Insights into ACO genes across Rosaceae: evolution, expression, and regulatory networks in fruit development.

BACKGROUND: ACO (1-aminocyclopropane-1-carboxylic acid) serves as a pivotal enzyme within the plant ethylene synthesis pathway, exerting influence over critical facets of plant biology such as flowering, fruit ripening, and seed development. OBJECTIVE: This study aims to identify ACO genes from representative Rosaceae genomes, reconstruct their phylogenetic relationships by integrating synteny information, and investigate their expression patterns and networks during fruit development. METHODS: we utilize a specialized Hidden Markov Model (HMM), crafted on the sequence attributes of ACO gene-encoded proteins, to systematically identify and analyze ACO gene family members across 12 representative species within the Rosaceae botanical family. Through transcriptome analysis, we delineate the expression patterns of ACO genes in six distinct Rosaceae fruits. RESULTS: Our investigation reveals the presence of 62 ACO genes distributed among the surveyed Rosaceae species, characterized by hydrophilic proteins predominantly expressed within the cytoplasm. Phylogenetic analysis categorizes these ACO genes into three discernible classes, namely Class I, Class II, and Class III. Further scrutiny via collinearity assessment indicates a lack of collinearity relationships among these classes, highlighting variations in conserved motifs and promoter types within each class. Transcriptome analysis unveils significant disparities in both expression levels and trends of ACO genes in fruits exhibiting respiratory bursts compared to those that do not. Employing Weighted Gene Co-Expression Network Analysis (WGCNA), we discern that the co-expression correlation of ACO genes within loquat fruit notably differs from that observed in apples. Our findings, derived from Gene Ontology (GO) enrichment results, signify the involvement of ACO genes and their co-expressed counterparts in biological processes linked to terpenoid metabolism and carbohydrate synthesis in loquat. Moreover, our exploration of gene regulatory networks (GRN) highlights the potential pivotal role of the GNAT transcription factor (Ejapchr1G00010380) in governing the overexpression of the ACO gene (Ejapchr10G00001110) within loquat fruits. CONCLUSION: The constructed HMM of ACO proteins offers a precise and systematic method for identifying plant ACO proteins, facilitating phylogenetic reconstruction. ACO genes from representative Rosaceae fruits exhibit diverse expression and regulative patterns, warranting further function characterizations.

Lactic Acidosis Induced by Excessive Use of a Long-Acting Beta Agonist.

Lactic acidosis is associated with poorer clinical outcomes in critical care. The causes of this condition are divided into two groups: type A (tissue hypoxia) and type B (metabolic abnormalities). Of these, drug-induced lactic acidosis is categorized as type B and is often overlooked due to clinicians' poor awareness. We herein report a rare case of drug-induced lactic acidosis due to excessive use of a long-acting beta agonist (LABA) in a patient with asthma-chronic obstructive pulmonary disease overlap exacerbation. He initially presented with markedly elevated lactate and metabolic acidosis with unknown etiology. A detailed medical interview revealed that he had inhaled a large amount of LABA on the day of admission, which led to our final diagnosis. The patient's respiratory status and lactate levels gradually improved with the appropriate use of inhalation therapy. While there have been many recent reports of lactic acidosis caused by short-acting beta agonists, our case suggests that excessive use of LABAs may also lead to lactic acidosis. Clinicians should be aware of the possibility that LABAs can cause lactic acidosis because poor awareness of the condition may lead to inappropriate patient care.

Medicare Payments and ACOs for Dementia Patients Across Race and Social Vulnerability.

OBJECTIVES: This study investigated variations in Medicare payments for Alzheimer's disease and related dementia (ADRD) by race, ethnicity, and neighborhood social vulnerability, together with cost variations by beneficiaries' enrollment in Accountable Care Organizations (ACOs). METHODS: We used merged datasets of longitudinal Medicare Beneficiary Summary File (2016-2020), the Social Vulnerability Index (SVI), and the Medicare Shared Savings Program (MSSP) ACO to measure beneficiary-level ACO enrollment at the diagnosis year of ADRD. We analyzed Medicare payments for patients newly diagnosed with ADRD for the year preceding the diagnosis and for the subsequent 3 years. The dataset included 742,175 Medicare fee-for-service (FFS) beneficiaries aged 65 and older with a new diagnosis of ADRD in 2017 who remained in the Medicare FFS plan from 2016 to 2020. RESULTS: Among those newly diagnosed, Black and Hispanic patients encountered higher total costs compared to White patients, and ADRD patients living in the most vulnerable areas experienced the highest total costs compared to patients living in other regions. These cost differences persisted over 3 years postdiagnosis. Patients enrolled in ACOs incurred lower costs across all racial and ethnic groups and SVI areas. For ADRD patients living in the areas with the highest vulnerability, the cost differences by ACO enrollment of the total Medicare costs ranged from $4,403.1 to $6,922.7, and beneficiaries' savings ranged from $114.5 to $726.6 over three years post-ADRD diagnosis by patient's race and ethnicity. CONCLUSIONS: Black and Hispanic ADRD patients and ADRD patients living in areas with higher social vulnerability would gain more from ACO enrollment compared to their counterparts.

Movement of ACC oxidase 3 mRNA from seeds to flesh promotes fruit ripening in apple.

Xenia, the phenomenon in which the pollen genotype directly affects the phenotypic characteristics of maternal tissues (i.e., fruit ripening), has applications in crop production and breeding. However, the underlying molecular mechanism has yet to be elucidated. Here, we investigated whether mobile mRNAs from the pollen affect the ripening and quality-related characteristics of the fruit using cross-pollination between distinct Malus domestica (apple) cultivars. We demonstrated that hundreds of mobile mRNAs originating from the seeds are delivered to the fruit. We found that the movement of one of these mRNAs, ACC oxidase 3 (MdACO3), is coordinated with fruit ripening. Salicylic acid treatment, which can cause plasmodesmal closure, blocks MdACO3 movement, indicating that MdACO3 transcripts may move through the plasmodesmata. To assess the role of mobile MdACO3 transcripts in apple fruit, we created MdACO3-GFP-expressing apple seeds using MdACO3-GFP-overexpressing pollen for pollination and showed that MdACO3 transcripts in the transgenic seeds move to the flesh, where they promote fruit ripening. Furthermore, we demonstrated that MdACO3 can be transported from the seeds to fruit in the fleshy-fruited species tomato and strawberry. These results underscore the potential of mobile mRNAs from seeds to influence fruit characteristics, providing an explanation for the xenia phenomenon. Notably, our findings highlight the feasibility of leveraging diverse pollen genomic resources, without resorting to genome editing, to improve fruit quality.

Optimization of Phloretin-loaded Nanospanlastics for Targeting of FAS/SREBP1c/AMPK/ OB-Rb Signaling Pathway in HFD-induced Obesity.

OBJECTIVES: Obese patients are at increased risk for CVD, which is the main cause of premature death and has been a major cause of disability and ill health in recent years. PTN, a natural dihydrochalcone flavonoid, has a variety of pharmacological characteristics. This article aimed to prepare PTN-NSLs to evaluate their anti-obesity activity. METHODS: Morphology, Particle size, zeta potential, UV-vis, entrapment efficiency, FT-IR spectra, and an in vitro release study of PTN-NSLs were described. PTN-NSLs were also tested for their anti-obesity properties in obese rats. The LD50 of PTN-NSLs was calculated, as was the 1/20 LD50 prepared for the treatment of obese rats. Also, the level of glycemic, oxidative stress and inflammatory biomarkers were estimated in the obese rat's model. RESULTS: The synthesized PTN-NSLs were uniform, spherically shaped, and well dispersed with no aggregation noted, with a size range of 114.06 ± 8.35 nm. The measured zeta potential value of PTN-NSLs was -32.50.8 mv. Also, the UV spectra of PTN and PTN-NSLs have strong absorption at 225 and 285 nm. Also, the LD50 of PTN-NSLs was found to be 2750 mg/kg.b.w. Moreover, administrating obese rats with PTN-NSLs resulted in improved glycemic features as well as GSH, SOD, GPx, GR, IL10, TBARs, and IL-6 levels, as well as attenuated FAS, SREBP1c, AMPK, ACO, CPT1, and OB-Rb gene expression. CONCLUSIONS: Administration of PTN-NSLs significantly attenuated the levels of glycemic, oxidative stress, and inflammatory biomarkers. The biochemical and PCR findings are aided by histological investigations. Also, the present findings imply that PTN-NSLs might be a promising pharmacological tool for the treatment of obesity-related diseases.

Optimal channel dynamic selection for Constructing lightweight Data EEG-based emotion recognition.

At present, most methods to improve the accuracy of emotion recognition based on electroencephalogram (EEG) are achieved by means of increasing the number of channels and feature types. This is to use the big data to train the classification model but it also increases the code complexity and consumes a large amount of computer time. We propose a method of Ant Colony Optimization with Convolutional Neural Networks and Long Short-Term Memory (ACO-CNN-LSTM) which can attain the dynamic optimal channels for lightweight data. First, transform the time-domain EEG signal to the frequency domain by Fast Fourier Transform (FFT), and the Differential Entropy (DE) of the three frequency bands (α, ß and γ) are extracted as the feature data; Then, based on the DE feature dataset, ACO is employed to plan the path where the electrodes are located in the brain map. The classification accuracy of CNN-LSTM is used as the objective function for path determination, and the electrodes on the optimal path are used as the optimal channels; Next, the initial learning rate and batchsize parameters are exactly matched the data characteristics, which can obtain the best initial learning rate and batchsize; Finally, the SJTU Emotion EEG Dataset (SEED) dataset is used for emotion recognition based on the ACO-CNN-LSTM. From the experimental results, it can be seen that: the average accuracy of three-classification (positive, neutral, negative) can achieve 96.59 %, which is based on the lightweight data by means of ACO-CNN-LSTM proposed in the paper. Meanwhile, the computer time consumed is reduced. The computational efficiency is increased by 15.85 % compared with the traditional CNN-LSTM method. The accuracy can achieve more than 90 % when the data volume is reduced to 50 %. In summary, the proposed method of ACO-CNN-LSTM in the paper can get higher efficiency and accuracy.

Multiple-Junction-Based Traffic-Aware Routing Protocol Using ACO Algorithm in Urban Vehicular Networks.

The burgeoning interest in intelligent transportation systems (ITS) and the widespread adoption of in-vehicle amenities like infotainment have spurred a heightened fascination with vehicular ad-hoc networks (VANETs). Multi-hop routing protocols are pivotal in actualizing these in-vehicle services, such as infotainment, wirelessly. This study presents a novel protocol called multiple junction-based traffic-aware routing (MJTAR) for VANET vehicles operating in urban environments. MJTAR represents an advancement over the improved greedy traffic-aware routing (GyTAR) protocol. MJTAR introduces a distributed mechanism capable of recognizing vehicle traffic and computing curve metric distances based on two-hop junctions. Additionally, it employs a technique to dynamically select the most optimal multiple junctions between source and destination using the ant colony optimization (ACO) algorithm. We implemented the proposed protocol using the network simulator 3 (NS-3) and simulation of urban mobility (SUMO) simulators and conducted performance evaluations by comparing it with GSR and GyTAR. Our evaluation demonstrates that the proposed protocol surpasses GSR and GyTAR by over 20% in terms of packet delivery ratio, with the end-to-end delay reduced to less than 1.3 s on average.

Ethylene induced AcNAC3 and AcNAC4 take part in ethylene synthesis through mediating AcACO1 during kiwifruit (Actinidia chinensis) ripening.

BACKGROUND: Ethylene plays a vital role in the ripening process of kiwifruit. A terrific amount of transcription factors (TFs) have been shown to regulate ethylene synthesis in various fruits. RESULTS: In this research, two new NAC TFs, named AcNAC3 and AcNAC4, were isolated from kiwifruit, which belonged to NAM subfamily. Bioinformatics analysis showed that both AcNAC3 and AcNAC4 were hydrophilic proteins with similar three-dimensional structures. The expression levels of AcNAC3, AcNAC4 and AcACO1 increased during kiwifruit ripening, as well as were induced by ethylene and repressed by 1-methylcyclopropene (1-MCP). Correlation analysis exhibited that ethylene production was positively correlated with the expression levels of AcNAC3, AcNAC4 and AcACO1. Moreover, both AcNAC3 and AcNAC4 acted as transcriptional activators and could bind to and activate AcACO1 promoter. CONCLUSION: All results unveiled that the ethylene-induced AcNAC3 and AcNAC4 were transcriptional activators, and might participate in kiwifruit ripening and ethylene biosynthesis through activating AcACO1, providing a new insight of ethylene synthetic regulation during kiwifruit ripening. © 2024 Society of Chemical Industry.

Early-life house dust mite aeroallergen exposure augments cigarette smoke-induced myeloid inflammation and emphysema in mice.

BACKGROUND: Longitudinal studies have identified childhood asthma as a risk factor for obstructive pulmonary disease (COPD) and asthma-COPD overlap (ACO) where persistent airflow limitation can develop more aggressively. However, a causal link between childhood asthma and COPD/ACO remains to be established. Our study aimed to model the natural history of childhood asthma and COPD and to investigate the cellular/molecular mechanisms that drive disease progression. METHODS: Allergic airways disease was established in three-week-old young C57BL/6 mice using house dust mite (HDM) extract. Mice were subsequently exposed to cigarette smoke (CS) and HDM for 8 weeks. Airspace enlargement (emphysema) was measured by the mean linear intercept method. Flow cytometry was utilised to phenotype lung immune cells. Bulk RNA-sequencing was performed on lung tissue. Volatile organic compounds (VOCs) in bronchoalveolar lavage-fluid were analysed to screen for disease-specific biomarkers. RESULTS: Chronic CS exposure induced emphysema that was significantly augmented by HDM challenge. Increased emphysematous changes were associated with more abundant immune cell lung infiltration consisting of neutrophils, interstitial macrophages, eosinophils and lymphocytes. Transcriptomic analyses identified a gene signature where disease-specific changes induced by HDM or CS alone were conserved in the HDM-CS group, and further revealed an enrichment of Mmp12, Il33 and Il13, and gene expression consistent with greater expansion of alternatively activated macrophages. VOC analysis also identified four compounds increased by CS exposure that were paradoxically reduced in the HDM-CS group. CONCLUSIONS: Early-life allergic airways disease worsened emphysematous lung pathology in CS-exposed mice and markedly alters the lung transcriptome.

Anaplerotic Therapy Using Triheptanoin in Two Brothers Suffering from Aconitase 2 Deficiency.

Citric acid cycle deficiencies are extremely rare due to their central role in energy metabolism. The ACO2 gene encodes the mitochondrial isoform of aconitase (aconitase 2), the second enzyme of the citric acid cycle. Approximately 100 patients with aconitase 2 deficiency have been reported with a variety of symptoms, including intellectual disability, hypotonia, optic nerve atrophy, cortical atrophy, cerebellar atrophy, and seizures. In this study, a homozygous deletion in the ACO2 gene in two brothers with reduced aconitase 2 activity in fibroblasts has been described with symptoms including truncal hypotonia, optic atrophy, hyperopia, astigmatism, and cerebellar atrophy. In an in vivo trial, triheptanoin was used to bypass the defective aconitase 2 and fill up the citric acid cycle. Motor abilities in both patients improved.

Optimizing Driving Parameters of the Jumbo Drill Efficiently with XGBoost-DRWIACO Framework: Applied to Increase the Feed Speed.

The jumbo drill is a commonly used driving equipment in tunnel engineering. One of the key decision-making issues for reducing tunnel construction costs is to optimize the main driving parameters to increase the feed speed of the jumbo drill. The optimization of the driving parameters is supposed to meet the requirements of high reliability and efficiency due to the high risk and complex working conditions in tunnel engineering. The flaws of the existing optimization algorithms for driving parameter optimization lie in the low accuracy of the evaluation functions under complex working conditions and the low efficiency of the algorithms. To address the above problems, a driving parameter optimization method based on the XGBoost-DRWIACO framework with high accuracy and efficiency is proposed. A data-driven prediction model for feed speed based on XGBoost is established as the evaluation function, which has high accuracy under complex working conditions and ensures the high reliability of the optimized results. Meanwhile, an improved ant colony algorithm based on dimension reduction while iterating strategy (DRWIACO) is proposed. DRWIACO is supposed to improve efficiency by resolving inefficient iterations of the ant colony algorithm (ACO), which is manifested as falling into local optimum, converging slowly and converging with a slight fluctuation in a certain dimension. Experimental results show that the error by the proposed framework is less than 10%, and the efficiency is increased by over 30% compared with the comparison methods, which meets the requirements of high reliability and efficiency for tunnel construction. More importantly, the construction cost is reduced by 19% compared with the actual feed speed, which improves the economic benefits.

PPARγ attenuates cellular senescence of alveolar macrophages in asthma-COPD overlap.

BACKGROUND: Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) represents a complex condition characterized by shared clinical and pathophysiological features of asthma and COPD in older individuals. However, the pathophysiology of ACO remains unexplored. We aimed to identify the major inflammatory cells in ACO, examine senescence within these cells, and elucidate the genes responsible for regulating senescence. METHODS: Bioinformatic analyses were performed to investigate major cell types and cellular senescence signatures in a public single-cell RNA sequencing (scRNA-Seq) dataset derived from the lung tissues of patients with ACO. Similar analyses were carried out in an independent cohort study Immune Mechanisms Severe Asthma (IMSA), which included bulk RNA-Seq and CyTOF data from bronchoalveolar lavage fluid (BALF) samples. RESULTS: The analysis of the scRNA-Seq data revealed that monocytes/ macrophages were the predominant cell type in the lung tissues of ACO patients, constituting more than 50% of the cells analyzed. Lung monocytes/macrophages from patients with ACO exhibited a lower prevalence of senescence as defined by lower enrichment scores of SenMayo and expression levels of cellular senescence markers. Intriguingly, analysis of the IMSA dataset showed similar results in patients with severe asthma. They also exhibited a lower prevalence of senescence, particularly in airway CD206 + macrophages, along with increased cytokine expression (e.g., IL-4, IL-13, and IL-22). Further exploration identified alveolar macrophages as a major subtype of monocytes/macrophages driving cellular senescence in ACO. Differentially expressed genes related to oxidation-reduction, cytokines, and growth factors were implicated in regulating senescence in alveolar macrophages. PPARγ (Peroxisome Proliferator-Activated Receptor Gamma) emerged as one of the predominant regulators modulating the senescent signature of alveolar macrophages in ACO. CONCLUSION: The findings suggest that senescence in macrophages, particularly alveolar macrophages, plays a crucial role in the pathophysiology of ACO. Furthermore, PPARγ may represent a potential therapeutic target for interventions aimed at modulating senescence-associated processes in ACO.Key words ACO, Asthma, COPD, Macrophages, Senescence, PPARγ.

Neopterin in patients with COPD, asthma, and ACO: association with endothelial and lung functions.

BACKGROUND AND OBJECTIVE: Endothelial dysfunction has been widely recognized in chronic airway diseases, including chronic obstructive pulmonary disease (COPD) and asthma; however, it remains unclear in asthma-COPD overlap (ACO). Neopterin (NP), a metabolite of guanosine triphosphate, is a novel biomarker for identifying the increased risk of adverse cardiovascular events. This study aims to investigate the association of NP with endothelial dysfunction and impaired lung function in COPD, asthma, and ACO patients. METHODS: A total of 77 subjects were prospectively recruited. All the participants underwent lung function test, endothelial function evaluation, including pulse wave velocity (PWV) and flow-mediated dilation (FMD), and blood sample detection. Moreover, the effect of NP on endothelial cells (ECs) in anoxic environments was assessed in vitro. RESULTS: Endothelial function was significantly decreased in the COPD and ACO patients compared with that in the healthy controls (P < 0.05). Forced expiratory volume in 1 s (FEV1) was negatively correlated with PWV and positively correlated with FMD (P < 0.05). NP was significantly increased in patients with chronic respiratory diseases compared with that in the control group, with COPD being the highest, followed by asthma, and ACO as the last (P < 0.05). The plasma level of NP exhibited negative correlations with FEV1 and positive correlations with PWV (P < 0.05). In vitro, a high level of NP increased the reactive oxygen species (ROS) and decreased the mitochondrial membrane potential (ΔΨm) of ECs dose-dependently in a hypoxic environment (P < 0.05). CONCLUSION: NP was related to disease severity of chronic airway diseases and involved in the pathogenesis of endothelial dysfunction. A high NP level may contribute to endothelial dysfunction by increasing the oxidative stress of ECs dose-dependently in a hypoxic environment. Our findings may provide a novel evaluation and therapeutic target for endothelial dysfunction related to chronic airway diseases.

Functional mechanism study of the allelochemical myrigalone A identifies a group of ultrapotent inhibitors of ethylene biosynthesis in plants.

Allelochemicals represent a class of natural products released by plants as root, leaf, and fruit exudates that interfere with the growth and survival of neighboring plants. Understanding how allelochemicals function to regulate plant responses may provide valuable new approaches to better control plant function. One such allelochemical, Myrigalone A (MyA) produced by Myrica gale, inhibits seed germination and seedling growth through an unknown mechanism. Here, we investigate MyA using the tractable model Dictyostelium discoideum and reveal that its activity depends on the conserved homolog of the plant ethylene synthesis protein 1-aminocyclopropane-1-carboxylic acid oxidase (ACO). Furthermore, in silico modeling predicts the direct binding of MyA to ACO within the catalytic pocket. In D. discoideum, ablation of ACO mimics the MyA-dependent developmental delay, which is partially restored by exogenous ethylene, and MyA reduces ethylene production. In Arabidopsis thaliana, MyA treatment delays seed germination, and this effect is rescued by exogenous ethylene. It also mimics the effect of established ACO inhibitors on root and hypocotyl extension, blocks ethylene-dependent root hair production, and reduces ethylene production. Finally, in silico binding analyses identify a range of highly potent ethylene inhibitors that block ethylene-dependent response and reduce ethylene production in Arabidopsis. Thus, we demonstrate a molecular mechanism by which the allelochemical MyA reduces ethylene biosynthesis and identify a range of ultrapotent inhibitors of ethylene-regulated responses.

PPARγ Attenuates Cellular Senescence of Alveolar Macrophages in Asthma- COPD Overlap.

Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) represents a complex condition characterized by shared clinical and pathophysiological features of asthma and COPD in older individuals. However, the pathophysiology of ACO remains unexplored. We aimed to identify the major inflammatory cells in ACO, examine senescence within these cells, and elucidate the genes responsible for regulating senescence. Bioinformatic analyses were performed to investigate major cell types and cellular senescence signatures in a public single-cell RNA sequencing (scRNA-Seq) dataset derived from the lung tissues of patients with ACO. Similar analyses were carried out in an independent cohort study Immune Mechanisms Severe Asthma (IMSA), which included bulk RNA-Seq and CyTOF data from bronchoalveolar lavage fluid (BALF) samples. The analysis of the scRNA-Seq data revealed that monocytes/ macrophages were the predominant cell type in the lung tissues of ACO patients, constituting more than 50% of the cells analyzed. Lung monocytes/macrophages from patients with ACO exhibited a lower prevalence of senescence as defined by lower enrichment scores of SenMayo and expression levels of cellular senescence markers. Intriguingly, analysis of the IMSA dataset showed similar results in patients with severe asthma. They also exhibited a lower prevalence of senescence, particularly in airway CD206 + macrophages, along with increased cytokine expression (e.g., IL-4, IL-13, and IL-22). Further exploration identified alveolar macrophages as a major subtype of monocytes/macrophages driving cellular senescence in ACO. Differentially expressed genes related to oxidation-reduction, cytokines, and growth factors were implicated in regulating senescence in alveolar macrophages. PPARγ (Peroxisome Proliferator-Activated Receptor Gamma) emerged as one of the predominant regulators modulating the senescent signature of alveolar macrophages in ACO. Collectively, the findings suggest that senescence in macrophages, particularly alveolar macrophages, plays a crucial role in the pathophysiology of ACO. Furthermore, PPARγ may represent a potential therapeutic target for interventions aimed at modulating senescence-associated processes in ACO.

Intrathecal administration of a novel siRNA modality extends survival and improves motor function in the SOD1G93A ALS mouse model.

Antisense oligonucleotides (ASOs) were the first modality to pioneer targeted gene knockdown in the treatment of amyotrophic lateral sclerosis (ALS) caused by mutant superoxide dismutase 1 (SOD1). RNA interference (RNAi) is another mechanism of gene silencing in which short interfering RNAs (siRNAs) effectively degrade complementary transcripts. However, delivery to extrahepatic tissues like the CNS has been a bottleneck in the clinical development of RNAi. Herein, we identify potent siRNA duplexes for the knockdown of human SOD1 in which medicinal chemistry and conjugation to an accessory oligonucleotide (ACO) enable activity in CNS tissues. Local delivery via intracerebroventricular or intrathecal injection into SOD1G93A mice delayed disease progression and extended animal survival with superior efficacy compared with an ASO resembling tofersen in sequence and chemistry. Treatment also prevented disease-related declines in motor function, including improvements in animal mobility, muscle strength, and coordination. The ACO itself does not target any specific complementary nucleic acid sequence; rather, it imparts benefits conducive to bioavailability and delivery through its chemistry. The complete conjugate (i.e., siRNA-ACO) represents a novel modality for delivery of duplex RNA (e.g., siRNA) to the CNS that is currently being tested in the clinic for treatment of ALS.

A new path planning strategy integrating improved ACO and DWA algorithms for mobile robots in dynamic environments.

This article is concerned with the path planning of mobile robots in dynamic environments. A new path planning strategy is proposed by integrating the improved ant colony optimization (ACO) and dynamic window approach (DWA) algorithms. An improved ACO is developed to produce a globally optimal path for mobile robots in static environments. Through improvements in the initialization of pheromones, heuristic function, and updating of pheromones, the improved ACO can lead to a shorter path with fewer turning points in fewer iterations. Based on the globally optimal path, a modified DWA is presented for the path planning of mobile robots in dynamic environments. By deleting the redundant nodes, optimizing the initial orientation, and improving the evaluation function, the modified DWA can result in a more efficient path for mobile robots to avoid moving obstacles. Some simulations are conducted in different environments, which confirm the effectiveness and superiority of the proposed path planning algorithms.

The value of bronchodilator response in FEV1 and FeNO for differentiating between chronic respiratory diseases: an observational study.

BACKGROUND: There is no uniform standard for a strongly positive bronchodilation test (BDT) result. In addition, the role of bronchodilator response in differentiating between asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO) in patients with a positive BDT result is unclear. We explored a simplified standard of a strongly positive BDT result and whether bronchodilator response combined with fractional exhaled nitric oxide (FeNO) can differentiate between asthma, COPD, and ACO in patients with a positive BDT result. METHODS: Three standards of a strongly positive BDT result, which were, respectively, defined as post-bronchodilator forced expiratory volume in 1-s responses (ΔFEV1) increasing by at least 400 mL + 15% (standard I), 400 mL (standard II), or 15% (standard III), were analyzed in asthma, COPD, and ACO patients with a positive BDT result. Receiver operating characteristic curves were used to determine the optimal values of ΔFEV1 and FeNO. Finally, the accuracy of prediction was verified by a validation study. RESULTS: The rates of a strongly positive BDT result and the characteristics between standards I and II were consistent; however, those for standard III was different. ΔFEV1 ≥ 345 mL could predict ACO diagnosis in COPD patients with a positive BDT result (area under the curve [AUC]: 0.881; 95% confidence interval [CI] 0.83-0.94), with a sensitivity and specificity of 90.0% and 91.2%, respectively, in the validation study. When ΔFEV1 was < 315 mL combined with FeNO < 28.5 parts per billion, patients with a positive BDT result were more likely to have pure COPD (AUC: 0.774; 95% CI 0.72-0.83). CONCLUSION: The simplified standard II can replace standard I. ΔFEV1 and FeNO are helpful in differentiating between asthma, COPD, and ACO in patients with a positive BDT result.

Exploring the association between asthma and chronic comorbidities: impact on clinical outcomes.

Asthma remains a significant global health challenge. While both the incidence and mortality rates have shown a decline, older individuals with asthma exhibit not just more severe symptoms but also demonstrate an elevated mortality rate. This phenomenon could be attributed to the presence of chronic comorbidities that exert an influence on clinical outcomes among adult patients with asthma. This review aims to present various aspects of asthma comprehensively, including the prevalence, incidence, mortality rates, and causes of death in adult patients with asthma. Additionally, this review delves into the impact of chronic comorbidities that contribute to the morbidity and mortality of patients with asthma on a global scale, encompassing conditions such as chronic kidney disease, diabetes mellitus, lung cancer, obesity, and cardiovascular disease, concerning asthma. Furthermore, the manuscript reviews the distinctions between asthma and asthma chronic obstructive pulmonary disease overlap and adds perspective on asthma as an occupational lung disease. Thus, this review aims to enhance clinicians' awareness of the significance of chronic comorbidities in the management of patients with asthma. It seeks to provide insights that contribute to a more comprehensive approach to managing patients with asthma who also have comorbid conditions.

Resistencia a la corrosión y citotoxicidad de los aceros inoxidables expuestos a soluciones de cloruro / Corrosion resistance and cytotoxicity of stainless steels exposed to chloride solutions / Resistência à corrosão e citotoxicidade de aços inoxidáveis expostos a soluções de cloretos

Objetivo: Analizar la resistencia a la corrosión por picaduras de aceros inoxidables AISI 304 y AISI 420 en un medio que contiene cloruros (solu-ción de NaCl al 0,9 y 3,5%, en masa), así como su citotoxicidad, in vitro, en muestras con y sin corrosión por picaduras. Método: Estudio experimental. Se utilizaron técnicas de polarización potenciodinámica cíclica (PPC) para caracterizar el alcance y la forma del ataque corrosivo a las muestras. Se utilizó el método de difusión en agar y evaluación de la viabilidad de la línea celular NCTC clon 929 (CCIAL 020) para evaluar la citotoxicidad de las muestras de acero con y sin picaduras. Resultados: El acero AISI 304 presentó una resistencia a la corrosión superior al acero AISI 420. Los valores de potencial de picadura disminuyeron para ambos aceros cuando aumentó la concentración de cloruros en la solución agresiva. Hubo toxicidad celular moderada (grado 3 ­ ISO 10993-5) en todas las muestras. Conclusión: Los resultados corroboraron las recomendaciones para evitar la inmersión innecesaria de instrumentos en soluciones salinas. La citotoxicidad moderada de estos aceros desaconseja su uso en dispositivos implantables, reservándolos solo para instrumentos quirúrgicos. (AU)

Objective: To analyze the pitting corrosion resistance of AISI 304 and AISI 420 stainless steels in chloride-containing medium (0.9 and 3.5% NaCl solution, by weight), as well as their cytotoxicity,in vitro, in samples with and without pitting corrosion. Method: This is an experimental study. Cyclic potentiodynamic polarization (CPP) techniques were used to characterize the extent and shape of the corrosive attack on the samples. The agar diffusion and viability evaluation method of the NCTC clone 929 cell line (CCIAL 020) was used to evaluate the cytotoxicity of samples of steels with and without pitting. Results: The AISI 304 steel showed superior corrosion resistance to the AISI 420 steel. The values of the pitting potentials decreased for both steels when the chloride concentration in the aggressive solution was increased. There was moderate cell toxicity (grade 3 ­ ISO 10993-5) in all samples. Conclusions: The results corroborated the recommendations to avoid unnecessary immersion of the instruments in saline solutions. Moderate cytotoxicity to these steels contraindicates their use in implantable devices, only in surgical instruments. (AU)

Objetivo: Analisar a resistência à corrosão por pites dos aços inoxidáveis AISI 304 e AISI 420 em meio contendo cloretos (solução de NaCl a 0,9 e 3,5%, em massa), assim como sua citotoxicidade,in vitro, em amostras com e sem corrosão por pites. Método: Estudo experimental. Utilizaram-se téc-nicas de polarização potenciodinâmica cíclica (PPC) para caracterizar extensão e forma do ataque corrosivo nas amostras. O método de difusão em ágar e avaliação da viabilidade da linhagem celular NCTC clone 929 (CCIAL 020) foi empregado para avaliar a citotoxicidade de amostras dos aços com e sem pites. Resultados: O aço AISI 304 apresentou resistência à corrosão superior ao aço AISI 420. Os valores dos potenciais de pite caíram para ambos os aços quando se aumentou a concentração de cloretos na solução agressiva. Houve moderada toxicidade celular (grau 3 ­ ISO 10993-5) em todas as amostras. Conclusão: Os resultados corroboraram as recomendações para evitar a imersão desnecessária dos instrumentais em soluções salinas. A citotoxicidade moderada para esses aços contraindica seu uso em dispositivos implantáveis, apenas em instrumentos cirúrgicos. (AU)