Reduction Of Damage Research Articles

Sunset Yellow protects against oxidative damage and exhibits chemoprevention in chemically induced skin cancer model

Skin cancer and other skin-related inflammatory pathologies are rising due to heightened exposure to environmental pollutants and carcinogens. In this context, natural products and repurposed compounds hold promise as novel therapeutic and preventive agents. Strengthening the skin’s antioxidant defense mechanisms is pivotal in neutralizing reactive oxygen species (ROS) and mitigating oxidative stress. Sunset Yellow (SY) exhibits immunomodulatory characteristics, evidenced by its capacity to partially inhibit the secretion of proinflammatory cytokines, regulate immune cell populations, and modulate the activation of lymphocytes. This study aimed to investigate the antioxidant and anti-genotoxic properties of SY using in-silico, in vitro, and physiochemical test systems, and to further explore its potential role in 7,12-dimethylbenz(a) anthracene (DMBA)/ 12-o-tetradecanoylphorbol-13-acetate (TPA)-induced two-stage skin carcinogenesis. In vitro experiments showed that pre-treatment of SY significantly enhanced the cell viability of HaCaT cells when exposed to tertiary-Butyl Hydrogen Peroxide (tBHP). This increase was accompanied by reduced ROS levels, restoration of mitochondrial membrane potential, and notable reduction in DNA damage in (SY + tBHP) treated cells. Mechanistic investigations using DPPH chemical antioxidant activity test and potentiometric titrations confirmed SY’s antioxidant properties, with a standard reduction potential (Eo\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${E}^{o}$$\\end{document}) of 0.211 V. Remarkably, evaluating the effect of topical application of SY in DMBA/TPA-induced two-step skin carcinogenesis model revealed dose-dependent decreases in tumor latency, incidence, yield, and burden over 21-weeks. Furthermore, computational analysis and experimental validations identified GSK3β, KEAP1 and EGFR as putative molecular targets of SY. Collectively, our findings reveal that SY enhances cellular antioxidant defenses, exhibits anti-genotoxic effects, and functions as a promising chemopreventive agent.

Toxic effects of triclosan on hepatic and intestinal lipid accumulation in zebrafish via regulation of m6A-RNA methylation

Triclosan (TCS), recognized as an endocrine disruptor, has raised significant concerns due to its widespread use and potential health risks. To explore the impact of TCS on lipid metabolism, both larval and adult zebrafish were subjected to acute and chronic exposure to TCS. Through analyzes of biochemical and physiological markers, as well as Oil Red O (ORO) and hematoxylin and eosin (H&E) staining, our investigation revealed that TCS exposure induced hepatic and intestinal lipid accumulation in larval and adult zebrafish, leading to structural damage and inflammatory responses in these tissues. The strong affinity of TCS with PPARγ and subsequent pathway activation indicate that PPARγ pathway plays a crucial role in TCS-induced lipid buildup. Furthermore, we observed a decrease in m6A-RNA methylation levels in the TCS-treated group, which attributed to the increased activity of the demethylase FTO and concurrent suppression of the methyltransferase METTL3 gene expression by TCS. The alteration in methylation dynamics is identified as a potential underlying mechanism behind TCS-induced lipid accumulation. To address this concern, we explored the impact of folic acid—a methyl donor for m6A-RNA methylation—on lipid accumulation in zebrafish. Remarkably, folic acid administration partially alleviated lipid accumulation by restoring m6A-RNA methylation. This restoration, in turn, contributed to a reduction in inflammatory damage observed in both the liver and intestines. Additionally, folic acid partially mitigates the up-regulation of PPARγ and related genes induced by TCS. These findings carry substantial implications for understanding the adverse effects of environmental pollutants such as TCS. They also emphasize the promising potential of folic acid as a therapeutic intervention to alleviate disturbances in lipid metabolism induced by environmental pollutants.

Critical impacts of energy targeting on the sustainability of advanced biobutanol separation

Biobutanol stands out as an advanced renewable biofuel, yet its production through fermentation yields a low butanol concentration, necessitating expensive and energy-intensive separation methods, particularly by distillation. Alternative approaches, including adsorptive separation, have emerged, with the 2-column zeolite-based process showing promise. This study employed Aspen Plus for simulating adsorptive separation, utilized Pinch technology for heat integration, and analyzed various alternatives using the life cycle assessment (LCA) approach. Compared to the base case, which relied on our previously acquired experimental data and further purification through atmospheric distillation, the adoption of indirect heating/cooling adsorption reduced heating energy demand by 59.5%. Additionally, cooling energy usage was increased notably by 68.9%, and chilling prerequisites were eliminated. The implementation of Pinch technology further reduced heating and cooling energy requirements by approximately 36%. Multi-pressure distillation was also explored, revealing its potential to reduce heating energy consumption by 46.6%, accompanied by a modest 6.2% increase in cooling energy demand. A gate-to-gate LCA framework was used to evaluate the environmental impacts. The results showed that the combination of indirect heating/cooling adsorption, multi-pressure distillation, and energy-efficient practices resulted in over a 98% reduction in damages related to human health, ecosystem well-being, and resource depletion compared to the base case. Prioritization of key performance indicators revealed that human health had the most significant influence, with prominent midpoint effects attributed to human toxicity and global warming. This study underscores the pivotal role of energy targeting in curtailing energy consumption and enhancing the sustainability of adsorptive biobutanol separation.

Pyridostigmine attenuated high-fat-diet induced liver injury by the reduction of mitochondrial damage and oxidative stress via α7nAChR and M3AChR.

Obesity is a major cause of nonalcohol fatty liver disease (NAFLD), which is characterized by hepatic fibrosis, lipotoxicity, inflammation, and apoptosis. Previous studies have shown that an imbalance in the autonomic nervous system is closely related to the pathogenesis of NAFLD. In this study, we investigated the effects of pyridostigmine (PYR), a cholinesterase (AChE) inhibitor, on HFD-induced liver injury and explored the potential mechanisms involving mitochondrial damage and oxidative stress. A murine model of HFD-induced obesity was established using the C57BL/6 mice, and PYR (3 mg/kg/d) or placebo was administered for 20 weeks. PYR reduced the body weight and liver weight of the HFD-fed mice. Additionally, the serum levels of IL-6, TNF-α, cholesterol, and triglyceride were significantly lower in the PYR-treated versus the untreated mice, corresponding to a decrease in hepatic fibrosis, lipid accumulation, and apoptosis in the former. Furthermore, the mitochondrial morphology improved significantly in the PYR-treated group. Consistently, PYR upregulated ATP production and the mRNA level of the mitochondrial dynamic factors OPA1, Drp1 and Fis1, and the mitochondrial unfolded protein response (UPRmt) factors LONP1 and HSP60. Moreover, PYR treatment activated the Keap1/Nrf2 pathway and upregulated HO-1 and NQO-1, which mitigated oxidative injury as indicated by decreased 8-OHDG, MDA and H2 O2 levels, and increased SOD activity. Finally, PYR elevated acetylcholine (ACh) levels by inhibiting AChE, and upregulated the α7nAChR and M3AChR proteins in the HFD-fed mice. PYR alleviated obesity-induced hepatic injury in mice by mitigating mitochondrial damage and oxidative stress via α7nAChR and M3AChR.

Study the regularity of micro-texture parameters of bone milling tool surface for wettability improved and bone surface damage reduction

Study the regularity of micro-texture parameters of bone milling tool surface for wettability improved and bone surface damage reduction

Perennial flower margins reduce orchard fruit damage by rosy apple aphid, Dysaphis plantaginea (Homoptera: Aphididae)

Abstract Sown or natural flower strips are a commonly used management practice in agroecosystems and have been demonstrated to increase the abundance of predators of orchard pests. There is less evidence of the extent to which such strips can reduce pest damage in orchards. Here we examined the effect of managed, perennial flower margins on fruit damage by an economically significant crop pest, Dysaphis plantaginea, rosy apple aphid, in conventional apple orchards over 2 years, compared to orchards without flower margins. We found orchard flower margins reduced the percentage of apple trees with fruit damage by D. plantaginea, from 80% to 48%. In 2021, a period of severe infestation (65% of trees had fruit damage), there was reduced spread of D. plantaginea on infested apple trees and the number of trees with fruit damage was significantly reduced up to 50 m into orchards. During 2022, a period of lower infestation (25% of trees damaged), fruit damage was significantly reduced up to 10 m from the flower margin. A significant reduction in predation of aphids from bait cards in flower margin compared with control orchards suggests specialists, rather than generalist predators, may be driving the positive effects of the margin on pest pressure. There was no significant effect of flower margins on abundance of important aphid predators, including Syrphidae (hoverflies) and Coccinellidae (ladybirds). Synthesis and applications: To our knowledge, this study is the first to detect a reduction in fruit damage by pests at harvest in orchards with a flower margin. We highlight the potential for established perennial flower margins to deliver measurable, sustainable, D. plantaginea control benefits and provide insights into the optimal spatial arrangement of flower strips in orchards.

Orthopaedic robot assisted closed reduction and cannulated screw internal fixation for the treatment of femoral neck fractures

To investigate the preliminary clinical effect of closed reduction and cannulated nail internal fixation for femoral neck fracture assisted by robot navigation and positioning system. From July 2019 to January 2020, 16 cases of femoral neck fracture （navigation group） were treated with closed reduction and internal fixation guided by robot system, including 7 males and 9 females, aged 25 to 72 years old with an average of （53.61±5.45） years old；Garden classification of fracture：3 cases of typeⅠ, 3 cases of typeⅡ, 8 cases of type Ⅲ, 2 cases of type Ⅳ. Non navigation group （control group）：20 cases of femoral neck fracture were treated with closed reduction and hollow nail internal fixation, 8 males and 12 females, aged 46 to 70 years old with an average of （55.23±4.64） years old；Garden typeⅠin 2 cases, typeⅡin 4 cases, type Ⅲ in 11 cases, type Ⅳ in 3 cases. The operation time, fluoroscopy times, guide needle drilling times, screw adjustment times, intraoperative bleeding volume and other indicators of two groups were evaluated. Both groups were followed up for 12 to 18 months with an average of （15.6±2.8） months. The fractures of both groups were healed without delayed union and nonunion. There was no significant difference in healing time between two groups（P=0.782）. There was no significant difference in Harris scores between two groups at the last follow-up（P=0.813）. There was no significant difference in operation time between two groups（P>0.05）. There were significant differences between two groups in fluoroscopy times, guide needle drilling times, hollow screw replacement times, and intraoperative bleeding volume（P<0.05）. Closed reduction and hollow screw internal fixation assisted by robot navigation system for femoral neck fracture has the advantages of minimally invasive operation, precise screw placement, and reduction of X-ray radiation damage during operation.

Foliar Application of Biostimulant Mitigates Water Stress Effects on Soybean

Climate change has emerged as a challenge for soybean cultivation around the world, stimulating the development of technological alternatives that aim to mitigate the damage caused by water deficit. From this perspective, algae extract-based biostimulants have been tested to reduce water stress in several crops, but little is known about their effects on soybean. Thus, we hypothesize that a commercial biostimulant based on Ascophyllum nodosum can improve the physiological performance and water relations of Glycine max plants subjected to water deficit. To test this hypothesis, we set up an experiment in controlled conditions in a greenhouse, considering five treatments (control; application of biostimulant; water deficit (WD); WD + application of biostimulant; and WD + split application of biostimulant). The experiment was designed in completely randomized blocks with four replications per treatment and conducted in polyethylene pots containing 10 L of soil and three plants per pot. The irrigation was carried out daily; the water deficit was 50% soil moisture at field capacity, starting at the R1 stage (beginning of flowering, where there is at least one flower open at any node on the plant) and maintained for ten days. The biostimulant was applied concurrently with the onset of water deficit. We confirmed the hypothesis that foliar application of 1.0 L ha−1 of the biostimulant reduces the deleterious effects of the common water deficit at the beginning of the reproductive stage of soybean through the reduction of damage from oxidative stress (reduction of malondialdehyde synthesis by 31.2% in relation to the WD plants), maintenance of water potential and cellular homeostasis (10.2% increase in relative water content when compared with WD plants), and conservation of the contents of chlorophyll in leaves and stimulation of photosynthesis and carboxylation (68% increase in net photosynthetic rate and 49.3% increase in carboxylation efficiency in relation to WD plants). However, when applied in installments, the biostimulant was not efficient in reducing soybean water stress. Therefore, we conclude that the application of a biostimulant based on A. nodosum can help reduce the harmful effects of water deficit on soybean plants, opening up perspectives for the mass use of this extract in agricultural crops produced on a large scale.

Preliminary report of field reconnaissance on the 6 February 2023 Kahramanmaras Earthquakes in Türkiye

AbstractOn February 6, a successive rupture of major faults in the Eastern Anatolian Fault Zone and Cardak-Surgu fault triggered a strong mainshock (Mw 7.7) and a major aftershock (Mw 7.6) in Kahramanmaras. The successive earthquake sequence hit southern provinces in Türkiye and northern regions in Syria, causing severe fatality and economic loss. After the earthquakes, the International Consortium on Geo-disaster Reduction (ICGdR) organized an investigation team, involving specialists from China, Japan and Türkiye, to conduct a primary field reconnaissance on seismic damage of infrastructure and ground failures. The 10-day reconnaissance, including a mini-symposium at the Istanbul Technical University (ITU), was conducted from 25 March to 3 April and specifically focused on fault ruptures, liquefaction, landslide, rockfall and lateral spreading along the major ruptured faults from Antakya in Hatay to Goksun in Kahramanmaras, passing through provinces of Gaziantep, Adıyaman and Malatya. By this reconnaissance, a large amount of original seismic data was collected and a primary understanding was established for further steps on mitigation and reduction of seismic damages and its secondary geohazards.

Apical papilla stem cell-derived exosomes regulate lipid metabolism and alleviate inflammation in the MCD-induced mouse NASH model

Stem cells from the apical papilla(SCAPs) exhibit remarkable tissue repair capabilities, demonstrate anti-inflammatory and pro-angiogenic effects, positioning them as promising assets in the realm of regenerative medicine. Recently, the focus has shifted towards exosomes derived from stem cells, perceived as safer alternatives while retaining comparable physiological functions. This study delves into the therapeutic implications of exosomes derived from SCAPs in the methionine-choline-deficient (MCD) diet-induced mice non-alcoholic steatohepatitis (NASH) model. We extracted exosomes from SCAPs. During the last two weeks of the MCD diet, mice were intravenously administered SCAPs-derived exosomes at two distinct concentrations (50 μg/mouse and 100 μg/mouse) biweekly. Thorough examinations of physiological and biochemical indicators were performed to meticulously evaluate the impact of exosomes derived from SCAPs on the advancement of NASH in mice induced by MCD diet. This findings revealed significant reductions in body weight loss and liver damage induced by the MCD diet following exosomes treatment. Moreover, hepatic fat accumulation was notably alleviated. Mechanistically, the treatment with exosomes led to an upregulation of phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK) levels in the liver, enhancing hepatic fatty acid oxidation and transporter gene expression while inhibiting genes associated with fatty acid synthesis. Additionally, exosomes treatment increased the transcription levels of key liver mitochondrial marker proteins and the essential mitochondrial biogenesis factor. Furthermore, the levels of serum inflammatory factors and hepatic tissue inflammatory factor mRNA expression were significantly reduced, likely due to the anti-inflammatory phenotype induced by exosomes in macrophages. The above conclusion suggests that SCAPs-exosomes can improve NASH.

Soat2 inhibitor avasimibe alleviates acute pancreatitis by suppressing acinar cell ferroptosis.

Ferroptosis, characterized by lipid peroxidation, plays a significant role in the pathogenesis of acute pancreatitis (AP). While sterol O-acyltransferase 2 (Soat2) is known for its crucial regulatory role in cholesterol homeostasis, its involvement in the development of AP remains unreported. We conducted this study to identify the pivotal role of Soat2 in AP using transcriptomic databases. Subsequently, we confirmed its alterations through both in vitro and in vivo experimental models. Furthermore, we performed intervention with the Soat2 inhibitor avasimibe to evaluate pancreatic tissue pathology and serum enzymatic levels and observe inflammatory cell infiltration through immunohistochemistry. Additionally, changes in indicators related to ferroptosis were also observed. The results showed that in the AP mouse model, the protein and mRNA levels of Soat2 were significantly increased. Following avasimibe administration, there was a decrease in serum amylase levels, reduction in pancreatic tissue pathological damage, and attenuation of inflammatory cell infiltration. Furthermore, avasimibe administration resulted in downregulation of ferroptosis-related indicators. In conclusion, our findings suggest that the Soat2 inhibitor avasimibe protects against AP in mice through inhibition of the ferroptosis.

Heterometallic bridged Pt(II)‐Zn(II) complexes: Influence of the substituent in 4′‐position in inert terpy ligand on antigenotoxicity, potential antitumor activity and mechanism of interactions of the complexes with biomolecules

The synthesis and characterization of novel hetrometallic complexes [{cis‐PtCl(NH3)2(μ‐4,4′‐bipyridyl)ZnCl(terpy‐Cl)}](ClO4)2 (C1a), [{trans‐PtCl(NH3)2(μ‐4,4′‐bipyridyl)ZnCl(terpy)}](ClO4)2 (C2a), [{cis‐PtCl(NH3)2(μ‐pyrazine)ZnCl(terpy‐Cl)}](ClO4)2 (C3a) and [{trans‐PtCl(NH3)2(μ‐pyrazine)ZnCl(terpy‐Cl)}](ClO4)2 (C4a) (where terpy‐Cl = 4′‐chloro‐2,2′:6′,2′′‐terpyridine) was done. Acid–base titrations were performed by UV–Vis spectrophotometric method to evaluate the pKa values of corresponding aqua complexes. Interactions between complexes and important biomolecules, guanosine‐5′‐monophosphate (5′‐GMP) and glutathione (GSH) were examined by 1H NMR spectroscopy. The chloride substituent at the 4′ position on the middle pyridine ring of terpyridine ligand significantly affects the coordination of biomolecules, as well as overall stability of complexes. The complexes were evaluated in vitro for the antioxidant prevention of DNA damages. All tested novel complexes demonstrated a significant reduction in DNA damage against oxidative modifications of DNA caused by the hydroxyl and peroxyl radicals. Also, cytotoxicity evaluation showed that significant cytotoxicity occurs only after long‐term effect of C1a, C2a and C3a, complexes in HCT‐116 cells. Molecular docking studies predict results in agreement with experimental research.

Photoaging of biodegradable nanoplastics regulates their toxicity to aquatic insects (Chironomus kiinensis) by impairing gut and disrupting intestinal microbiota

Biodegradable plastic, a widely used ecofriendly alternative to conventional plastic, easily form nanoplastics (NPs) upon environmental weathering. However, the effects and underlying mechanisms governing the toxicity of photoaged biodegradable NPs to aquatic insects are not understood. In this study, we investigated the photoaging of polylactic acid nanoplastics (PLA-NPs, a typical biodegradable plastic) that were placed under xenon arc lamp for 50 days and 100 days and compared the toxicity of virgin and photoaged PLA-NPs to Chironomus kiinensis (a dominant aquatic insect). The results showed that photoaged PLA-NPs significantly decreased the body weight, body length and emergence rate of C. kiinensis. Additionally, photoaged PLA-NPs induced more severe gut oxidative stress, histological damage, and inflammatory responses than virgin PLA-NPs. Furthermore, the alpha diversity of gut microbiota was lower in photoaged PLA-NPs group than virgin PLA-NPs. The relative abundance of key gut bacteria related to intestinal barrier defense, immunity, and nutrient absorption was reduced more significantly in photoaged PLA-NPs group than virgin PLA, indirectly leading to stronger gut damage and growth reduction. A stronger impact of photoaged PLA-NPs on the gut and its microbiota occurred because photoaging reduced the size of NPs from 255.5 nm (virgin PLA) to 217.1 nm (PLA-50) and 182.5 nm (PLA-100), induced surface oxidation and enhancement of oxidative potential, and improved the stability of NPs, thereby exacerbating toxicity on the gut and its microbiota. This study provides insights into the effects of biodegradable NPs on aquatic insects and highlights the importance of considering biodegradable nanoplastic aging in risk assessments.

Rate sensitive plasticity-based damage model for concrete under dynamic loading

In this manuscript, a rate-sensitive plasticity-based damage model for concrete subjected to dynamic loads is presented. The developed rate-sensitive damage model incorporates the key experimental evidence related to strain rate and damage rate. With increasing strain rates, the model is able to predict a decrease in the rate of damage evolution due to artificial stiffening effects together with a final higher level of damage. The major contribution of the work is to include the effect of damage rate, strain rate and also to consider all the physical mechanisms of damage. This is achieved by using a power law model to relate the rate of damage to the equivalent plastic strain rate. The damage parameter considers hydrostatic, tension and compression damage. Such a damage definition helps in the prediction of pulverized damage due to a loss in cohesive strength at increased hydrostatic stress, shear-induced compressive damage and tensile microcracking. Strong volumetric deformation of the material that includes hydrostatic and compaction damage is also considered in the model. Because hydrostatic damage accounts for the reduction in stiffness and compaction damage accounts for the increase in stiffness under pure compressive loading. A strain rate-dependent failure surface is considered and with increasing strain rate there is an increase in the size of the failure surface which is capped at an upper limiting value. The incremental effective stress-strain relationship is defined in terms of rate of damage, accumulated damage and viscosity parameters reflecting the inherent inertial, thermal and viscous mechanisms respectively. The stress-strain relationship in the model also accounts for stress reversals that occur due to interference of an incident and reflected wave, by including a Heaviside function. The developed model is implemented in LS-DYNA using vectorized UMAT. Verification, validation and parameterization of the developed model have been made through several numerical analyses.

Mechanisms driving fasting-induced protection from genotoxic injury in the small intestine.

Genotoxic agents such as doxorubicin (DXR) can cause damage to the intestines that can be ameliorated by fasting. How fasting is protective and the optimal timing of fasting and refeeding remain unclear. Here, our analysis of fasting/refeeding-induced global intestinal transcriptional changes revealed metabolic shifts and implicated the cellular energetic hub mechanistic target of rapamycin complex 1 (mTORC1) in protecting from DXR-induced DNA damage. Our analysis of specific transcripts and proteins in intestinal tissue and tissue extracts showed that fasting followed by refeeding at the time of DXR administration reduced damage and caused a spike in mTORC1 activity. However, continued fasting after DXR prevented the mTORC1 spike and damage reduction. Surprisingly, the mTORC1 inhibitor, rapamycin, did not block fasting/refeeding-induced reduction in DNA damage, suggesting that increased mTORC1 is dispensable for protection against the initial DNA damage response. In Ddit4-/- mice [DDIT4 (DNA-damage-inducible transcript 4) functions to regulate mTORC1 activity], fasting reduced DNA damage and increased intestinal crypt viability vs. ad libitum-fed Ddit4-/- mice. Fasted/refed Ddit4-/- mice maintained body weight, with increased crypt proliferation by 5 days post-DXR, whereas ad libitum-fed Ddit4-/- mice continued to lose weight and displayed limited crypt proliferation. Genes encoding epithelial stem cell and DNA repair proteins were elevated in DXR-injured, fasted vs. ad libitum Ddit4-/- intestines. Thus, fasting strongly reduced intestinal damage when normal dynamic regulation of mTORC1 was lost. Overall, the results confirm that fasting protects the intestines against DXR and suggests that fasting works by pleiotropic - including both mTORC1-dependent and independent - mechanisms across the temporally dynamic injury response.NEW & NOTEWORTHY New findings are 1) DNA damage reduction following a 24-h fast depends on the timing of postfast refeeding in relation to chemotherapy initiation; 2) fasting/refeeding-induced upregulation of mTORC1 activity is not required for early (6 h) protection against DXR-induced DNA damage; and 3) fasting increases expression of intestinal stem cell and DNA damage repair genes, even when mTORC1 is dysregulated, highlighting fasting's crucial role in regulating mTORC1-dependent and independent mechanisms in the dynamic recovery process.

Effects of obstructive sleep apnea treatment on neurodegenerative biomarker neurofilament light chain and cognitive performance.

Obstructive sleep apnea is associated with cognitive impairment and increased risk for neurodegenerative diseases. Obstructive sleep apnea treatment with positive airway pressure therapy helps to improve cognitive symptoms and reduces long-term dementia risk. To test whether these treatment effects are due to a reduction in neuronal damage, we examined longitudinal changes in the neurodegenerative serum neurofilament light chain and cognitive performance of patients with obstructive sleep apnea. In this study, 17 patients with obstructive sleep apnea completed baseline and follow-up (9 month after starting PAP treatment) investigation of sleep, daytime symptoms, cognitive testing and serum neurofilament light chain measurements. Depending on treatment adherence and efficacy, participants were assigned either to the effective treatment (n = 10) or non-effective treatment group (n = 7). As results at baseline lower mean oxygen saturation during sleep was associated with higher serum neurofilament light chain. Patients in the non-effective treatment group showed a significant increase of age-adjusted percentile of serum neurofilament light chain levels at follow-up, whereas serum neurofilament light chain values remained constant in the effective treatment group. At a functional level, effective treatment leads to an improvement in processing speed, which was not the case in the non-effective treatment group. Longitudinal changes of age-adjusted serum neurofilament light chain levels were associated with changes in cognitive performance. To conclude, this longitudinal observational study showed that effective obstructive sleep apnea treatment positively affects the amount of neuronal damage as well as working memory performance. As cognitive symptoms might not only be attributed to obstructive sleep apnea-related sleep deficiency, but also neurodegeneration, our results underline the importance of treatment adherence and efficacy for the prevention of neuronal damage and cognitive consequences.

Inhibition of Glial Activation and Subsequent Reduction in White Matter Damage through Supplementation with a Combined Extract of Wheat Bran, Citrus Peel, and Jujube in a Rat Model of Vascular Dementia.

Vascular dementia (VaD) is the second most common type of dementia after Alzheimer's disease. In our previous studies, we showed that wheat bran extract (WBE) reduced white matter damage in a rat VaD model and improved memory in a human clinical trial. However, starch gelatinization made the large-scale preparation of WBE difficult. To simplify the manufacturing process and increase efficacy, we attempted to find a decoction containing an optimum ratio of wheat bran, sliced citrus peel, and sliced jujube (WCJ). To find an optimal ratio, the cell survival of C6 (rat glioma) cultured under hypoxic conditions (1% O2) was measured, and apoptosis was assessed. To confirm the efficacies of the optimized WCJ for VaD, pupillary light reflex, white matter damage, and the activation of astrocytes and microglia were assessed in a rat model of bilateral common carotid artery occlusion (BCCAO) causing chronic hypoperfusion. Using a combination of both searching the literature and cell survival experiments, we chose 6:2:1 as the optimal ratio of wheat bran to sliced citrus peel to sliced jujube to prepare WCJ. We showed that phytic acid contained only in wheat bran can be used as an indicator component for the quality control of WCJ. We observed in vitro that the WCJ treatment improved cell survival by reducing apoptosis through an increase in the Bcl-2/Bax ratio. In the BCCAO experiments, the WCJ-supplemented diet prevented astrocytic and microglial activation, mitigated myelin damage in the corpus callosum and optic tract, and, consequently, improved pupillary light reflex at dosages over 100 mg/kg/day. The results suggest that the consumption of WCJ can prevent VaD by reducing white matter damage, and WCJ can be developed as a safe, herbal medicine to prevent VaD.

Comparison of UESCOPE VL 400, I-View, Non-Channeled Airtraq Videolaryngoscopes and Macintosh Laryngoscope for Tracheal Intubation in Simulated Out-of-Hospital Conditions: A Randomized Crossover Manikin Study.

The aim of the study was to test the hypothesis that the results obtained with three different types of video laryngoscopes (UESCOPE VL-400, I-View, Non-Channeled Aitraq) with and without an endotracheal stylet should be better than the results obtained with a Macintosh laryngoscope in a simulated out-of-hospital scenario by a person without clinical experience. Primary outcome measures were the time taken to successfully achieve tracheal intubation (TI). Secondary outcomes included the grade of glottic view (Cormack and Lehane grades 1-4), the incidence of successful TI, the number of audible dental clicks indicating potential dental damage, the level of effort required to perform TI, and the operator's comfort during the procedure. The time required to achieve tracheal intubation successfully was significantly longer with the Macintosh laryngoscope and Airtraq than with the other video laryngoscopes. The use of the stylet significantly reduced the time required for tracheal intubation with the Macintosh laryngoscope (21.8 sec. vs. 24.0 sec., p = 0.026), UESCOPE VL 400 (18.1 sec. vs. 23.4 sec., p = 0.013), and Airtraq (22.7 sec. vs. 34.5 sec., p < 0.001). There were no significant differences in intubation time when using the I-View with or without stylets. No differences were observed in the Cormack-Lehane grading. The success rate of intubation was 100% for the Macintosh and I-View laryngoscopes used with or without stylets and for the UESCOPE VL 400 and Airtraq laryngoscopes used with stylets. Without stylets, the success rate of intubation was 96.6% for the UESCOPE VL 400 and 86.6% for the Airtraq. There were no significant differences in the risk of dental damage between the Macintosh, UESCOPE VL 400, I-View, and Airtraq laryngoscopes, regardless of the use of stylets (without and with stylets). The use of stylets significantly reduced dental damage only for the Airtraq laryngoscope: 8 (26.6%) vs. 2 (6.6%). Statistically significant differences in perceived exertion were observed between the mentioned laryngoscopes, both with and without stylets. However, there were no differences in the comfort of use between the laryngoscopes, regardless of the use of stylets (without and with stylets. The use of stylets led to better comfort in the case of the Macintosh (2.5 vs. 3, p = 0.043) and UESCOPE VL 400 (2 vs. 3, p = 0.008) laryngoscopes. In our study, the I-View and UESCOPE VL-400 video laryngoscopes provided better intubation results than the Macintosh laryngoscope in terms of time needed to intubate, glottis visibility, and reduction in dental damage. The use of the stylet did not significantly improve the intubation results compared to the results obtained in direct laryngoscopy. Due to the small study group and the manikin model, additional studies should be performed on a larger study group.

Endoplasmic Reticulum Stress Promotes Neuronal Damage in Neonatal Hypoxic-Ischemic Brain Damage by Inducing Ferroptosis.

Hypoxic-ischemic brain damage (HIBD) poses a significant risk of neurological damage in newborns. This study investigates the impact of endoplasmic reticulum stress (ERS) on neuronal damage in neonatal HIBD and its underlying mechanisms. HIBD neonatal rat model was constructed and pre-treated with 4-phenylbutiric acid (4-PBA). Nissl and TUNEL staining were utilised to assess neuronal damage and apoptosis in rat brains. HIBD cell model was established by inducing oxygen-glucose deprivation (OGD) in rat H19-7 neurons, which were then pre-treated with Thapsigargin (TG), Ferrostatin-1 (Fer-1), or both. Cell viability and apoptosis of H19-7 neurons were analysed using cell counting kit-8 assay and TUNEL staining. GRP78-PERK-CHOP pathway activity and glutathione peroxidase-4 (GPX4) expression in rat brains and H19-7 neurons were assessed using Western blot. Ferroptosis-related indicators, including glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA) and iron content, were measured using commercial kits in both rat brains and H19-7 neurons. GRP78-PERK-CHOP pathway was overactivated in HIBD neonatal rats' brains, which was mitigated by 4-PBA treatment. 4-PBA treatment demonstrated a reduction in neuronal damage and apoptosis in HIBD-affected neonatal rat brains. Furthermore, it attenuated ferroptosis in rats by increasing GPX4, GSH and SOD while decreasing MDA and iron content. In the OGD-induced H19-7 neurons, Fer-1 treatment counteracted the suppressive effects of TG on viability, the exacerbation of apoptosis, the promotion of ferroptosis and the activation of the GRP78-PERK-CHOP pathway. Overall, ERS facilitates neuronal damage in neonatal HIBD by inducing ferroptosis. Consequently, the suppression of ERS may represent a promising therapeutic strategy for treating neonatal HIBD.

Identification and application of an endophytic fungus Arcopilus aureus from Panax notoginseng against crop fungal disease.

Endophytic fungi are important microbial resources for developing novel antibacterial and antifungal drugs to prevent and control crop diseases. Panax notoginseng has been used as a Chinese medicinal herb for a long time, as it has various bioactivities. However, information on endophytic fungi isolated from Panax notoginseng is rare. In this study, an endophytic fungus known as SQGX-6, which was later identified as the golden hair fungus Arcopilus aureus, was isolated from Panax notoginseng. SQGX-6 was extracted using ethyl acetate, and the active components of the fungus were identified using ultra-performance liquid chromatography-mass spectrometry (UHPLC-MS). The antifungal and antioxidant activities of the extract were determined and evaluated in vitro and in vivo. SQGX-6 and its extract inhibited the growth of Corn stalk rot (Fusarium graminearum), Corn southern leaf blight (Helminthosporium maydis), and Tomato gray mold (Botrytis cinerea) in vitro. The free radical scavenging rates for 2,2-Diphenyl-1-pyridinyl hydrazide (DPPH) radical scavenging activity, 3-Ethylbenzothiazoline-6-Sulfonic Acid Radical scavenging (ABTS) activity were also downregulated by the SQGX-6 extract. In vivo, the SQGX-6 extract inhibited the mycelial growth rates of the three aforementioned fungi and downregulated malondialdehyde (MDA) content and upregulated peroxidase (POD) and phenylalanine ammonia-lyase (PAL) content in fruits, leading to significant reduction in damage to cherry tomatoes caused by Botrytis cinerea. UHPLC-MS was performed to identify various active substances, including Alkaloids, Azoles, Benzofurans, Coumarins, Flavonoids, Organic acids, Phenols, and plant growth regulators contained in the extract. These results suggested that the endophytic fungus SQGX-6 of Panax notoginseng and its extract have excellent antifungal and antioxidant activities, and thus, it is an important microbial resource for the developing novel drugs against plant fungal infections.