Severe Damage Research Articles

Apolipoprotein C3-rich low-density lipoprotein (AC3RL) exacerbates cerebral ischaemic stroke injury by increasing BBB leakage via LOX-1

Abstract Background Ischaemic stroke causes the abrupt reduction or cessation of blood flow to the brain results in a cascade of events that can compromise blood-brain barrier (BBB) integrity. We revealed that an increase in apolipoprotein C3 (ApoC3)-rich low-density lipoprotein (AC3RL) is associated with endothelial cell apoptosis and inflammatory responses, indicating that AC3RL is one of the risk factors for cardiovascular events. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) triggers a cascade of events within endothelial cells that leads to endothelial dysfunction. Purpose We aimed to investigate whether AC3RL affects BBB permeability via the LOX-1, and thus increases brain damage. Methods We collected the whole blood from normal and patients with ischaemic events and separated them by centrifugation. AC3RL were collected using FPLC. We performed middle cerebral artery occlusion (MCAO) surgery to induce ischaemic stroke using B6 (C57BL/6) and LOX-1-/- mice injected with AC3RL. Triphenyl tetrazolium chloride (TTC) and Evans blue stains were accessed to confirm brain injury and BBB permeability. Results FPLC results showed that patients with ischaemic events presented higher levels of AC3RL compared to normal people. TTC stain showed the increased area of ischaemic penumbra damage in B6 mice with AC3RL injection, and LOX-1-/- mice with AC3RL injection were significantly protected. Evans blue dye leakage was observed in the brain tissues of B6 mice with AC3RL injection. LOX-1-/- mice with AC3RL injection revealed a decrease in BBB permeability. The modified neurological severity score (mNSS) method revealed a significant rise in B6 mice with AC3RL injection, which suggested a decline in motor and nervous function. LOX-1-/- mice with AC3RL injection significantly improved in motor and neurological functioning. Conclusions We demonstrate that AC3RL, through its effects on LOX-1, is associated with an increased risk of BBB damage after stroke. Therefore, pharmacological inhibition of AC3RL-LOX-1 interaction will be the main strategy to reduce severe brain damage. Figure 1: (A) AC3RL percentage (%) in individuals. Normal: healthy people, Ischemic event: patients who have experienced an ischemic event. **p < 0.001 vs. Normal group. (B, C) TTC stain of brain tissue after euthanasia to pinpoint the site of brain damage. The white portion of the mice brains indicated the site of the injury. (D, E) Evans blue dye leakage study in mice brains exhibited BBB permeability changes. (F) Assessment of mice's motor and neurological performance using the mNSS. Data are expressed as the mean ± SEM. **p < 0.001, ****p < 0.0001 vs. sham group, ##p < 0.001 vs. B6 I.V. AC3RL group.Graphical abstractFigure 1.

Promise and challenges of traditional Chinese medicine, specifically Calculus bovis, in liver cancer treatment

Liver cancer, one of the most common malignancies worldwide, ranks sixth in incidence and third in mortality. Liver cancer treatment options are diverse, including surgical resection, liver transplantation, percutaneous ablation, transarterial chemoembolization, radiotherapy, chemotherapy, targeted therapy, immunotherapy, and traditional Chinese medicine (TCM). A multidisciplinary team (MDT) is essential to customize treatment plans based on tumor staging, liver function, and performance status (PS), ensuring individualized patient care. Treatment decisions require a MDT to tailor strategies based on tumor staging, liver function, and PS, ensuring personalized care. The approval of new first-line and second-line drugs and the establishment of standard treatments based on immune checkpoint inhibitors have significantly expanded treatment options for advanced liver cancer, improving overall prognosis. However, many patients do not respond effectively to these treatments and ultimately succumb to the disease. Modern oncology treatments, while extending patient survival, often come with severe side effects, resistance, and damage to the body, negatively impacting quality of life. Huang et al 's study published at World Journal of Gastroenterology rigorously validates the anticancer properties of Calculus bovis , enhancing our understanding of TCM and contributing to new liver cancer treatment strategies. For over 5000 years, TCM has been used in East Asian countries like China to treat various diseases, including liver conditions. Analysis of real-world clinical data suggests that for patients with advanced-stage tumors lacking effective treatments, integrated TCM therapies could provide significant breakthroughs.

Colchicine as a therapeutic option for the treatment of pulmonary arterial hypertension (PAH) in a rat model

Abstract Introduction Pulmonary arterial hypertension (PAH) is a cardiovascular disease that is characterized by severe structural and functional damages, resulting from the obstructive remodeling of the pulmonary vasculature and consequent right ventricular pressure overload. The current therapy mainly focuses on the pulmonary vascular system, with uncertain efficacy. Therefore, it is crucial to explore new therapeutic approaches. The mechanism of colchicine is complex and not-fully understood, but it has been proven to exert cardiopulmonary protective effects. Methods PAH induction was carried out in 8-week-old male WKY rats with a single subcutaneous injection of 60 mg/kg monocrotaline. Monocrotaline, a pyrrolizidine alkaloid, is metabolized in liver and induces inflammatory processes, which can cause PAH in rats. Starting from day 14 after MCT injection, the animals received three times a week intraperitoneal colchicine treatment at a dose of 0.5 mg/kg for two weeks. Echocardiographic examinations were performed during the study. At the end of the study, besides histological examination of the right ventricles and lungs [arterial wall thickness (WT%) and area (WA%)], the expression and phosphorylation levels of the proteins involved in cardiac remodeling were evaluated using Western blot. We assessed the pyruvate dehydrogenase (PDH) enzyme activity in the heart, which plays an important role in energy metabolism. We also examined the production of cytokines and chemokines in the right ventricle. Results The VW/BW ratio in the colchicine-treated group was significantly reduced compared to the MCT group (p<0.01). Echocardiographic parameters, EF% and E/e' ratio – characterizing the left ventricular function – did not differ considerably between the groups during the treatment. The TAPSE and PAT values characterizing right ventricular function improved in the MCT+C group (p<0.05). Collagen deposition and TGFβ level were significantly reduced by colchicine (p<0.05) in PAH animals. In the MCT+C group, the vascular remodeling (WT% and WA%) significantly decreased compared to the MCT group (p<0.01). The expression of α-SMA in vessel walls was most pronounced in the MCT group (p<0.01), which was significantly reduced by colchicine treatment. The phosphorylation of prosurvival signaling factors (ERK1/2, Akt1, GSK3β) was significantly increased in the MCT+C group (p<0.01) compared to the MCT group. In the right ventricle, PDH enzyme activity increased in the MCT+C group compared to the MCT group (p<0.01). According to cytokine array, cytokines involved in mediating fibrosis and inflammatory processes (TIMP-1, VEGF, L-selectin, CXCL7) showed increased secretion in the MCT group, which was moderately attenuated by colchicine treatment. Conclusion Colchicine treatment reduced the extent of fibrosis and inflammation, improved the structure of the pulmonary vasculature, and enhanced right ventricular function and energy supply.

Genetic and metabolic engineering approaches for enhanced biodesulfurization of petroleum fractions

Sulfur, an abundant component of crude oil, causes severe damage to the environment, poses risks to human health, and poisons the catalysts used in combustion engines. Hydrodesulfurization, the conventionally used method, is not sufficient to remove thiophenes like dibenzothiophene (DBT) and other aromatic heterocyclic compounds. The push for “ultra-clean” fuels, with sulfur content less than 15 ppm, drives the need for deep desulfurization. Thus, in conjunction with hydrodesulfurization, efficient and eco-friendly methods of deep desulfurization, like biodesulfurization, are desirable. In biodesulfurization, naturally desulfurizing microorganisms are used, with genetic engineering and biotechnology, to reduce the sulfur content of crude oil to below 15 ppm. In this review, we describe genetic and metabolic engineering approaches reported to date to develop more efficient methods to carry out biodesulfurization, making it a practically applicable reality.

Cumulative damage characteristics of rock samples under cyclic low energy inclined plane impact

The ore pass wall in underground mines is often damaged by the impact and wear caused by unloaded ores. Studying the mechanisms of rock damage and failure under different impact angles can provide technical insights for the design and maintenance of the ore passes. This study employed an inclined impact experimental device along with a drop hammer loading test machine to perform cyclic low-energy impact tests on sandstone samples at five different inclined plane angles. The porosity of the rock samples was measured using a nuclear magnetic resonance (NMR) detection system, which provided data on porosity, T2 spectrum distribution, and NMR images of the samples after different numbers of impacts at different slope angles. The results indicate that: (1) Under cyclic inclined plane impact loading, an increase in the inclination angle, leads to reduced damage to the rock sample. The rock sample impacted at a 45° inclined plane exhibited the most severe damage. Rock samples with large inclination angles are more prone to experience rupture fractures at the tip of the inclined plane, primarily due to shear-tensile failure. The porosity changes dramatically at initially slope angles, resulting in greater damage. (2) As the number of impacts increases, the porosity of the samples first decreases, then increases, and subsequently decreases again. This progression corresponds to the closure of large pores following the first impact, followed by the expansion of micropores into macropores after 5 impacts, ultimately leading to gradual degradation of the samples until failure. (3) As the number of impacts increases, new cracks form within the rock sample and small cracks expand. Despite an increase in the number of micropores, the macropores still exert a significant influence on the rock samples, with the macropore spectrum area accounting for over 95%.

Increased Susceptibility of Cardiac Tissue to PM2.5-Induced Toxicity in Uremic Cardiomyopathic Rats Is Linked to Elevated Levels of Mitochondrial Dysfunction.

Patients with chronic kidney disease (CKD) frequently develop uremic cardiomyopathy, characterized by mitochondrial dysfunction as one of its pathologically significant mediators. Given that PM2.5 specifically targets cardiac mitochondria, exacerbating toxicity, this study addresses the potential alterations in the severity of PM2.5 toxicity in the context of CKD conditions. Female Wistar rats were exposed to PM2.5 at a concentration of 250 μg/m3 daily for 3 h for 21 days after which an adenine-induced CKD model was developed. While both PM2.5 exposure and the induction of CKD in rats lead to cardiomyopathy, the CKD animals exposed to PM2.5 exhibited a notably severe extent of myocardial hypertrophy and fibrosis. ECG recordings in CKD+ PM2.5 animals revealed a depressed ST segment and prolonged QRS interval, with both PM2.5 and CKD animals displaying an elevated ST segment. Subcellular level analysis confirmed a significantly low mitochondrial copy number and a severe decline in mitochondrial bioenergetic function in the CKD+ PM2.5 group. The prominent decline in PGC1-α further affirmed the severe mitochondrial functional deterioration in CKD+ PM2.5 animals compared to other experimental groups. Additionally, myocardial calcification was enhanced in CKD+ PM2.5 animals, heightening the susceptibility of CKD animals to PM2.5 toxicity. In summary, our findings suggest that the increased vulnerability of CKD myocardium to PM2.5-induced toxicity may be attributed to severe mitochondrial damage and increased calcification in the myocardium.

Low-Field Magnetic Resonance Imaging for the Detection of Medial Meniscal Lesions in Cranial Cruciate-Deficient Stifle Joints in Dogs

Background: The aim of this study was to substantiate the ability of noninvasive low-field magnetic resonance imaging (lfMRI) to accurately depict meniscal lesions, thereby establishing lfMRI as a viable option for the diagnosis of meniscal pathology. Study Design: This was a prospective, controlled study. Materials and Methods: In each of 57 stifle joints, 5 predefined lfMRI sequences using a 0.25 T lfMRI were used. The scans were evaluated by an experienced surgeon (DECVS) and through external assessment by a radiologist (DECVDI). The patients were divided into two groups depending on their meniscal status after lfMRI. Dogs (Group 1; n = 33) without lfMRI evidence of medial meniscal pathology underwent TPLO, whereas concurrent craniomedial mini-arthrotomy was performed in patients with suspected meniscal lesions (Group 2; n = 24). Gait assessment was performed 6 weeks later and 6 months postoperatively. Results: Cohen’s kappa value of 0.8571 corresponds to a high level of agreement between the observers. A significant correlation was found between preoperative lameness severity and intraoperative meniscal damage (p < 0.04). The results showed a highly significant correlation between meniscal injuries on MRI and intraoperative findings (p < 0.0001). Conclusions: LfMRI appears to be a noninvasive, reliable imaging tool for the detection of medial meniscal lesions in cranial cruciate-deficient stifle joints, aiming to avoid (minimally) invasive diagnostics in healthy menisci.

A Low Mach Preconditioned Harmonic Balance Solver for Cavity Flutter Computations

Abstract Labyrinth seal flutter is a critical phenomenon in turbomachinery, as it can lead to severe structural vibrations and potential component damage. Accurate prediction and mitigation of flutter are paramount to ensuring the reliability and performance of modern turbomachinery systems. This paper explores the numerical computation of a labyrinth seal flutter test case using a low Mach preconditioned harmonic balance (HB) solver and investigates how this approach can improve the accuracy and response time of flutter computations. HB solvers have gained prominence in turbomachinery computations for their ability to efficiently capture unsteady flow phenomena and significantly reduce computational time compared to time-domain analyses. In labyrinth seals, however, the flow is often characterized by low Mach numbers, and preconditioning for these conditions has been shown to significantly improve convergence and accuracy. The goal of this paper is to demonstrate how to implement low Mach preconditioning in a HB solver in the frequency domain. We employ iterative preconditioning to alleviate the stiffness associated with density-based solvers under low Mach conditions and analyze the effect of the preconditioning parameters on the convergence rate. Furthermore, we address inaccuracies linked to the classical Roe solver in low Mach scenarios by adapting it to the low Mach preconditioned governing equations. Through the combined utilization of iterative preconditioning and a preconditioned Roe solver, this study aims to improve convergence rates and the overall quality of flutter predictions. We demonstrate the method with an academic labyrinth seal test case originally presented by Corral et al. (“Higher Order Conceptual Model for Labyrinth Seal Flutter,” ASME J. Turbomach., 143(7), p. 071006). While previous investigations have primarily relied on linearized frequency domain solvers and reduce-order models, in this research a preconditioned HB solver is applied to this test case.

Numerical simulation and risk assessment of toluene tank leakage in petrochemical industries, China.

Large-capacity toluene storage tank leakage accidents can lead to severe casualties and environmental damage. In this study, numerical simulation of the toluene leakage accidents is performed using PHAST and ALOHA softwares across 16 scenarios. The present research focuses on the dispersion of toluene lethal and toxicity clouds, as well as the associated risks from vapor cloud explosions and pool fires resulting from the large-capacity toluene storage tank leakage. Meanwhile, the effects of influential factors such as leakage height, wind speed, ambient temperature, and atmospheric stability on toluene leakage accidents are also discussed, and then the worst-case scenario of the toluene leakage accident is obtained. The effects of wind speed, ambient temperature, leakage height, and atmospheric stability on outcomes such as toxic clouds, vapor dispersion, explosions, and pool fires are also analyzed. The result reveals that toxic cloud dispersion increases with ambient temperature, while the impact of vapor cloud explosions and pool fires decreases with the increase of leak heights. Wind speed significantly affects pool fire spread. The influential factors related to maximizing hazard range including low leak heights, low wind speeds, high temperatures, and stable conditions are obtained. Risk analysis indicates that vapor cloud explosions significantly impact outdoor potential loss of life (PLLoutdoor) compared with other incidents. Scenario 4 within a directional range from 33.8 to 56.3° shows the highest incident frequencies, highlighting its importance for risk monitoring. These findings are crucial for enhancing emergency response strategies and safety protocols in industrial safety management.

Exogenous hydrogen sulfide increased Nicotiana tabacum L. resistance against drought by the improved photosynthesis and antioxidant system

Drought stress is an abiotic stressor that impacts photosynthesis, plant growth, and development, leading to decreased crop yields. Sodium hydrosulfide (NaHS), an exogenous additive, has demonstrated potential regulatory effects on plant responses to polyethylene glycol-induced drought stress in tobacco seedlings. Compared to the control, drought stress induced by 15 g/L PEG-6000 significantly reduced several parameters in tobacco seedlings: shoot dry weight (22.83%), net photosynthesis (37.55%), stomatal conductance (33.56%), maximum quantum yield of PSII (Fv/Fm) (11.31%), photochemical quantum yield of PSII (ΦPSII) (25.51%), and photochemical quenching (qP) (18.17%). However, applying NaHS, an H2S donor, mitigated these effects, ultimately enhancing photosynthetic performance in tobacco seedlings. Furthermore, optimal NaHS concentration (0.4 mM) effectively increased leaf stomatal aperture, relative water content (RWC) and root activity, as well as facilitated the absorption of N, K, Mg and S. It also enhanced the accumulation of soluble sugar and proline content to maintain osmotic pressure balance under drought stress. Compared to drought alone, pretreatment with NaHS also bolstered the antioxidant defense system in leaves, leading to 22.93% decrease in hydrogen peroxide (H2O2) content, a 22.19% decrease in malondialdehyde (MDA) content and increased activities of ascorbate peroxidase (APX) by 28.13%, superoxide dismutase (SOD) by 17.07%, peroxidase (POD) by 46.99%, and catalase (CAT) by 65.27%. Consequently, NaHS protected chloroplast structure and attenuated chlorophyll degradation, thus mitigating severe oxidative damage. Moreover, NaHS elevated endogenous H2S levels, influencing abscisic acid (ABA) synthesis and the expression of receptor-related genes, collaboratively participating in the response to drought stress. Overall, our findings provide valuable insights into exogenous NaHS’s role in enhancing tobacco drought tolerance. These results lay the foundation for further research utilizing H2S-based treatments to improve crop resilience to water deficit conditions.

Clinical manifestations of alpine pit viper (Trimeresurus gracilis) bites

Introduction The alpine pit viper, Trimeresurus gracilis, is an endemic species in Taiwan. The incidence of human envenoming is rare. Case summaries We present three events in two patients bitten by Trimeresurus gracilis. In the first patient, envenoming inflicted pain, local bleeding, hemorrhagic bulla, and progressive swelling, leading to necrosis of the bite wound. In the second patient, the two snakebites caused pain and progressive swelling. There were no systemic effects such as organ damage or neurological deficits observed. A paraspecific antivenom against Trimeresurus stejnegeri and Protobothrops mucrosquamatus was used to treat both patients, with a favorable outcome in each. Discussion Combined with the clinical manifestations of two previously reported cases of Trimeresurus gracilis envenoming, the known effects of Trimeresurus gracilis venom in humans include local toxicities, severe soft-tissue damage, compartment syndrome, and coagulopathy without spontaneous systemic bleeding. The paraspecific antivenom, which has demonstrable cross-neutralization effects in animal studies, appeared to be effective against the local toxicities as the patients showed prompt cessation of the progression of their swelling. Conclusions The knowledge of clinical manifestations and management approaches to Trimeresurus gracilis envenoming is helpful for patient care. The use of the paraspecific antivenom should be considered in managing such envenoming.

Dynamic Responses and Damage of a Model Ship in Multi-Rock Grounding

Ship grounding onto multiple rocks is one of the scenarios where a ship may suffer severe hull damage, thus leading to some serious consequences, such as casualties, oil spill pollution, and property damage. Ship bottom raking is the most common and severe damage type in grounding caused by sharp rocks moving against the bottom plate. This paper investigates the dynamic responses of ship grounding onto multiple sharp rocks, which has rarely been studied in the literature. Nine ship grounding in-tank model tests were conducted to provide experimental data for ship grounding onto a single rock or multiple rocks. A simplified scaled ship model with replaceable bottom plating was designed and used in the model test. Some artificial cone rock models with a 1 mm tip radius and a 15° semi-apex angle were assumed. The damage modes of the bottom plating and motions during ship grounding onto multiple rocks were obtained and recorded in the model tests, as well as the longitudinal grounding resistances. The effects of the initial relative height of each rock and the size of rock distribution on the structural damage mode and dynamic response of a ship model in multi-rock ship grounding were investigated. In addition, the results obtained from single-rock and multi-rock ship grounding model tests are compared.

Chronic stress-mediated dysregulations in inflammatory, immune and oxidative circuitry impairs the therapeutic response of methotrexate in experimental autoimmune disease models.

Chronic stress is significantly implicated in the worsening of autoimmune disorders, contributing to elevated inflammation and diminished therapeutic efficacy. Here, in this study, we investigated the detrimental impact of an 8-week chronic unpredictable stress (CUS) protocol on the progression of arthritis and psoriasis using collagen-induced arthritis (CIA) and imiquimod (IMQ)-induced psoriasis rat models, respectively. Our objective was to elucidate how prolonged stress exacerbates disease severity and impairs the effectiveness of treatment drug. Following the induction of CIA and IMQ, rats were subjected to an 8-week CUS paradigm designed to simulate chronic stress conditions. Moreover, after 5 weeks of CUS, methotrexate (MTX; 2 mg/kg, administered once weekly for 3 weeks, intraperitoneally) was introduced as a therapeutic intervention. The severity of CUS-induced effects and the therapeutic impairment of MTX in arthritis and psoriasis rats were assessed through pathological examination of joint and epidermal tissues, respectively. Additionally, we measured various pro-inflammatory cytokine levels, including NF-κB (nuclear factor kappa B), IFN-γ (interferon-gamma), TNF-α (tumour necrosis factor alpha), IL (interleukin)-1β, IL-6, IL-17 and IL-23 using enzyme-linked immunosorbent assay (ELISA), analysed immune cells through complete haematological profiling and evaluated oxidative stress markers. Our findings revealed that CUS significantly aggravated the pathological features of both arthritis and psoriasis. Prolonged stress exposure led to heightened inflammatory responses, increased oxidative stress and more severe tissue damage. Moreover, the therapeutic efficacy of MTX was notably reduced in stressed rats compared to non-stressed, underscoring the detrimental effects of chronic stress on treatment outcomes. Taken together, our results emphasize the importance of considering chronic stress as a critical factor in the management of autoimmune diseases.

Numerical simulation of the temporal and spatial evolution of sandstone pore type reservoir damage types and severity

During the oilfield development process, various factors can cause different types of reservoir damage, leading to reduced oil well production or even shutdown, and decreased water injection capacity in water wells, resulting in significant economic losses for the oilfield. However, formation damage control measures must be based on the quantitative diagnosis of the types and degrees of reservoir damage. This paper establishes a spatiotemporal evolution numerical model for 12 common types of damage during the oil and gas exploration and development process, based on the material balance theory and Fick’s diffusion law in reservoir damage processes. This model achieves numerical simulation of the degree of various reservoir damage types in different spatiotemporal domains. The overall damage degree of a specific well’s evolution with time and space is further simulated in simple superposition way. The sequential core flow experiment was carried out in the laboratory, and then compared with the calculation results. The accuracy is above 90%. Finally, using field test data, the simulation results show a 95% or higher degree of agreement with the actual field measurements, proving that the reservoir damage spatiotemporal evolution quantitative simulation technology established in this paper has high accuracy and practicality.

Estimation of Vs30 and site classification of Bhaktapur district, Nepal using microtremor array measurement

The severe damage observed in the Kathmandu Basin, Nepal, during past earthquakes necessitates a thorough study of the seismic behavior of the basin sediments. As the shear-wave velocity is directly related to the elastic shear modulus of the material, it is essential to determine it to incorporate the behavior of the soil in the design of the structure. Hence, we determined average shear-wave velocity in upper 30 m (Vs30) of soil in Bhaktapur district in the eastern part of the Kathmandu Basin at 73 observation points, employing two methods involving the use of non-invasive microtremor array measurements (MAMs). These MAMs are widely used for determining subsurface soil characteristics by analyzing the ambient vibrations of the ground. The first method involves inversion using a genetic algorithm, and the second is a method for obtaining Vs30 directly from the dispersion curve. We found that Vs30 in the southeastern part of the study area was higher than that in other parts. Conversely, Vs30 in the western region was lower. The calculated Vs30 values were used to classify the sites. The elevated eastern and southeastern areas with high Vs30 were categorized as dense soil or soft rock, whereas the areas with low Vs30 that had suffered significant damage during the 2015 Gorkha earthquake were classified as soft soil sites.Graphical

Development of a Matrix for Seismic Isolators Using Recycled Rubber from Vehicle Tires

Over recent decades, numerous strong earthquakes have caused widespread devastation, including citywide destruction, significant loss of life, and severe structural damage. Seismic base isolation is a well-established method for mitigating earthquake-induced risks in buildings; however, its high cost often limits its implementation in developing countries. Simultaneously, the global rise in vehicle numbers has led to the accumulation of discarded tires, intensifying environmental challenges. In response to these issues, this study investigates the development of a seismic isolator matrix using recycled rubber from vehicle tires, proposed as a sustainable and cost-effective alternative. Ten recycled rubber matrices were experimentally evaluated for their physical and mechanical properties. The matrix with optimal granulometry and binder content, demonstrating superior performance, was identified. This optimized matrix underwent further validation through compression and cyclic shear tests on reduced-scale prototypes of fiber-reinforced isolators, which included five prototype designs, two of which featured flexible reinforcement. The best-performing prototype comprised a recycled rubber matrix with 15% binder and glass fiber, exhibiting vertical stiffness and damping characteristics superior to those of natural rubber. Specifically, this prototype achieved a damping ratio of up to 22%, surpassing the 10% minimum required for seismic isolation, along with a vertical stiffness of 45 kN/mm, critical for withstanding the vertical loads transferred by buildings. These findings suggest that the recycled tire rubber matrix, when combined with glass fiber, is a viable material for the production of seismic isolators. This combination utilizes discarded materials, contributing to environmental sustainability.

Notoginsenoside R1 Attenuates Cisplatin-Induced Ototoxicity by Inducing Heme Oxygenase-1 Expression and Suppressing Oxidative Stress

Cisplatin-induced ototoxicity occurs in approximately half of patients treated with cisplatin, and pediatric patients are more likely to be affected than adults. The oxidative stress elicited by cisplatin is a key contributor to the pathogenesis of ototoxicity. Notoginsenoside R1 (NGR1), the main bioactive compound of Panax notoginseng saponins, has antioxidant and antiapoptotic effects. This study investigated the ability of NGR1 to protect against cisplatin-induced damage in auditory HEI-OC1 cells and neonatal murine cochlear explants. The viability of HEI-OC1 cells treated with NGR1 and cisplatin was greater than that of cells treated with cisplatin alone. The results of Western blots and immunostaining for cleaved caspase-3 revealed that the level of cleaved caspase-3 in the cells treated with cisplatin was repressed by NGR1. NGR1 attenuated cisplatin-induced cytotoxicity in HEI-OC1 cells. Intracellular reactive oxygen species (ROS) were detected with a DCFDA assay and immunostaining for 4-HNE. The result revealed that its expression was induced by cisplatin and was significantly reduced by NGR1. Moreover, NGR1 can promote heme oxygenase-1 (HO-1) expression at both the mRNA and protein levels. ZNPPIX, an HO-1 inhibitor, was administered to cisplatin-treated cells to investigate the role of HO-1 in the protective effect of NGR1. The suppression of HO-1 activity by ZNPPIX markedly abolished the protective effect of NGR1 on cisplatin-treated cells. Therefore, NGR1 protects cells from cisplatin-induced damage by activating HO-1 and its antioxidative activity. In cochlear explants, NGR1 protects cochlear hair cells and attenuates cisplatin-induced ototoxicity by inhibiting ROS generation. In the group treated with cisplatin alone, prominent loss of outer hair cells and severe damage to the structure of the stereociliary bundles of inner and outer hair cells were observed. Compared with the group treated with cisplatin alone, less loss of outer hair cells (p = 0.009) and better preservation of the stereociliary bundles of hair cells were observed in the group treated with cisplatin and NGR1. In conclusion, these findings indicate that NGR1 can protect against cisplatin-induced ototoxicity by inducing HO-1 expression and suppressing oxidative stress.

Bidirectional seismic fragility analysis of double-deck viaduct frame piers based on stripe-cloud method

To evaluate the influence of bidirectional seismic action on the seismic fragility of double-deck viaduct fram pier (DVFP), this study employs a vector-valued intensity measure (IM) [PGA, Sa (T1, 5 %)], in tandem with the stripe-cloud method. The study compares the median values of Sa and the damage probability difference index (DI) to analyze the fragility of DVFP under both unidirectional and bidirectional seismic actions. Additionally, this research investigates the sensitivity of bidirectional seismic fragility of DVFP to the incidence angles. The results indicate a notable decrease in the median Sa values for DVFP are observed under bidirectional seismic action, with decreases of 28.6 %, 24.3 %, 20.9 %, and 18.8 % corresponding to four damage states, as compared to those under unidirectional seismic action, and the corresponding parameter DIs are measured at 0.122, 0.182, 0.245, and 0.291, respectively. Notably, the most severe damage to DVFP occurs when the bidirectional seismic incidence angle is within the range of 120–135°. At this angle, the median Sa values at four damage states are 85.8 %, 86.1 %, 87.6 %, and 88.6 %, respectively, compared to the angle of 0°. Therefore, neglecting the influence of bidirectional seismic incidence angles may lead to an underestimation of the bidirectional seismic fragility of DVFP.

Effectiveness of CI as an alternative to ABI for hearing loss in patients with vestibular schwannomas: A multicenter study in Japan

ObjectiveNF2-related schwannomatosis (NF2) is characterized by bilateral vestibular schwannomas (VS), often causing severe damage to the bilateral auditory function. Auditory brainstem implantation (ABI) provides hearing-impaired patients with an opportunity to reacquire auditory sensation through electrical stimulation of auditory neurons in the cochlear nucleus. However, ABI is not covered by public health insurance in Japan, leading to a large difference in financial burden compared to cochlear implantation (CI). The aim of the present study was to demonstrate the effectiveness of CI as an alternative to ABI for hearing reacquisition in patients with profound hearing loss caused by VS. MethodsTo investigate the current situation of ABI and CI for hearing reconstruction in VS patients, we conducted a questionnaire survey of 102 facilities in Japan. Based on the responses to the questionnaire, a multicenter research group consisting of otolaryngologists and neurosurgeons was established. We collected detailed data on patients with VS who underwent ABI (n = 7, all NF2) and CI (n = 14 [nine NF2, and five non-NF2]). ResultsSome sense of hearing was obtained in all patients but one with CI indicating the efficacy of CI and ABI for profound hearing loss caused by VS. The mean hearing levels were 45.4 dB HL in the ABI patients and 32.7 dB HL in the CI patients, indicating that CI was effective as an alternative to ABI. ConclusionThe results of the present study suggest the effectiveness of CI as an alternative to ABI for hearing reacquisition in patients with profound hearing loss caused by VS. Level of evidence4.

Functional response and predatory potential of Neoseiulus newsami (Acari: Phytoseiidae) against Megalurothrips usitatus (Thysanoptera: Thripidae)

Megalurothrips usitatus, is an important pest of cowpeas Vigna unguiculata, that causes severe damage to cowpea crops in Southeast Asia and Hainan Province in China. Neoseiulus newsami is a natural enemy of M. usitatus that was first reported from Ledong Li Autonomous County, Hainan, China. Here, we evaluated the potential of N. newsami as a biocontrol agent for use against M. usitatus. In laboratory tests, N. newsami showed a similar rate of attack on this pest as did the better-known species Neoseiulus barkeri. The functional response curve of N. newsami fed M. usitatus showed that more 1st instar prey were consumed by N. newsami at higher prey densities, indicating a Type III functional. The maximum attack coefficient (a) was 0.063 ± 0.011 and the handling time per consumed prey (Th) was 0.58 ± 0.09. The maximum attack rate (T/Th) was 41.37. Neoseiulus newsami showed higher predation and oviposition rates than did N. barkeri or Neoseiulus cucumeris. Our results suggest that N. newsami has a higher predation capacity against M. usitatus.