Feline eye-inspired artificial vision for enhanced camouflage breaking under diverse light conditions.

Biologically inspired artificial vision research has led to innovative robotic vision systems with low optical aberration, wide field of view, and compact form factor. However, challenges persist in object detection and recognition against complex backgrounds and varied lighting. Inspired by the feline eye, which features a vertically elongated pupil and tapetum lucidum, this study introduces an artificial vision system designed for superior object detection and recognition in a monocular framework. Using a slit-like elliptical aperture and a patterned metal reflector beneath a hemispherical silicon photodiode array, the system reduces excessive light and enhances photosensitivity. This design achieves clear focus under bright light and enhanced sensitivity in dim conditions. Theoretical and experimental analyses demonstrate the system's ability to filter redundant information and detect camouflaged objects in diverse lighting, representing a substantial advancement in monocular camera technology and the potential of biomimicry in optical innovations.

Damage-Free Plasma Source for Atomic-Scale Processing.

As atomic-scale etching and deposition processes become necessary for manufacturing logic and memory devices at the sub-5 nm node, the limitations of conventional plasma technology are becoming evident. For atomic-scale processes, precise critical dimension control at the sub-1 nm scale without plasma-induced damage and high selectivity between layers are required. In this paper, a plasma with very low electron temperature is applied for damage-free processing on the atomic scale. In plasmas with an ultralow electron temperature (ULET, Te < 0.5 eV), ion energies are very low, and the ion energy distribution is narrow. The absence of physical damage in ULET plasma is verified by exposing 2D structural material. In the ULET plasma, charging damage and radiation damage are also expected to be suppressed due to the extremely low Te. This ULET plasma source overcomes the limitations of conventional plasma sources and provides insights to achieve damage-free atomic-scale processes.

Pentraxin3 mediates inflammation and adipogenesis in Graves' orbitopathy pathogenesis.

Pentraxin 3 (PTX3) is a prototypic humoral soluble pattern-recognition molecule known to function in immunity-related inflammation. Given the lack of information on the precise functions of PTX3 in the pathogenesis of Graves' orbitopathy (GO), this study investigated the role of PTX3 in the inflammation and adipogenesis mechanism of GO. We first compared the PTX3 expression between orbital tissues from patients with GO and normal controls, using real-time polymerase chain reaction, which estimated significantly higher PTX3 transcript levels in the GO tissues than in the normal tissues. In addition, PTX3 production was markedly increased upon interleukin (IL)-1ß and adipogenic stimulation. We then evaluated the effects of silencing PTX3 in primary orbital fibroblast cultures by analyzing the expression levels of pro-inflammatory cytokines, adipogenesis-related proteins, and downstream transcription factors in cells transfected with or without a small interfering RNA against PTX3, using western blot. Silencing PTX3 attenuated the IL-1ß-induced secretion of pro-inflammatory cytokines, including IL-6, IL-8, monocyte chemotactic protein-1, intercellular adhesion molecule-1, and cyclooxygenase-2, and suppressed the IL-1ß-mediated activation of p38 kinase, nuclear factor-κB, and extracellular signal-regulated kinase. Moreover, PTX3 knockdown suppressed adipogenic differentiation, as assessed using Oil Red O staining, as well as the expression of adipogenesis-associated transcription factors including peroxisome proliferator activator-γ, CCAAT/enhancer-binding proteins α and ß, adipocyte protein 2, adiponectin, and leptin. Thus, this study suggests that PTX3 plays a significant role in the pathogenesis of GO and may serve as a novel therapeutic target for the condition.

Development of Low-Pressure Die-Cast Al-Zn-Mg-Cu Alloy Propellers Part II: Simulations for Process Optimization.

With the increasing demand for high-performance leisure boat propellers, this study explores the development of high-strength aluminum alloy propellers using the low-pressure die-casting (LPDC) process. In Part I of the study, we identified the optimal alloy compositions for Al-6Zn-2Mg-1.5Cu propellers and highlighted the challenges of hot tearing at the junction between the hub and blades. In this continuation, we developed a coupled thermal fluid stress analysis model using ProCAST software to optimize the LPDC process. By adjusting casting parameters such as the melt supply temperature, initial mold temperature, and curvature radius between the hub and blades, we minimized hot tearing and other casting defects. The results were validated through simulations and practical applications, showing significant improvements in the quality and structural integrity of the propellers. Non-destructive testing using X-ray CT confirmed the reduction in internal defects, demonstrating the effectiveness of the simulation-based approach for alloy design and process optimization.

Differences in impact on disease or lung injury depending on the physicochemical characteristics of harmful chemicals in the PAH model.

The number of individuals with underlying medical conditions has been increasing steadily. These individuals are relatively vulnerable to harmful external factors. But it has not been proven that the effects of hazardous chemicals may differ depending on their physicochemical properties. This study determines the toxic effects of two chemicals with high indoor exposure risk and different physicochemical properties on an underlying disease model. A pulmonary arterial hypertension (PAH) model was constructed by a single subcutaneous injection of monocrotaline (MCT; 60 mg/kg) into Sprague-Dawley rats. After three weeks, formaldehyde (FA; 2.5 mg/kg) and polyhexamethylene guanidine (PHMG; 0.05 mg/kg) were administered once via intratracheal instillation, and rats were necropsied one week later. Exposure to FA and PHMG affected organ weight and the Fulton and toxicity indices in rats induced with PAH. FA promoted bronchial injury and aggravated PAH, while PHMG only induced alveolar injury. Additionally, the differentially expressed genes were altered following exposure to FA and PHMG, as were the associated diseases (cardiovascular disease and pulmonary fibrosis, respectively). In conclusion, inhaled chemicals with different physicochemical properties can cause damage to organs, such as the lungs and heart, and can aggravate underlying diseases. This study elucidates indoor inhaled exposure-induced toxicities and alerts patients with pre-existing diseases to the harmful chemicals.

Rebound Pain After Arthroscopic Cuff Repair With Interscalene Brachial Plexus Block Anesthesia Is Reduced by Surgeon-Administered Multimodal Shoulder Injections: A Prospective Randomized Controlled Trial.

PURPOSE: To compare the effects of additional multimodal shoulder injections on postoperative rebound pain in patients undergoing arthroscopic rotator cuff repair (ASRCR) under interscalene brachial plexus block (ISBPB) anesthesia. METHODS: A single-blind randomized controlled trial was conducted with 67 patients between April and December 2023. Patients undergoing ASRCR who received ISBPB anesthesia, rather than general anesthesia, with a minimum follow-up period of 48 hours were included. The injection group received 40 mL of 0.75% ropivacaine, 20 mg morphine, 1:200,000 epinephrine, and saline solution, totaling 100 mL. After surgery, the injection was administered to the subacromial space (50 mL) with blind suprascapular nerve block (25 mL) and blind axillary nerve block (25 mL). Control subjects received 100 mL of saline solution. Intravenous patient-controlled analgesia (IV-PCA) was used as adjuvant analgesia for all patients. The primary outcome was evaluated using the visual analog scale (VAS) pain score at 12 hours after surgery, with secondary outcomes of the incidence of rebound pain and VAS pain scores at 0, 2, 4, 8, 24, 36, and 48 hours postoperatively. Fentanyl in the IV-PCA and rescue analgesic amounts, complications, and patient satisfaction were recorded. RESULTS: Sixty-seven patients (32 in the injection group, 35 in the control group) with a mean age of 61.1 ± 9.0 years were included. The primary outcome assessment, VAS pain score at 12 hours, significantly favored the injection group (2.7 ± 0.93 vs 4.1 ± 1.70, P < .001). The incidence of rebound pain was 18.8% and 65.7% in the injection and control groups, respectively (18.8% vs 65.7%, P < .001). The injection group reported better VAS pain scores at 24, 36, and 48 hours and lower fentanyl use over the 48-hour postoperative period (P = .014). The use of rescue analgesics was similar between groups, and no complications were associated with multimodal shoulder injections. Satisfaction levels were similar in both groups. CONCLUSIONS: The present study found that patients who underwent multimodal shoulder injections during ASRCR under ISBPB anesthesia had significantly lower VAS pain scores at 12 hours postoperatively and reduced incidence of rebound pain compared with the control group. Pain levels were consistently lower from 12 to 48 hours postoperatively. Additionally, the injection group had reduced opioid consumption within the first 48 hours postoperatively, with no complications observed. LEVEL OF EVIDENCE: Level I, randomized controlled trial.

Prenatal cigarette smoke exposure sensitizes acetaminophen-induced liver injury by modulating miR-34a-5p in male offspring mice.

Introduction: Cigarette smoke (CS) exacerbates the severity of diseases not only in lungs, but also in systemic organs having no direct contact with smoke. In addition, smoking during pregnancy can have severe health consequences for both the mother and the fetus. Therefore, our aim was to evaluate effects of prenatal exposure to CS on acetaminophen (APAP)-induced acute liver injury (ALI) in offspring. Methods: Female C57BL/6 mice on day 6 of gestation were exposed to mainstream CS (MSCS) at 0, 150, 300, or 600 µg/L for 2 h a day, 5 days a week for 2 weeks using a nose-only exposure system. At four weeks old, male offspring mice were injected intraperitoneally with a single dose of APAP at 300 mg/kg body weight to induce ALI. Results: Maternal MSCS exposure significantly amplified pathological effects associated with ALI as evidenced by elevated serum alanine aminotransferase levels, increased hepatocellular apoptosis, higher oxidative stress, and increased inflammation. Interestingly, maternal MSCS exposure reduced microRNA (miR)-34a-5p expression in livers of offspring. Moreover, treatment with a miR-34a-5p mimic significantly mitigated the severity of APAP-induced hepatotoxicity. Overexpression of miR-34a-5p completely abrogated adverse effects of maternal MSCS exposure in offspring with ALI. Mechanistically, miR-34a-5p significantly decreased expression levels of hepatocyte nuclear factor 4 alpha, leading to down-regulated expression of cytochrome P450 (CYP)1A2 and CYP3A11. Discussion: Prenatal exposure to MSCS can alter the expression of miRNAs, even in the absence of additional MSCS exposure, potentially increasing susceptibility to APAP exposure in male offspring mice.

Association between Pentosan Polysulfate and Subsequent Maculopathy: Insights from a Nationwide Population-Based Study in Korea.

PURPOSE: To determine the association between pentosan polysulfate (PPS) use and the subsequent development of maculopathy in Asian population. DESIGN: A nationwide population-based retrospective cohort study using the Health Insurance Review and Assessment Service database. PARTICIPANTS: 103,553 individuals in the PPS user group and 205,792 individuals in the PPS non-user group, all newly diagnosed with cystitis between 2009 and 2020. METHODS: The association between PPS use and maculopathy was evaluated using a time dependent Cox proportional hazard model. Additionally, two sensitivity analyses were conducted by defining PPS users as individuals with an observation period over 6 months from the initial prescription or those with cumulative dose exceeding 9 g, employing the same analysis. MAIN OUTCOME MEASURES: The outcome measures included the hazard ratios (HR) representing the association between PPS use and maculopathy. RESULTS: PPS use was associated with an increased risk of subsequent maculopathy in univariate (HR, 1.7; 95% confidence intervals [CI], 1.66-1.75) and multivariate analysis (HR, 1.34; 95% CI, 1.31-1.38). These results were also confirmed in two sensitivity analyses. The mean cumulative dose of PPS for the cohort was 37.2 ± 76.7 g. CONCLUSIONS: In this nationwide cohort study involving an Asian population, individuals with cystitis using PPS exhibit an increased risk of developing subsequent maculopathy.

Effects of Ulmus macrocarpa Extract and Catechin 7-O-ß-D-apiofuranoside on Muscle Loss and Muscle Atrophy in C2C12 Murine Skeletal Muscle Cells.

Muscle atrophy is known to be one of the symptoms leading to sarcopenia, which significantly impacts the quality of life, mortality, and morbidity. Therefore, the development of therapeutics for muscle atrophy is essential. This study focuses on addressing muscle loss and atrophy using Ulmus macrocarpa extract and its marker compound, catechin 7-O-ß-D-apiofuranoside, by investigating their effects on biomarkers associated with muscle cell apoptosis. Additionally, protein and gene expression in a muscle atrophy model were examined using Western blotting and RT-PCR. Ulmus macrocarpa has been used as food or medicine due to its safety, including its roots, barks, and fruit. Catechin 7-O-ß-D apiofuranoside is an indicator substance of plants of the Ulmus genus and has been reported to have various effects such as antioxidant and anti-inflammatory effects. The experimental results demonstrated that catechin glycoside and Ulmus macrocarpa extract decreased the expression of the muscle-degradation-related proteins Atrogin-1 and Muscle RING-Finger protein-1 (MuRF1) while increasing the expression of the muscle-synthesis-related proteins Myoblast determination (MyoD) and Myogenin. Gene expression confirmation experiments validated a decrease in the expression of Atrogin and MuRF1 mRNA and an increase in the expression of MyoD and Myogenin mRNA. Furthermore, an examination of muscle protein expression associated with the protein kinase B (Akt)/forkhead box O (FoxO) signaling pathway confirmed a decrease in the expression of FoxO, a regulator of muscle protein degradation. These results confirm the potential of Ulmus macrocarpa extract to inhibit muscle apoptosis, prevent muscle decomposition, and promote the development of functional materials for muscle synthesis, health-functional foods, and natural-product-derived medicines.

INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION AND POOR VISUAL ACUITY.

PURPOSE: To investigate the significance of intravitreal anti-vascular endothelial growth factor treatment in patients with neovascular age-related macular degeneration and poor visual acuity. METHODS: Retrospective study of patients with neovascular age-related macular degeneration with baseline best-corrected visual acuity of ≤20/200. Patients were divided into regular treatment and scarce treatment groups according to whether they underwent consecutive intravitreal anti-vascular endothelial growth factor treatments at intervals of ≤4 months or not. RESULTS: A total of 131 eyes were included: 87 and 44 eyes in the regular treatment and scarce treatment groups, respectively. The regular treatment group showed significantly improved preservation of lesion size at both Years 1 and 2, with significantly fewer incidences of new subretinal hemorrhage. Improvements in visual acuity, reduction in central subfield macular thickness, and maximal height of choroidal neovascularization were significantly favorable in the regular treatment group at Year 1, and central subfield macular thickness was significantly decreased at Year 2. Survival analysis revealed that the regular treatment group had significantly greater preservation of visual acuity and lesion size than that in the scarce treatment group. CONCLUSION: Maintaining intravitreal anti-vascular endothelial growth factor treatment for patients with neovascular age-related macular degeneration and poor vision showed significant advantages in visual acuity and lesion size stability and reduced the incidence of new subretinal hemorrhage, which suggests preservation of paracentral vision.

Clinical outcomes of two-stage revision arthroplasty using a spiked tibial cement spacer in infected total knee arthroplasty.

PURPOSE: A tibial cement spacer (TCS) with spikes offers better initial stability than a conventional TCS and reduces spacer-related problems in two-stage revision total knee arthroplasty (R-TKA) for infection. We compared the clinical outcomes of two-stage revision arthroplasty for infected TKA using spiked TCS with that of conventional TCS. METHODS: This retrospective cohort study included 29 patients who underwent two-stage revision arthroplasty using an articulating cement spacer and who could be followed up for at least one year. Group S comprised 14 patients using spiked TCS, whereas Group C comprised 15 patients using conventional TCS. Demographic data, the interval from first to second stage revision, motion arc, numerical rating scale (NRS), Knee Society (KS) score, serum levels of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and frequency of repeating the first-stage and infection recurrence after R-TKA between the groups were analyzed. RESULTS: No significant differences were observed in the female ratio and mean age between both groups. The mean interval between the first and second stage revision was significantly shorter in Group S than in Group C. The mean motion arc was significantly larger in Group S than in Group C. The mean NRS was significantly lower in Group S than in Group C. The mean KS score in Group S was significantly higher than that in Group C. Serum ESR and CRP levels did not differ between the groups. The frequency of repeating the first stage was lower in Group S than in Group C. However, the recurrence rate after R-TKA was higher in Group S than in Group C. CONCLUSION: Compared with conventional TCS, spiked TCS shortened the period until R-TKA and improved pain and function levels. However, no significant difference existed in the rate of infection recurrence after R-TKA.

Spatiotemporal regulation of dental pulpal innervation in the rat.

The dental pulp is a highly innervated tissue transmitting pain-related sensations in the tooth. Consequently, understanding the intricacies of its innervation mechanism in odontogenesis is crucial for gaining insights into dental pain and developing dental pain-modulating agents. This study examined neuroregulatory molecules such as neurotrophic factors (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], neurotrophin-4 [NTF-4], and neurturin [NRTN]) and neuroinhibitory factors (slit2, ephrin isoforms and netrin-1) in developing rat teeth with follicles. NGF, BDNF and NRTN transcriptions showed time-dependent upregulation, particularly during the root formation stage. In contrast, NTF-4 mRNA was highly expressed at the cap stage, but became downregulated over time. Slit2 and ephrin-B2 expression was distinct at the cap stage and then downregulated in a time-dependent manner. Ephrin-A5 and netrin-1 expression did not significantly change. Immunofluorescence analysis revealed a robust expression of both ephrin-B2 and slit2 in the outer and inner dental epithelia of the enamel organ, a non-neurogenic tissue, during the cap stage of 3rd molar germs. In contrast, BDNF was predominantly localized in dental papilla cells and odontoblasts during the root formation stage. These results suggest that neuroregulatory molecules, such as BDNF, slit2 and ephrin-B2, may be important in identifying therapeutic targets for modulating dental pulp pain.

Trends and Barriers in Diabetic Retinopathy Screening: Korea National Health and Nutritional Examination Survey 2016-2021.

BACKGROUND: The prevalence of diabetes is increasing globally, highlighting the importance of preventive healthcare. This study aimed to identify the diabetic retinopathy (DR) screening rates and risk factors linked to DR screening nonadherence in the Korean population through a nationally representative sample survey. METHODS: Among the Korea National Health and Nutrition Examination Survey database from 2016 to 2021, participants aged ≥ 40 years with diabetes were included. The weighted estimate for nonadherence to DR screening within a year was calculated. Risk factor analyses were conducted using univariate and multivariate logistic regression. RESULTS: Among the 3,717 participants, 1,109 (29.5%) underwent DR screening within the past year, and this national estimate exhibited no statistically significant difference from 2016 to 2021 (P = 0.809). Nonadherence to annual DR screening was associated with residing in rural areas, age ≥ 80 years, low educational level, self-reported good health, absence of ocular disease, current smoking, lack of exercise and dietary diabetes treatment, and no activity limitation (all P < 0.05). CONCLUSION: The recent DR screening rate in Korea was relatively low. Factors associated with apathy and complacency towards personal health were associated with the nonadherence to DR screening. Educational interventions have the potential to enhance the annual screening rate for diabetic patients.

Impact of Childhood Maltreatment on Cognitive Function and Its Relationship With Emotion Regulation in Young Adults.

Objectives: Childhood maltreatment can negatively impact cognitive development, including executive function, working memory, and processing speed. This study investigated the impact of childhood maltreatment on cognitive function in young adults using various measurements, including computerized tests, and their relationship with emotional dysregulation. Methods: We recruited 149 healthy individuals with and without maltreatment experiences and used the Wechsler Adult Intelligence Scale IV (WAIS-IV) and a computerized battery to analyze cognitive function. Results: Both the WAIS-IV and computerized tests revealed that individuals with a history of childhood maltreatment had decreased cognitive function, especially in terms of working memory and processing speed. These individuals tended to employ maladaptive emotion regulation strategies. Among cognitive functions, working memory is negatively related to maladaptive emotion regulation strategies such as catastrophizing. Conclusion: This study highlights the effects of childhood maltreatment on cognitive function in young adulthood. Moreover, the study suggests clinical implications of cognitive interventions for improving emotion regulation and cognitive function in individuals with a history of childhood maltreatment.

Topological Fermi-arc surface state covered by floating electrons on a two-dimensional electride.

Two-dimensional electrides can acquire topologically non-trivial phases due to intriguing interplay between the cationic atomic layers and anionic electron layers. However, experimental evidence of topological surface states has yet to be verified. Here, via angle-resolved photoemission spectroscopy (ARPES) and scanning tunnelling microscopy (STM), we probe the magnetic Weyl states of the ferromagnetic electride [Gd2C]2+·2e-. In particular, the presence of Weyl cones and Fermi-arc states is demonstrated through photon energy-dependent ARPES measurements, agreeing with theoretical band structure calculations. Notably, the STM measurements reveal that the Fermi-arc states exist underneath a floating quantum electron liquid on the top Gd layer, forming double-stacked surface states in a heterostructure. Our work thus not only unveils the non-trivial topology of the [Gd2C]2+·2e- electride but also realizes a surface heterostructure that can host phenomena distinct from the bulk.

Development of Low-Pressure Die-Cast Al-Zn-Mg-Cu Alloy Propellers-Part â : Hot Tearing Simulations for Alloy Optimization.

Recent advances in the leisure boat industry have spurred demand for improved materials for propeller manufacturing, particularly high-strength aluminum alloys. While traditional Al-Si alloys like A356 are commonly used due to their excellent castability, they have limited mechanical properties. In contrast, 7xxx series alloys (Al-Zn-Mg-Cu based) offer superior mechanical characteristics but present significant casting challenges, including hot-tearing susceptibility (HTS). This study investigates the optimization of 7xxx series aluminum alloys for low-pressure die-casting (LPDC) processes to enhance propeller performance and durability. Using a constrained rod-casting (CRC) method and finite element simulations, we evaluated the HTS of various alloy compositions. The results indicate that increasing Zn and Cu contents generally increase HTS, while a sufficient Mg content of 2 wt.% mitigates this effect. Two optimized quaternary Al-Zn-Mg-Cu alloys with relatively low HTS were selected for LPDC propeller production. Simulation and experimental results demonstrated the effectiveness of the proposed alloy compositions, highlighting the need for further process optimization to prevent hot tearing in high Mg and Cu content alloys.

Effect of patent complete revascularization on the akinetic myocardial segments.

OBJECTIVES: The aims of the study were (i) to examine the changes in echocardiographic parameters and (ii) to compare the fate of myocardial segments with akinesia and without akinesia on preoperative echocardiography after coronary artery bypass grafting. METHODS: One hundred one patients who underwent complete revascularization, who were assessed by preoperative, before discharge, postoperative 3- and 12-month echocardiographic examinations, and who showed all patent grafts at postoperative 1-year angiograms were included. Echocardiographic left ventricular ejection fraction was assessed, and a 16-segment model was adopted for regional analysis of the left ventricle. A total of 1616 segments were analysed based on a 6-point scale: 1 = normal (N = 1083), 2 = mild hypokinesia (N = 2), 3 = moderate hypokinesia (N = 74), 4 = severe hypokinesia (N = 150), 5 = akinesia without thinning (N = 259) and 6 = akinesia with thinning (N = 48). RESULTS: The serial left ventricular ejection fraction measured preoperatively, before discharge, at postoperative 3- and 12-months were 0.48 ± 0.14, 0.49 ± 0.12, 0.49 ± 0.10 and 0.54 ± 0.10, respectively. The left ventricular ejection fraction significantly increased over time during the postoperative 12 months (P < 0.001). Wall motion scores tended to decrease over time in both segment groups with akinesia and without akinesia (P < 0.001), and improvement of the wall motion was significantly higher in the segment group with akinesia than in the segment group without akinesia (P < 0.001). CONCLUSIONS: The left ventricular ejection fraction and regional wall motion improved over time during the postoperative 12 months, regardless of the presence of an akinetic segment. Complete revascularization including akinetic myocardium should be considered when performing coronary artery bypass grafting.

CBP Expression Contributes to Neuropathic Pain via CREB and MeCP2 Regulation in the Spared Nerve Injury Rat Model.

Background and Objectives: This study aimed to investigate the relationship between neuropathic pain and CREB-binding protein (CBP) and methyl-CpG-binding protein 2 (MeCP2) expression levels in a rat model with spared nerve injury (SNI). Materials and Methods: Rat (male Sprague-Dawley white rats) models with surgical SNI (n = 6) were prepared, and naive rats (n = 5) were used as controls. The expression levels of CBP and MeCP2 in the spinal cord and dorsal root ganglion (DRG) were compared through immunohistochemistry at 7 and 14 days after surgery. The relationship between neuropathic pain and CBP/MeCP2 was also analyzed through intrathecal siRNA administration. Results: SNI induced a significant increase in the number of CBPs in L4 compared with contralateral DRG as well as with naive rats. The number of MeCP2 cells in the dorsal horn on the ipsilateral side decreased significantly compared with the contralateral dorsal horn and the control group. SNI induced a significant decrease in the number of MeCP2 neurons in the L4 ipsilateral DRG compared with the contralateral DRG and naive rats. The intrathecal injection of CBP siRNA significantly inhibited mechanical allodynia induced by SNI compared with non-targeting siRNA treatment. MeCP2 siRNA injection showed no significant effect on mechanical allodynia. Conclusions: The results suggest that CBP and MeCP2 may play an important role in the generation of neuropathic pain following peripheral nerve injury.

The identification of effective tumor-suppressing neoantigens using a tumor-reactive TIL TCR-pMHC ternary complex.

Neoantigens are ideal targets for cancer immunotherapy because they are expressed de novo in tumor tissue but not in healthy tissue and are therefore recognized as foreign by the immune system. Advances in next-generation sequencing and bioinformatics technologies have enabled the quick identification and prediction of tumor-specific neoantigens; however, only a small fraction of predicted neoantigens are immunogenic. To improve the predictability of immunogenic neoantigens, we developed the in silico neoantigen prediction workflows VACINUSpMHC and VACINUSTCR: VACINUSpMHC incorporates physical binding between peptides and MHCs (pMHCs), and VACINUSTCR integrates T cell reactivity to the pMHC complex through deep learning-based pairing with T cell receptors (TCRs) of putative tumor-reactive CD8 tumor-infiltrating lymphocytes (TILs). We then validated our neoantigen prediction workflows both in vitro and in vivo in patients with hepatocellular carcinoma (HCC) and in a B16F10 mouse melanoma model. The predictive abilities of VACINUSpMHC and VACINUSTCR were confirmed in a validation cohort of 8 patients with HCC. Of a total of 118 neoantigen candidates predicted by VACINUSpMHC, 48 peptides were ultimately selected using VACINUSTCR. In vitro validation revealed that among the 48 predicted neoantigen candidates, 13 peptides were immunogenic. Assessment of the antitumor efficacy of the candidate neoepitopes using a VACINUSTCR in vivo mouse model suggested that vaccination with the predicted neoepitopes induced neoantigen-specific T cell responses and enabled the trafficking of neoantigen-specific CD8 + T cell clones into the tumor tissue, leading to tumor suppression. This study showed that the prediction of immunogenic neoantigens can be improved by integrating a tumor-reactive TIL TCR-pMHC ternary complex.