Polyhexamethylene guanidine phosphate induces pyroptosis via reactive oxygen species-regulated mitochondrial dysfunction in bronchial epithelial cells.

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.

CO2-Free Ethylene Oxide Production via Liquid-Phase Epoxidation with Fe2O3/MSM Catalyst.

In this study, we present an approach for ethylene oxide (EO) production that addresses environmental concerns by eliminating greenhouse gas emissions. Our catalyst, Fe2O3/MSM, was synthesized using a hydrothermal method, incorporating Fe2O3 nanoparticles into a well-structured mesoporous silica matrix (MSM). We selected peracetic acid as the oxidant, enabling CO2-free EO production while yielding valuable by-products such as acetic acid, monoethylene glycol, and diethylene glycol. X-ray diffraction (XRD), X- ray photoelectron spectroscopy (XPS), and Brunauer-Emmett-Teller (BET) analyses confirmed the heteroatom structure of the catalysts and porosity, while Transmission electron microscopy (TEM) analysis provided insights into its morphology. Then, the synthesized catalyst was used in the liquid-phase epoxidation of ethylene for EO production. Our systematic experiments involved varying critical parameters such as temperature, ethylene to oxidant ratio, catalyst dosage, and solvent to optimize EO selectivity and ethylene conversion. The results of this study demonstrated an 80.2 % ethylene conversion to EO with an EO selectivity of 87.6 %. The production process yielded valuable by-products without CO2 emissions, highlighting its environmental friendliness.

Nanocrystalline Cellulose-Supported Iron Oxide Composite Materials for High-Performance Lithium-Ion Batteries.

Nanocrystalline cellulose (NCC) can be converted into carbon materials for the fabrication of lithium-ion batteries (LIBs) as well as serve as a substrate for the incorporation of transition metal oxides (TMOs) to restrain the volume expansion, one of the most significant challenges of TMO-based LIBs. To improve the electrochemical performance and enhance the longer cycling stability of LIBs, a nanocrystalline cellulose-supported iron oxide (Fe2O3) composite (denoted as NCC-Fe2O3) is synthesized and utilized as electrodes in LIBs. The obtained NCC-Fe2O3 electrode exhibited stable cycling performance, better capacity, and high-rate capacity, and delivered a specific discharge capacity of 576.70 mAh g-1 at 100 mA g-1 after 1000 cycles. Moreover, the NCC-Fe2O3 electrode was restored and showed an upward trend of capacity after working at high current densities, indicating the fabricated composite is a promising approach to designing next-generation high-energy density lithium-ion batteries.

Chemical Hypoxia Induces Pyroptosis in Neuronal Cells by Caspase-Dependent Gasdermin Activation.

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 (CoCl2) to trigger hypoxia and then evaluated the cellular and molecular responses to hypoxic conditions. Our data revealed that CoCl2 induced cell growth inhibition and the expression of hypoxia-inducible factor-1α in SH-SY5Y cells. Exposure to CoCl2 elicits excessive accumulation of cytosolic and mitochondrial ROS in SH-SY5Y cells. CoCl2-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 CoCl2-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.

Coronary Artery Occlusion with Sharp Blood Pressure Drop during General Anesthesia Induction: A Case Report.

Most anesthetics reduce cardiac functions and lower blood pressure (BP), potentially causing excessive BP reduction in dehydrated patients or those with heart conditions, such as coronary artery disease (CAD). Considering the increased prevalence of cardiovascular disease with age, anesthesiologists must be cautious about BP reduction during general anesthesia in older adults. In the present case, a 76-year-old male patient with undiagnosed CAD in a hypovolemic state experienced a significant drop in systolic BP to the fifties during propofol and sevoflurane anesthesia. Despite the use of vasopressors, excessive hypotension persisted, leading to anesthesia suspension. Subsequent cardiac examinations, including computed tomography heart angio and calcium score, and coronary angiogram, revealed a near total occlusion of the proximal left anterior descending coronary artery (pLAD) and the formation of collateral circulation. After 5 days of hydration and anticoagulation medications and confirmation of normovolemic state, general anesthesia was attempted again and successfully induced; a normal BP was maintained throughout the surgery. Thus, it is important to conduct a thorough cardiac evaluation and maintain normovolemia for general anesthesia in older adults.

Modulation of synaptic transmission through O-GlcNAcylation.

O-GlcNAcylation is a posttranslational modification where N-acetylglucosamine (O-GlcNAc) is attached and detached from a serine/threonine position by two enzymes: O-GlcNAc transferase and O-GlcNAcase. In addition to roles in diabetes and cancer, recent pharmacological and genetic studies have revealed that O-GlcNAcylation is involved in neuronal function, specifically synaptic transmission. Global alteration of the O-GlcNAc level does not affect basal synaptic transmission while the effect on synaptic plasticity is unclear. Although synaptic proteins that are O-GlcNAcylated are gradually being discovered, the mechanism of how O-GlcNAcylated synaptic protein modulate synaptic transmission has only been reported on CREB, synapsin, and GluA2 subunit of AMPAR. Future research enabling the manipulation of O-GlcNAcylation in individual synaptic proteins should reveal hidden aspects of O-GlcNAcylated synaptic proteins as modulators of synaptic transmission.

Real-Time Spatiotemporal Measurement of Extracellular Signaling Molecules Using an Aptamer Switch-Conjugated Hydrogel Matrix.

Cells rely on secreted signaling molecules to coordinate essential biological functions including development, metabolism, and immunity. Unfortunately, such signaling processes remain difficult to measure with sufficient chemical specificity and temporal resolution. To address this need, an aptamer-conjugated hydrogel matrix that enables continuous fluorescent measurement of specific secreted analytes - in two dimensions, in real-time is developed. As a proof of concept, real-time imaging of inter-cellular cyclic adenosine 3',5'-monophosphate (cAMP) signals in Dictyostelium discoideum amoeba cells is performed. A set of aptamer switches that generate a rapid and reversible change in fluorescence in response to cAMP signals is engineered. By combining multiple switches with different dynamic ranges, measure cAMP concentrations spanning three orders of magnitude in a single experiment can be measured. These sensors are embedded within a biocompatible hydrogel on which cells are cultured and their cAMP secretions can be imaged using fluorescent microscopy. Using this aptamer-hydrogel material system, the first direct measurements of oscillatory cAMP signaling that correlate closely with previous indirect measurements are achieved. Using different aptamer switches, this approach can be generalized for measuring other secreted molecules to directly visualize diverse extracellular signaling processes and the biological effects that they trigger in recipient cells.

NULISA: a proteomic liquid biopsy platform with attomolar sensitivity and high multiplexing.

The blood proteome holds great promise for precision medicine but poses substantial challenges due to the low abundance of most plasma proteins and the vast dynamic range of the plasma proteome. Here we address these challenges with NUcleic acid Linked Immuno-Sandwich Assay (NULISA™), which improves the sensitivity of traditional proximity ligation assays by ~10,000-fold to attomolar level, by suppressing assay background via a dual capture and release mechanism built into oligonucleotide-conjugated antibodies. Highly multiplexed quantification of both low- and high-abundance proteins spanning a wide dynamic range is achieved by attenuating signals from abundant targets with unconjugated antibodies and next-generation sequencing of barcoded reporter DNA. A 200-plex NULISA containing 124 cytokines and chemokines and other proteins demonstrates superior sensitivity to a proximity extension assay in detecting biologically important low-abundance biomarkers in patients with autoimmune diseases and COVID-19. Fully automated NULISA makes broad and in-depth proteomic analysis easily accessible for research and diagnostic applications.

NULISA: a novel proteomic liquid biopsy platform with attomolar sensitivity and high multiplexing.

The blood proteome holds great promise for precision medicine but poses substantial challenges due to the low abundance of most plasma proteins and the vast dynamic range across the proteome. We report a novel proteomic technology - NUcleic acid Linked Immuno-Sandwich Assay (NULISA™) - that incorporates a dual capture and release mechanism to suppress the assay background and improves the sensitivity of the proximity ligation assay by over 10,000-fold to the attomolar level. It utilizes pairs of antibodies conjugated to DNA oligonucleotides that enable immunocomplex purification and generate reporter DNA containing target- and sample-specific barcodes for a next-generation sequencing-based, highly multiplexed readout. A 200-plex NULISA targeting 124 cytokines and chemokines and 80 other immune response-related proteins demonstrated superior sensitivity for detecting low-abundance proteins and high concordance with other immunoassays. The ultrahigh sensitivity allowed the detection of previously difficult-to-detect, but biologically important, low-abundance biomarkers in patients with autoimmune diseases and COVID-19. Fully automated NULISA addresses longstanding challenges in proteomic analysis of liquid biopsies and makes broad and in-depth proteomic analysis accessible to the general research community and future diagnostic applications.

How to Solve Anatomical Mismatch in Fixation of Acetabular Fractures Using an Anatomical Quadrilateral Surface Plate.

The anatomical quadrilateral surface buttress plate developed for the quadrilateral surface in an acetabular fracture, a type of fracture difficult to reduce using screws and plates due to its thinness, is a useful implant that makes surgical treatment easier. However, the anatomical structure is different for each patient, and it often does not match the contour of this plate, making detailed bending difficult. Here, we introduce a simple method for controlling the degree of reduction using this plate.

Correction: CO2 free production of ethylene oxide via liquid phase epoxidation of ethylene using niobium oxide incorporated mesoporous silica material as the catalyst.

[This corrects the article DOI: 10.1039/D2RA07240H.].

CO2 free production of ethylene oxide via liquid phase epoxidation of ethylene using niobium oxide incorporated mesoporous silica material as the catalyst.

Ethylene Oxide (EO) is an essential raw material used in various consumer products like different glycol derivatives, ethoxylates, and polymers. We hydrothermally synthesize niobium oxide incorporated with mesoporous silica material (Nb/MSM), an efficient catalyst for CO2 free-ethylene oxide (EO) production via partial oxidation of ethylene. The structural properties of Nb/MSM catalysts were characterized using XRD, TEM, and N2 adsorption-desorption. The catalytic activity of synthesized materials in liquid phase epoxidation (LPE) of ethylene was evaluated in the presence of peracetic acid (PAA) as an oxidant to avoid the production of CO2 and also minimize metal leaching. GC chromatography was used to investigate the successful production of EO, and a peak with a retention time (RT) of 9.01 min served as confirmation. Various reaction parameters viz. temperature, catalyst concentration, ethylene to PAA molar ratio, and solvent effect were investigated in order to optimize the reaction conditions for enhancing the ethylene conversion and selectivity for EO production. By this approach, the challenges of greenhouse gas production and metal leaching were addressed which were associated with previously reported catalysts.

Gadoxetate disodium-enhanced MRI for diagnosis of hepatocellular carcinoma in patients with chronic liver disease: late portal venous phase may improve identification of enhancing capsule.

PURPOSE: To investigate added value of late portal venous phase (LPVP) for identification of enhancing capsule (EC) on gadoxetate disodium-enhanced MRI (GD-MRI) for diagnosing hepatocellular carcinoma (HCC) in patients with chronic liver disease (CLD). METHODS: This retrospective study comprised 116 high-risk patients with 128 pathologically proven HCCs who underwent GD-MRI including arterial phase, conventional portal venous phase (CPVP, 60 s), LPVP (mean, 104.4 ± 6.7 s; range, 90-119 s), and transitional phase (TP, 3 min). Two independent radiologists assessed the presence of major HCC features, including EC on CPVP and/or TP (CPVP/TP) and EC on LPVP. The frequency of EC was compared on GD-MRI between with and without inclusion of LPVP. The radiologists assigned Liver Imaging Reporting and Data System (LI-RADS) v2018 categories before and after identifying EC on LPVP. RESULTS: Of the total 128 HCCs, 74 and 73 revealed EC on CPVP/TP for reviewer 1 and 2, respectively. After inclusion of LPVP, each reviewer identified seven more EC [Reviewer 1, 57.8% (74/128) vs. 63.3% (81/128); Reviewer 2, 57.0% (73/128) vs. 62.5% (80/128); P = 0.016, respectively]. Sensitivities of LR-5 assignment for diagnosing HCCs were not significantly different in GD-MRI with or without LPVP for EC identification [Reviewer 1, 71.9% (92/128) vs. 72.7% (93/128); Reviewer 2, 75.0% (96/128) vs. 75.8% (97/128); P = 1.000, respectively]. CONCLUSION: Including the LPVP in GD-MRI may improve identification of EC of HCC in patients with CLD. However, LI-RADS v2018 using GD-MRI showed comparable sensitivity for diagnosing HCC regardless of applying LPVP for EC.

Mitochondrial Reactive Oxygen Species in TRIF-Dependent Toll-like Receptor 3 Signaling in Bronchial Epithelial Cells against Viral Infection.

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-κB) 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-κB 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.

The Prevalence of Clostridium difficile Colitis and Effect on All-Cause Mortality in Elderly Patients after Hip Fracture Surgery: A Korean Nationwide Cohort Study.

Background: This study aimed to investigate the prevalence of Clostridium difficile colitis (CDC) in elderly patients with hip fractures using a nationwide cohort database and to analyze the effect of CDC on the all-cause mortality rate after hip fracture. Methods: This retrospective nationwide study identified subjects from the Korean National Health Insurance Service-Senior cohort. The subjects of this study were patients who were over 65 years old and underwent surgical treatment for hip fractures from January 1, 2002, to December 31, 2015. The total number of patients included in this study was 10,158. The diagnostic code used in this study was A047 of the International Classification of Diseases, 10th revision for identifying CDC. Procedure codes for C. difficile culture or toxin assay were BY021 and BY022. CDC patients were defined as follows: patients treated with oral vancomycin or metronidazole over 10 days and patients with procedure codes BY021 and BY022 or diagnostic code A047 after hip fracture. Incidence date (index date, time zero) of hip fracture for analyzing risk of all-cause mortality was defined as the date of discharge. A generalized estimating equation model with Poisson distribution and logarithmic link function was used for estimating adjusted risk ratios and 95% confidence intervals to assess the association between CDC and cumulative mortality risk. Results: The prevalence of CDC during the hospitalization period in the elderly patients with hip fractures was 1.43%. Compared to the non-CDC group, the CDC group had a 2.57-fold risk of 30-day mortality after discharge, and a 1.50-fold risk of 1-year mortality after discharge (p < 0.05). Conclusions: The prevalence of CDC after hip fracture surgery in elderly patients was 1.43%. CDC after hip fracture in the elderly patients significantly increased the all-cause mortality rate after discharge.

Artificial intelligence and machine learning on diagnosis and classification of hip fracture: systematic review.

BACKGROUND: In the emergency room, clinicians spend a lot of time and are exposed to mental stress. In addition, fracture classification is important for determining the surgical method and restoring the patient's mobility. Recently, with the help of computers using artificial intelligence (AI) or machine learning (ML), diagnosis and classification of hip fractures can be performed easily and quickly. The purpose of this systematic review is to search for studies that diagnose and classify for hip fracture using AI or ML, organize the results of each study, analyze the usefulness of this technology and its future use value. METHODS: PubMed Central, OVID Medline, Cochrane Collaboration Library, Web of Science, EMBASE, and AHRQ databases were searched to identify relevant studies published up to June 2022 with English language restriction. The following search terms were used [All Fields] AND (", "[MeSH Terms] OR (""[All Fields] AND "bone"[All Fields]) OR "bone fractures"[All Fields] OR "fracture"[All Fields]). The following information was extracted from the included articles: authors, publication year, study period, type of image, type of fracture, number of patient or used images, fracture classification, reference diagnosis of fracture diagnosis and classification, and augments of each studies. In addition, AI name, CNN architecture type, ROI or important region labeling, data input proportion in training/validation/test, and diagnosis accuracy/AUC, classification accuracy/AUC of each studies were also extracted. RESULTS: In 14 finally included studies, the accuracy of diagnosis for hip fracture by AI was 79.3-98%, and the accuracy of fracture diagnosis in AI aided humans was 90.5-97.1. The accuracy of human fracture diagnosis was 77.5-93.5. AUC of fracture diagnosis by AI was 0.905-0.99. The accuracy of fracture classification by AI was 86-98.5 and AUC was 0.873-1.0. The forest plot represented that the mean AI diagnosis accuracy was 0.92, the mean AI diagnosis AUC was 0.969, the mean AI classification accuracy was 0.914, and the mean AI classification AUC was 0.933. Among the included studies, the architecture based on the GoogLeNet architectural model or the DenseNet architectural model was the most common with three each. Among the data input proportions, the study with the lowest training rate was 57%, and the study with the highest training rate was 95%. In 14 studies, 5 studies used Grad-CAM for highlight important regions. CONCLUSION: We expected that our study may be helpful in making judgments about the use of AI in the diagnosis and classification of hip fractures. It is clear that AI is a tool that can help medical staff reduce the time and effort required for hip fracture diagnosis with high accuracy. Further studies are needed to determine what effect this causes in actual clinical situations.

Orthopedic Patients with Mental Disorder: Literature Review on Preoperative and Postoperative Precautions.

Because of the increasing global trend of patients with mental disorders, orthopedic surgeons are more likely to encounter orthopedic patients with mental disorders in clinical settings. Identifying the characteristics of these patients and implementing psychiatric management can affect the clinical outcome of orthopedic treatment. Thus, orthopedic surgeons need to assess the psychiatric medical history of orthopedic patients with mental disorders before surgery and understand the psychological and behavioral patterns of patients with mental disorders. In addition, appropriate psychiatric consultations and evaluations are necessary to prevent worsening of mental disorders before and after surgery.

Analysis of risk factor for nail breakage in patients with mechanical failures after proximal femoral nail antirotation in intertrochanteric fractures.

ABSTRACT: Breakage of the intramedullary nail is a rare complication after proximal femoral nail antirotation (PFNA) in intertrochanteric fracture treatment. The purpose of this study was (1) to investigate the frequency of nail breakage among the patients who were treated for mechanical failure after PFNA for intertrochanteric/pertrochanteric fracture, and (2) to determine the risk factors for nail breakage in PFNA treatment of intertrochanteric fracture.To identify mechanical failure after internal fixation using PFNA, we retrospectively reviewed the data of 35 patients (35 hips) who required reoperation after PFNA with a helical blade for intertrochanteric/pertrochanteric fracture between June 2005 and June 2018.We evaluated the frequency of breakage of PFNA and compared the demographic and radiologic parameters between the breakage and control (non-breakage) groups. We also compared the lever arm for the load of stress from the fulcrum according to the centrum-collum-diaphyseal (CCD) angle of blade by using reverse design technique.Among the 25 patients with mechanical failure after PFNA except 10 patients with peri-implant infection and osteonecrosis, 7 (28.0%) showed breakage of PFNA at average of 8 months (range, 5-13 months) after index surgery. A larger horizontal offset (the horizontal distance from the lateral surface of the IM nail and the medial tip of helical blade) was associated with an increased risk of nail breakage. A CCD angle of 130° has a shorter lever arm for the load of stress from the fulcrum, meaning a higher stress for nail breakage, although there was no association between CCD angle and breakage of the nail.Our study suggested that higher horizontal offset and a higher CCD angle can increase the risk of breakage of the PFNA nail at the aperture for the helical blade.

Differential Diagnosis of Thick Myocardium according to Histologic Features Revealed by Multiparametric Cardiac Magnetic Resonance Imaging.

Left ventricular (LV) wall thickening, or LV hypertrophy (LVH), is common and occurs in diverse conditions including hypertrophic cardiomyopathy (HCM), hypertensive heart disease, aortic valve stenosis, lysosomal storage disorders, cardiac amyloidosis, mitochondrial cardiomyopathy, sarcoidosis and athlete's heart. Cardiac magnetic resonance (CMR) imaging provides various tissue contrasts and characteristics that reflect histological changes in the myocardium, such as cellular hypertrophy, cardiomyocyte disarray, interstitial fibrosis, extracellular accumulation of insoluble proteins, intracellular accumulation of fat, and intracellular vacuolar changes. Therefore, CMR imaging may be beneficial in establishing a differential diagnosis of LVH. Although various diseases share LV wall thickening as a common feature, the histologic changes that underscore each disease are distinct. This review focuses on CMR multiparametric myocardial analysis, which may provide clues for the differentiation of thickened myocardium based on the histologic features of HCM and its phenocopies.