patient-specific optimal therapy are extremely slow4. In particular, the major hurdle in performing rapid antimicrobial susceptibility testing (AST) remains in the lengthy blood culture procedure, which has long been considered unavoidable due to the limited number of pathogens present in the patient's blood. Here we describe an ultra-rapid AST method that bypasses the need for traditional blood culture, thereby demonstrating potential to reduce the turnaround time of reporting drug susceptibility profiles by more than 40-60 h compared with hospital AST workflows. Introducing a synthetic beta-2-glycoprotein I peptide, a broad range of microbial pathogens are selectively recovered from whole blood, subjected to species identification or instantly proliferated and phenotypically evaluated for various drug conditions using a low-inoculum AST chip. The platform was clinically evaluated by the enrolment of 190 hospitalized patients suspected of having infection, achieving 100% match in species identification. Among the eight positive cases, six clinical isolates were retrospectively tested for AST showing an overall categorical agreement of 94.90% with an average theoretical turnaround time of 13 ± 2.53 h starting from initial blood processing.

Engineered Regenerative Isolated Peripheral Nerve Interface for Targeted Reinnervation.

A regenerative peripheral nerve interface (RPNI) offers a therapeutic solution for nerve injury through reconstruction of the target muscle. However, implanting a transected peripheral nerve into an autologous skeletal muscle graft in RPNI causes donor-site morbidity, highlighting the need for tissue-engineered skeletal muscle constructs. Here, an engineered regenerative isolated peripheral nerve interface (eRIPEN) is developed using 3D skeletal cell printing combined with direct electrospinning to create a nanofiber membrane envelop for host nerve implantation. In this in vivo study, after over 8 months of RPNI surgery, the eRIPEN exhibits a minimum Feret diameter of 15-20 µm with a cross-sectional area of 100-500 µm2, representing the largest distribution of myofibers. Furthermore, neuromuscular junction formation and muscle contraction with a force of ≈28 N are observed. Notably, the decreased hypersensitivity to mechanical/thermal stimuli and an improved tibial functional index from -77 to -56 are found in the eRIPEN group. The present novel concept of eRIPEN paves the way for the utilization and application of tissue-engineered constructs in RPNI, ultimately realizing neuroprosthesis control through synaptic connections.