Unveiling Direct Electrochemical Oxidation of Methane at the Ceria/Gas Interface.

Solid oxide fuel cells (SOFCs) stand out in sustainable energy systems for their unique ability to efficiently utilize hydrocarbon fuels, particularly those from carbon-neutral sources. CeO2-δ (ceria) based oxides embedded in SOFCs are recognized for their critical role in managing hydrocarbon activation and carbon coking. However, even for the simplest hydrocarbon molecule, CH4, the mechanism of electrochemical oxidation at the ceria/gas interface is not well understood and the capability of ceria to electrochemically oxidize methane remains a topic of debate. This lack of clarity stems from the intricate design of standard metal/oxide composite electrodes and the complex nature of electrode reactions involving multiple chemical and electrochemical steps. This study presents a Sm-doped ceria thin-film model cell that selectively monitors CH4 direct-electro-oxidation on the ceria surface. Using impedance spectroscopy, operando X-ray photoelectron spectroscopy, and density functional theory, it is unveiled that ceria surfaces facilitate C─H bond cleavage and that H2O formation is key in determining the overall reaction rate at the electrode. These insights effectively address the longstanding debate regarding the direct utilization of CH4 in SOFCs. Moreover, these findings pave the way for an optimized electrode design strategy, essential for developing high-performance, environmentally sustainable fuel cells.

Repeatable Acoustic Vaporization of Coated Perfluorocarbon Bubbles for Micro-Actuation Inspired by Polypodium aureum.

Polypodium aureum, a fern, possesses a specialized spore-releasing mechanism like a catapult induced by the quick expansion of vaporized bubbles. This study introduces lipid-coated perfluorocarbon droplets to enable repeatable vaporization-condensation cycles, inspired by the repeatable vaporization of Polypodium aureum. Lipid-perfluorocarbon droplets have been considered not to exhibit repeatable oscillations due to bubble collapse of the low surface tension of lipid layers. However, a single lipid-dodecafluoropentane droplet with a diameter of 9.17 µm shows expansion-contraction oscillations over 4000 cycles by changing lipid composition and applying a low-power 1.7 MHz ultrasound to induce the partial vaporization of the droplets. The optimal combinations of shell composition, droplet fabrication, and acoustic conditions can minimize the damage on shell structure and promote a quick recovery of damaged shell layers. The highly expanding oscillatory microbubbles provide a new direction for fuel-free micro- or nanobots, as well as biomedical applications of contrast agents and drug delivery.

Retrospective Analysis of Ultrasound-Guided Serial-Injection Triple Nerve Block Efficacy in Cementless Bipolar Hemiarthroplasty for Femoral Neck Fracture.

BACKGROUND: Femoral neck fractures are effectively treated with bipolar hemiarthroplasty (BHA) surgery, yet postoperative pain management remains a challenge. This study explores the efficacy of multimodal pain management in minimizing opioid use and enhancing recovery. METHODS: A retrospective analysis of 87 patients who underwent BHA between September 2016 and September 2020 was conducted. Patients were analyzed in two groups: Group I (n = 42), receiving serial-injection nerve blocks (SINBs) before and after surgery, and Group II (n = 41), with no SINB. Notably, all nerve blocks for Group I were performed after November 2017, following the implementation of this technique in our protocol. Pain and analgesic medication usage were assessed over 72 h post-surgery, along with hospitalization duration and perioperative complications. RESULTS: Group I patients exhibited significantly lower pain scores at 6, 12, 24, and 48 h post-surgery, alongside reduced incidences of postoperative nausea and vomiting (PONV) and delirium compared with Group II (p < 0.05). CONCLUSIONS: Utilizing sequential lower limb nerve blocks under ultrasound guidance in BHA surgeries effectively reduces early postoperative pain and associated adverse effects. This approach demonstrates potential benefits in pain management, leading to diminished narcotic usage and lower risks of PONV and delirium.

Ginseng (Panax ginseng) leaf extract modulates the expression of heme oxygenase-1 to attenuate osteoclast differentiation.

Osteoporosis is an aging disease characterized by an imbalance between bone formation and resorption. However, drugs that inhibit bone resorption have various adverse effects. Ginseng (Panax ginseng), a prominent herbal medicine in East Asia for >2000 years, is renowned for its manifold beneficial properties, including antioxidant, anti-cancer, anti-diabetic, and anti-adipogenic activities. Despite its long history of use, the pharmacological functions of ginseng leaves are not yet fully comprehended. In this study, we evaluated the potential effects of ginseng leaf extract (GLE) on receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast differentiation in RAW264.7 macrophage cells. Tartrate-resistant acid phosphatase (TRAP) staining revealed that GLE had significant anti-osteoclastogenic activity. GLE significantly reduced mRNA levels of osteoclast differentiation markers including TRAP, nuclear factor of activated T cell cytoplasmic 1, and cathepsin K. It also suppressed the production of reactive oxygen species (ROS) and secretion of high mobility group box-1 (HMGB1) in RANKL-treated RAW264.7 cells. In addition, GLE upregulated dose- and time-dependently the expression of heme oxygenase-1 (HO-1), eventually suppressing ROS production and HMGB1 secretion. This effects of GLE were significantly reversed by Tin Protoporphyrin IX dichloride, an inhibitor of HO-1, and HO-1 shRNA, indicating that HO-1 potently inhibits RANKL-induced osteoclast differentiation by inhibiting ROS production and HMGB1 secretion. Taken together, these observations suggest that GLE could have therapeutic potential as a natural product-derived medicine for the treatment of bone disorders.

Assessing bone mineral density in non-weight bearing regions of the body: a texture analysis approach using abdomen and pelvis computed tomography Hounsfield units-a cross-sectional study.

Background: Highlighting a gap in comprehending bone microarchitecture's intricacies using dual-energy X-ray absorptiometry (DXA), this study aims to bridge this chasm by analyzing texture in non-weight bearing regions on axial computed tomography (CT) scans. Our goal is to enrich osteoporosis patient management by enhancing bone quality and microarchitecture insights. Methods: Conducted at Busan Medical Center from March 1, 2013, to August 30, 2022, 1,320 cases (782 patients) were screened. After applying exclusion criteria, 458 samples (296 patients) underwent bone mineral density (BMD) assessment with both CT and DXA. Regions of interest (ROIs) included spine pedicle's maximum trabecular area, sacrum Zone 1, superior/inferior pubic ramus, and femur's greater/lesser trochanters. Texture features (n=45) were extracted from ROIs using gray-level co-occurrence matrices. A regression model predicted BMD, spotlighting the top five influential texture features. Results: Correlation coefficients ranged from 0.709 (lowest for total femur BMD) to 0.804 (highest for femur intertrochanter BMD). Mean squared error (MSE) values were also provided for lumbar and femur BMD/bone mineral content (BMC) metrics. The most influential texture features included contrast_32, correlation_32_v, and three other metrics. Conclusions: By melding traditional DXA and CT texture analysis, our approach presents a comprehensive bone health perspective, potentially revolutionizing osteoporosis diagnostics.

PDZ Peptide of the ZO-1 Protein Significantly Increases UTP-Induced MUC8 Anti-Inflammatory Mucin Overproduction in Human Airway Epithelial Cells.

Mucus hyperproduction and hypersecretion are observed often in respiratory diseases. MUC8 is a glycoprotein synthesized by epithelial cells and generally expressed in the respiratory track. However, the physiological mechanism by which extracellular nucleotides induce MUC8 gene expression in human airway epithelial cells is unclear. Here, we show that UTP could induce MUC8 gene expression through P2Y2-PLCß3-Ca2+ activation. Because the full-length cDNA sequence of MUC8 has not been identified, a specific siRNA-MUC8 was designed based on the partial cDNA sequence of MUC8. siRNA-MUC8 significantly increased TNF-α production and decreased IL-1Ra production, suggesting that MUC8 may downregulate UTP/P2Y2-induced airway inflammation. Interestingly, the PDZ peptide of ZO-1 protein strongly abolished UTP-induced TNF-α production and increased IL-1Ra production and MUC8 gene expression. In addition, the PDZ peptide dramatically increased the levels of UTP-induced ZO proteins and TEER (trans-epithelial electrical resistance). These results show that the anti-inflammatory mucin MUC8 may contribute to homeostasis, and the PDZ peptide can be a novel therapeutic candidate for UTP-induced airway inflammation.

Axial Neck Pain after Cervical Laminoplasty with Preserving C7 Spinous Process Using C7 Arcocristectomy: A Prospective Study.

STUDY DESIGN: Single-blinded, randomized, single-center, prospective study. PURPOSE: This study aims to compare the radiographical and clinical outcomes between C7 laminoplasty and C7 arcocristectomy, which preserves the C7 spinous process. OVERVIEW OF LITERATURE: Laminoplasty is a widely used surgical method that decompresses the cervical spinal cord. However, axial neck pain is one of the major factors of dissatisfaction, and still, it is not clearly solved the reduction method of postoperative axial neck pain. METHODS: Thirty-one patients with multilevel cervical spondylotic myelopathy who required C6-C7 level decompression surgery were operated and followed up for 24 months. One group (15 patients) received C7 arcocristectomy without laminoplasty, and the other group (16 patients) received C7 laminoplasty. Flexion, neutral, and extension angles were measured using the Cobb method at C2-C7 to evaluate preoperative and postoperative radiographic parameters. Range of motion (ROM), ROM preservation rate of the cervical spine, C2-C7 sagittal vertical axis (SVA), and T1 slope were measured using C-spine lateral X-ray. The Visual Analog Scale (VAS) and modified Japanese Orthopedic Association (JOA) score were used to compare preoperative and postoperative clinical symptoms. RESULTS: Flexion, neutral, extension angles of the cervical spine, C2-C7 SVA, T1 slope, ROM, ROM preservation rate, and modified JOA score were not significantly different between the two groups (p>0.05). In the C7 arcocristectomy group, the average postoperative VAS for axial neck pain was increased in 13.3% (2/15) of the patients, whereas in the C7 laminoplasty group, the average postoperative VAS was increased in 43.8% (7/16) of the patients (p=0.018). CONCLUSIONS: C7 arcocristectomy, which preserves the C7 spinous process and posterior structures, is a useful technique for relieving axial neck pain.

Risk Factors of the 2-Year Mortality after Bipolar Hemiarthroplasty for Displaced Femoral Neck Fracture.

Purpose: This study investigates the relationship between preoperative neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-C-reactive protein ratio (LCR), albumin, and 2-year mortality in elderly patients having hemiarthroplasty for displaced femoral neck fracture (FNF). Materials and Methods: We retrospectively reviewed 284 elderly patients who underwent hemiarthroplasty for Garden type IV FNF from September 2014 to September 2020. Using the receiver operating characteristic curve, optimal cutoff values for LCR, NLR, and albumin were established, and patients were categorized as low or high. Associations with 2-year mortality were evaluated through univariate and multivariate Cox regression analyses. Results: Of the 284 patients, 124 patients (45.9%) died within 2 years post-surgery. The optimal cutoff values were: LCR at 7.758 (specificity 58.5%, sensitivity 25.0%), NLR at 3.854 (specificity 39.2%, sensitivity 40.0%), and albumin at 3.750 (specificity 65.9%, sensitivity 21.9%). Patients with low LCR (<7.758), high NLR (≥3.854), and low albumin (<3.750) had a statistically significant reduced survival time compared to their counterparts. Conclusion: Lower preoperative LCR and albumin levels, along with higher NLR, effectively predict 2-year mortality and 30-day post-surgery complications in elderly patients with Garden type IV FNF undergoing hemiarthroplasty.

Effectiveness of ultrasound-guided dual nerve block in the below-knee amputation.

PURPOSE: Below knee amputation (BKA) is a common surgical procedure for diabetic foot ulcers and necrotizing lower limb fasciitis patients. However, it is a painful procedure and inadequate postoperative analgesia impedes rehabilitation and prolongs hospitalization. An ideal pain management regimen should provide superior analgesia while minimizing opioid consumption and improving rehabilitation. METHODS: We retrospectively reviewed medical charts of 218 patients who underwent BKA for diabetic foot ulcer or necrotizing lower limb fasciitis at a single center between January 2017 and September 2020. Two groups were analyzed: patients who received dual nerve block (DNB) before surgery (Group I; n = 104), and patients who did not (Group II; n = 93). By the exclusion criteria, 21 patients were excluded. The femoral and sciatic nerves were each blocked separately under ultrasound guidance. This procedure was performed immediately before the operation. RESULTS: Group I patients' subjective pain scores were significantly lower than that of Group II at 6, 12, and 24 h after BKA (P < 0.05). Group I's morphine milligram equivalent (MME) was significantly lower than those of Group II at 72 h after BKA (P < 0.05). Moreover, the rate of postoperative nausea and vomiting (PONV) and delirium was significantly lower in Group I patients than that in Group II patients. CONCLUSION: Ultrasound-guided lower extremity nerve block surgery is excellent for early postoperative pain control, could be used as an accurate and effective pain control method, and can reduce the side effects of opioid consumption after BKA.

Functional Magnetic Resonance Imaging and Diffusion Tensor Imaging for Language Mapping in Brain Tumor Surgery: Validation With Direct Cortical Stimulation and Cortico-Cortical Evoked Potential.

OBJECTIVE: Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging-derived tractography (DTI-t) contribute to the localization of language areas, but their accuracy remains controversial. This study aimed to investigate the diagnostic performance of preoperative fMRI and DTI-t obtained with a simultaneous multi-slice technique using intraoperative direct cortical stimulation (DCS) or corticocortical evoked potential (CCEP) as reference standards. MATERIALS AND METHODS: This prospective study included 26 patients (23-74 years; male:female, 13:13) with tumors in the vicinity of Broca's area who underwent preoperative fMRI and DTI-t. A site-by-site comparison between preoperative (fMRI and DTI-t) and intraoperative language mapping (DCS or CCEP) was performed for 226 cortical sites to calculate the sensitivity and specificity of fMRI and DTI-t for mapping Broca's areas. For sites with positive signals on fMRI or DTI-t, the true-positive rate (TPR) was calculated based on the concordance and discordance between fMRI and DTI-t. RESULTS: Among 226 cortical sites, DCS was performed in 100 sites and CCEP was performed in 166 sites. The specificities of fMRI and DTI-t ranged from 72.4% (63/87) to 96.8% (122/126), respectively. The sensitivities of fMRI (except for verb generation) and DTI-t were 69.2% (9/13) to 92.3% (12/13) with DCS as the reference standard, and 40.0% (16/40) or lower with CCEP as the reference standard. For sites with preoperative fMRI or DTI-t positivity (n = 82), the TPR was high when fMRI and DTI-t were concordant (81.2% and 100% using DCS and CCEP, respectively, as the reference standards) and low when fMRI and DTI-t were discordant (≤ 24.2%). CONCLUSION: fMRI and DTI-t are sensitive and specific for mapping Broca's area compared with DCS and specific but insensitive compared with CCEP. A site with a positive signal on both fMRI and DTI-t represents a high probability of being an essential language area.

Red clover (Trifolium pratense L.) extract inhibits ferroptotic cell death by modulating cellular iron homeostasis.

ETHNOPHARMACOLOGICAL RELEVANCE: Red clover (Trifolium pratense L.) is a traditional Chinese medicine and use as herbal medicine which has the effects of regulating menopausal symptoms, heart problem, inflammatory disease, psoriasis and cognitive deficits. In previous reported, the studies of red clover were mainly focused on clinical practice. the pharmacological functions of red clover not fully elucidated. AIM OF THE STUDY: To identify the molecules that regulate ferroptosis, we examined whether red clover (Trifolium pratense L.) extracts (RCE) affected ferroptosis induced by chemical treatment or cystine/glutamate antiporter (xCT) deficiency. MATERIALS AND METHODS: Cellular models for ferroptosis were induced by erastin/Ras-selectiv lethal 3 (RSL3) treatment or xCT deficiency in mouse embryonic fibroblasts (MEFs). Intracellular iron and peroxidized lipid levels were determined using Calcein-AM and BODIPY-C11 fluorescence dyes, respectively. Protein and mRNA were quantified by Western blot and real-time polymerase chain reaction, respectively. RNA sequencing analysis was performed on xCT-/- MEFs. RESULTS: RCE significantly suppressed ferroptosis induced by both erastin/RSL3 treatment and xCT deficiency. The anti-ferroptotic effects of RCE correlated to ferroptotic phenotypic changes such as cellular iron accumulation and lipid peroxidation in cellular ferroptosis models. Importantly, RCE affected levels of iron metabolism-related proteins including iron regulatory protein 1, ferroportin 1 (FPN1), divalent metal transporter 1, and transferrin receptor. RNA sequencing analysis of xCT-/- MEFs identified that expression of cellular defense genes was upregulated, while expression of cell death-related genes was downregulated, by RCE. CONCLUSION: RCE potently suppressed ferroptosis triggered both by erastin/RSL3 treatment and xCT deficiency by modulating cellular iron homeostasis. This is the first report that RCE has therapeutic potential in diseases associated with ferroptotic cell death, particularly ferroptosis induced by dysregulation of cellular iron metabolism.

Repair of severed recurrent thenar branch of median nerve after open carpal tunnel release.

An anatomical understanding of median nerve variation is essential for successful decompression of carpal tunnel syndrome (CTS). Although iatrogenic injury of the thenar branch after carpal tunnel release (CTR) has not been reported in many cases, it can cause serious damage to the patient. In case of rapidly progressing thenar atrophy after CTS surgery, thenar branch of median nerve injury should be suspected. Nerve conduction examination and ultrasound before surgery can be a useful tool for diagnosis.

Exploring user perspectives on a robotic arm with brain-machine interface: A qualitative focus group study.

Brain-machine Interface (BMI) is a system that translates neuronal data into an output variable to control external devices such as a robotic arm. A robotic arm can be used as an assistive living device for individuals with tetraplegia. To reflect users' needs in the development process of the BMI robotic arm, our team followed an interactive approach to system development, human-centered design, and Human Activity Assistive Technology model. This study aims to explore the perspectives of people with tetraplegia about activities they want to participate in, their opinions, and the usability of the BMI robotic arm. Eight people with tetraplegia participated in a focus group interview in a semistructured interview format. A general inductive analysis method was used to analyze the qualitative data. The 3 overarching themes that emerged from this analysis were: 1) activities, 2) acceptance, and 3) usability. Activities that the users wanted to do using the robotic arm were categorized into the following 5 activity domains: activities of daily living (ADL), instrumental ADL, health management, education, and leisure. Participants provided their opinions on the needs and acceptance of the BMI technology. Participants answered usability and expected standards of the BMI robotic arm within 7 categories such as accuracy, setup, cost, etc. Participants with tetraplegia have a strong interest in the robotic arm and BMI technology to restore their mobility and independence. Creating BMI features appropriate to users' needs, such as safety and high accuracy, will be the key to acceptance. These findings from the perspectives of potential users should be taken into account when developing the BMI robotic arm.

PPARδ Activation Mitigates 6-OHDA-Induced Neuronal Damage by Regulating Intracellular Iron Levels.

Intracellular iron accumulation in dopaminergic neurons contributes to neuronal cell death in progressive neurodegenerative disorders such as Parkinson's disease. However, the mechanisms of iron homeostasis in this context remain incompletely understood. In the present study, we assessed the role of the nuclear receptor peroxisome proliferator-activated receptor δ (PPARδ) in cellular iron homeostasis. We identified that PPARδ inhibited 6-hydroxydopamine (6-OHDA)-triggered neurotoxicity in SH-SY5Y neuroblastoma cells. PPARδ activation with GW501516, a specific PPARδ agonist, mitigated 6-OHDA-induced neuronal damage. Further, PPARδ activation also suppressed iron accumulation, which contributes to 6-OHDA-induced neuronal damage. PPARδ activation attenuated 6-OHDA-induced neuronal damage in a similar manner to that of the iron chelator deferoxamine. We further elucidated that PPARδ modulated cellular iron homeostasis by regulating expression of divalent metal transporter 1, ferroportin 1, and ferritin, but not transferrin receptor 1, through iron regulatory protein 1 in 6-OHDA-treated cells. Interestingly, PPARδ activation suppressed 6-OHDA-triggered generation of reactive oxygen species and lipid peroxides. The effects of GW501516 were abrogated by shRNA knockdown of PPARδ, indicating that the effects of GW501516 were PPARδ-dependent. Taken together, these findings suggest that PPARδ attenuates 6-OHDA-induced neurotoxicity by preventing intracellular iron accumulation, thereby suppressing iron overload-associated generation of reactive oxygen species and lipid peroxides, key mediators of ferroptotic cell death.

TNF-α Induces Mitophagy in Rheumatoid Arthritis Synovial Fibroblasts, and Mitophagy Inhibition Alleviates Synovitis in Collagen Antibody-Induced Arthritis.

Mitophagy is a selective form of autophagy that removes damaged mitochondria. Increasing evidence indicates that dysregulated mitophagy is implicated in numerous autoimmune diseases, but the role of mitophagy in rheumatoid arthritis (RA) has not yet been reported. The aim of the present study was to determine the roles of mitophagy in patient-derived RA synovial fibroblasts (RASFs) and in the collagen antibody-induced arthritis mouse model. We measured the mitophagy marker PTEN-induced putative kinase 1 (PINK1) in RASFs treated with tumor necrosis factor-α (TNF-α) using Western blotting and immunofluorescence. Arthritis was induced in PINK1-/- mice by intraperitoneal injection of an anti-type II collagen antibody cocktail and lipopolysaccharide. RA severity was assessed by histopathology. PINK1 expression and damaged mitochondria increased in TNF-α treated RASFs via increased intracellular levels of reactive oxygen species. PINK1 knockdown RASFs decreased cellular migration and invasion functions. In addition, PINK1-/- mice with arthritis exhibited markedly reduced swelling and inflammation relative to wild-type mice with arthritis. Taken together, these findings suggest that regulation of PINK1 expression in RA could represent a potential therapeutic and diagnostic target for RA.

Preservation of language function by mapping the arcuate fasciculus using intraoperative corticocortical evoked potential under general anesthesia in glioma surgery.

OBJECTIVE: Intraoperative language mapping under general anesthesia is imperative for brain tumor surgery because awake surgery is not always feasible. Monitoring corticocortical evoked potential (CCEP) is known to be a useful method for tracking neuronal connectivity and localizing functional areas. The authors evaluated the clinical benefit of intraoperative CCEP monitoring for language function preservation in patients undergoing glioma surgery. METHODS: Between January 2019 and June 2021, the authors performed a total of 29 consecutive glioma surgeries using CCEP monitoring under general anesthesia because of a risk of speech impairment; these were analyzed. Language area mapping was implemented by the anterior language area to posterior language area CCEP method for arcuate fasciculus mapping, and tumor resection was performed while avoiding the localized language areas. Language function before and after surgery was evaluated by the Controlled Oral Word Association Test (COWAT). RESULTS: Intraoperative CCEP was successfully monitored in 25 patients (86.2%), and a valid signal was undetectable in the other 4 patients. Language function evaluation was possible before and after surgery in a total of 20 patients. Overall, the preservation rate of language function was 65.0%, and the deterioration rate was 35.0% after tumor resection with CCEP monitoring. Among those 8 patients with preoperative COWAT scores ≥ 18, 5 patients (62.5%) successfully preserved their language function, with COWAT scores > 18 after tumor resection. Among the 12 patients with preoperative deteriorated language function (COWAT score < 18), 8 patients (66.7%) showed improvement or preserved language function after surgery. CONCLUSIONS: Intraoperative CCEP monitoring of the arcuate fasciculus is an acceptable technology for the preservation of language function under general anesthesia in glioma surgery in patients in whom awake surgery is not feasible.

Enpp2 Expression by Dendritic Cells Is a Key Regulator in Migration.

Enpp2 is an enzyme that catalyzes the conversion of lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), which exhibits a wide variety of biological functions. Here, we examined the biological effects of Enpp2 on dendritic cells (DCs), which are specialized antigen-presenting cells (APCs) characterized by their ability to migrate into secondary lymphoid organs and activate naïve T-cells. DCs were generated from bone marrow progenitors obtained from C57BL/6 mice. Enpp2 levels in DCs were regulated using small interfering (si)RNA or recombinant Enpp2. Expression of Enpp2 in LPS-stimulated mature (m)DCs was high, however, knocking down Enpp2 inhibited mDC function. In addition, the migratory capacity of mDCs increased after treatment with rmEnpp2; this phenomenon was mediated via the RhoA-mediated signaling pathway. Enpp2-treated mDCs showed a markedly increased capacity to migrate to lymph nodes in vivo. These findings strongly suggest that Enpp2 is necessary for mDC migration capacity, thereby increasing our understanding of DC biology. We postulate that regulating Enpp2 improves DC migration to lymph nodes, thus improving the effectiveness of cancer vaccines based on DC.

Peroxisome proliferator-activated receptor δ rescues xCT-deficient cells from ferroptosis by targeting peroxisomes.

Ferroptosis is a recently recognized process of cell death characterized by accumulation of iron-dependent lipid peroxides. Herein, we demonstrate that peroxisome proliferator-activated receptor δ (PPARδ) inhibits ferroptosis of mouse embryonic fibroblasts (MEFs) derived from cysteine/glutamate transporter (xCT)-knockout mice. Activation of PPARδ by the specific ligand GW501516 led to a dose-dependent decrease in ferroptotic cell death triggered by xCT deficiency, along with decreased levels of intracellular iron accumulation and lipid peroxidation. These effects of GW501516 were abolished by PPARδ-targeting small interfering RNA (siRNA) and the PPARδ inhibitor GSK0660, indicating that PPARδ inhibits xCT deficiency-induced ferroptosis. In addition, GW501516-activated PPARδ time- and dose-dependently upregulated catalase expression at both the mRNA and protein levels. This PPARδ-mediated upregulation of catalase was markedly attenuated in cells treated with PPARδ-targeting siRNA and GSK0660, indicating that expression of catalase is dependent on PPARδ. Consistently, the effects of GW501516 on ferroptosis of xCT-deficient MEFs were counteracted in the presence of 3-amino-1,2,4-triazole, a specific inhibitor of catalase, suggesting that catalase is essential for the effect of PPARδ on ferroptosis triggered by xCT deficiency. GW501516-activated PPARδ stabilized peroxisomes through catalase upregulation by targeting peroxisomal hydrogen peroxide-mediated lysosomal rupture, which led to ferroptosis of xCT-deficient MEFs. Collectively, these results demonstrate that PPARδ modulates ferroptotic signals in xCT-deficient MEFs by regulating catalase expression.

Effects of percutaneous injection laryngoplasty on voice and swallowing problems in cancer-related unilateral vocal cord paralysis.

BACKGROUND: Unilateral vocal cord paralysis may result from nerve compression by tumors or direct nerve injuries during tumor resections, which can cause dysphonia or dysphagia, and reduced quality of life. OBJECTIVES: This prospective, single-group study aimed to investigate the effect of percutaneous injection laryngoplasty on voice and swallowing function in patients with cancer-related unilateral vocal cord paralysis. METHODS: Patients underwent percutaneous injection laryngoplasty with hyaluronic acid under local anesthesia. Stroboscopy and videofluoroscopic swallowing study were conducted to evaluate the voice- and swallowing-related outcome measures, respectively. The participants were evaluated before injection laryngoplasty, as well as after two weeks and three months. RESULTS: Injection laryngoplasty significantly improved the glottal gap, vocal fold position, Maximum Phonation Time, and Voice Handicap Index-10. Post-hoc analysis using Bonferroni correction showed that the improvements occurred within two post-treatment weeks and remained at three post-treatment months. In the subgroup analysis, the patients who underwent injection laryngoplasty within 8 weeks from onset showed significantly higher improvements in the videofluoroscopic dysphagia scale and swallowing function than the patients who received the procedure after 8 weeks or more. CONCLUSION: Percutaneous injection laryngoplasty improves glottal closure and voice in patients with cancer-related unilateral vocal cord paralysis. Early injection laryngoplasty may lead to greater benefits on swallowing function. LEVEL OF EVIDENCE: 4.

TGF-ß/IL-7 Chimeric Switch Receptor-Expressing CAR-T Cells Inhibit Recurrence of CD19-Positive B Cell Lymphoma.

Chimeric antigen receptor (CAR)-T cells are effective in the treatment of hematologic malignancies but have shown limited efficacy against solid tumors. Here, we demonstrated an approach to inhibit recurrence of B cell lymphoma by co-expressing both a human anti-CD19-specific single-chain variable fragment (scFv) CAR (CD19 CAR) and a TGF-ß/IL-7 chimeric switch receptor (tTRII-I7R) in T cells (CD19 CAR-tTRII-I7R-T cells). The tTRII-I7R was designed to convert immunosuppressive TGF-ß signaling into immune-activating IL-7 signaling. The effect of TGF-ß on CD19 CAR-tTRII-I7R-T cells was assessed by western blotting. Target-specific killing by CD19 CAR-tTRII-I7R-T cells was evaluated by Eu-TDA assay. Daudi tumor-bearing NSG (NOD/SCID/IL2Rγ-/-) mice were treated with CD19 CAR-tTRII-I7R-T cells to analyze the in vivo anti-tumor effect. In vitro, CD19 CAR-tTRII-I7R-T cells had a lower level of phosphorylated SMAD2 and a higher level of target-specific cytotoxicity than controls in the presence of rhTGF-ß1. In the animal model, the overall survival and recurrence-free survival of mice that received CD19 CAR-tTRII-I7R-T cells were significantly longer than in control mice. These findings strongly suggest that CD19 CAR-tTRII-I7R-T cell therapy provides a new strategy for long-lasting, TGF-ß-resistant anti-tumor effects against B cell lymphoma, which may lead ultimately to increased clinical efficacy.