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Nitazoxanide (NTZ), an FDA-approved drug, was originally developed for the treatment of parasitic infections. Recent studies have revealed that NTZ may also be effective in treating other diseases, including inflammatory diseases, cancer, and bacterial and viral infections. Therefore, we investigated whether NTZ could inhibit specific inflammatory pathways and reprogram metabolic processes in psoriasis to regulate inflammation. To investigate the symptom-alleviating effects of NTZ on psoriasis and its underlying mechanisms, we used an imiquimod-induced psoriatic-like skin inflammation mouse model and IL-17-stimulated human keratinocytes. NTZ inhibited the transition of metabolic programs induced by IL-17-mediated inflammation in human keratinocytes. In particular, NTZ suppressed glucose uptake and the associated actions stimulated by IL-17 and reduced enhanced oxidative phosphorylation. NTZ inhibits the mTOR signaling pathway by inducing AMPK, and prevents the development of dysfunctional mitochondria characterised by high mitochondrial mass and high levels of ROS. Moreover, the administration of NTZ in a mouse model of psoriasis, an IL-17-mediated skin disease, inhibited the accumulation of damaged mitochondria and suppressed Th17-mediated inflammatory responses. These findings provide preclinical evidence that NTZ may be effective in treating psoriasis and suggest that targeting the energy metabolic pathways in the skin could be beneficial for the treatment and prevention of psoriasis., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Blue thermally activated delayed fluorescence (TADF) top-emitting organic light-emitting diodes (TEOLEDs) have garnered widespread interest because of their 100% internal quantum efficiency (η int ) and high intensity due to microcavity effects. However, their external quantum efficiency (η ext ) is limited by total internal reflection from the thin-film encapsulation (TFE) required by TEOLEDs and their susceptibility to moisture and oxygen. This paper introduces a novel approach in which TiO 2 nanoparticles (NPs) are incorporated into a negative photoresist, and Al 2 O 3 is applied to form a nanolaminated TFE layer. This TFE layer decreases the water vapor transmission rate (WVTR), enhances light extraction efficiency and viewing angle characteristics. Moreover, the optical property can be modulated by adjusting the TiO 2 NP content and a planarization layer, maintaining a total transmittance of approximately 70%. The barrier properties assessed via electrical Ca tests show that TFE achieves WVTRs below 10 -5 g m -2 day -1 under ambient conditions. When applied to blue TADF TEOLEDs, the TFE improves electroluminescence by 23.78% and external quantum efficiency by 32.31%. As the viewing angle shifts from 0° to 45°, the CIE coordinate and peak wavelength shifts decrease from 0.067 to 0.044 and 14 to 8 nm, respectively. These results can be theoretically explained based on Mie scattering efficiency and Snell's law, as analyzed by finite-difference time-domain simulations.

This study introduces an organic light-emitting diode (OLED) light extraction method using a wavy-patterned polydimethylsiloxane (PDMS) substrate created via oxygen (O 2 ) plasma treatment. A rapid fabrication process adjusted the flow, pressure, duration, and power of the O 2 plasma treatment to replicate the desired wavy structure. This method allowed the treated samples to maintain over 90% total transmittance and enabled controlled haze adjustments from 10% to 70%. Finite-difference time-domain (FDTD) simulations were employed to determine optimal amplitudes and periods for the wavy structure to maximize optical performance. Further experiments demonstrated that bottom-emitting green fluorescent OLEDs constructed on these substrates achieved an external quantum efficiency (EQE) of 3.5%, representing a 97% improvement compared to planar PDMS OLEDs. Additionally, color purity variation was minimized to 0.044, and the peak wavelength shift was limited to 10 nm, ensuring consistent color purity and intensity even at wide viewing angles. This study demonstrates the potential of this cost-effective and efficient method in advancing high-quality display.

Shiga toxins (Stxs), produced by Shigella dysenteriae serotype 1 and certain Escherichia coli pathotypes, cause hemorrhagic colitis, which can progress to hemolytic uremic syndrome (HUS) and central nervous system (CNS) pathology. The underlying mechanisms of toxin-induced inflammation remain unclear. The p38 mitogen-activated protein kinase (MAPK) and its downstream target, MAPKAPK2 (MK2), play key roles in various cellular responses. We identified Tristetraprolin (TTP) as a novel substrate of MK2 in Stx-intoxicated cells. Western blot analysis showed that Stxs induce phosphorylation of MK2 (Thr334) and TTP in globotriaosylceramide (Gb 3 )-positive cells, including D-THP-1 macrophage-like cells and HK-2 renal epithelial cells, but not in Gb 3 -negative T84 colon carcinoma cells. After treatment with wild-type Stx, the activity of phosphorylated MK2 and TTP persists for up to 8 h, while Stx2a mut , which lacks N-glycosidase activity, causes transient MK2/TTP phosphorylation. This suggests that Stxs selectively mediate MK2 and TTP activation in a Gb 3 -dependent manner. Knockdown of TTP in Stx2a-treated D-THP-1 cells upregulates proinflammatory cytokines such as TNF-α, IL-1β, IL-6, IL-8, MCP-1, and MIP-1α. The MK2 inhibitor PF-3644022 significantly reduces TTP phosphorylation and blocks the production of IL-6, IL-8, MCP-1, and MIP-1α in Stx2a-stimulated HK-2 cells. In conclusion, the MK2-TTP signaling pathway regulates the inflammatory response induced by Stxs in toxin-sensitive cells.

Psoriasis is a chronic inflammatory skin disorder characterized by abnormal immune responses and keratinocyte hyperproliferation. Limonin, a bioactive compound found in citrus fruits, has anti-inflammatory properties in various models; however, its effects on psoriasis are not fully understood. We investigated the therapeutic potential of limonin in a 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced psoriasis mouse model. Mice were treated with TPA to induce psoriasis-like skin lesions, followed by intraperitoneal administration of limonin (200 or 400 μg/mouse) for six days. The results showed that limonin improved psoriasis-related symptoms in a psoriasis-like mouse model by suppressing the mRNA expression of pro-inflammatory cytokines and inflammation-related antimicrobial peptides and regulating the expansion of myeloid cells and T cells. Specifically, limonin reduced glucose uptake and oxidative phosphorylation to shift the metabolic program in the inflamed skin cells of psoriasis-like mice. Limonin activates AMPK and proteins related to mTOR inhibition, thereby suppressing the mTOR signaling pathway. It also inhibits mitochondrial mass and mitochondrial ROS production, thereby preventing the development of dysfunctional mitochondria in inflamed skin cells. Overall, limonin modulates key immune responses and metabolic pathways related to inflammation and mitochondrial health in psoriasis. Therefore, it is a promising natural candidate for the treatment of psoriasis and various inflammatory skin diseases.

Background: The incidence of epistaxis during nasotracheal intubation via the left nostril is more frequent than that during intubation via the right nostril. This study evaluated the effect of the reverse bevel and tip direction of the nasotracheal tube on the incidence of epistaxis during nasotracheal intubation via the left nostril., Methods: Patients undergoing right-sided maxillofacial surgery requiring left nasotracheal intubation were randomly allocated to the control (tracheal tube in the conventional direction) or reverse (a 180˚ reverse direction, with the tube bevel facing the nasal septum and the leading edge (i.e., the tip) of the bevel pointing away from the nasal septum) groups (n = 37 for both). The primary outcome was the incidence of epistaxis evaluated using videolaryngoscopy., Results: The incidence of epistaxis in the reverse group was significantly lower than that in the control group (9 [24.3%] vs. 20 [54.1%], P = 0.009; relative risk: 0.45, 95% CI [0.24, 0.85], absolute risk reduction: 29.8%, number needed to treat: 3). The severity of epistaxis was significantly lower in the reverse group (P = 0.002). The first attempt nasal passage (P = 0.027) was significantly higher in the reverse group. Postoperative nasal pain was lower (P < 0.001), and patient satisfaction was higher (P < 0.001) in the reverse group. Nasotracheal tube-related complications did not occur in either group., Conclusions: The reverse bevel and tip direction of the nasotracheal tube reduced the incidence and severity of epistaxis and increased patient satisfaction among patients undergoing left nasotracheal intubation.

Cathepsin L (CTSL), a cysteine cathepsin protease of the papain superfamily, plays a crucial role in cancer progression and metastasis. Dysregulation of CTSL is frequently observed in tumor malignancies, leading to the degradation of extracellular matrix and facilitating epithelial-mesenchymal transition (EMT), a key process in malignant cancer metastasis. This review mainly provides a comprehensive information about recent findings on natural inhibitors targeting CTSL and their anticancer effects, which have emerged as potent anticancer therapeutic agents or metastasis-suppressive adjuvants. Specifically, inhibitors are categorized into small-molecule and macromolecule inhibitors, with a particular emphasis on cathepsin propeptide-type macromolecules. Additionally, the article explores the molecular mechanisms of CTSL involvement in cancer metastasis, highlighting its regulation at transcriptional, translational, post-translational, and epigenetic levels. This work underscores the importance of understanding natural CTSL inhibitors and provides researchers with practical insights to advance the relevant fields and discover novel CTSL-targeting inhibitors from natural sources., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Pseudomonas putida KT2440 encodes a defense system that rigidifies membranes by a cytochrome c-type cis/trans fatty acid isomerase (CTI). Despite its potential as an industrial biocatalyst for directly regulating the geometric isomerism of monounsaturated fatty acids, its original catalytic and structural properties have remained elusive. In this study, the catalytic nature of wild-type CTI purified P. putida KT2440 against dietary monounsaturated fatty acids was investigated. It showed substrate preference for palmitoleic acid (C 16:1 , cis-Δ 9 ), along with substrate promiscuity with chain length and double bond position (palmitoleic acid>cis-vaccenic acid>oleic acid). Under determined optimum reaction conditions, its catalytic efficiency (k cat /K m ) was evaluated as 5.13 × 10 2  M -1 ·sec -1 against palmitoleic acid. Furthermore, computational predictions of the protein structure revealed its monoheme cytochrome c-type domain and a parasol-like transmembrane domain, suggesting its catalytic mode of action. For effective cis/trans isomerization, the ethylene double bond of monounsaturated fatty acids should be precisely positioned at the heme center of CTI, indicating that its substrate specificity can be determined by the alkyl chain length and the double bond position of the fatty acid substrates. These findings shed light on the potential of CTI as a promising biocatalyst for the food and lipid industry., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Catheter-related bladder discomfort (CRBD) is problematic in patients with a urinary catheter. Transcutaneous electrical nerve stimulation (TENS) is a non-invasive analgesic modality used to relieve various types of pain., Objectives: We evaluated the effect of TENS on CRBD after transurethral resection of bladder tumours (TURBT)., Design: A randomised controlled trial., Setting: A large university tertiary hospital, from October 2022 to March 2023., Patients: Patients requiring urinary catheterisation after TURBT., Intervention: In this randomised controlled trial, patients were randomly allocated to the TENS ( n   =  56) or control ( n   =  56) groups. CRBD manifests as a burning sensation with an urge to void or discomfort in the suprapubic area. Moderate to severe CRBD was defined as patients self-reporting CRBD symptoms with or without behavioural response, including attempts to remove the urinary catheter, intense verbal reactions, and flailing limbs. TENS was performed from the end of surgery to 1 h postoperatively., Main Outcome Measure: The primary endpoint was considered moderate to severe CRBD immediately postoperatively. Secondary endpoints included moderate to severe CRBD at 1, 2 and 6 h postoperatively. Additionally, postoperative pain, patient satisfaction, and TENS-related adverse effects were evaluated., Results: Moderate to severe CRBD immediately postoperatively was significantly less frequent in the TENS group than in the control group: 10 (17.9%) vs. 34 (60.7%); P  < 0.001; relative risk (95% CI) = 0.294 (0.161 to 0.536); absolute risk reduction = 0.43; number needed to treat = 2.3. Moderate to severe CRBD differed between the two groups at 1 h postoperatively: 1 (1.8%) vs. 16 (28.6%); P  < 0.001; relative risk = 0.06 (95% CI 0.01 to 0.46); absolute risk reduction = 0.27; number needed to treat = 3.7. The TENS group exhibited a significantly lower score for postoperative pain at 1 h (1.8 ± 0.6 vs. 2.2 ± 0.4; P  < 0.001, mean difference (95% CI) = 0.4 (0.2 to 0.6) and a higher score for patient satisfaction, 5.0 (4.0 to 6.0) vs. 3.0 (3.0 to 4.0); P  < 0.001; median difference (95% CI) = 2.0 (1.0 to 2.0)., Conclusions: TENS reduced moderate to severe CRBD, decreased postoperative pain, and increased patient satisfaction after TURBT., Clinical Trial Registry: Clinical Research Information Service (KCT0007450)., (Copyright © 2024 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Retinal vascular disease is the leading cause of visual impairment. Although intravitreal drug injections are the most suitable approach for addressing retinal disorders, existing clinical treatments necessitate repeated administration, imposing a substantial burden on patients with various intraocular complications. This study introduces an injectable and biodegradable hyaluronan microgel (Hm)-embedded gelatin-poly(ethylene glycol)-tyramine hydrogel (HmGh) designed for sustained intravitreal ranibizumab (RBZ) delivery to reduce patient burden and minimize the side effects associated with frequent injections. Hm exhibited a controlled RBZ loading capacity and release profile. HmGh effectively controlled the initial burst release and overall release profile. Cytocompatibility and cellular drug efficacy were also demonstrated. In an animal study, HmGh maintained RBZ concentrations in the vitreous and retina for >120 d. Pharmacokinetic studies showed that the half-life of RBZ-loaded HmGh in the vitreous and retina was 2.55 and 2.05 times longer than that of RBZ-loaded Hm, respectively, and 9.58 and 38.46 times longer than that of RBZ solution, respectively. Importantly, the initial RBZ elimination from HmGh to the aqueous humor was significantly reduced compared to that from the Hm and RBZ solutions. Intraocular degradation and safety were comprehensively evaluated using fundus imaging and histological analyses. In conclusion, this injectable microgel-embedded hydrogel formulation is a promising prolonged drug delivery system for treating various posterior segment eye diseases., Competing Interests: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article., (© 2024 Shenyang Pharmaceutical University. Published by Elsevier B.V.)

Purpose: Ventral hernias are a common complication of laparotomy, posing challenges particularly when primary fascial closure is unattainable. Although chemical component separation using preoperative botulinum toxin A (BTX) injections has emerged as a promising adjunct, objective evidence of its efficacy remains limited. This study aimed to objectively assess the effect of preoperative BTX on traction force during ventral hernia repair., Methods: A prospective, single-blind study was conducted on patients with midline incisional hernias following liver transplantation. BTX was administered unilaterally, and the traction force required to medially advance the anterior rectus sheath was measured intraoperatively. Pre- and post-injection CT scans were analyzed for changes in hernia size and LAW muscle measurements. Statistical analyses were performed to evaluate traction force differences between BTX-injected and uninjected sides., Results: Ten patients underwent hernia repair with primary fascial closure achieved in all cases. Comparison of pre- and post-injection CT scans showed no significant changes in hernia size. LAW muscle length increased by 1.8 cm, while thickness decreased by 0.2 cm. Intraoperative traction force measurements revealed a significant reduction on the BTX-injected side compared to the uninjected side (p < 0.0001). The traction force ratio on the BTX-injected to the uninjected side averaged 57%, indicating the efficacy of BTX in reducing tension., Conclusion: Preoperative BTX significantly reduces traction force during ventral hernia repair, highlighting its potential as an adjunctive therapy in complex cases. While challenges remain in patient selection and outcome assessment, BTX offers a promising avenue for enhancing abdominal wall reconstruction outcomes and reducing surgical complications., (© 2024. The Author(s).)

High-energy impacts, like vehicle crashes or falls, can lead to pelvic ring injuries. Rapid diagnosis and treatment are crucial due to the risks of severe bleeding and organ damage. Pelvic radiography promptly assesses fracture extent and location, but struggles to diagnose bleeding. The AO/OTA classification system grades pelvic instability, but its complexity limits its use in emergency settings. This study develops and evaluates a deep learning algorithm to classify pelvic fractures on radiographs per the AO/OTA system. Pelvic radiographs of 773 patients with pelvic fractures and 167 patients without pelvic fractures were retrospectively analyzed at a single center. Pelvic fractures were classified into types A, B, and C using medical records categorized by an orthopedic surgeon according to the AO/OTA classification system. Accuracy, Dice Similarity Coefficient (DSC), and F1 score were measured to evaluate the diagnostic performance of the deep learning algorithms. The segmentation model showed high performance with 0.98 accuracy and 0.96-0.97 DSC. The AO/OTA classification model demonstrated effective performance with a 0.47-0.80 F1 score and 0.69-0.88 accuracy. Additionally, the classification model had a macro average of 0.77-0.94. Performance evaluation of the models showed relatively favorable results, which can aid in early classification of pelvic fractures., (© 2024. The Author(s).)

Introduction: The geriatric nutritional risk index (GNRI) can easily identify malnutrition-associated morbidity and mortality. We investigated the association between preoperative GNRI and 30-d mortality in geriatric burn patients who underwent surgery., Methods: The study involved geriatric burn patients (aged ≥ 65 y) who underwent burn surgery between 2012 and 2022. The GNRI was computed using the following formula: 1.489 × serum albumin concentration (mg/L) + 41.7 × patient body weight/ideal body weight. Patients were dichotomized into the high GNRI (≥ 82) and low GNRI (< 82) groups. GNRI was evaluated as an independent predictor of 30-d postoperative mortality. The study also evaluated the association between GNRI and sepsis, the need for continuous renal replacement therapy (CRRT), major adverse cardiac events (MACE), and pneumonia., Results: Out of 270 patients, 128 (47.4%) had low GNRI (< 82). Multivariate Cox regression analysis revealed that low GNRI was significantly associated with 30-d postoperative mortality (hazard ratio: 1.874, 95% confidence interval [CI]: 1.146-3.066, P = 0.001). Kaplan-Meier analysis revealed that the 30-day mortality rate differed significantly between the low and high GNRI groups (log-rank test, P < 0.001). The 30-d postoperative mortality (hazard ratio: 2.677, 95% CI: 1.536-4.667, P < 0.001) and the incidence of sepsis (odds ratio [OR]: 2.137, 95% CI: 1.307-3.494, P = 0.004), need for CRRT (OR: 1.919, 95% CI: 1.101-3.344, P = 0.025), MACE (OR: 1.680, 95% CI: 1.018-2.773, P = 0.043), and pneumonia (OR: 1.678, 95% CI: 1.019-2.764, P = 0.044), were significantly higher in the low GNRI group than in the high GNRI group., Conclusions: Preoperative low GNRI was associated with increased 30-d postoperative mortality, sepsis, need for CRRT, MACE, and pneumonia in geriatric burn patients., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Within-individual coupling between measures of brain structure and function evolves in development and may underlie differential risk for neuropsychiatric disorders. Despite increasing interest in the development of structure-function relationships, rigorous methods to quantify and test individual differences in coupling remain nascent. In this article, we explore and address gaps in approaches for testing and spatially localizing individual differences in intermodal coupling. We propose a new method, called CIDeR, which is designed to simultaneously perform hypothesis testing in a way that limits false positive results and improve detection of true positive results. Through a comparison across different approaches to testing individual differences in intermodal coupling, we delineate subtle differences in the hypotheses they test, which may ultimately lead researchers to arrive at different results. Finally, we illustrate the utility of CIDeR in two applications to brain development using data from the Philadelphia Neurodevelopmental Cohort., Competing Interests: Declaration of competing interest AAB receives consulting income from Octave Bioscience and holds equity in Centile Bioscience.

EGFRvIII is expressed only in tumor cells and strongly in glioblastoma and is considered a promising target in cancer diagnosis and therapy. Aptamers are synthetic single-stranded oligonucleotides that bind to biochemical target molecules with high binding affinity and specificity. This study examined the potential of the 68 Ga-NOTA-EGFRvIII aptamer as a nuclear imaging probe for visualizing EGFRvIII-expressing glioblastoma by positron emission tomography (PET). EGFRvIII aptamer was selected using the SELEX technology, and flow cytometry and fluorescence microscopy verified the high binding affinity to EGFRvIII positive U87MG vIII 4.12 glioma cells but not to EGFRvIII negative U87MG cells. The EGFRvIII aptamer was conjugated with a chelator (1,4,7-triazanonane-1,4,7-triyl)triacetic acid (NOTA) for 68 Ga-labeling. The 68 Ga-NOTA-EGFRvIII aptamer was prepared using the preconcentration-based labeling method with a high radiolabeling yield at room temperature. Ex vivo biodistribution analyses confirmed the significantly higher tumor uptake of the 68 Ga-NOTA-EGFRvIII aptamer in EGFRvIII-expressing xenograft tumors than that in EGFRvIII negative tumors, confirming the specific tumor uptake of the 68 Ga-NOTA-EGFRvIII aptamer in vivo. PET imaging studies revealed a high retention rate of the 68 Ga-NOTA-EGFRvIII aptamer in U87MG vIII 4.12 tumors but only low uptake levels in U87-MG tumors, suggesting that the 68 Ga-NOTA-EGFRvIII aptamer may be used as a PET imaging agent for EGFRvIII-expressing glioblastoma.

Background: Continuous intravenous infusion of remimazolam may be suitable for sedation in patients undergoing regional anaesthesia. However, there have been no studies comparing remimazolam and dexmedetomidine for this purpose. This study compared emergence from sedation between dexmedetomidine and remimazolam following continuous intravenous infusion in patients undergoing spinal anaesthesia. Methods: This double-blinded, randomised controlled trial assessed the sedative effects of dexmedetomidine and remimazolam. Following spinal anaesthesia, patients were sedated using continuous intravenous infusion of either dexmedetomidine (D group) or remimazolam (R group).The D group received dexmedetomidine administered at 6 mL/kg/h (6 µg/kg/h) for 10 minutes, followed by 1 mL/kg/h (1 µg/kg/h). The R group received remimazolam administered at 6 mL/kg/h (6 mg/kg/h) for 10 minutes, followed by 1 mL/kg/h (1 mg/kg/h). Sedation levels were evaluated using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale. The time to reach MOAA/S ≤ 3 from the start of drug infusion and the time to reach MOAA/S = 5 from the end of infusion were recorded. Hemodynamic parameters and respiratory rate were also monitored. Results: The R group reached MOAA/S ≤ 3 significantly faster than the D group during induction of sedation (4 ± 1 minutes and 11 ± 3 minutes, respectively, p < 0.001). The R group also reached MOAA/S = 5 significantly faster than the D group during emergence from sedation (11 ± 3 minutes and 16 ± 5 minutes, respectively, p < 0.001). Both groups maintained stable hemodynamic parameters and respiratory rate without any significant differences, although the mean heart rate was significantly lower in the D group than in the R group after the start of infusion. Conclusion: Remimazolam demonstrated significantly faster induction of and emergence from sedation compared to dexmedetomidine, with no significant differences in haemodynamics or respiratory depression., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Pyroptosis is a form of programmed cell death characterized by gasdermin (GSDM)-mediated pore formation in the cell membrane, resulting in the release of pro-inflammatory cytokines and cellular lysis. Increasing evidence has shown that pyroptosis is responsible for the progression of various pulmonary disorders. The inhalation of polyhexamethylene guanidine (PHMG) causes severe lung inflammation and pulmonary toxicity; however, the underlying mechanisms are unknown. Therefore, in this study, we investigate the role of pyroptosis in PHMG-induced pulmonary toxicity. We exposed bronchial epithelial cells, BEAS-2B, to PHMG phosphate (PHMG-p) and evaluated cell death type, reactive oxygen species (ROS) levels, and relative expression levels of pyroptosis-related proteins. Our data revealed that PHMG-p reduced viability and induced morphological alterations in BEAS-2B cells. Exposure to PHMG-p induced excessive accumulation of mitochondrial ROS (mtROS) in BEAS-2B cells. PHMG-p activated caspase-dependent apoptosis as well as NLRP3/caspase-1/GSDMD-mediated- and caspase-3/GSDME-mediated pyroptosis through mitochondrial oxidative stress in BEAS-2B cells. Notably, PHMG-p reduced mitochondrial respiratory function and induced the translocation of Bax and cleaved GSDM into the mitochondria, leading to mitochondrial dysfunction. Our results enhanced our understanding of PHMG-p-induced lung toxicity by demonstrating that PHMG-p induces pyroptosis via mtROS-induced mitochondrial dysfunction in bronchial epithelial cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Telmisartan is considered more potent than valsartan. Hemodynamic response during anesthesia induction may be influenced by anti-hypertension (HTN) medication. The present study compared the effect of anti-HTN medications on post-induction hypotension during noncardiac surgeries., Methods: This observational study standardized the anesthetic regimen across patients, with hypotension defined as mean blood pressure (BP) of less than 65 mmHg. The hemodynamic changes within 5 min before and after endotracheal intubation, and within 10 min before and after surgical incision were measured. Transthoracic echocardiographic evaluation of the left ventricle (LV) during anesthesia induction was performed. The primary endpoint was the decline in mean BP after anesthetic administration in telmisartan and valsartan groups. Multivariate logistic regression analysis was used to identify predictors of post-induction hypotension., Results: Data from 157 patients undergoing noncardiac surgery were analyzed. No significant differences were found in mean BP decline between the two groups during anesthesia induction. Hemodynamic changes and LV ejection fraction (EF) during anesthesia induction were similar between the groups. Age and preoperative initial mean BP in operation room (OR) were associated with post-induction hypotension in both groups., Conclusions: The angiotensin receptor blocker (ARB) type did not influence post-induction hypotension during anesthesia induction. Age and preoperative initial mean BP in OR were associated with post-induction hypotension in patients taking ARBs.

Depending on the degree of fracture, pelvic fracture can be accompanied by vascular damage, and in severe cases, it may progress to hemorrhagic shock. Pelvic radiography can quickly diagnose pelvic fractures, and the Association for Osteosynthesis Foundation and Orthopedic Trauma Association (AO/OTA) classification system is useful for evaluating pelvic fracture instability. This study aimed to develop a radiomics-based machine-learning algorithm to quickly diagnose fractures on pelvic X-ray and classify their instability. data used were pelvic anteroposterior radiographs of 990 adults over 18 years of age diagnosed with pelvic fractures, and 200 normal subjects. A total of 93 features were extracted based on radiomics:18 first-order, 24 GLCM, 16 GLRLM, 16 GLSZM, 5 NGTDM, and 14 GLDM features. To improve the performance of machine learning, the feature selection methods RFE, SFS, LASSO, and Ridge were used, and the machine learning models used LR, SVM, RF, XGB, MLP, KNN, and LGBM. Performance measurement was evaluated by area under the curve (AUC) by analyzing the receiver operating characteristic curve. The machine learning model was trained based on the selected features using four feature-selection methods. When the RFE feature selection method was used, the average AUC was higher than that of the other methods. Among them, the combination with the machine learning model SVM showed the best performance, with an average AUC of 0.75±0.06. By obtaining a feature-importance graph for the combination of RFE and SVM, it is possible to identify features with high importance. The AO/OTA classification of normal pelvic rings and pelvic fractures on pelvic AP radiographs using a radiomics-based machine learning model showed the highest AUC when using the SVM classification combination. Further research on the radiomic features of each part of the pelvic bone constituting the pelvic ring is needed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Park et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We selectively improved the viewing angle characteristics and light extraction efficiency of blue thermally activated delayed fluorescence (TADF) organic light-emitting diodes (OLEDs) by tailoring a nanofiber-shaped Si 3 N 4 layer, which was used as an internal scattering layer. The diameter of the polymer nanofibers changed according to the mass ratio of polyacrylonitrile (PAN) and poly(methyl methacrylate) (PMMA) in the polymer solution for electrospinning. The Si 3 N 4 nanofiber (SNF) structure was fabricated by etching an Si 3 N 4 film using the PAN/PMMA nanofiber as a mask, making it easier to adjust parameters, such as the diameter, open ratio, and height, even though the SNF structure was randomly shaped. The SNF structures exhibited lower transmittance and higher haze with increasing diameter, showing little correlation with their height. However, all the structures demonstrated a total transmittance of over 80%. Finally, by applying the SNF structures to the blue TADF OLEDs, the external quantum efficiency was increased by 15.6%. In addition, the current and power efficiencies were enhanced by 23.0% and 25.6%, respectively. The internal light-extracting SNF structure also exhibited a synergistic effect with the external light-extracting structure. Furthermore, when the viewing angle changed from 0° to 60°, the peak wavelength and CIE coordinate shift decreased from 20 to 6 nm and from 0.0561 to 0.0243, respectively. These trends were explained by the application of Snell's law to the light path and were ultimately validated through finite-difference time-domain simulations.

With the recent increase in traffic accidents, pelvic fractures are increasing, second only to skull fractures, in terms of mortality and risk of complications. Research is actively being conducted on the treatment of intra-abdominal bleeding, the primary cause of death related to pelvic fractures. Considerable preliminary research has also been performed on segmenting tumors and organs. However, studies on clinically useful algorithms for bone and pelvic segmentation, based on developed models, are limited. In this study, we explored the potential of deep-learning models presented in previous studies to accurately segment pelvic regions in X-ray images. Data were collected from X-ray images of 940 patients aged 18 or older at Gachon University Gil Hospital from January 2015 to December 2022. To segment the pelvis, Attention U-Net, Swin U-Net, and U-Net were trained, thereby comparing and analyzing the results using five-fold cross-validation. The Swin U-Net model displayed relatively high performance compared to Attention U-Net and U-Net models, achieving an average sensitivity, specificity, accuracy, and dice similarity coefficient of 96.77%, of 98.50%, 98.03%, and 96.32%, respectively., (© 2024. The Author(s).)

In neuroimaging studies, combining data collected from multiple study sites or scanners is becoming common to increase the reproducibility of scientific discoveries. At the same time, unwanted variations arise by using different scanners (inter-scanner biases), which need to be corrected before downstream analyses to facilitate replicable research and prevent spurious findings. While statistical harmonization methods such as ComBat have become popular in mitigating inter-scanner biases in neuroimaging, recent methodological advances have shown that harmonizing heterogeneous covariances results in higher data quality. In vertex-level cortical thickness data, heterogeneity in spatial autocorrelation is a critical factor that affects covariance heterogeneity. Our work proposes a new statistical harmonization method called spatial autocorrelation normalization (SAN) that preserves homogeneous covariance vertex-level cortical thickness data across different scanners. We use an explicit Gaussian process to characterize scanner-invariant and scanner-specific variations to reconstruct spatially homogeneous data across scanners. SAN is computationally feasible, and it easily allows the integration of existing harmonization methods. We demonstrate the utility of the proposed method using cortical thickness data from the Social Processes Initiative in the Neurobiology of the Schizophrenia(s) (SPINS) study. SAN is publicly available as an R package., (© 2024 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Tenascin-C is an extracellular matrix glycoprotein strongly expressed in coronary atherosclerotic plaque. Aptamers are single-stranded oligonucleotides that bind to specific target molecules with high affinity. This study hypothesized that tenascin-C expression at atherosclerotic plaque in vivo could be detected by tenascin-C specific aptamers using positron emission tomography (PET). This paper reports the radiosynthesis of a fluorine-18 ( 18 F)-labeled tenascin-C aptamer for the biodistribution and PET imaging of the tenascin-C expression in apolipoprotein E-deficient (ApoE -/- ) mice. The aortas ApoE -/- mice showed significantly increased positive areas of Oil red O staining than control C57BL/6 mice, and tenascin-C expression was detected in foam cells accumulated in the subendothelial lesions of ApoE -/- mice. The ex vivo biodistribution of the 18 F-labeled tenascin-C aptamer showed significantly increased uptake at the aorta of ApoE -/- mice, and ex vivo autoradiography of aorta revealed the high accumulation of the 18 F-labeled tenascin-C aptamer in the atherosclerotic lesions of ApoE -/- mice, which was consistent with the location of the atherosclerotic plaques detected by Oil red O staining. PET imaging of the 18 F-labeled tenascin-C aptamer revealed a significantly higher mean standardized uptake in the aorta of the ApoE -/- mice than the control C57BL/6 mice. These data highlight the potential use of tenascin-C aptamer to diagnose atherosclerotic lesions in vivo., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background/aims: : Risk scoring systems for upper gastrointestinal (UGI) bleeding have not been well validated for tumor bleeding. This study aimed to identify risk factors for mortality in patients with UGI cancer bleeding and to develop a predictive model., Methods: : Consecutive patients with UGI cancers who underwent esophagogastroduodenoscopy for suspected bleeding were retrospectively included. Patient characteristics, endoscopic findings and 30-day mortality were assessed. A predictive model was made based on risk factors for mortality using logistic regression, and the area under the curve (AUC) of this model was calculated. It was then compared with other risk scoring systems., Results: : In a total of 264 patients, 193 had tumor bleeding. Among them, 108 (56.0%), 76 (39.4%), and nine (4.7%) patients received conservative treatment, endoscopic therapy, and non-endoscopic hemostasis, respectively. Rebleeding occurred in 23 (21.3%), 26 (34.2%), and one (11.1%) patient(s), respectively. Our new model is composed of altered mental status, renal failure, rebleeding, age older than 65 years, and low serum albumin (all p<0.05). This model predicted 30-day mortality with an AUC of 0.79 (95% confidence interval, 0.72 to 0.86), which was significantly higher than AUCs of the Glasgow-Blatchford score, Rockall, and AIMS65 score (AUC=0.61, 0.64, and 0.69, respectively, all p<0.05)., Conclusions: : Our new scoring system provides a better prediction of 30-day mortality than existing scoring systems in patients with UGI cancer bleeding. This new scoring system can be used to predict and prepare these patients who are known to have high mortality.

In neuroimaging studies, combining data collected from multiple study sites or scanners is becoming common to increase the reproducibility of scientific discoveries. At the same time, unwanted variations arise by using different scanners (inter-scanner biases), which need to be corrected before downstream analyses to facilitate replicable research and prevent spurious findings. While statistical harmonization methods such as ComBat have become popular in mitigating inter-scanner biases in neuroimaging, recent methodological advances have shown that harmonizing heterogeneous covariances results in higher data quality. In vertex-level cortical thickness data, heterogeneity in spatial autocorrelation is a critical factor that affects covariance heterogeneity. Our work proposes a new statistical harmonization method called SAN (Spatial Autocorrelation Normalization) that preserves homogeneous covariance vertex-level cortical thickness data across different scanners. We use an explicit Gaussian process to characterize scanner-invariant and scanner-specific variations to reconstruct spatially homogeneous data across scanners. SAN is computationally feasible, and it easily allows the integration of existing harmonization methods. We demonstrate the utility of the proposed method using cortical thickness data from the Social Processes Initiative in the Neurobiology of the Schizophrenia(s) (SPINS) study. SAN is publicly available as an R package.

Current clinical therapeutic efficacy for the treatment of osteo- and rheumatoid-arthritis is obviously limited. Although mesenchymal stem cells (MSCs) are considered as a source of promising regenerative therapy, un-modified or genetically engineered MSCs injected in vivo restrict their clinical utility because of the low drug efficacy and unpredicted side effect, respectively. Herein, a strategy to enhance the migration efficacy of MSCs to inflamed joints via an inflammation-mediated education process is demonstrated. To reinforce the limited anti-inflammatory activity of MSCs, gold nanostar loaded with triamcinolone is conjugated to MSC. Furthermore, near-infrared laser-assisted photothermal therapy (PTT) induced by gold nanostar significantly elevates the anti-inflammatory efficacy of the developed drugs, even in advanced stage arthritis model. An immunological regulation mechanism study of PTT is first suggested in this study; the expression of the interleukin 22 receptor, implicated in the pathogenesis of arthritis, is downregulated in T lymphocytes by PTT, and Th17 differentiation from naïve CD4 T cell is inhibited. Collectively, inflammation-targeting MSCs conjugated with triamcinolone-loaded gold nanostar (Edu-MSCs-AuS-TA) promote the repolarization of macrophages and decrease neutrophil recruitment in joints. In addition, Edu-MSCs-AuS-TA significantly alleviate arthritis-associated pain, improve general locomotor activity, and more importantly, induce cartilage regeneration even for severe stages of arthritis model., (© 2023 Wiley-VCH GmbH.)

Carbohydrate-antigens widely existed on glycoproteins and glycosphingolipids of all mammalian cells play a crucial role in self-defense and immunity. Xeno-reactive antibodies included in natural human sera play a protecting role in an acute phase-rejection of xenotransplantation. In this study, we investigated the effect of an alteration of glycosylation-pattern, caused by human sialyltransferases such as hST3Gal II or hST6GalNAc IV, on human serum mediated cytotoxicity in pig kidney PK15 cells. From LDH cytotoxicity assay, cytotoxicity to human serum was significantly increased in hST3Gal II and hST6GalNAc IV-transfected PK15 cells, as compared to the control. In the hST6Gal I-carrying cells, the cytotoxicity to human serum was rather decreased. Moreover, flow cytometry analysis revealed that an alteration of pig glycosylation-pattern by hST3Gal II or hST6GalNAc IV influences on a binding of human IgM or IgG, respectively, in pig kidney cells, regardless of Gal antigen alteration. Finally, we found that hST6GalNAc IV contributed to increase of terminal disialylated tetrasaccharide structure, disialyl T antigen, as evidenced by increase of the MAL II lectin binding capacity in the hST6GalNAc IV-transfected PK15 cells, compared with control. Therefore, our results suggest that carbohydrate antigens, such as disialyl T antigen, newly synthesized by the ST3Gal II- and ST6GalNAc IV are potentially believed to be new xeno-reactive elements., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Luminous efficiency is a pivotal factor for assessing the performance of optoelectronic devices, wherein light loss caused by diverse factors is harvested and converted into the radiative mode. In this study, we demonstrate a nanoscale vacuum photonic crystal layer (nVPCL) for light extraction enhancement. A corrugated semi-transparent electrode incorporating a periodic hollow-structure array was designed through a simulation that utilizes finite-difference time-domain computational analysis. The corrugated profile, stemming from the periodic hollow structure, was fabricated using laser interference lithography, which allows the precise engineering of various geometrical parameters by controlling the process conditions. The semi-transparent electrode consisted of a 15 nm thick Ag film, which acted as the exit mirror and induced microcavity resonance. When applied to a conventional green organic light-emitting diode (OLED) structure, the optimized nVPCL-integrated device demonstrated a 21.5% enhancement in external quantum efficiency compared to the reference device. Further, the full width at half maximum exhibited a 27.5% reduction compared to that of the reference device, demonstrating improved color purity. This study presents a novel approach by applying a hybrid thin film electrode design to optoelectronic devices to enhance optical efficiency and color purity.

Background: The cause of early septic failure after two-stage exchange revision total knee arthroplasty (TKA) for chronic periprosthetic joint infection (PJI) and the factors affecting it are not well known. The purpose of this study was to determine the surgical outcomes and the risk factors for early septic failure after two-stage revision TKA for chronic PJI., Methods: We identified a total of 246 adult patients who met the Musculoskeletal Infection Society (MSIS) diagnostic criteria for chronic PJI at two academic tertiary hospitals from March 2012 to December 2018. Finally, 151 patients who consecutively received two-stage exchange revision TKA for chronic PJI and who had a minimum 3-year follow-up were enrolled and retrospectively reviewed. Successful surgical treatment was evaluated for two-stage revision TKA and risk factors for early septic failure were identified., Results: Early septic failures occurred within 3 years after reimplantation in 48 patients (31.8%). After accounting for potentially confounding variables, we found that male patient [odds ratio (OR): 2.753, 95% confidence interval (CI) 1.099-6.893, p = 0.031], fungus or mycobacterial infection (OR: 5.224, 95% CI 1.481-18.433, p = 0.01), and positive culture at reimplantation (OR: 4.407, 95% CI 1.255-15.480, p = 0.021) were independently associated with early septic failure after two-stage exchange revision TKA., Conclusion: Male patients, fungus or mycobacterial infection, and positive culture at reimplantation were independently associated with an increased risk of early septic failure after two-stage exchange revision TKA despite normal C-reactive protein values prior to reimplantation. Further prospective and high-quality studies are needed to determine the risk factors of two-stage exchange revision TKA for chronic PJI., Level of Evidence: level IV; retrospective comparison; treatment study., (© 2024. The Author(s).)

Hypoxia-induced neuronal death is a major cause of neurodegenerative diseases. Pyroptosis is a type of inflammatory programmed cell death mediated by elevated intracellular levels of reactive oxygen species (ROS). Therefore, we hypothesized that hypoxia-induced ROS may trigger pyroptosis via caspase-dependent gasdermin (GSDM) activation in neuronal cells. To test this, we exposed SH-SY5Y neuronal cells to cobalt chloride (CoCl 2 ) to trigger hypoxia and then evaluated the cellular and molecular responses to hypoxic conditions. Our data revealed that CoCl 2 induced cell growth inhibition and the expression of hypoxia-inducible factor-1α in SH-SY5Y cells. Exposure to CoCl 2 elicits excessive accumulation of cytosolic and mitochondrial ROS in SH-SY5Y cells. CoCl 2 -induced hypoxia not only activated the intrinsic (caspases-3, -7, and -9) apoptotic pathway but also induced caspase-3/GSDME-dependent and NLRP3/caspase-1/GSDMD-mediated pyroptosis in SH-SY5Y cells. Importantly, inhibition of caspase-3 and -1 using selective inhibitors ameliorated pyroptotic cell death and downregulated GSDM protein expression. Additionally, treatment with a ROS scavenger significantly suppressed caspase- and pyroptosis-related proteins in CoCl 2 -treated SH-SY5Y cells. Our findings indicate that hypoxia-mediated ROS production plays an important role in the activation of both apoptosis and pyroptosis in SH-SY5Y neuronal cells, thus providing a potential therapeutic strategy for hypoxia-related neurological diseases.

Purpose: To conduct systematic review and meta-analysis to evaluate effects of neoadjuvant chemotherapy (NAC) on survival and histopathological outcomes of variant histology (VH) of urothelial carcinoma (UC) of bladder., Methods: This systematic review was registered in PROSPERO (CRD42023389115). Literature search was conducted in PubMed/Medline, Embase, and Cochrane Library for studies published up to January 2023. Population, intervention, comparator, outcome, and study design were as follows: bladder cancer patients with VH (population), neoadjuvant chemotherapy (intervention), radical cystectomy only (comparators), oncological survival and pathologic response (outcomes), and retrospective or prospective (study design)., Results: Finally, a total of 17 studies were included in the present study (quantitative analysis, n = 17; qualitative analysis, n = 12). Pooled HR was 0.49 (95% CI: 0.31-0.76; P = .002) for OS. Pooled HR was 0.61 (95% CI: 0.38-0.98; P = .04) for CSS. Pooled HR was 0.44 (95% CI: 0.21-0.93; P = .03) in PFS. Pooled OR was 6.61 (95% CI: 4.50-9.73; P < .00001) in complete pathologic response. Pooled OR was 9.59 (95% CI: 3.56-25.85; P < .00001) in any pathologic response. Evidence quality assessments for each 5 comparisons using the GRADE approach were that Certainty was moderate in 1, low in 1, and very low in 3., Conclusions: Administration of NAC before surgery in bladder cancer patients with VH might confer better survival outcomes and higher pathologic down staging rate than no administration of NAC before surgery., Competing Interests: Disclosure The authors report no conflicts of interest in relation to this work., (Copyright © 2023. Published by Elsevier Inc.)

Mtb (Mycobacterium tuberculosis) is a pathogenic bacterium that causes tuberculosis infection (TB). Mtb-secreted proteins have recently been investigated as virulence factors, as well as therapeutic and vaccine possibilities. The early-secreted antigen target MTB48 is one of these proteins that has been explored as a cocktail antigen in the serodiagnosis of active tuberculosis. However, there exists no information about the function or control of MTB48's inflammatory activity in macrophages at the site of inflammation. As a result, the goal of this research was to figure out what processes are involved in MTB48's function. MTB48 stimulated inflammation in LPS induced macrophages at both the protein and mRNA levels, which was interesting. MTB48 aided LPS induced IB phosphorylation and NF-κB translocation. MTB48 also led to the phosphorylation of MAPK signaling protein. These findings imply that MTB48 can enhance inflammatory activity via NF-κB and MAPK signaling by upregulating COX-2, iNOS, NO and PGE 2 . Many tuberculosis antigens have been tested for the development of rapid serological diagnosis. The results of this study suggest that MTB48 is a very high conservative antigen and is a major factor causing inflammatory reactions, suggesting that it can help control and diagnose tuberculosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Over the past few decades, food scientists have investigated a wide range of emulsifiers to manufacture stable and safe emulsion-based food products. More recently, the development of emulsifiers with multi-functionality, which is the ability to have more than two functions, has been considered as a promising strategy for resolving rancidification and microbial contamination in emulsions. Erythorbyl fatty acid esters (EFEs) synthesized by enzymatic esterification of hydrophilic erythorbic acid and hydrophobic fatty acid have been proposed as multi-functional emulsifiers since they simultaneously exhibit amphiphilic, antioxidative, and antibacterial properties in both aqueous and emulsion systems. This review provides current knowledge about EFEs in terms of enzymatic synthesis and multi-functionality. All processes for synthesizing and identifying EFEs are discussed. Each functionality of EFEs and the proposed mechanism are described with analytical methodologies and experimental details. It would provide valuable insights into the development and application of a multi-functional emulsifier in food emulsion chemistry., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

15 N-Labeled azides are important probes for infrared and magnetic resonance spectroscopy and imaging. They can be synthesized by reaction of primary amines with a 15 N-labeled diazo-transfer reagent. We present the synthesis of 15 N-labeled 2-azido-1,3-dimethylimidazolinium salts 1 as a 15 N-labeled diazo-transfer reagent. Nitrosation of 1,3-dimethylimidazolinium-2-yl hydrazine ( 2 ) with Na 15 NO 2 under acidic conditions gave 1 as a 1:1 mixture of α- and γ- 15 N-labeled azides, α- and γ- 1 , rather than γ- 1 alone. The isotopomeric mixture thus obtained was then subjected to the diazo-transfer reaction with primary amines 3 to afford azides 4 as a 1:1 mixture of β- 15 N-labeled azides β- 4 and unlabeled ones 4' . The efficient and inexpensive synthesis of 1 as a 1:1 mixture of α- and γ- 1 using Na 15 NO 2 instead of Na 15 NNN facilitates their wide use as a 15 N-labeled diazo-transfer reagent for preparing 15 N-labeled azides as molecular probes., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Introduction: The purpose of this study was to evaluate peripheral nerve block (PNB) effectiveness in postoperative pain management and surgical outcomes for displaced femoral-neck fracture in geriatric patients (&gt;70 years) who underwent bipolar hemiarthroplasty (BHA)., Methods: From January 2017 to December 2021, 231 geriatric patients with displaced femoral-neck fracture who consecutively underwent BHA were retrospectively reviewed. Patients were divided into two groups: the patient-controlled analgesia (PCA) group (n = 132) who received only intravenous (IV) PCA for postoperative pain management, and all others who received PNB with IV PCA (PNB+PCA) such as femoral nerve block or fascia iliaca compartment block after surgery (n = 99). Primary outcomes were postoperative visual analog scale (VAS) at rest and during activity at 6, 24, and 48 h postoperatively. Secondary outcomes were postoperative complications, changes in hemoglobin, length of hospital stay, and total morphine usage after surgery., Results: Postoperative resting VAS at 6 h and 48 h was significantly lower in the PNB+PCA group compared with the PCA group (p = 0.075, p = 0.0318, respectively). However, there was no significant difference in either resting VAS at 24 h or active VAS. Complications of pneumonia and delirium until 1 month postoperative were significantly lower in the PNB + PCA group than the PCA group (p = 0.0022, p = 0.0055, respectively)., Conclusion: PNB with IV PCA seems to have a beneficial effect on geriatric femoral-neck patients who underwent BHA with postoperative analgesia for reducing postoperative resting pain and complications, especially pneumonia and delirium., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Introduction: Frailty is a reduced physiological reserve condition associated with postoperative morbidity and mortality. The chart-derived frailty index (CFI) can measure frailty using demographic and laboratory values. We evaluated the association of preoperative CFI with 90-d mortality after burn surgery., Methods: This large retrospective study included burn intensive care unit (ICU) patients between 2012 and 2021 and calculated CFI using the sum of the following five variables: age >70 y, body mass index <18.5 kg/m 2 , hematocrit <35%, albumin <3.4 g/dL, and creatinine >2.0 mg/dL; high CFI was a score of 3-5. Postoperative 90-d mortality rate, major adverse cardiac events (MACE), pneumonia, continuous renal replacement therapy (CRRT) requirement, and prolonged ICU stay (>60 d) were evaluated., Results: Of 1118 patients, 147 (13.1%) had high CFI. High CFI patients had a higher 90-d mortality rate than did low CFI patients (38.8% versus 22.6%, P < 0.001). A high CFI was significantly associated with postoperative 90-d mortality (hazard ratio = 4.124, 95% confidence interval = 2.980-5.707, P < 0.001) in multivariate Cox regression analysis. Kaplan-Meier analysis revealed significantly different postoperative 90-d mortality rates between patients with high and low CFIs (log-rank test, P < 0.001). Incidences of postoperative MACE, pneumonia, the need for CRRT, and prolonged ICU stay were significantly higher in patients with high CFIs than in those with low CFIs., Conclusions: Preoperative high CFI was associated with increased 90-d mortality, MACE, pneumonia, CRRT requirement, and ICU stay following burn surgery., (Copyright © 2023 Elsevier Inc. All rights reserved.)

To investigate the molecular characteristics and antibiotic resistance of Staphylococcus aureus isolates from patients with diarrhea in Korea, 327 S. aureus strains were collected between 2007 and 2022. The presence of staphylococcal enterotoxin (SE) and toxic shock syndrome toxin-1 (TSST-1) genes in S. aureus isolates was determined by PCR. The highest expression of the TSST-1 gene was found in the GIMNO type (43.1% of GIMNO type). GIMNO type (Type I) refers to each staphylococcal enterotoxin (SE) gene gene (initials of genes): G =  seg ; I =  sei ; M =  selm ; N =  seln ; O =  selo . Moreover, Type I isolates showed a significantly higher resistance to most antibiotics. A total of 195 GIMNO-type S. aureus strains were analyzed using multilocus sequence typing (MLST), and 18 unique sequence types (STs) were identified. The most frequent sequence type was ST72 (36.9%), followed by ST5 (22.1%) and ST30 (16.9%). Interestingly, ST72 strains showed a higher prevalence of MRSA than the other STs. In conclusion, our results were the first reported for S. aureus strains in Korea, which significantly expanded S. aureus genotype information for the surveillance of pathogenic S. aureus and may provide important epidemiological information to resolve several infectious diseases caused by S. aureus ., Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01478-9., Competing Interests: Conflict of interestThe authors declare no conflict of interest., (© The Korean Society of Food Science and Technology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Toll-like receptor 3 (TLR3) plays an important role in double-stranded RNA recognition and triggers the innate immune response by acting as a key receptor against viral infections. Intracellular reactive oxygen species (ROS) are involved in TLR3-induced inflammatory responses during viral infections; however, their relationship with mitochondrial ROS (mtROS) remains largely unknown. In this study, we show that polyinosinic-polycytidylic acid (poly(I:C)), a mimic of viral RNA, induced TLR3-mediated nuclear factor-kappa B (NF- κ B) signaling pathway activation and enhanced mtROS generation, leading to inflammatory cytokine production. TLR3-targeted small interfering RNA (siRNA) and Mito-TEMPO inhibited inflammatory cytokine production in poly(I:C)-treated BEAS-2B cells. Poly(I:C) recruited the TLR3 adaptor molecule Toll/IL-1R domain-containing adaptor, inducing IFN (TRIF) and activated NF- κ B signaling. Additionally, TLR3-induced mtROS generation suppression and siRNA-mediated TRIF downregulation attenuated mitochondrial antiviral signaling protein (MAVS) degradation. Our findings provide insights into the TLR3-TRIF signaling pathway and MAVS in viral infections, and suggest TLR3-mtROS as a therapeutic target for the treatment of airway inflammatory and viral infectious diseases.

Purpose: Rheumatoid arthritis (RA) is a highly prevalent form of autoimmune disease that affects nearly 1% of the global population by causing severe cartilage damage and inflammation. Despite its prevalence, previous efforts to prevent the perpetuation of RA have been hampered by therapeutics' cytotoxicity and poor delivery to target cells. The present study exploited drug repositioning and nanotechnology to convert metformin, a widely used antidiabetic agent, into an anti-rheumatoid arthritis drug by designing poly(lactic-co-glycolic acid) (PLGA)-based spheres. Moreover, this study also explored the thermal responsiveness of the IL-22 receptor, a key regulator of Th-17, to incorporate photothermal therapy (PTT) into the nanodrug treatment., Materials and Methods: PLGA nanoparticles were synthesized using the solvent evaporation method, and metformin and indocyanine green (ICG) were encapsulated in PLGA in a dropwise manner. The nanodrug's in vitro anti-inflammatory properties were examined in J744 and FLS via real-time PCR. PTT was induced by an 808 nm near-infrared (NIR) laser, and the anti-RA effects of the nanodrug with PTT were evaluated in DBA/1 collagen-induced arthritis (CIA) mice models. Further evaluation of anti-RA properties was carried out using flow cytometry, immunofluorescence analysis, and immunohistochemical analysis., Results: The encapsulation of metformin into PLGA allowed the nanodrug to enter the target cells via macropinocytosis and clathrin-mediated endocytosis. Metformin-encapsulated PLGA (PLGA-MET) demonstrated promising anti-inflammatory effects by decreasing the expression of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), increasing the expression of anti-inflammatory cytokines (IL-10 and IL-4), and promoting the polarization of M1 to M2 macrophages in J774 cells. The treatment of the nanodrug with PTT exhibited more potent anti-inflammatory effects than free metformin or PLGA-MET in CIA mice models., Conclusion: These results demonstrated that PLGA-encapsulated metformin treatment with PTT can effectively ameliorate inflammation in a spatiotemporal manner., Competing Interests: The authors declare that they have no competing financial interests or personal relationships that may have influenced the work reported in this study., (© 2023 Kim et al.)

Background: A postoperative radiograph in total hip arthroplasty (THA) is usually obtained to evaluate the inclination and anteversion of the acetabular components. However, there is no gold-standard method for calculating the exact inclination and anteversion of the acetabular components on post-THA radiographs. We aimed to measure the actual anteversion of the acetabular component on postoperative radiographs by obtaining correlation data between the virtual and actual acetabular component positioning using virtual three-dimensional (3D) surgery., Methods: A total of 64 hip scans of 32 patients who underwent lower-extremity computed tomography (CT) were retrospectively reviewed. We reconstructed 3D models of the 64 hips using customized computer software (Mimics). Furthermore, to identify the safe zone of acetabular component position in THA, we performed virtual 3D surgery simulations for five anteversion (-10°, 0°, 10°, 20°, and 30°) and five inclination (20°, 30°, 40°, 50°, and 60°) types. We analyzed the acetabular anatomy using 3D models to measure the radiographic, anatomical, and operative anteversion (RA, AA, OA) and inclination (RI, AI, OI) angles. Additionally, we used the Woo-Morrey (WM) method to calculate the anteversion angle in the reconstructed cross-table lateral (CL) radiographs and determined the correlation between these measurements., Results: The safe zone of the acetabular component was visualized on post-THA CL radiographs using the WM method of anteversion measurement based on the different anteversions and inclinations of the acetabular component. The AA, RA, OA, OI, and WM differed significantly between males and females ( p value < 0.05). As the anatomical inclination or anteversion increased, the WM anteversion measurements also increased. The radiographic anteversion measurement best matched the WM method of measurement, followed by anatomical and operative methods., Conclusions: The actual anteversion of the acetabular component after THA can be measured on CL radiographs with the WM method using a 3D virtual program, with good reproducibility.

Brain age prediction is a practical method used to quantify brain aging and detect neurodegenerative diseases such as Alzheimer's disease (AD). However, very few studies have considered brain age prediction as a biomarker for the conversion of cognitively normal (CN) to mild cognitive impairment (MCI). In this study, we developed a novel brain age prediction model using brain volume and cortical thickness features. We calculated an acceleration of brain age (ABA) derived from the suggested model to estimate different diagnostic groups (CN, MCI, and AD) and to classify CN to MCI and MCI to AD conversion groups. We observed a strong association between ABA and the 3 diagnostic groups. Additionally, the classification models for CN to MCI conversion and MCI to AD conversion exhibited acceptable and robust performances, with area under the curve values of 0.66 and 0.76, respectively. We believe that our proposed model provides a reliable estimate of brain age for elderly individuals and can identify those at risk of progressing from CN to MCI. This model has great potential to reveal a diagnosis associated with a change in cognitive decline., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Clusterwise inference is a popular approach in neuroimaging to increase sensitivity, but most existing methods are currently restricted to the General Linear Model (GLM) for testing mean parameters. Statistical methods for testing variance components, which are critical in neuroimaging studies that involve estimation of narrow-sense heritability or test-retest reliability, are underdeveloped due to methodological and computational challenges, which would potentially lead to low power. We propose a fast and powerful test for variance components called CLEAN-V ( CLEAN for testing V ariance components). CLEAN-V models the global spatial dependence structure of imaging data and computes a locally powerful variance component test statistic by data-adaptively pooling neighborhood information. Correction for multiple comparisons is achieved by permutations to control family-wise error rate (FWER). Through analysis of task-fMRI data from the Human Connectome Project across five tasks and comprehensive data-driven simulations, we show that CLEAN-V outperforms existing methods in detecting test-retest reliability and narrow-sense heritability with significantly improved power, with the detected areas aligning with activation maps. The computational efficiency of CLEAN-V also speaks of its practical utility, and it is available as an R package., Competing Interests: Declaration of Competing Interest None.

Enterotoxigenic Escherichia coli (ETEC) is a major cause of illness and death but has no effective therapy. The heat-labile enterotoxin LT is a significant virulence factor produced by ETEC. The heat-labile enterotoxin-B (LT-B) subunit may enter host cells by binding to monosialotetrahexosylganglioside-a (GM1a), a monosialoganglioside found on the plasma membrane surface of animal epithelial cells. This research was conducted to develop conformationally comparable peptides to the carbohydrate epitope of GM1a for the treatment of ETEC. We used the LT-B subunit to select LT-B-binding peptides that structurally resemble GM1a. The ganglioside microarray and docking simulations were used to identify three GM1a ganglioside-binding domain (GBD) peptides based on LT-B recognition. Peptides had an inhibiting effect on the binding of LT-B to GM1a. The binding capacity, functional inhibitory activity, and in vitro effects of the GBD peptides were evaluated using HCT-8 cells, a human intestinal epithelial cell line, to evaluate the feasibility of deploying GBD peptides to combat bacterial infections. KILSYTESMAGKREMVIIT was the most efficient peptide in inhibiting cellular absorption of LT-B in cells. Our findings offer compelling evidence that GM1a GBD-like peptides might act as new therapeutics to inhibit LT-B binding to epithelial cells and avoid the subsequent physiological consequences of LT., (© 2023. Springer Nature Limited.)

Patau syndrome (trisomy 13) is a severe disorder associated with multiple systemic defects. Patau syndrome is commonly associated with ocular abnormalities but rarely associated with congenital glaucoma. To obtain a better surgical view, palatoplasty requires neck extension during surgery. The intraocular pressure (IOP) of patients with Patau syndrome can increase owing to the neck extension position while undergoing palatoplasty, particularly in those with congenital glaucoma. Here, we describe a case with increased IOP measured using a rebound tonometer during palatoplasty in a pediatric patient with Patau syndrome and congenital glaucoma. This case shows that it may be important to reduce the degree of neck extension and shorten the operation time to minimize any increase in the IOP during palatoplasty in pediatric patients with Patau syndrome accompanied by congenital glaucoma.

Study Objective: We evaluated the effect of vitamin C administration on postoperative catheter-related bladder discomfort (CRBD)., Design: A double-blind, randomized controlled trial., Setting: University tertiary hospital., Patients: The participants were patients undergoing transurethral resection of bladder tumor., Intervention: Patients were randomly assigned to either vitamin C (n = 59) or control (n = 59). The vitamin C group received 1 g of vitamin C intravenously and the control group received normal saline, administered after the induction of anesthesia., Measurements: The primary endpoint was moderate or greater CRBD immediately postoperatively. Secondary outcomes included the incidence of moderate or greater CRBD at 1, 2, and 6 h postoperatively. The symptom of CRBD is either a burning sensation with an urge to void or discomfort in the suprapubic area. Moderate CRBD was defined as spontaneously reported by the patient without any behavioral responses, such as attempts to remove the urinary catheter, intense verbal reactions, and flailing limbs. Severe CRBD was spontaneously reported by the patient with behavioral responses. Patient satisfaction scores were also evaluated., Main Results: The group that received vitamin C exhibited a significantly lower incidence of moderate or greater CRBD immediately postoperatively compared with the control group (17 [28.8%] vs. 40 [67.8%], p < 0.001, relative risk [95% confidence interval] = 0.426 [0.274-0.656]). The vitamin C group also showed a significantly lower incidence of moderate or greater CRBD at 1 and 2 h postoperatively compared with the control group (10 [16.9%] vs. 25 [42.4%], p = 0.003; and 5 [8.5%] vs. 16 [27.1%], p = 0.008, respectively). However, there was no significant difference in the incidence of moderate or greater CRBD 6 h postoperatively. Patient satisfaction scores were significantly higher in the vitamin C group than in the control group (5.0 ± 1.3 vs. 4.4 ± 1.4, p = 0.009)., Conclusions: Patients who received vitamin C had decreased CRBD and improved patient satisfaction following transurethral resection of bladder tumor., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Intraocular pressure (IOP) can increase with postural changes, which can cause ocular complications. Neck extension is commonly used during palatoplasty to improve surgical angulation. This study evaluates whether neck extension affects IOP during palatoplasty., Methods: In this prospective observational study, IOP was measured using a rebound tonometer at four specific time points: T1, 10 min after anaesthesia while in the supine position; T2, 5 min after neck extension; T3, at completion of palatoplasty with neck extended; and T4, 5 min after returning to the supine position. The primary outcome was the IOP at T2, and the secondary outcomes were the IOPs at T3 and T4. Haemodynamic and respiratory variables were also measured at each time point., Results: Thirty-seven patients were included. IOP at T2 was significantly higher than at T1 (15.8 ± 3.4 mmHg vs 10.5 ± 2.8 mmHg, P < 0.001), and IOPs at T3 and T4 were also significantly higher than at T1 (T3 vs T1: 18.9 ± 3.6 mmHg vs 10.5 ± 2.8 mmHg, P < 0.001; T4 vs T1: 13.3 ± 3.7 mmHg vs 10.5 ± 2.8 mmHg, P < 0.001). However, no significant differences were observed for the haemodynamic and respiratory variables at any time point., Conclusion: Our findings indicate that the intraoperative neck extension position during palatoplasty significantly increases IOP in paediatric cleft palate patients undergoing a palatoplasty., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Aptamers have great potential for diagnostics and therapeutics due to high specificity to target molecules. However, studies have shown that aptamers are rapidly distributed and excreted from blood circulation due to nuclease degradation. To overcome this issue and to improve in vivo pharmacokinetic properties, inverted deoxythymidine (idT) incorporation at the end of aptamer has been developed. The goal of this study was to evaluate the biological characterization of 3'-idT modified ErbB2 aptamer and compare with that of unmodified aptamer via nuclear imaging. ErbB2-idT aptamer was labeled with radioisotope F-18 by base-pair hybridization using complementary oligonucleotide platform. The hyErbB2-idT aptamer demonstrated specific binding to targets in a ErbB2 expressing SK-BR-3 and KPL4 cells in vitro. Ex vivo biodistribution and in vivo imaging was studied in KPL4 xenograft bearing Balb/c nu/nu mice. 18F-hyErbB2-idT aptamer had significantly higher retention in the tumor (1.36 ± 0.17%ID/g) than unmodified 18F-hyErbB2 (0.98 ± 0.19%ID/g) or scrambled aptamer (0.79 ± 0.26% ID/g) at 1 h post-injection. 18F-hyErbB2-idT aptamer exhibited relatively slow blood clearance and delayed excretion by the renal and hepatobiliary system than 18F-hyErbB2 aptamer. In vivo PET imaging study showed that 18F-hyErbB2-idT aptamer had more stronger PET signals on KPL4 tumor than 18F-hyErbB2 aptamer. The results of this study demonstrate that attachment of idT at 3'-end of aptamer have a substantial influence on biological stability and extended blood circulation led to enhanced tumor uptake of aptamer., Competing Interests: INTEROLOGP Coporation provided support in the form of salaries for JH Lee, but this does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Park et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)