The rise in both the frequency of natural disasters and the ubiquity of artificial intelligence has led to novel applications of new technologies in improving disaster response processes, such as the labor-intensive assessment of disaster damages. Assessment of residential and commercial structure damages, a precursory step to government agencies being able to provide most of their financial assistance, has benefited from aerial and satellite imagery-based computer vision models; however, limitations of using such imagery include the ground structures being obscured by clouds or smoke, as well as the lack of resolution to distinguish individual structures from others. Using a different data source, we propose a damage severity classification model using ground-level imagery, focusing on residential structures damaged by wildfires. This classifier, a Vision Transformer (ViT) model trained on over 18,000 professionally labeled images of damaged homes from the 2020-2022 California wildfires, has achieved an accuracy score of over 95%. Further, we have open sourced the training dataset–the first of its kind and scale–as well as built a publicly available web application prototype, which we demoed to and received feedback from disaster response officials, both of which further contribute to the broader literature beyond the proposed model.

After decades of studies, the pathogenesis of Autism Spectrum Disorder (ASD) remains unclear and there still lackseffective treatment strategies for core symptoms. Our recent work, combined with others’ research in a diversity ofmodels and clinical trials, suggested a concise, but potentially rational theory that can illustrate the key of the pathogenesis and treatment of ASD from the aspect of damage control.

The loss of integrity and adverse effect on mechanical properties can be concluded as attributing miro/macro-mechanics damage in structures, especially in composite structures. Damage as a progressive degradation of material continuity in engineering predictions for any aspects of initiation and propagation requires to be identified by a trustworthy mechanism to guarantee the safety of structures. Besides the materials design, structural integrity and health are usually prone to be monitored clearly. One of the most powerful methods for the detection of damage is machine learning (ML). This paper presents the state of the art of ML methods and their applications in structural damage and prediction. Popular ML methods are identified and the performance and future trends are discussed.

Bone injury is a common side effect of radiotherapy to tumors, which is a long-term response after damage to osteoblasts, especially reducing osteoblasts proliferation and differentiation. Currently, there are few studies on radiation-induced bone injury, the molecules involved in the ionizing radiation (IR) induced osteoblasts damage remain need to be excavated. In this study, the optimal IR damage conditions (8Gy, 2.22Gy/min) were firstly determined by measuring cell proliferation, cell cycle, cell apoptosis and further cell differentiation and mineralization abilities and the related genes (p-AKT, p-ERK1/2, cyclinB, BAX, BCL2, ALP, OPN, RUNX2, Collagen1) expression level changes in radiation-induced osteoblast injury model. Then, we screened 26 differentially expressed genes after the RNA-sequencing of the 8 Gy-irradiated MC3T3-E1 cells, and they were mainly involved in DNA damage and repair, cell apoptotic progress and cell cycle regulation, meanwhile, participated in several main pathway including PI3K-AKT signaling pathway, p53 signaling pathway and signaling pathway involved in cell cycle and cell senescence. We focused on verifying the differential expression genes and confirmed the MDM2, NOTCH1, CDKN1A and GCLC were upregulated after IR treatment, suggesting the key roles in the response of the IR. In addition, regarding on our sequencing results, the DNA damage and repair were also verified and the results suggested that IR induced DNA damage and repair in MC3T3-E1 cells. In summary, IR damaged MC3T3-E1 cells by inhibiting cell proliferation, impacting cell cycle process, inducing cell apoptosis and affecting the osteoblasts differentiation, which maybe due to the DNA damage and the differential expression of the key genes (MDM2, NOTCH1, CDKN1A and GCLC ).

This paper constructs a model of climate-related damage for small island developing states (SIDS). We focus on the loss of private productive capital stocks through extreme climate events. In contrast to most economic analyses of climate impacts, which assume temperature-dependent damage functions, we draw on the engineering literature to allow for a greater or lesser degree of anticipation of climate change when designing capital stocks and balancing current adaptation expenditure against future loss & damage. We apply the model to tropical storm damage in the small island developing state of Barbados and show how anticipatory behavior changes the damage to infrastructure for the same degree of climate change. Thus, in the model, damage depends on behavior as well as climate variables.

A rehabilitation technique for asphalt pavements with geosynthetic is the application of impregnated nonwoven geotextiles between deteriorated and new asphalt overlays. The performance investigation of impregnated geotextiles proves that they are enhancing in mechanical and hydraulic properties. Although, the installation process may cause severe impacts on these materials’ performance. During the installation, the geotextile suffers damage due to the traffic of high load vehicles, as compactors and pavers, and the friction with granular materials found under its layer or poured above it. This paper aims to investigate how the damage caused by granular materials on nonwoven geotextiles impregnated with different asphalt emulsions effect on their strength resistance and permittivity. From two types of nonwoven geotextiles: polypropylene and polyethylene terephthalate, the comparison uses geotextiles in three conditions: not impregnated, impregnated with asphalt emulsion of rapid setting, and impregnated with asphalt emulsion changed by an elastomeric polymer. Part of the samples followed the damage according to ISO 10722 procedure, placed between three different scenarios of granular materials, applying gravel, sand, and clay. After the damage process, the samples were submitted to mechanical and hydraulic properties evaluations.

After an earthquake, assessing the seismic vulnerability of buildings is essential for prioritizing emergency response, guiding reconstruction, and ensuring public safety. Accurate and timely evaluation of structural damage plays a vital role in mitigating further risks and facilitating in-formed decision-making during disaster recovery. This study investigates the performance of various Generative Artificial Intelligence (GAI) models, developed by different companies with diverse model sizes and context windows, in analysing post-earthquake images. The primary objective was to evaluate the models' effectiveness in classifying structural damage according to the EMS-98 scale (with 5 levels of damage), which ranges from minor damage to total destruction. For masonry buildings, the correct classification rates varied widely across models, from 28.6% to 64.3%, with mean damage grade errors ranging from 0.50 to 0.79. In the case of reinforced concrete buildings, correct classification rates ranged from 37.5% to 75.0%, with mean damage grade errors between 0.50 and 0.88. The use of fine-tuning could probably improve the results substantially. Improving the accuracy of GAI models could significantly reduce the time and resources needed to assess post-earthquake damage, namely when comparing with more traditional approaches. The results achieved thus far demonstrate the promise of GAI models for rapid, automated, and ac-curate damage evaluation, which is critical for expediting decision-making in disaster response scenarios.

Fibre-reinforced composite structures under complex loads exhibit gradual damage behaviour with a degradation of effective mechanical properties and change of their structural dynamic behaviour. Damage manifests itself as spatial increase of inter-fibre failure and delamination-growth, resulting in local changes of stiffness. These changes affect not only the residual strengths but more importantly the structural dynamic behaviour. In case of composite rotors, this can lead to catastrophic failure if an eigenfrequency coincides with the rotational speed. The description and analysis of the gradual damage behaviour of composite rotors therefore provides the fundamentals for a better understanding of unpredicted structural phenomena. The gradual damage behaviour on the example of composite rotors and the resulting damage-dependent dynamic behaviour is experimentally investigated under propagating damage for combined out-of-plane and in-plane loads. A novel observation is reported, where monotonic increase of damage results in non-monotonic frequency shift of significant amount of eigenfrequencies.

In order to study the effect of TiB2 particles on the mechanical properties of TiB2/6061Al composites, a series of TiB2/6061Al 3D representative volume element (RVE) were established based on SEM photos. This model took into account the ductile damage of the matrix and the traction separation behavior of the interface, and the linear damage evolution law was introduced to characterize the stiffness degradation behavior of the matrix elements. The mixed boundary conditions were used for RVE tensile experiments, and the accuracy of the predicted result was verified by the agreement of the experimental stress-strain curve. Results show that the addition of TiB2 particles can effectively promote the load-bearing capacity of the composite, but elongation is reduced. With the weight fraction of TiB2 increasing from 2.5% to 12.5%, the elastic modulus, yield strength, and tensile strength are increased by 8%, 10.37%, and 11.55% respectively, while the elongation decreased by 10%. The clustering rate of the TiB2 particles is also an important factor affecting the toughness of the composites. With the increase in the clustering rate of TiB2 particles from 20% to 80%, the load-bearing capacity of the composites is not improved, and the elongation of the composites is reduced by 8%. Moreover, the high strain region provides a fast expansion path for crack propagation and the particle spacing is a crucial factor that affects the stress field.

High costs for the repair of concrete structures can be prevented if damage at an early stage of degradation is detected and precautionary maintenance measures are applied. To this end, we use numerical wave propagation simulations to identify simulated damage in concrete using convolutional neural networks (CNN). Damage in concrete subjected to compression is modeled at the mesoscale using the discrete element method. Ultrasonic wave propagation simulation on the damaged concrete specimens are performed using the rotated staggered finite-difference grid method. The simulated ultrasonic signals are used to train a CNN based classifier capable of classifying three different damage stages (microcrack initiation, microcrack growth and microcrack coalescence leading to macrocracks). The performance of the classifier is improved by refining the dataset via an analysis of the averaged envelope of the signal. The classifier using the refined dataset has an overall accuracy of 90%.

When earthquake damage occurs, it is extremely important to quickly identify the presence or absence of such damage. In this study, we developed and evaluated a new remote sensing index to automatically determine "damage" by image analysis when damage greater than partial destruction of a house by an earthquake or tsunami occurs. The accuracy of the houses estimated as "damaged" was high and sufficient for the initial assessment of damage. The results of this research are expected to be utilized for more rapid damage assessment after a disaster.

Astaxanthin (ATX) is a carotenoid nutraceutical with a poor bioavailability due to its high lipophilicity. We tested a new tailored nano-droplet capable of solubilizing ATX in an oil-in-water micro-environment (LDS-ATX, manufactured by Lyotropic Delivery Systems (LDS)), for its capacity to improve ATX pharmacokinetic profile and anti-oxidant efficacy. We used liquid chromatography tandem mass spectrometry (LC-MS/MS) to compare the pharmacokinetic profile of ATX and LDS-ATX and protein carbonylation and lipid peroxidation assays to compare their basal and lipopolysaccharide (LPS)-induced oxidative damage. Our results show that only LPS-induced oxidative damage was corrected by ATX and LDS-ATX. While in the liver and muscle LDS-ATX was more efficacious than ATX in attenuating oxidative damage to both proteins and lipids, only oxidative damage to lipids was preferably corrected by LDS-ATX in the brain. These results strongly suggest improvement of ATX bioavailability and efficacy by the LDS-ATX nano-formulation.

The main consequence of radiation damage on a Silicon-Photomultiplier (SiPM) is a significant increase in the dark current. If the SiPM is not adequately cooled, the power dissipation causes it to heat up, which in turn affects its performance based on the temperature. In order to investigate this heating effect, experiments were carried out using a KETEK SiPM glued on an Al2O3 substrate, as well as HPK SiPMs that were either glued onto an Al2O3 substrate or a flexible PCB. The assemblies were connected either directly to a temperature-controlled chuck on a probe station or through layers of materials with well-defined thermal resistance. A DC-mode LED was used to illuminate the SiPM, and the resulting SiPM current was measured to determine the steady-state temperature. This temperature depended on the power dissipated in the multiplication region of the SiPM and the thermal resistance. This information can be utilized to adjust the SiPMs working point, taking into account the effects of self-heating. Similarly, this approach can be applied to packaged SiPMs that have an unknown thermal contact to a heat sink.

Recently on the November 4, 2022 at 03:00 PM, a M_ww 5.6 earthquake struck Cianjur district of West Java province, Indonesia. To our best knowledge, an earthquake will cause a massive damage to the manmade infrastructure and this responsible for a massive casualty. A building damage is affected by various determinant factors. One of important factors is the geological bedrock variations. Here this research aiming to elaborate the associations of geological bedrocks in Cianjur district with residential building damages caused by recent earthquakes. The results confirm that majority of building damages account for 54.67% of the total building was associated with quaternary volcanic bedrocks. The second massive building damages were observed for Andesitic Dacitic volcanic rocks accounted for 32.07%. To conclude, elaborations of geological bedrock-building damage will contribute to the better planning in the future that can reduce the damages in the urban settings.

Samarinda City is one of the most attractive cities in Borneo Island (Indonesia) and also as a capital city of EastBorneo Province. The expansion of urban areas becomes essential due to rapid population and housing demand. Base on the statistical report, the annual population growth rate is 0.018% from the year 2016-2017 with a total population of 843446 inhabitants. Many natural disasters occur in some areas in this city, especially flooding. This natural disaster occurs almost every year, many people suffered and forced to evacuate. In 2018 there is 3 flood event with 28311 people was suffered and evacuated, and 5170 houses were flooded [1]. During the flood event, it was very possible to gain damages to their property and make traffic stuck. One common way to reducing the damages is using Early Warning Systems (EWS). Early warning is a major element for disaster risk reduction, including damages. To prevent and mitigate the impact of a disaster, many countries had taken action to build various methods of a public warning system. An effective early warning system focused on people-centered and comprises the following element, such as risk knowledge, technical monitoring and service, communication and dissemination of warnings, and community response capability [2]. Related to the existing condition which Samarinda is a Muslim-dominated city and obviously has a lot of a number of mosques. This is a good potency to develop an early warning system because every mosque has a loudspeaker for echoing Adzan (Muslim prayer-calling). With this existing condition, the loudspeaker can be utilized as a flood outdoor-voice warning announcer. The aim of this study is to briefly introduce the strategy of dissemination early warning by utilizing mosques. The hope of early warning dissemination is giving enough time to the people to evacuate their property to reduce damages and possibly to giving information to avoiding traffic stuck (in a certain location)due to flooding. The results of this study can be used as input for decision-makers to develop effective flood management strategies and policies, especially in the case of an early warning system where not well-developed in Samarinda.

Historic sites are important components of every city's cultural history because they preserve rich historical knowledge and distinctive values passed down from previous generations to the present. Due to the progress of urbanization and modernization, many historic sites face pressure from damage and transformation. In this paper, a method for assessing cultural heritage damage was developed to measure the extent of spatial damage in historic sites. Using sample data obtained in Xiyang, Qixian, and Xiaoyi, all historic cities in Shanxi Province, Mainland China, and combined weights were estimated using the Delphi technique and the CRITIC weight method. Following this, the Spatial Damage Degree Model (SDDM) based on K-means cluster analysis and K-nearest neighbor (KNN) classification was developed. The findings show that the model efficiently solves the problem of assessing spatial damage levels in historic sites. Through multiple linear regression analysis, it was shown that the damage to historic sites was predominantly caused by three factors: natural erosion, construction damage, and planning and policy. SDDM was used to calculate the spatial damage levels of historic sites, allowing conservators to fully comprehend the features and concerns related to historic sites. As a result, more scientific and rational preservation approaches may be developed, improving the efficiency of historic site restoration and conservation and encouraging the sustainable development of urban and rural heritage.

Psoriasis is a multi-factorial immune-mediated disease that affects approximately 2% of the UK population and 2.5% worldwide. The condition can impact multiple organs, including the skin and joints. In moderate to severe cases, systemic and topical medications may not provide adequate relief, and as a result, biologic treatments are often administered as a monotherapy or in combination with other treatments. While biologic treatments are more effective than systemic and topical medications in treating psoriasis, patients require close supervision and monitoring while receiving this type of treatment. Liposomes are highly versatile and can be employed for therapy and research applications. They enhance drug retention at the site of administration, thereby reducing systemic side effects. Our study was the first to investigate the genotoxicity of secukinumab, an ideal biologic treatment for psoriasis (a human IgG1k antibody, anti-IL17A), in bulk and liposome nanoparticles on the lymphocytes of psoriasis patients compared to healthy individuals. We evaluated and com-pared the genotoxicity of secukinumab in bulk and liposomal form using the Comet and micronucleus assays. Both assays demonstrated that secukinumab in both forms did not ex-hibit genotoxicity and reduced DNA damage following treatment of the lymphocytes from healthy individuals and psoriatic patients with secukinumab bulk and liposomes format. Both concentrations of secukinumab used (2.1 and 2.8 µg/mL) effectively decreased H2O2-induced DNA damage in both groups to nearly the level of the negative control. Secukinumab bulk and liposome form significantly decreased H2O2-induced damage and efficiently attenuated its adverse effects both in the Comet (p<0.0001) and micronucleus assays (p<0.01). Overall, secukinumab in both forms exhibited protective and an-ti-genotoxic effects by demonstrating its potential to reduce DNA damage caused by oxida-tive stress and by not inducing any further damage in the lymphocytes of either healthy in-dividuals or patients.

InGaN-based red micro light-emitting diodes (µLEDs) of different sizes prepared in this work. The red GaN epilayers were grown on a 4-inch sapphire substrate through metal organic chemical vapor deposition (MOCVD). Etching, sidewall treatment, and p- and n- contact deposition was involved in the fabrication process. Initially, the etching process would cause undesirable damages to the GaN sidewalls, which leads to an increase in leakage current. Hence, we employed KOH wet treatment to rectify the defects on the sidewalls and conducted a comparative and systematic analysis on electrical as well as optical properties. We observed that the µLEDs with a size of 5µm exhibited substantial leakage current, which was effectively mitigated by the application of KOH wet treatment. In terms of optical performance, the arrays with KOH demonstrated improved Light Output Power (LOP). Additionally, while photoelectric performance exhibited a decline with increasing current density, the devices treated with KOH consistently outperformed their counterparts in terms of optoelectronic efficiency. It is noteworthy that the optimized devices displayed enhanced photoelectric characteristics without significantly altering their original peak wavelength and FWHM. Our findings point to the elimination of surface non-radiative recombination by KOH wet treatment, thereby enhancing the performance of small-sized red µLEDs which has significant potential in realizing full-color micro-displays in near-eye projection applications.

Despite being extremely potent against malignancies, cisplatin (CIS) has limited practical applicability due to its adverse effects such as testicular damage. Consequently, it becomes necessary to reduce its toxicity. In this study, cilostazol, a selective phosphodiesterase-3 inhibitor that is frequently used in the treatment of intermittent claudication, was examined for its ability to abrogate CIS-induces testicular toxicity and its ameliorative effect was compared with two phosphodiesterase inhibitors, tadalafil and pentoxifylline. The study also focused on the possible mechanisms involved in the proposed protective effect. Ten groups of rats were included; Group (1): control, Groups (2-4): 5 mg/kg tadalafil or 75 mg/kg pentoxifylline or 20 mg/kg cilostazol respectively), Group (5):7 mg/kg CIS, Group (6&7): CIS + 5 mg/kg tadalafil or 75 mg/kg pentoxifylline, Group (8-10) CIS+ 5, 10 or 20 mg/kg cilostazol respectively. CIS treated rats showed a significant decrease in testicular function, serum testosterone and reduced glutathione levels, and significant elevation in malondialdehyde, total nitrite levels, tumor necrosis factor-alpha and nuclear factor-kappa β alongside caspase-3. These outcomes were confirmed by marked testicular architecture deterioration. Contrary, Cilostazol in a dose-dependent manner showed potential protection against testicular toxicity, reversion of the disrupted testicular function and improvement of the histological alterations through rebalancing of oxidative stress, inflammatory and apoptotic biomarkers. In addition, cilostazol exerted more pronounced protective effect in comparison to tadalafil and pentoxifylline. In conclusion, administrations of cilostazol might ameliorate cisplatin-induced testicular impairment through alteration of oxidative stress, inflammation, and apoptotic pathway, offering a promising treatment for cisplatin -intoxication in the testes.

Free-edge effect is one of the factors affecting the mechanical properties of three-dimensional woven composites under tensile load. However, current research is relatively poorly understood regarding the effect of free-edge on the stiffness and strength of the material. This paper aims at examining the influence of free-edge effect on the mechanical properties of 3D woven composites under tension through experimental and simulation mathods. The three-dimensional DIC technique is used to collect the full-field strains on the specimen surface during the test, and the stress-strain differences in different regions in the width direction are analyzed, and the overlap of the curves in each region is found to be high. Experimental studies are conducted on specimens of different widths (within the range of 15-20 mm), and the results indicate that the differences in mechanical properties of 3D woven composites under tension loading in this width range are not significant. A progressive damage finite element model is developed for calculation and compared with experimental results.

The coffee leaf miner Leucoptera coffeella (Guérin-Mèneville & Perrottet), is a key pest in coffee producing countries. During their development, the larvae feed on the palisade parenchyma of the leaves forming mines. As a result, the photosynthetic area of the plant decreases, affecting coffee production. Despite the severity of the damage caused by coffee leaf miner (CLM), morphological aspects of the larval development and the adult genitalia remain unknown. It is important to identify more susceptible targets to an efficient and narrow control by natural or synthetic approaches, relies on determining the larval instars. Equally important is the sexing of the adult, in experiments aiming efficient ways to control CLM, as the study of pheromone-based control methods. This work presents the first morphological description of the four larval instars and the adult genitalia of L. coffeella. In each larval instar, we measured the Mean ± SD (mm) of the cephalic capsules (1^st 0,14±0,03; 2^nd 0,25±0,04; 3^rd 0,32±0,03; 4^th 0,42±0,03) and observed the following morphological details: primary setae, prolegs, crochets and ecdysial line of the cephalic capsule. In the adults, we observed the sexual structures present in both genitalia: male - bulbus ejaculatorius, valva, anellus, gnathos and aedeagus and female - ovipositor, sclerite and corpus bursae. The dissection of the adult specimens confirmed that the external morphology corresponds to the correct sex attribution in CLM adults. These results may support innovative and improved control strategies for CLM Integrated Pest Management (IPM).

The structural performance of reinforced concrete relies heavily on the bond between reinforcement and concrete. In nonlinear finite element analyses, bond is either modelled by merged, also called perfect bond, or coincident with slip, also called bond-slip, approaches. Here, the performance of these two approaches for the modelling of failure of reinforced concrete was investigated using a damage-plasticity constitutive model in LS-DYNA. Firstly, the influence of element size on the response of tension-stiffening analyses with the two modelling approaches was investigated. Then, the results of the two approaches were compared for plain and fibre reinforced tension stiffening and a drop weight impact test. It was shown that only the coincident with slip approach provided mesh insensitive results. However, both approaches were capable of reproducing the overall response of the experiments in the form of load and displacements satisfactorily for the meshes used.

Drilling and blasting is the conventional method used for rock fragmentation in open pit mining. Blast-induced damage can reduce the level of stability of benches and pit slopes. To develop an optimal blast design, an adequate knowledge of the rock properties and in-situ fractures is needed. Fractures are generally the paths of least resistance for explosive energy and can affect the intensity of blast-induced damage. Discrete Fracture Networks (DFN) are 3D representations of joint systems used for estimating the distribution of in-situ fractures in a rock mass. The combined finite/discrete element method (FDEM) can be used to simulate the complex rock breakage process during a blast. The objective of this paper is to develop a methodology for assessing the influence of in-situ joints on the post-blast fracturing and the associated wall damage in 2D bench blasts scenarios. First, a simple one-blasthole scenario is analyzed with the FDEM software Irazu 2D and calibrated based on a laboratory-scale blasting experiment available from previous literature. Secondly, more complex scenarios consisting of one-blasthole models at the bench-scale were simulated. A bench blast without DFN (base case) and one with DFN, were numerically simulated. The model with DFN demonstrated that the growth path and intensity of blast-induced fractures were governed by pre-existing fractures which led to smaller wall damage area. The damage intensity for the base case scenario is about 42% higher than for the blast model with DFN included, which highlights the significance of in-situ fractures in the resulting blast damage intensity. The methodology for developing the DFN-included blasting simulation provides a more realistic modeling process for blast-induced wall damage assessment. This results in a better characterization of the blast damage zone and can lead to improved slope stability analyses.

Floods are among the most serious natural disasters worldwide; they cause enormous crop losses every year and threaten world food security. There are many studies focused on flood impact assessments for administrative districts but fewer on postdisaster impact assessments for specific crops. Therefore, this study used remote sensing data, including the normalized difference vegetation index (NDVI), elevation data, slope data, and rainfall data, combined with crop growing season data to construct a crop flood damage assessment index (CFAI). First, an analytic hierarchy process (AHP) was used to assign weights to the impact factors; then, the weighted composite score method was used to calculate the CFAI; and finally, the impact was classified as slight, moderate, or severe based on the magnitude of the CFAI . This method was used for the Missouri River floods of 2019 in the U.S. Due to the lack of measured data, the disaster vegetation damage index (DVDI) was used to validate the results. The combined approach achieved a high degree of consistency in spatial distribution. The CFAI can respond well to the degree of crop impact after flooding, providing new ideas and reference standards for agriculture-related departments.

Phenylketonuria is an inherited metabolic disorder that leads to neurobehavioral dysfunction. The main treatment is a low-phenylalanine diet and/or the cofactor tetrahydrobiopterin. Regular outpatient follow-up care and measurement of the phenylalanine level in the blood are required. We aimed to analyze the economic burden of phenylketonuria on families and the state. The pa-tients with phenylketonuria were divided into three groups according to their treatment: a low-phenylalanine diet group (n= 50), a tetrahydrobiopterin group (n= 44) and a group taking tetra-hydrobiopterin together with the diet (n= 25). A comparative cost analysis was carried out. The annual economic burden to the state was calculated to average €18801±15345 and was lowest in the diet group, then in the tetrahydrobiopterin group and highest in the tetrahydrobiopterin+diet group (p < 0.001). Out-of-pocket costs amounted to €1531±1173 per year, and indirect losses aver-aged €2125±1930 per year for all families. The economic loss was significantly lower in the fami-lies taking tetrahydrobiopterin than in the other groups (p=0.001). The combined use of medical nutrition and BH4 treatments has been shown to increase the economic harm to the state. Reim-bursing low-protein products and increasing the rate of patients eligible for financial allowances may reduce the economic harm to families.

To evaluate whether the extent of cardiac damage in severe aortic stenosis (AS) might be associated with the occurrence of conduction system disorders after TAVI. A total of 153 symptomatic patients with severe AS who had a TAVI were categorized before the procedure according to the extent of cardiac damage: stage 1 (13.5%): no or LV damage; stage 2 (58.8%): left atrial/mitral valve damage, atrial fibrillation (AF); stage 3 (27.7%): low-flow state, pulmonary vasculature/tricuspid valve/RV damage. After TAVI, 34% of patients exhibited LBBB and 10% high-degree atrioventricular block (HD-AVB). No patient in group 1 developed HD-AVD whereas new LBBB was frequent in groups 2 and 3. Twenty-one patients presented with resolutive paroxysmal AF with a higher rate for each group increment (group 1: n=0, 0%; group 2: n=11,15.7%; group 3: n=10, 30.3%) (p = 0.012). Patients in group 3 had the higher rate of permanent pacemaker implantation (PPMI) (group 1: n=1, 6.3%; group 2: n=7,10%; group 3: n=9, 27.3%) (p=0.012). No patient in group 1 died during the hospital stay. In conclusion, cardiac damage staging of AS might help identify patients at higher risk of conduction disorders and PPMI requirement after TAVI.

This paper discusses the theoretical and experimental correlations between fatigue and static strength statistical distributions. We use a two-parameter residual strength model that obeys the qualitative Strenght-Life Equal-Rank (SLERA) assumption for guidance. The modeling approach consists of recovering the model's parameters by best fitting the constant amplitude (CA) fatigue data at a given stress ratio, R, and the experimental Weibull parameters of the static strength distribution function. Once the model's parameters are fixed, its capabilities, potential, and limits are discussed by comparing its predictions with residual strength and fatigue data obtained at different stress ratios, R. Moreover, from a preliminary analysis, the theoretical extension of the model's capabilities to variable amplitude loadings is conceptualized. The application of Miner's rule is also discussed and compared with a new damage rule to analyze the fatigue responses under variable amplitude loadings.

Wildfires can be destructive to highway infrastructure. Despite the substantial number of wildfires experienced every year, research on the physical impacts of wildfire on highways has been understudied. This research examines historical and potential future highway physical damage from wildfires. To accomplish our research objectives, we examined three major areas related to physical harm to highways and the consequences of that damage – physical characteristics, roadway impacts, and traffic impacts. These categories were subsequently broken into additional metrics, the first being physical characteristics, which includes length of highway affected and reduced average daily traffic (RADT) impacts during the event. Roadway impacts were broken into the number of trees requiring removal (those that present a danger either standing or fallen), pavement damage (burning asphalt concrete), slope/rock scaling (loose hazard rocks/vegetation), and structural damage (guardrail, signs, and delineators). Traffic impacts included the need for traffic control, road closures required, and reduced annual average daily traffic (RAADT) impacts for the year. The physical characteristics on the three highways researched during the 2020 Oregon Labor Day wildfires (Beachie Creek, Archie Creek, and Holiday Farm) indicated less than 61% of the highways were affected. The highway impacts, which included damage from hazard trees, damage to various structures – guardrail, signs, and delineators as well as bridges, slope/rock scaling damage and pavement destruction – averaged 34% for the three highways, while the three of eight arterial highway routes studied in the Oregon Cascades saw a 21% reduction in AADT. Results from this study can be used not only to assess physical damage to highways from wildfires, but as a baseline for measuring and assessing potential future wildfire highway impacts.

This paper presents an approach to damage identification in beams by modal curvatures based on the use of beamforming algorithms. These processors have been successfully used in acoustics for the last thirty years to solve the inverse problems encountered in source recognition and image reconstruction, based on ultrasonic waves. In addition, beamformers apply to a broader range of problems in which the forward solutions are computable and measurable, especially regarding the field of structural vibrations, where the use of such estimators has not received attention to date. In this paper, modal curvatures will play the role of the replica vectors of the imaging field. By means of numerical studies and experimental tests on a steel beam, we motivate the choice of modal curvatures as observed quantities. Furthermore, we compare the performance of the Bartlett and minimum variance distortionless beamformers (MVDR) with an estimator based on the simple minimization of the difference between model and measured data. The results suggest that the application of the MVDR beamformer is highly effective, especially in cases of slight damage between two sensors. MVDR enabled both damage localization, and quantification.

The paper explores the potential of a low-cost advanced video-based technique for the assessment of structural damage induced to buildings by seismic loading. A low-cost high-speed video camera was utilized for motion magnification (MM) processing of footages of a two-story reinforced concrete frame building subjected to shaking table tests. The damage after seismic loading was estimated by analyzing the dynamic behavior (i.e. in terms of modal parameters) and the structural deformations of the building in the MM videos. The results by MM were compared for method validation to damage assessment obtained by the analyses of conventional accelerometers and high-precision optical markers tracked by a passive 3D motion capture system. Also, 3D laser scanning to obtain an accurate survey of the building geometry before and after the seismic tests was carried out. In particular, accelerometers were also processed and analyzed by using several stationary and non-stationary techniques with the aim to analyze the linear behavior of the undamaged structure and the nonlinear structural behavior during damaging shaking table tests. The proposed MM-based procedure provided accurate estimate of the main modal frequency and the damage location through the analysis of modal shapes, which were confirmed by advanced analyses of accelerometric data.

Excessive intake of fluoride, one of the trace elements to maintain health, leads to liver injury. Tetramethylpyrazine (TMP) is a kind of traditional Chinese medicine monomer with good antioxidant and hepatoprotective function. The aim of this study was to investigate the effect of TMP on liver injury induced by acute fluorosis. A total of 60 1-month-old male Institute of Cancer Research mice without carriage of pathogenic bacteria were selected. All mice were fed adaptively for one week, and then randomly divided into 5 groups: control (K) group, model (F) group, low-dose (LT) group, medium-dose (MT) group and high-dose (HT) group. The control and model group were given distilled water, while 40 mg/kg (LT), 80 mg/kg (MT) and 160 mg/kg (HT) TMP were fed by gavage for two weeks with the maximum gavage volume of mice is 0.2ml/10g/d. Except for the control group, all groups were given fluoride (35 mg/kg) by intraperitoneal injection on the last day of the experiment. The results of this study showed that compared with the model group, TMP alleviated the pathological changes of liver induced by fluoride and improved the ultrastructure of liver cells; TMP significantly decreased the levels of ALT, AST and MDA (P <0.05), and increased the levels of T-AOC, T-SOD and GSH (P <0.05). The results of mRNA detection showed that TMP significantly increased the mRNA expression levels of Nrf2, HO-1, CAT, GSH-Px and SOD in liver compared with model group (P <0.05). In conclusion, TMP can inhibit oxidative stress by activating Nrf2 pathway and alleviate liver injury induced by fluoride.

Critical infrastructures are those that are essential. For this type of infrastructure, it is necessary to implement analytical methodologies that will allow us to quickly obtain the susceptibility or resilience and possible damage generated in extreme precipitation episodes, through a holistic perspective in which the factors linked to hydrological risk intervene. In particular, urban hydraulic infrastructures are analyzed considering the degree of criticality, defined as the number of interactions on the different activities of the population. For this purpose, a hydrological risk analysis methodology is required. This methodology is focused on an integral approach of the system indicators to be analyzed and linked to the hydrological threat. This work proposes to delimit and analyze those factors that involve risk using an analytical expression. This model will estimate the damage to these infrastructures breaking down the factors involved in the risk equation and analyzing their variability according to the intrinsic characteristics linked to them as well as the interaction with external factors.

Magnetorheological processing was applied to polish the working surfaces of the ZnGeP2 single crystal, in which a non-aqueous liquid with magnetic particles of carbonyl iron with the addition of nanodiamonds was used. Samples of a single crystal ZnGeP2 with an angstrom level of surface roughness were received. the use of MRP has allowed more accurately characterizing possible structural defects that have emerged on the surface of a single crystal and have a size of ~ 0.5-1.5 μm. the LIDT value at the indicated or-ders of magnitude of the surface roughness parameters is determined not by the quality of polishing, but by the number of point depressions caused by physical limitations of the structural configuration of the crystal volume. These results are in good agreement with the assumption made about a significant effect of the concentration of dislocations in a ZnGeP2 crystal on LIDT.

Hepatitis delta virus (HDV) infection causes the most severe form of viral hepatitis but little is known about the molecular mechanisms involved. The recently developed HDV mouse model based on the delivery of HDV replication-competent genomes using adeno-associated vectors (AAV) develop a liver pathology very similar to the human disease, and allowed us to perform mechanistic studies. We have generated different AAV-HDV mutants to eliminate the expression HDV antigens (HDAgs), characterized them both in vitro and in vivo. We confirmed that S-HDAg is essential for HDV replication and cannot be replaced by L-HDAg or host cellular proteins, and the L-HDAg is essential for HDV infectious particle production. We have also found that the lack of L-HDAg resulted in the increase of of S-HDAg expression levels and the exacerbation of liver damage which is T cell independent but is associated with an increment in liver inflammation. Interestingly, early expression of L-HDAg significantly ameliorated the liver damage induced by the mutant expressing only the S-HDAg. In summary, the use of AAV-HDV represents a very attractive platform to interrogate in vivo the role of viral components in the HDV life cycle and to better understand the mechanism of HDV-induced liver pathology.

To quantify damage to reinforced concrete (RC) column members after an earthquake, an engineer needs to know the maximum applied force that was generated by the earthquake. Therefore, in this work, piezoceramic transducers are used to detect the applied force on an RC column member under dynamic loading. To investigate the use of post-embedded piezoceramic sensors in detecting the force that is applied to RC columns, eight full-size RC column specimens with various failure modes are tested under specific earthquake loadings. Post-embedded piezoceramic sensors are installed at a range of depths (70-80 mm) beneath the surface of a column specimen to examine the relationship between the signals that are obtained from them and the force applied by the dynamic actuator. The signals that are generated by the post-embedded piezoceramic sensors, which correlate with the applied force, are presented. These results indicate that the post-embedded piezoceramic sensors have great potential as tools for measuring the maximum applied force on an RC column in an earthquake. Restated, signals that are obtained from post-embedded piezoceramic sensors on an RC column in an earthquake can be used to determine the applied force and corresponding damage or residual seismic capacity.

Current understanding of mechanisms of cellular resistance to genotoxic stress is incomplete but is critical for a variety of medical applications. Recent developments in the CRISPR/Cas technologies open new opportunities for targeted interrogation of resistance genes and pathways. In the present work, we used nuclease dead Cas9 constructs to achieve targeted overexpression of endogenous genes encoding two essential subunits of DNA damage sensor complex, XPC and HR23B, in HEK293T cells. Both individual and simultaneous overexpression of the two genes was achieved and the effects on cellular resistance to ionizing radiation and paraquat was examined. Using the fluorometric microculture cytotoxicity assay, we showed that simultaneous, but not separate overexpression of the two genes lead to a 30% increase in survivability. Irradiated cells that overexpressed both XPC and HR23B genes showed higher clonogenic capacity and proliferation rate compared to the irradiated transfection control as revealed by the clonogenic survival assay. Modulation of the gene expression did not affect cell resistance to paraquat. In summary, our results demonstrate a high potential of CRISPR/dCas9-enabled multiplex overexpression of stress-response genes in functionally justified combinations, exemplified here by the XPC-HR23B complex, for achieving an enhanced cellular radioresistance.

The use of fluoride (F^-) for decreasing the prevalence and incidence of tooth decay was the greatest worldwide preventive public health measure of the 20th century. There have been controversial reports about the benefits of the use of F^-, because in small amounts it helps prevent dental caries, but in high concentrations it can be potentially toxic and harmful to dental and systemic health. Since the mid-20th century, F^- has been studied by toxicologists, looking at its deleterious effects in human populations. During the last decade, the interest on the undesirable effects has resurfaced because of the knowledge that it interacts with the cellular system, even in low doses, with a very small safety margin. Acute ingestion of toxic amounts of fluoride can cause corrosive gastric mucosa injury. Also respiratory effects such as bleeding, pulmonary edema, tracheostomy and shortness of breath, have been observed in individuals who inhale hydrogen fluoride. Some researchers had shown that F^- is an oxidizing agent and a well-known reversible enzymatic inhibitor that interferes with the enzyme activity of at least 80 proteins, can altered the intracellular redox equilibrium, lipid peroxidation, as well as, alteration in the gene expression and apoptosis induction. The primary purpose of this review is to examine findings of the action of inorganic F^-, and an overview of hard and soft tissue disturbances, known as fluorosis. The goal of this review is to enhance understanding of the mechanisms by which F^- affects cells with an emphasis on human tissue-specific events.

The purpose of the present study was to examine if 14 days of supplementation with a pine bark extract leading up to and following an exercise test would increase performance and reduce biomarkers associated with muscle damage, inflammation and oxidative stress. The study used a double-blind, placebo controlled, cross-over design. Participants ingested either 800mg pine bark extract or placebo for 14 days prior to the first exercise trial and for 2 days post-exercise. On the exercise day, participants submitted a pre-exercise blood sample, then completed a VO₂ peak test until volitional failure. A post-blood sample was collected 1 hour after completion of exercise. Participants returned at 24 & 48 hours after the exercise testing for measures of muscle pain in the lower body using an algometer. Participants then had a 7-day washout period before beginning to crossing over to the alternate treatment. Analysis via ordinal regression demonstrated a significant difference in oxidative stress in the pine bark extract group compared to placebo (ChiSq = 2.63; p = 0.05). The pine bark extract was effective at affording protection from oxidative stress post exercise. Further work should be undertaken to evaluate the findings with other exercise modes or in participants with known metabolic syndrome.

Based on PVDF (piezoelectric sensing techniques), this paper attempts to study the propagation law of shock waves in brittle materials during the process of three-wavelength laser irradiation of polysilicon, and discusses the formation mechanism of thermal shock failure. The experimental results show that the vapor pressure effect and the plasma pressure effect in the process of pulsed laser irradiation lead to the splashing of high temperature and high density melt. With the decrease of the laser wavelength, the laser breakdown threshold decreases and the shock wave is weakened. Because of pressure effect of the laser shock, the brittle fracture zone is at the edge of the irradiated area. The surface tension gradient and surface shear wave caused by the surface wave are the result of coherent coupling between optical and thermodynamics. The average propagation velocity of laser shock wave in polysilicon is 8.47×103m/s, and the experiment has reached the conclusion that the laser shock wave pressure peak exponentially distributes attenuation in the polysilicon.

Abstract Background In tumors, somatic mutagenesis presumably drives DNA damage response (DDR) via altered regulatory pathways increasing genomic instability and proliferative activity. These considerations led to the standard therapeutic strategy against cancer: the disruption of mutation activated DNA repair pathways of tumors. Purpose Justifying that cancer cells are not enemies to be killed, but rather they are ill human cells having the remnants of physiologic regulatory pathways. Results 1. Genomic instability and cancer development may be originated from the flaw of estrogen signal rather than excessive estrogen signaling. 2. Healthy cells with genomic instability exhibit somatic mutations helping DNA restitution. 3. Somatic mutations in tumor cells aim the restoration of DNA damage rather than further genomic derangement. 4. In tumors, estrogen signal drives the pathways of DNA stabilization leading to apoptotic death. 5. In the peritumoral cellular infiltration, the genomic damage of tumor induces inflammatory cytokine secretion and increased estrogen synthesis. In the inflammatory cells, increased growth factor receptor (GFR) signal confers unliganded activation of estrogen receptors (ERs). 6. In tumor cells responsive to genotoxic therapy, constitutive mutations help the upregulation of estrogen signal and consequential apoptosis. In tumors non responsive to genotoxic therapy, the possibilities for ER activation via either liganded or unliganded pathway, are exhausted leading to farther genomic instability and unrestrained proliferation. Conclusion Understanding the real character and behavior of human tumors at molecular level suggests that we should learn the genome repairing methods of tumors and follow them by supportive therapy rather than provoking additional genomic damages.

Advanced machine learning algorithms, have the potential to be successfully applied to many areas of system modelling. In the present study the capability of ten machine learning algorithms in predicting the structural damage of an 8-storey reinforced concrete frame building subjected to single and successive ground motions is examined. From this point of view, the initial damage state of the structural system, as well as 16 well known ground motion intensity measures are adopted as the features of the machine-learning algorithms that aim to predict the structural damage after each seismic event. The structural analyses are performed considering both real and artificial mainshock–aftershock sequences, while the structural damage is expressed in terms of two overall damage indices. The comparative study results in the most efficient damage index, as well as the most promising machine learning algorithm in predicting the structural response of a reinforced concrete building under single or multiple seismic events. Finally, the configured methodology deployed in a user-friendly web-application.

Aging is a gradual and irreversible physiological process that leads to declines in tissue and cell functions, along with an increased risk of developing various age-related diseases. The primary driving force associated with aging is the accumulation of damaged genetic material in the cell, such as DNA. DNA damage can be caused by endogenous and exogenous factors, which leads to genome instability, mitochondrial dysfunction, epigenetic modifications, and proteostatic disturb. Another driving force associated with aging is the disruption of cellular metabolism. This disruption is closely linked to alterations in the function of metabolic pathways, including insulin/IGF-1 and mTOR, which regulate crucial cellular processes like cell growth, cell proliferation, and apoptosis. The activation of the insulin/IGF-1 signaling pathway highly promotes cell growth and proliferation, while also inhibits autophagy and increasing ROS production. This ultimately leads to accelerated aging. Another crucial signaling pathway is the mTOR signaling pathway. It is responsible for detecting nutrient availability and controlling cell growth and metabolism. The dysregulation of mTOR function can lead to the development of neurodegenerative diseases, which are characterized by the aggregation of protein. Activation of transposable elements is the other driving force of aging, caused by changes in DNA methylation and the loss of heterochromatin. As a result, this leads to DNA damage, genomic instability, and inflammation. The aim of this review is to elucidate the consequence of DNA damage and other associated factors drive aging.

PARP inhibitors are used in tumor therapy exploiting their inhibitory role in DNA repair. Radiation therapy leads to DNA damage in the affected region comprising both tumor tissue and adjacent normal tissue. In addition, radiotherapy has long-standing effects on DNA integrity. The mechanisms for this are not well understood. We studied normal tissue damage of the lung after application of ionizing radiation (IR) in two well established rat models comprising both external (eIR) and internal (iIR) ionizing radiation. We found a nearly complete (~350-fold) loss of PARP-1 in the irradiated tissue in both models but no change in PARylated protein. This may be explained by the strong decrease in both ARH3 and PARG, both deparylating enzymes. We demonstrate, that of all these proteins are expressed in type II pneumocytes, but also in type I pneumocytes and the bronchiolar epithelium. The data suggest a severe disturbance of PARylation in these cells which may affect their major functions such as maintenance of the integrity of the alveolar wall. It is likely that the application of PARP inhibitors could have cumulative effects in radiation-damaged normal tissue.

Zirconia-reinforced lithium silicate (ZLS) is utilized as a material for prosthetic tooth crowns, offering enhanced strength compared to other dental glass-ceramics. In this study, we investigate a commercial ZLS material, provided in a fully crystallized form. We examine the effects of an optional post-processing heat treatment on micro-contact damage using controlled indentation tests simulating the primary modes of contact during chewing: axial and sliding. Our findings indicate that the heat treatment does not affect mechanical properties such as the elastic modulus, hardness and indentation fracture toughness. However, it does enhance the resistance to contact damage by fracture and chipping in both axial and sliding modes, as well as the resistance to crack initiation measured from sliding tests. This improvement is attributed to the refinement of the flaw population achieved through the heat treatment. The results are analysed within the framework of contact and fracture mechanics, and the implications for prosthetic dentistry are briefly discussed.

Ferroptosis, a regulated form of cell death characterized by iron-dependent lipid peroxide accumulation, plays a pivotal role in various pathological conditions, including neurodegenerative diseases. While reasonable evidence for ferroptosis exist e.g. in Parkinson’s disease or Alzheimer’s disease, there are only few reports on amyotrophic lateral sclerosis (ALS), a fast progressive and incurable neurodegenerative disorder characterized by progressive motor neuron degeneration. Initial studies, however, highlight that ferroptosis might be significantly involved in ALS. Key features of ferroptosis include oxidative stress, glutathione depletion, mitochondrial and dysfunction alterations in mitochondrial morphology, mediated by proteins such as GPX4, xCT, ACSL4 FSP1, Nrf2 and TfR1. Induction of ferroptosis involves small molecule compounds like erastin and RSL3, which disrupt system Xc- and GPX4 activity, respectively, yielding in lipid peroxidation and cellular demise. Mutations in Fused in Sarcoma (FUS) are associated with familial ALS. Pathophysiological hallmarks of FUS-ALS involve mitochondrial dysfunction and oxidative damage, implicating ferroptosis as putative cell death pathway in motor neuron demise. However, mechanistic understanding of ferroptosis in ALS, particularly FUS-ALS, remains limited. Here, we investigated ferroptosis vulnerability in a FUS-ALS cell model, revealing mitochondrial disturbance and increased susceptibility for ferroptosis in cells harboring the mutant FUS variant. This was accompanied by altered expression of ferroptosis-associated proteins, particularly by dramatic reduction of xCT expression, leading to cellular imbalance of the redox system and increased lipid peroxidation. Iron chelation with deferoxamine as well as inhibition of the mitochondrial calcium uniporter (MCU) significantly alleviated ferroptotic cell death and lipid peroxidation. These findings suggest a link between ferroptosis and FUS-ALS, offering potential therapeutic targets.

(1) Background: Ultra-endurance exercise involves a high physical impact, resulting in muscle damage, inflammatory response and production of free radicals that alter the body's oxidative state. Supplementation with antioxidants, such as beetroot, may improve recovery in ultra-endurance runners. The aim of this study was to determine whether there is a correlation between the beetroot intake and the recovery of serum oxidative status, inflammatory response and muscle damage parameters after an ultra-endurance race. (2) Methods: An observational and longitudinal study was conducted by means of surveys and blood samples collected from 32 runners during the IX Penyagolosa Trails CSP® race and the two following days. The variables C-reactive protein (CRP), lactate dehydrogenase (LDH), creatine kinase (CK), the activity of the antioxidant enzymes glutathione peroxidase (GPx) and glutathione reductase (GR), as well as the oxidative damage markers malondialdehyde (MDA), carbonyl groups (CG) and loss of muscle strength using the Squat Jump test (SJ) were analyzed to discriminate whether beetroot consumption can modulate the recovery of ultra-trail runners. (3) Results: Significant differences were observed between runners who ingested beetroot and those who did not, in terms of oxidative status, specifically in serum GPx activity at 24 and 48 hours, muscle damage variables CK and LDH and in SJ test at the finish line. Therefore, the intake of supplements containing beetroot positively influences the recovery of serum oxidative status and muscle damage after ultra-endurance running.

N6-methyladenosine (M6A) modification is the most abundant internal chemical modification on RNA molecules in eukaryotes and can affect mRNA metabolism and regulate RNA transcription, nuclear export, splicing, degradation, translation, ets, and has a significant impact on various aspects of physiology or pathobiology. Radiotherapy is the most common measure of tumor treatment, variety of cellular intrinsic mechanisms affect the responses of cells to ionizing radiation (IR) and effectiveness of cancer radiotherapy. In this review, we summarize and discuss the recent advances about the roles and mechanisms of RNA M6A methylation in cellular responses to radiation-induced DNA damage response, and outcomes of cancer radiotherapy. Insights into the RNA M6A methylation in radiation biology may facilitate the improvement of therapeutic strategies for cancer radiotherapy as well as radioprotection on normal tissues.

Melon pest management relies on the excessive application of pesticides. Reducing pesticide spraying has become a global issue for environmental sustainability and human health. Therefore, developing a new cropping system that is sustainable and eco-friendly is important. This study found that melon seedlings irrigated with ultrafine water containing H2 and O2 (UFW) produced more root hairs, increased shoot height, and produced more flowers than the control irrigated with reverse osmosis (RO) water. Surprisingly, we also discovered that UFW irrigation significantly reduced aphid infestation in melon. Based on cryo-scanning electron microscope (cryo-SEM) observations, UFW treatment enhanced trichome development and prevented aphid infestation. To investigate whether it was H2 or O2 that helped to deter insect infestation, we prepared UF water enrichment of H2 (UF+H2) and O2 (UF+O2) separately and irrigated melons. Cryo-SEM results indicated that both UF+H2 and UF+O2 can increase the density of trichomes in melon leaves and petioles. RT-qPCR showed that UF+H2 significantly increased the gene expression level of the trichome-related gene GLABRA2 (GL2). We planted melons in a plastic greenhouse and irrigated them with ultrafine water enrichment of hydrogen (UF+H2) and oxygen (UF+O2). The SPAD value, photosynthetic parameters, root weight, fruit weight, and fruit sweetness were all better than the control without ultrafine water irrigation. UFW significantly increased trichome development, enhanced insect resistance, and improved fruit traits. This system thus provides useful water management for pest control and sustainable agricultural production.

Breast cancer is a serious disease and the second leading cause of cancer-related death among women in the U.S. New treatments for this aggressive disease are urgently needed. Repurposing FDA-approved drugs for cancer treatment is an alternative that saves time and lowers the costs needed for drug development. In this study, we investigated the effects of proguanil, an anti-malarial drug, in breast cancer cells. Proguanil exhibited a significant cytotoxic effect on breast cancer cell lines including patient derived cell lines. Proguanil caused apoptosis through increased production of ROS and consequent decrease of mitochondrial membrane potential, mitochondrial respiration, and ATP production rates. ROS generation by proguanil was up to 3-fold higher when compared to the control. Proguanil treatment increased the expression of Bax, p-H2AX, cleaved-caspase 9, cleaved PARP, and down-regulated bcl-2 and survivin in breast cancer cell lines. The enlargement of 4T1 breast tumors in female Balb/c mice was suppressed by 55% through daily oral administration of 20mg/kg of proguanil. Western blot analyses of proguanil- treated tumors showed increased levels of p-H2AX, Bax, c-PARP, and c-caspase3 compared to control. Proguanil proved to be an efficient in vitro and in-vivo inhibitor of breast cancer cells, hence should be considered further for clinical investigation against breast cancer.

Cardiac hypertrophy typically follows myocardial damage, a process known to involve members of the Krüppel-Like Factors (KLFs) which have pro-hypertrophic and anti-hypertrophic roles. Our study delved into the molecular mechanisms underlying KLFs-cardiac hypertrophy interplay post myocardial infraction. We induced myocardial dam-age in rats using isoproterenol. Total RNA was extracted from the left ventricle and Quantitative Real Time RT-PCR was conducted to assess the expression of KLFs, cardiac commitment genes, inflammatory markers, and certain conduction-related genes. We devel-oped a computational approach to construct a proteomic network centered on KLFs. Initial results revealed early expression (2-3 days post-induction) of KLF3, KLF4 and KLF6, followed by the subsequent expression of KLF11 and KLF15 (5-8 days after induction). In the maturation stage, KLF12 and KLF13 regulators were found upregulated. IL-6 was gradually found to be upregulated through. Interaction analysis revealed KLF3, KLF8 and KLF12 interacted with cardiac electrical functions. RT-PCR confirmed up-regulation in cardiac genes linked to electrical function and scar maturation. Our findings underscore the central role of KLFs during the modulation of the cardiac hypertrophic response. Dysregulation of KLF expression resulted in damaged myocardium, participating in the progression of abnormal hypertrophy, highlighting their potential as therapeutic targets for heart diseases.

(Background) Phytotoxicity refers to the capacity of chemical substances or environmental factors to have a negative impact on plants. This is a crucial issue in both the context of crop cultivation and environmental protection. (Material and Methods) The research results were based on a 3-year field experiment conducted at the experimental station in Jadwisin (52°28′ N, 21°02′ E) on loamy soil. The experiment was set up using a randomized sub-block design in a split-split-plot arrangement, with three replications. The first-order factor consisted of potato cultivars, while the second-order factors were weed control methods: 1) Control – without protection; 2) mechanical weed control, extensive mechanical treatments to close rows; 3) Sencor 70 WG – pre-emergence (PRE) of potatoes; 4) Sencor 70 WG + Titus 25 WG + Trend 90 EC – PRE of potatoes; 5) Sencor 70 WG – post-emergence (POST) of potatoes; 6) Sencor 70 WG + Titus 25 WG + Trend 90 EC – POST of potatoes; 7) Sencor 70 WG + Fusilade Forte 150 EC – POST of potatoes; 8) Sencor 70 WG + Apyros 75 WG + Atpolan 80 SC – POST of potatoes. The phytotoxic effects of herbicides on potato plants and weeds were assessed every 7 days, starting from the date when the first signs of damage appeared, until they stabilized or disappeared. (Results:) Phytotoxic damage to potato and weed plants were caused by the chemical weed control methods used. The response of potato plants to herbicides was significantly related to the genetic traits of the cultivars and meteorological conditions in the years of research. (Conclusion:) Phytotoxicity is an important aspect in both agriculture and environmental protection. Research on its mechanisms and impact will enable the development of effective plant protection strategies and the preservation of ecosystem balance.

DNA damage response (DDR) pathways in keto-enol genotoxicity have not been characterized, and few studies have reported genotoxic effects in non-target organisms. The present study shows that concentrations of 11.2, 22.4, 37.3 mg/L of Movento® 240SC and 12.3, 24.6, 41.1 mg/L of Envidor® 240SC for 72 h oral exposure induced DSBs by significantly increasing the percentage of γH2AV expression in regions 2b and 3 from the germarium of wildtype females of Drosophila melanogaster Oregon R, compared to the control group (0.0 mg/L of insecticides), by confocal immunofluorescence microscopy. The comparison between both insecticides’ revels that only the Envidor® 240SC induces concentration-dependent DNA damage, as well as structural changes in the germarium. We determined that the DDR induced by Movento® 240SC depends on the activation of the ATMtefu, Chk1grp and Chk2lok kinases by significantly increasing the percentage of expression of γH2AX in regions 2b and 3 of the germarium, and that ATRmei-29D and p53dp53 kinases only respond at the highest concentration of 37.3 mg/L of Movento® 240SC. With the Envidor® 240SC insecticide, we determined that the DDR depends on the activation of the ATRmei-29D/Chk1grp and ATMtefu/Chk2lok kinases, and p53dp53 by significantly increasing the percentage of expression of γH2AX in the germarium.

Model-based approaches form the basis of the majority of damage detection and localization studies; however, built-in online detection technique can offer an alternative for future structural health monitoring technologies. Thus, in this paper, we present a dynamic localization algorithm for damage localization in functionally graded plates. The method depends on the creation of a grid matrix that contains the dynamic response of the structure over time. Subsequently, an optimization process is carried out via a linear equation representing the information contained within the grid to achieve accurate localization of damage. Due to the inherent sparsity of the localization nature, the FISTA algorithm has been employed as a problem solver. The approach is tested in the case of the functionally graded plate under clamped free boundary conditions. Several, damage scenarios were investigated for the case of damage signals on and off the grid. The results show that the proposed approach is capable of accurately predicting damage position and can be suitable for use in low size data systems.

Minute Virus of Mice (MVM) is an autonomous parvovirus of the Parvovirus family that replicates in mouse cells and transformed human cells. MVM genomes localize to cellular sites of DNA damage with the help of their essential non-structural phosphoprotein NS1 to establish viral replication centers. MVM replication induces a cellular DNA damage response that is mediated by signaling through the ATM kinase pathway, while inhibiting induction of the ATR kinase signaling pathway. However, the cellular signals regulating virus localization to cellular DNA damage response sites has remained unknown. Using chemical inhibitors to DNA damage response proteins, we have discovered that NS1 locallization to cellular DDR sites is independent of ATM or DNA-PK signaling, but is dependent on ATR signaling. Pulsing cells with an ATR inhibitor after S-phase entry leads to attenuated MVM replication. These observations suggest that the initial localization of MVM to cellular DDR sites depends on ATR signaling before it is inactivated by vigorous virus replication.

Identifying cracks in the incipient state is essential to prevent the failure of engineering structures. Detection methods relying on the analysis of the changes in modal parameters are widely used because of the advantages they present. In our previous research, we have found that eigenfrequencies were capable of indicating the position and depth of damage when sufficient vibration modes were considered. The damage indicator we developed was based on the relative frequency shifts (RFS). To calculate the RFSs for various positions and depths of a crack, we established a mathematical relation that involved the squared modal curvatures in the healthy state and the deflection of the healthy and damaged beam under dead mass, respectively. In this study, we propose to calculate the RFS for beams with several cracks by applying the superposition principle. We demonstrate that this is possible if the cracks are far enough from each other. In fact, if the cracks are close to each other, the superposition method does not work and we distinguish two cases: (i) when the cracks affect the same beam face, the frequency drop is less than the sum of the individual frequency drops, and (ii) on the contrary, cracks on opposite sides cause a decrease in frequency, which is greater than the sum of the frequency drop due to individual damage. When the RFS curves are known, crack assessment becomes an optimization problem, the cost function being the distance between the measured RFSs and all possible RFSs for several vibration modes. Thus, the RFS constitutes a benchmark that characterizes damage using only the eigenfrequencies. We can accurately locate multiple cracks and estimate their severity trough experiments and thus prove the reliability of the proposed method.

Calcineurin plays a key role in cardiovascular pathogenesis by exerting pro-apoptotic effects in cardiomyocytes; however, its involvement in the regulation of cardiomyocyte autophagy under chronic intermittent hypoxia (CIH) remains largely unknown. Here we showed that CIH induced calcineurin activity in H9C2 cells, resulting in the attenuation of adenosine monophos-phate-activated protein kinase (AMPK) signaling and inhibition of H9C2 cell autophagy. Au-tophagy, LC3-II levels, and AMPK phosphorylation were significantly elevated in response to CIH in H9C2 cells by day 3; however, these effects were reversed, and calcineurin activity and apoptosis were significantly increased by day 5. The calcineurin inhibitor, FK506, restored AMPK activation and LC3 protein levels, and reduced CIH-induced H9C2 cell apoptosis, while calcineurin overexpression significantly attenuated the increase in LC3 levels and enhanced H9C2 cell apop-tosis. Calcineurin inhibition failed to induce autophagy or alleviate apoptosis in H9C2 cells ex-pressing a dominant negative K45R AMPK mutant. Autophagy downregulation abrogated the protective effects of FK506-mediated calcineurin inhibition. These results indicated that calcineurin suppressed adaptive autophagy during CIH by downregulating AMPK activation. Our findings showed the underlying mechanisms of calcineurin and autophagy regulation during H9C2 cell survival in response to CIH, and suggested a new strategy for preventing CIH-induced cardiomyocyte damage.

In cotton cultivars, an insect that causes irreversible damage is the Spodoptera frugiperda, known as the fall armyworm. Since the visual detection of plants is a burdensome task for human inspection, the spectral information related to plant damage, registered on a spectral scale, can be useful. These measurements, associated with machine learning techniques, produce useful information for a rapid and non-invasive inspection method development. To contribute to this gap fulfillment, this paper proposes a machine learning framework to model the spectral response of cotton plants under the attack of the fall armyworm. Additionally, a theoretical model is presented, built from the results of the machine learning analysis, to infer this damage with up-to-date orbital sensors. The data was composed of the reflectance measurements collected at a cotton field with control plants and plants submitted to Spodoptera frugiperda damage. Their spectral response was recorded with a hand-held spectroradiometer ranging from 350 to 2,500 nm, for eight consecutive days. Different machine learning models were evaluated and the overall best model was defined by accuracies comparisons on a testing-set. A ranking approach was adopted based on the model accuracy, returning the most contributive wavelengths for the classification. Sequentially, an unsupervised neural network (Self-Organizing Map - SOM) was implemented to reduce data-dimensionality and assist in the definition of important spectral regions. The regions were associated with the spectral bands of the two sensors (OLI and MSI) and a theoretical model using a band simulation process with the overall best machine learning model was proposed. The results indicated that the Random Forest (RF) algorithm is the most suitable to predict cotton-plants damaged by insects and that the last day of analysis (8th day) was better to separate it, with F-measure equals 0.912. The ranking approach combined with the SOM method indicated the spectral regions at the red to near-infrared (650 to 1,350 nm) and shortwave infrared (1,570 to 1,640 nm) as the most important regions to the analysis. The proposed theoretical model simulated with the OLI and MSI sensor-bands returned an F-Measure of 0.865 and 0.886, respectively. In conclusion, this framework can be used to map cotton-plants under insect-attack. The theoretical model presents high accuracy to infer the insect-damaged on cotton plants based on multispectral bands from other sensors, being a useful tool for future research that intends to evaluate it in other areas and at different field scales.

The effect of the strain rate on damage in carbon black filled EPDM stretched during single and multiple uniaxial loading is investigated. This has been performed by analysing the stress-strain response, the evolution of damage by Digital Image Correlation (DIC), the associated dissipative heat source by InfraRed thermography (IR), and the chains network damage by swelling. The strain rates were selected to cover the transition from quasi-static to medium strain rate conditions. In single loading conditions, the increase of the strain rate yields in a preferential damage of the filler network while rubber network is preserved. Such damage is accompanied by a stress softening and an adiabatic heat source rise. Conversely, increasing the strain rate in cyclic loading conditions yields in a filler network accommodation and a high self-heating whose combined effect is proposed as a possible cause of the ability of filled EPDM to limit damage, by reducing cavities opening during loading and favoring cavities closing upon unloading.

Low soil nitrogen status of savanna soils in Nigeria contributes to the persistent Striga hermonthica (Del.) Benth. infestation that limits maize production. The application of nitrogen fertilizer to Striga-resistant hybrids may reduce Striga infection and increase grain yields. This study assessed the performance of maize hybrids at low (30 kg ha-1) and high (120 kg ha-1) nitrogen application under natural infestation with Striga at Kafin Madaki and Tudun Wada in 2014 and 2015. Results showed that the application of nitrogen at 120 kg ha-1 reduced number of Striga plants by 59% compared to application at 30 kg N ha-1 in Kafin Madaki and by 21% in Tudun Wada. Compared to 30 kg N ha-1, the 120 kg N ha-1 rate also reduced Striga damage rating by 22% in Kafin Madaki and by 33% in Tudun Wada across the hybrids. Hybrids 8338-1 (5.3) and OBASUPER 1 (4.3) were the only entries with Striga damage rating greater than 4.5 (SDR > 4.5) when averaged across the nitrogen levels at both locations. Grain yield was 86 and 98% higher in Kafin Madaki and Tudun Wada, respectively when N was applied at 120 kg N ha-1 than at 30 kg N ha-1. The hybrids M1124-3 and M1227-14 produced grain yields that were significantly higher than those of the other hybrids in all locations. The hybrid 8338-1 produced the lowest grain yield across locations. Our results showed that, the application of 120 kg N ha-1 to Striga resistant maize hybrids will reduce Striga infection and increase grain yield.

This randomized trial compared pea protein, whey protein, and water-only supplementation on muscle damage, inflammation, delayed onset of muscle soreness (DOMS), and physical fitness test performance during a 5-day period after a 90-minute eccentric exercise bout in non-athletic, non-obese males (n=92, ages 18-55 years). The two protein sources (0.9 g protein/kg divided into three doses/day) were administered under double blind procedures. The eccentric exercise protocol induced significant muscle damage and soreness, and reduced bench press and 30-second Wingate performance. Whey protein supplementation significantly attenuated post-exercise blood levels for biomarkers of muscle damage compared to water-only, with large effect sizes for creatine kinase and myoglobin during the 4th and 5th days of recovery (Cohen's d &gt;0.80); pea protein versus water supplementation had an intermediate, non-significant effect (Cohen's d &lt;0.50); and no significant differences between whey and pea protein were found. Whey and pea protein compared to water supplementation had no significant effects on post-exercise DOMS and the fitness tests. In conclusion, high intake of whey protein for 5 days after intensive eccentric exercise mitigated efflux of muscle damage biomarkers, with intake of pea protein having an intermediate effect in part due to the 24% lower leucine amino acid content.

Nigella sativa (NS) is an effective medicinal plant possessing noteworthy antioxidant property. In NS, there are more than hundred phyto-chemicals reported, out of which thymoquinone is the utmost active phyto-constituent having sturdy antioxidative property. Thymoquinone is a cyclicdione, when reacts with sodium azide, converts into α-azido ketones i.e its analogs which are handy with extensive range of reactions. Sodium azide induces stress in plants thereby, modulating the antioxidant system. The present investigation was planned to elucidate the effect of sodium azide at different concentrations (5µM, 10µM, 20µM, 50µM, 100µM and 200µM) on its secondary metabolites (mainly thymoquinone) in NS callus culture extract (NSE). The results showed sodium azide effect on thymoquinone content and a concentration dependent boost in antioxidant property. It was also observed that thymoquinone content and percent yield (analyzed by RP-HPLC; Reverse Phase- High Performance Liquid Chromatography) were minimum (0.033±0.006% and 0.420±0.045%, respectively) at 200 µM sodium azide used. Whereas, antioxidant activity (analyzed by DPPH; 2, 2-diphenyl-1-picrylhydrazyl) was found to be maximum (3.873±0.402%) at same dose. Further, analysis was done for inhibition of oxidative DNA damage at different concentrations of sodium azide on NSE, maximum inhibition of DNA damage (0.243±0.017%) was found at 200 µM concentration of sodium azide. When correlated, strong positive correlation was observed between percent yield and percent thymoquinone, antioxidant property and inhibition of DNA damage. Whereas, strong negative correlation was observed between percent yield and antioxidant property, percent thymoquinone and antioxidant property, percent thymoquinone and inhibition of DNA damage. The findings evidently point out that the content of thymoquinone, antioxidant property and inhibition of DNA damage was affected by sodium azide.

This paper analyses the evolution of the internal damage in two types of steel that show different fracture behaviours, with one of them being the initial material used for manufacturing prestressing steel wires, which shows a flat fracture surface perpendicular to the loading direction, and the other one being a standard steel used in reinforced concrete structures, which shows the typical cup-cone surface. 3mm-diameter cylindrical specimens are tested with a tensile test carried out in several loading stages and, after each of them, unloaded and analysed with X-ray tomography, which allows detection of internal damage throughout the tensile test. In the steel used for reinforcement, damage is developed progressively in the whole specimen, as predicted by Gurson-type models, while in the steel used for manufacturing prestressing steel-wire damage is developed only in the very last part of the test. In addition to the experimental study, a numerical analysis is carried out by means of the finite element method by using a Gurson model to reproduce the material behaviour.

Radical oxygen species formed in human tissue cells by many endogenous and exogenous pathways, cause extensive oxidative damage, which has been linked to various human diseases. This review paper provides an overview of lipid peroxidation and focuses on the free-radicals initiated processes of LDL oxidative modification and DNA oxidative damage, which are widely associated to the initiation and development of atherosclerosis and carcinogenesis, respectively. The article subsequently provides an overview of the recent human trials or even in vitro investigations on the potential of natural antioxidant compounds (such as carotenoids, vitamins C and E) to monitor LDL and DNA oxidative changes.

The use of salt rock for underground radioactive waste disposal facilities requires a comprehensive analysis of creep-damage process in salt rock. A computer-controlled creep setup is employed to carry out a creep test of salt rock lasted as long as 359 days under a constant uniaxial stress. The AE space-time evolution and energy releasing characteristics during creep test are studied in the meantime. A new creep-damage model is proposed on the basis of fractional derivative by combining the AE statistical regularity. It indicates that the AE data in non-decay creep process of salt rock can be divided into three stages. Furthermore, the parameters of new creep-damage model are determined by Quasi-Newton method. The fitting analysis suggests that the creep-damage model based on fractional derivative in this paper provides a precise description of full creep regions in salt rock.

Furazolidone (FZD) is a synthetic nitrofuran with the antiprotozoal and antibacterial activity. The proper mechanism of FZD induced toxicity is still unclear. This study aimed to investigate the protective effect of curcumin on FZD induced oxidative stress, DNA injury and apoptosis in human hepatocyte L02 cells. The results showed that curcumin treatment significantly ameliorated FZD induced cytotoxicity, characterized by decreasing the production of reactive oxygen species (ROS) and malondialdehyde, as well as increasing superoxide dismutase, catalase activities and glutathione contents. Moreover, curcumin pretreatment significantly inhibited FZD induced the loss of mitochondrial membrane potential, the activation caspase-9 and -3 and apoptosis. Comet assay showed that curcumin attenuated FZD induced DNA injury in a dose-dependent manner. Correspondingly, curcumin markedly reversed the up-regulation of p53, Bax, caspase-9 and -3 mRNA expressions and the down-regulation of Bcl-2 mRNA (all p<0.05 or 0.01). These results reveal that curcumin protects against FZD induced oxidative stress, DNA injury and cell apoptosis via inhibiting oxidative stress and mitochondrial pathway, which may be attributed to ROS scavenging and anti-oxidative ability of curcumin. Importantly, our study highlights that curcumin may be a potential way to prevent FZD-mediated oxidative DNA injury and apoptosis in human or animals.

Ellagitannins (ETs) are the group of tannins found in fruits, nuts and seeds; they undergo hydrolysis in the human digestive tract to form ellagic acid (EA). EA further converted into various forms of Urolithin derivatives (A, B, C, D, M-5, M-6 and M-7) by gut micro biota. Perhaps, the pharmacological properties of said Urolithins were extensively studied, while, little is known about the therapeutic role of synthetic Urolithin-C on oxidative stress induced eryptosis and tissue damage. Therefore, in the current study we investigated the ameliorative role of chemically syn-thesized Urolithin-C on sodium nitrite and Diclofenac (DFC) induced eryptosis and vital organ damage respectively. Urolithin-C was synthesized using chemical method and characterized by High-Performance Liquid Chromatography (HPLC), Nuclear Magnetic Resonance (NMR), Fourier Transform Infrared Spectroscopy (FTIR), and Liquid Chromatography Mass Spectroscopy (LC-MS). The synthesized Urolithin-C scavenged free radicals (DPPH, H2O2) and reduced ferric iron to ferrous iron, revealed its antioxidant activity. The observed antioxidant potential of Uro-lithin-C was investigated in sodium nitrite induced stress in RBC and Diclofenac induced tissue damage in rats. Interestingly, Urolithin-C normalized the sodium nitrate-induced oxidative stress in red blood cells by regulating stress markers, such as lipid peroxidation (LPO), total thiol (TT), and protein carbonyl content (PCC), and endogenous antioxidant enzymes superoxide dis-mutase (SOD) and catalase (CAT) in a dose dependent manner. Similar effect was also observed in the tissue homogenates of liver, kidney, heart and pancreas taken from the Diclofenac injected Sprague Dawley rats. The tissue sections (liver, kidney, heart and pancreas) obtained from the Diclofenac (DFC) received rats showed massive destruction of hepatocytes, nephrons, cardiocytes and pancreas. However, Urolithin-C received rats tissue sections showed normal histology compared to the positive (Silymarin) control treated groups. In addition, Urolithin-C regulated the key tissue specific biochemical markers in DFC injected Sprague Dawley rats serum strengthened its tissue protective role. In conclusion, chemically synthesized Urolithin-C regulated NaNO2 and diclofenac induced oxidative stress in RBC and vital organs through its antioxidant property.

Simple and complex clustered DNA damage represent critical initial damage caused by radiation. In this paper a multinomial probability model of clustered damage is developed with probabilities dependent on the energy imparted to DNA and surrounding water molecules. The model consists of four probabilities: A) direct damage of sugar-phosphate moieties leading to SSB, B) OH^- radical formation with subsequent SSB and BD formation, C) direct damage to DNA bases, and D) energy imparted to histone proteins and other molecules in a volume not leading to SSB or BD. These probabilities are augmented by introducing probabilities for relative location of SSB using a <10 bp criteria for double strand break (DSB), and for the possible success of radical attack to lead to SSB or BD. Model predictions for electrons, ⁴He and ¹²C ions are compared to experimental data and show good agreement. Thus, the developed model allows an accurate and rapid computational method to predict simple and complex clustered DNA damage as a function of radiation quality and to explore the resulting challenges to DNA repair.

In recent years, the assessment of damage scenarios of urban communities has become one of the central themes in local government policies, aimed at promoting effective seismic risk mitigation and improving the efficiency of rescue systems to manage emergencies. In Italy, the seismic hazard has become a topic issue since the 1982 Irpinia earthquake, and several ventures have been promoted to face the seismic mitigation of complex residential districts. The objective of this research is to define the damage scenarios of the city of Florence, where 97% of the building stock is designed without anti-seismic prescriptions. The urban vulnerability of Florence has been assessed on the basis of the current approaches available in technical literature, and it has been combined with the knowledge provided by the recent investigation on the subsoil. Once the possible damage scenarios have been defined, the resilience of the area has been determined and the population involved in the evacuation has been estimated.

The rise of antibiotic-resistant pathogens represents a significant global challenge in infectious disease control, which is amplified by the decline in the discovery of novel antibiotics. Staphylococcus aureus continues to be a highly significant pathogen causing infections in multiple organs and tissues in both healthcare institutions and community settings. The bacterium has become increasingly resistant to all available antibiotics. Consequently, there is an urgent need for novel small molecules that inhibit growth or impair survival of bacterial pathogens. Given their large structural and chemical diversity as well as often unique mechanisms of action, natural products represent an excellent avenue for the discovery and development of novel antimicrobial treatments. Anaephene A and B are two such naturally occurring compounds with significant antimicrobial activity against gram-positive bacteria. Here, we report the rapid syntheses and biological characterization of five novel anaephene derivatives, which display low cytotoxicity against mammalian cells but potent antibacterial activity against various S. aureus strains, including methicillin resistant S. aureus (MRSA) and the multi drug-resistant community acquired strain USA300LAC. A Sonogashira cross-coupling reaction served as the key step for the synthesis of the alkyl pyridinol products. Using the compound JC-01-074, which displays bactericidal activity already at low concentrations (MIC: 16 mg/ml), we provide evidence that alkyl pyridinols target actively growing and biofilm-forming cells and show that these compounds cause disruption and deformation of the staphylococcal membrane, indicating a membrane associated mechanism of action.

In order to solve the problem of structure damage location and degree identification, the weighted mean of vectors algorithm (INFO), a high-performance optimization one, was first introduced to identify structure damage. The genetic algorithm (GA) are improved to obtain a refined genetic algorithm (RGA). An objective function is constructed by combining the dynamic response transfer-ratio without modal analysis. INFO and RGA algorithms are used to optimize the objective function for damage identification. Though simulations, the INFO, RGA, GA algorithms were used to identify the damage on a simply supported beam and cantilevered plate with different levels of noise and different frequency spacing of pickup points. The simulations verify the effectiveness of the three damage identification methods, and the INFO algorithm has the highest damage identification accuracy, the RGA is second and the GA is the worst.

The motor protein Prestin found in the outer hair cells (OHCs) of the inner ear is responsible for producing high sensitivity and sharp frequency selectivity for mammalian hearing. Some studies have suggested that Prestin could serve as a serological biomarker for cochlear damage since OHCs are highly vulnerable to damage from various sources of insults. However, the reported data are inconsistent and lack appropriate negative controls. To investigate this further, we measured Prestin quantities in the bloodstream using ELISA kits from different companies. Wildtype (WT) mice were exposed to different ototoxic treatments, including noise exposure and ototoxic reagents that kill OHCs rapidly. Prestin-knockout (KO) mice were used as a negative control. Our data show that some ELISA kits were not able to detect Prestin specifically. The ELISA kit that could detect Prestin protein from cochlear homogenates failed to detect Prestin in the bloodstream despite significant damage to OHCs in cochleae. Furthermore, the optical densities of samples, which correlate to Prestin quantities, were significantly influenced by hemolysis in the samples. In conclusion, Prestin from OHCs is not a sensitive and reliable serological biomarker for detecting cochlear damage in mice.

Formidable and often seemingly insurmountable conceptual, technical, and methodological challenges hamper the measurement of oxidative stress in humans. For instance, fraught and flawed methods, such as the thiobarbituric acid reactive substances assay kits for lipid peroxidation, rate-limit progress. To advance translational redox research, we present ten comprehensive “cheat codes” for measuring oxidative stress in humans. The cheat codes include analytical approaches to assess reactive oxygen species, antioxidants, biomarkers of oxidative damage and redox regulation. They provide essential conceptual, technical, and methodological information inclusive of curated “do” and “don’t” guidelines. Given the biochemical complexity of oxidative stress, we present a research question-grounded decision tree guide for selecting the most appropriate cheat code (s) to implement in a prospective human experiment. Worked examples demonstrate the benefits of the decision tree-based cheat code selection tool. The ten cheat codes define an invaluable resource for measuring oxidative stress in humans.

L-Theanine, a unique non-protein amino acid, is an important bioactive component of green tea. Previous studies have shown that L-theanine has many potent health benefits, such as anti-anxiety effect, regulation of immune response, relaxing neural tension, reducing oxidative damage. However, little is known concerning whether L-theanine can improve the clearance of mitochondrial DNA (mtDNA) damage in organisms. Here, we reported that L-theanine treatment increased ATP production and improved mitochondrial morphology to extend the lifespan of UVC-exposed nematodes. Mechanistic investigations showed that L-theanine treatment enhanced the removal of mtDNA damage and extended lifespan by activating autophagy, mitophagy, mitochondrial dynamics, and mitochondrial unfolded protein response (UPRmt) in UVC-exposed nematodes. In addition, L-theanine treatment also up-regulated the expression of genes related to mitochondrial energy metabolism in UVC-exposed nematodes. Our study provided a theoretical basis for the possibility that tea drinking may prevent mitochondrial related diseases.

In a concrete beam initially crack is generated at the tension side under the effect of flexure, shear and torsional loadings. Accordingly, these weak concrete members require repair and/or strengthening to increase or restore their internal load capacity. In the current experimental and numerical investigations on concrete beam having different width to depth ratio of notch on its ultimate flexural load under one-point loading was considered. Further, the flexural behavior performance of notch concrete beam repaired with the three repair materials cement mortar, bacterial mortar and adhesive was also examined. Consequently, a comparative study is imple-mented between the experimental and numerical results. Concrete Damage plasticity (CDP) model was used for finite element numerical analysis of beam. The differences in numerical and experimental measured results ranges from 0.65 - 22.20 % for the ultimate load carrying capacity. As the notch size increases the ultimate load carrying capacity of beam was reduced. Addition-ally, linear regression model is used to predict the ultimate load values at an interval of 5 mm notch width up to maximum width of notch 100 mm. It can be observed that the ultimate load capacity for repaired beam is increased as compared to the notch beam for all the three repairing materials under consideration. The maximum ultimate load was increased in case of notch beam repaired using adhesive. As compared to the cement mortar the performance of the bacterial mortar in terms of the ultimate load was more. The bacterial mortar is found more sustainable and more durable as a repair material for the concrete structures.

With the deterioration of the bridge performance and ever-increasing amount of traffic, the bridge safety is becoming a concern for engineering community. A method that can assess the bridge's condition in real-time is urgently needed. The main factors that hinder the bridge condition assessment are the uncertain operational environments. A new moving principal component analysis (MPCA) based method is developed for structural damage detection of bridges in operational environments in this paper. Two main operational environmental factors: the environmental temperature and traffic loads, are studied in the assessment process to verify the robustness and practicality of the proposed method. The numerical and experimental results show that the proposed method is effective and accurate to assess the bridge condition in operational environments.

The insufficient toughness of concrete can lead to the occurrence of crack expansion, ultimately resulting in a decline in the physical and mechanical properties such as bearing capacity and deformation characteristics of structural components. In severe cases, this may lead to brittle failure, where the entire structure and system fail suddenly without significant deformation after being stressed. Additionally, during the process of shear and bending failure of reinforced concrete beams, the cracks generated on the side of the beam are mostly I-II composite cracks. Considering the material nonlinearity and geometric irregularity of reinforced concrete, it is of great significance to study the dynamic evolution law of crack expansion in reinforced concrete members. Based on experimental data, this paper aims to utilize the nonlinear finite element simulation software Abaqus to conduct finite element simulations of crack expansion in simple supported reinforced concrete beams. By accurately controlling the constitutive curves of concrete and reinforcement materials, the design of seismic performance of structural members can be enhanced, thereby making essential contributions to the preliminary analysis of actual crack control engineering. The nonlinear finite element results indicate that the joint cracks of the frame with the floor slab primarily manifest as flexural cracks, with the concrete damage degree of the floor slab being higher than that of the beam. This finding underscores the importance of considering the behavior of concrete and reinforcement materials in designing for seismic performance and crack control in actual engineering applications.

Cells respond to DNA double-strand breaks by initiating DSB repair and ensuing a cell cycle checkpoint. The primary responder to DSB repair is non-homologous end joining, an error prone repair pathway. However, when DSBs are generated after DNA replication in the G2 phase of the cell cycle, a second DSB repair pathway, homologous recombination, can come into action. Both ATM and ATR are important for DSB-induced DSB repair and checkpoint responses. One method of ATM and ATR working together is through the DNA end-resection of DSBs. As a readout and marker of DNA end-resection, RPA is phosphorylated at Ser4/Ser8 of the N-terminus of RPA32 in response to DSBs. Here, the significance of RPA32 Ser4/Ser8 phosphorylation in response to DNA damage, specifically in S phase to G2 phase of the cell cycle is examined. RPA32 Ser4/Ser8 phosphorylation in G2 synchronized cells is necessary for increases in TopBP1 and Rad9 accumulation on chromatin and full activation of the ATR-dependent G2 checkpoint. In addition, our data suggest RPA Ser4/Ser8 phosphorylation modulates ATM-dependent KAP-1 phosphorylation and Rad51 chromatin loading in G2 cells.

Aircraft heat exchangers play a crucial role in maintaining thermal balance and ensuring that essential components operate efficiently and safely. In this context, it is highly relevant to gain knowledge about the deterioration and the predominant damage mechanisms of these components. In this study, two different non-destructive methods are employed to analyze the damage initiation of a heat exchanger part during fatigue test. On the one hand, Acoustic Emission technique is employed using membrane-free microphones capable of capturing a broad bandwidth. The acoustic events were classified by a machine learning algorithm to determine their source and damage mechanisms. On the other side, Digital Image Correlation (DIC) allowed the measurement of the strain evolution along the test and more precisely, redistributions were considered as damage indicators. As a result, it was identified that AE served as early damage indicator as the cumulative number of events was in good agreement with the severity of the damage. With respect to classification two clear clusters ascribed to different type of events were identified. In the case of DIC, strain redistributions gave clear indications of damage or deterioration but at a later stage compared to AE

Bifenthrin (BF) is a new highly effective broad-spectrum insecticide that has gained widespread use. However, there is limited research on the potential toxic effects of bifenthrin pollution on amphibians. In this research, Chinese giant salamanders (CGS) were exposed to three different concentrations of BF (0, 0.04, and 4 g/L BF) for 1-week to investigate the toxic effects. Behavioral changes, liver pathology, oxidative stress factors, DNA damage, and transcriptome differences were observed and analyzed. The results showed that exposure to BF (0.04 and 4) significantly decreased the adenosine-triphosphate (ATP), superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), and 8-hydroxydeoxyguanosine (8-OHdG) contents in the brain, liver, and kidney of CGS, whereas the malondialdehyde (MDA) and reactive oxygen species (ROS) contents were increased. The liver tissue showed considerable inflammatory reactions and structural malformations. RNAseq analysis of the liver showed that BF caused abnormal antioxidant indices of CGS, which affected molecular function genes such as catalytic activity, ATP-dependent activity, metabolic processes, signaling and immune system processes, behavior and detoxification significantly up-regulated, resulting the differential genes were significantly enriched in calcium signaling pathway, PPARα signaling pathway and NF-kB signaling pathway. These results indicated that BF induced the abnormal production of free radicals to exceed the potential of the self-defense system, causing different degrees of oxidative damage and lipid peroxidation in the body, resulting in oxidative stress, abnormal lipid metabolism, DNA damage, tissue inflammation, and abnormal behavior. This work provides a theoretical basis for the rational use of pyrethrin and environmental risks assessment, and scientific guidance for the conservation of amphibian populations.

Cellular aging has drawn the attention of researchers, scientists, and biotech businesses for the treatment of a number of medical conditions. Cellular aging is primarily defined by consistent cessation of proliferative development in response to internal and external stressors, including DNA damage, telomere shortening, mitochondrial dysfunction, and regulation of the senescence-associated secretory phenotype (SASP). Disturbances involving these factors may contribute to age-related disease development. Therefore, the current review aims to explore anti-aging factors targeting DNA damage response and SASP regulation and their detailed signaling networks. In addition, it provides an opportunity for researchers to identify not only anti-aging targets, but also anti-aging therapeutic strategies based on identified and non-identified targets.

DNA damage repair lies at the core of all cells’ survival strategy, including cancerous. Therefore, targeting such repair mechanisms forms the major goal of cancer therapeutics. The mechanism of DNA repair has been tousled with the discovery of multiple kinases. Recent studies on Tousled like Kinases have brought significant clarity on the effectors of these kinases which stands to regulate DSB repair. In addition to their well-established role in the DDR and cell cycle checkpoint mediation after DNA damage or inhibitors of replication, their suspected involvement in the actual DSB repair process has more recently been strengthened by the important finding that TLK1 phosphorylates RAD54 and regulates some of its activities and localization in the cell. Earlier findings of its regulation of RAD9 during checkpoint deactivation as well as defined steps during NHEJ ends processing were earlier hints of its important involvement broadly in DSB repair. All this has opened up new avenues to target cancer cells in combination therapy with genotoxins and TLK inhibitors.

The contexts where there is mining and agriculture activities are potential sources of risk to human health due to contamination by chemical mixtures. This study explored the association between the frequency of micronuclei and pesticides in regions with ferronickel (Montelibano, Córdoba) and gold (Nechí, Antioquia) mining, and a closed native mercury mine (Aranzazu, Caldas). A cross-sectional study was carried out with 247 residents in the mining regions. Sociodemographic, occupational, and toxicological variables were ascertained. Blood and urine samples were taken for pesticide analysis (12 organochlorines, organophosphates, and carbamates), 68 chemical elements were quantified in hair, and micronuclei (MN) were quantified in lymphocytes. The mixtures of chemical elements were grouped through exploratory factor analysis. Prevalence ratios (PR) were estimated with robust variance Poisson regressions to explore associations. The highest concentrations of chemical elements were in the active mines. The potentially most toxic chemical mixture was observed in the ferronickel mine. Pesticides were detected in a low proportion of participants. The frequency of MN was similar in the three mining contexts. There was great heterogeneity in the exposure to pesticides and chemical elements. The “hormetic effect” of selenium is described, in which at low doses it acts as a chelator and at high doses it can enhance the toxic effects of other elements. It is proposed that future studies in mining contexts include the measurement of chemical mixtures to better assess exposure and potential adverse health effects.

Salmorejo is a homogenate based on tomato, olive oil and breadcrumbs commercialized as a “fresh-like” cold puree in Spain and other European countries. Salmorejo is thermolabile and requires pasteurising upon High Temperature, Short Time (HTST) conditions to inhibit microbes and enzymes. Due to its penetration, dielectric heating by radiofrequency (RF) might improve pasteurisation results of conventional heating (CH) in viscous products. The objective was to validate the pasteurisation temperature (70-100 °C, at 5 ºC intervals) for salmorejo processed by radiofrequency (operating at 27.12 MHz for 9.08 s) or conventional continuous heating. Salmorejo was prone to thermal damage upon HTST conditions. Main heat-induced changes include: orangeness, flavour homogenisation, loss of freshness, thickening, loss of vitamin C and lipid oxidation. A ‘fresh-like’ good quality salmorejo can be obtained using either conventional or radiofrequency pasteurisers. Both CH and RF equivalent treatments allowed a strong reduction of total and sporulated mesophilic microorganisms, and an adequate inhibition of the pectinmethylesterase, peroxidase and, to a lesser extent, polyphenoloxidase, but did not inhibit the polygalacturonase enzyme. Pasteurisation at 80 °C for 9.8 s (RF) or 10.9 s (CH) provided a good equilibrium in levels of microbiological and enzymatic inhibition and thermal damage to the product. Increasing this temperature does not improve enzyme inactivation levels and salmorejo may become overheated.

Selected glasses with 10 Na₂O + (90-x) P₂O₅ + x BCD where bypass cement dust (BCD) x value =10, 20, 30 in mol% were synthesized by recognizable melting annealing technique. Cooperative characterization of the prepared glasses were carried out through FTIR and SEM analysis before and after immersed in simulated body fluid (SBF) solution for 13 and 23 days at 37 ^oC. After immersion in SBF, apatite layer is produced on the glass surface after 13 day and increase after 23 day, showing good bioactivity after immersion in the SBF especially for bioglass sample with 30% BCD. A porous hydroxy apatite layer produced on the surface of SBF-glass composite and this layer became denser after more soaking time, periods were extended from 13 to 23 days. Atomic absorption spectroscopy explained the early period of soaking that cause release of both Si and Ca ions through the glass beside decreasing of phosphrous ions. Bioglass (BCD-30) is studied as shielding for gamma, protons and alphas by using Phy-X software, SRIM Monte Carlo simulation code and its subroutine TRIM. The gamma shielding parameters, mass stopping power (MSP), range for both proton (H- ions) and alpha (He- ions) in bioglass- BCD-30 and human bone tissue have estimated. Also, comparison between them is calculated in predicting the radiation damage and atomic displacements per atom (dpa).

This study investigated and classified typical structures in rural village and analyzed the vulnerability of various typical types of structures. Based on the statistics of earthquake damages with magnitudes above 5 from 1996 to 2013 in China, the damage matrixes of different types of structures in rural village are obtained. And The vulnerability index and the vulnerability equation of structure are crucial to assess the earthquake losses of typical structures under different magnitudes earthquakes. According to the seismic loss of different types of structures under different earthquake magnitudes, there are possible to improve the seismic resilience of the buildings in rural village. Moreover, the regional vulnerability is analyzed by β probability distribution function, and the comprehensive seismic performance index of different types of agricultural buildings in the region is obtained. The main research is to predict the loss of different types of structures under different earthquake magnitudes in the future, and to provide technical support for different types of building in rural village reinforcement.

Alzheimer’s disease (AD) is a genetically complex senile neurodegeneration with unknown etiology. The first gene discovered to be mutated in early-onset AD, the amyloid precursor protein (APP), has been widely assumed as a causal factor in the disease cascade due to its generation of Aβ species. APP has an evolutionarily conserved biological role and activates a signaling program with notable similarities to integrin—a cell adhesion receptor with a wide array of functions. Intriguingly, several AD genome-wide association study (GWAS) candidate genes, including the SHARPIN locus recently reported by us and others, influence signaling of the integrin pathway. Integrins are focal adhesion regulators and serve in nervous system development, synaptic plasticity, and Tau phosphorylation. These observations suggest that the function of APP probably goes beyond Aβ generation in AD. Aging—the strongest risk factor for AD—is associated with various clock-like events in cells. For instance, neurons are continuously impacted by stochastic ‘hits’ to their genomes in aging, in the forms of DNA damage, insertion-deletions, copy-number variations (CNVs) and other types of somatic mutations. DNA damage and somatic mutations can result in neoplastic changes and cancer in mitotically active cells. However, their consequences in post-mitotic cells such as aging neurons are less defined. The current hypothesis holds that the stochastic loss of DNA sequence data at random loci in aging affects longer genes by chance more frequently. As a result, the biological processes coordinated by long genes may be more vulnerable to such random aging effects. Curiously, as shown by us and others, long genes are strongly enriched for synapse- and cell adhesion-related ontologies, more than any other biological process or cellular compartment. In addition, among various cell types, neurons possess the highest levels of long gene expression and are therefore more vulnerable to such harmful effects. The long gene vulnerability hypothesis provides a simple link between aging and the genetic landscape of AD and warrants new strategies for disease modification.

Background: Morphological alterations in intracranial pressure pulse waveform (ICPPW) secondary to intracranial hypertension (ICP >20 mmHg) and reduction in intracranial compliance (ICC) are well known indicators of neurological severity. To date, no studies have documented the ICPPW modifications after intracranial hypertension resolution with decompressive craniectomy (DC). The present study aimed to assess the morphological alterations in ICPPW among neurocritical care patients with and without DC, by comparing the variations of ICPPW features according to elevations in mean ICP values. Methods: Patients requiring ICP monitoring because of severe traumatic or spontaneous conditions were included. Mean ICP values were compared with ICPPW features (P2/P1 ratio, TTP and pulse amplitude). Elevation in ICP was produced by means of ultrasound-guided manual internal jugular veins compression. Results were distributed for three groups: intact skull (exclusive burr hole for ICP monitoring), craniotomy/large fractures (group 2) or DC (group 3). Results: 57 patients were analyzed. 21 (36%) presented no skull defects, whereas 15 (26%) had DC. ICP was not significantly different between groups: ±13.59 for intact and ±17.66 mmHg for DC, with ICP induced elevation also similar between groups (p= 0.56). Significant elevation was observed for P2/P1 ratio for groups 1 and 2, whereas reduction was observed in group 3 (elevation of ±0.09 for groups 1 and 2, whereas reduction of 0.03 for group 3, p=0.01). Conclusion: In the present study, intracranial pressure pulse waveform analysis indicated that intracranial compliance was significantly more impaired among decompressive craniectomy patients, although ICPPW indicated DC to be protective for further influences of ICP elevations over the brain. Analysis of ICPPW seems to be an alternative to real time ICC assessment.

Galangin(Gal) is a natural active flavonoid compound separated from the roots and rhizomes of Alpinia ofcinarum Hance. Modern pharmacological studies have shown that Gal has a variety of biological activities such as anti-tumor, anti-fungal, anti-bacterial, anti-inflammatory, anti-ischemic stroke, suppressing vitiligo and Alzheimer’s disease, etc. The purpose of this research was to prepare a galangin self-microemulsion drug delivery system (Gal-SMEDDS) and compare its anti-oxidant activity and pharmacokinetics with free Gal.The average particle size of the prepared Gal-SMEDDS was approximately 21.33 nm, the polydispersity index was 0.096, the zeta potential was -4.09 mV, and the entrapment efficiency was 96.74%. Compared with free Gal, the release of Gal-SMEDDS was improved in vitro release experiment. Cell experiments showed that Gal had obvious anti-oxidation effect, and the effect of Gal-SMEDDS was better than that of free Gal. In vivo pharmacokinetic experiments showed that the pharmacokinetic parameters of Gal-SMEDDS were better than that of free Gal, which indicated that the self-microemulsion drug delivery system(SMEDDS) effectively increases the oral bioavailability of Gal and alters its pharmacokinetic parameters, such that it may be effective in the treatment of anti-oxidant.

Single-stand selective monofunctional uracil DNA glycosylase 1 (SMUG1) works to remove uracil and certain oxidized bases from DNA during base excision repair (BER). This review provides a historical characterization of SMUG1 and 5-hydroxymethyl-2'-deoxyuridine (5-hmdU) one important substrate of this enzyme. Biochemical and structural analyses provide remarkable insight into the mechanism of this glycosylase revealing SMUG1 has a unique helical wedge which influences damage recognition during repair. Rodent studies suggest that, while SMUG1 shares substrate specificity with another uracil glycosylase UNG2, loss of SMUG1 can have unique cellular phenotypes. This review highlights the multiple roles SMUG1 may play in preserving genome stability, and how the loss of SMUG1 activity may promote cancer. Finally, we discuss recent studies indicating SMUG1 has moonlighting functions beyond BER, playing a critical role in RNA processing including the RNA component of telomerase.

The purpose of this study was to better understand the interactive impact of two soil-borne pathogens, Phytophthora cactorum (as the primary pathogen) and Armillaria gallica (as secondary), on two-year-old seedlings of silver birch (Betula pendula) subjected to stress caused by mechanical defoliation simulating primary insect feeding. One year after treatments, the chlorophyll fluorescence measurement and gas chromatography coupled with mass spectrometry (GC-MS) were used to analyze the photosynthetic activity in leaves, the volatile organic compounds (VOCs) emitted by birch leaves and chemical compounds from roots. Only the infection of roots by P. cactorum increased photosynthetic rates in the leaves, which may suggest its cryptic development in contrast to fungi. The birch leaves in seedlings exposed to 50% defoliation, inoculation with P. cactorum and A. gallica emitted more aromatic carbonyls and alcohols, as well as half as much aliphatic esters, compared to untreated controls. In infected birch roots, the production of phenols, triterpenes and fatty alcohols increased, but fatty acids decreased. This was the first experimental confirmation of the pathogenicity of P. cactorum on silver birch seedlings in Poland. The most severe damage to roots took place only in the case of two-way or three-way interactions. Higher levels of aromatic carbonyls and alcohols in leaves, as well as phenolic compounds in roots of stressed birches (compared to control) suggest an activation of plant systemic acquired resistance (SAR).

As a medical student (Granada University Medical School, Spain), interested in Pediatrics, expended countless hours at the hospital pediatric facilities and got to know many of the children and their medical problems. A particular case, still vivid on my mind, awaken my scientific curiosity. One day, walking and talking with a seven years old child he unexpectedly felt down unconscious with multiple, incontrollable and erratic muscular contractions involving face, body and extremities and salivating. I was overwhelmed thinking it was the child’ last hour. At the time, my knowledge of epilepsy was nil. Following the seizures, the child was up, talking and walking with me as if nothing has happened and without any knowledge of the event. What could have caused the brain motor cortex to suddenly discharge that amount of altered activity causing generalized and erratic muscular contractions remains inexplicable. I migrated to USA, become a Pediatric (Developmental) Pathologist and Director of the Pediatrics Autopsy Service (1962-1999) at the Dartmouth-Hitchcock Medical Center, New Hampshire. I carried out countless postmortem studied of children brains, normal (unaltered) as well as those altered by hemorrhagic, hypoxic-ischemic and/or traumatic damage. With an NIH Fellowship, I spend one year (1967-68) at the Cajal Institute (Madrid, Spain) studying Cajal’ old Golgi preparations and learning about the method. Some of my Golgi studies of children’ brains have been published: The Human Brain. Prenatal Development and Structure, Springer, Heidelberg, Germany, 2012. The present monograph explores the developmental neuropathology of selected perinatal cortical injuries through their acute, subacute and chronic stages. Including: a) how an altered neuronal activity evolves in a damaged cortical region; b) how it moves through the cortex (epileptic auras); and c) how it reaches the motor cortex to be discharged as erratic and incontrollable muscular contractions. Understanding these processes should provide insights into the pathogenesis of epilepsy secondary to perinatal brain damage.

Mining can impact the environment, biodiversity and human health through direct and indirect practices. This study investigated the effects of gold mining on Gerbillus nanus, pointing to organ dysfunction and redox imbalance. Soil samples, Lycium shawii and G. nanus were collected from a site near a mining planet and a control site. Soil and L. shawii samples from the mining site showed a significant increase cadmium (Cd), cupper (Cu), mercury (Hg), arsenic (As), zinc (Zn), lead (Pb) and vanadium (V). Hepatic, renal and pulmonary Cd, Pb, Hg, Zn, Cu, Fe, As and V concentrations were increased significantly in G. nanus at the mining site. Markers of liver and kidney function were elevated in serum, and several histological manifestations were demonstrated in liver, kidney and lung of G. nanus at the mining site. Malondialdehyde and nitric oxide were increased, and glutathione and antioxidant enzyme were declined in the liver and kidney of G. nanus. In conclusion, mining practices triggered tissue damage and oxidative stress in G. nanus living close to the mining site. These findings can represent the scientific basis for evaluating the environmental and health impact of mining in the on the nearby communities.

To gain insight into riser motions and associated fatigue damage due to vortex-induced vibration (VIV), data loggers such as strain sensors and/or accelerometers are sometimes deployed on risers to monitor their motion in different current velocity conditions. Accurate reconstruction of the riser response and empirical estimation of fatigue damage rates over the entire riser length using measurements from a limited number of sensors can help in efficient utilization of the costly measurements recorded. Several different empirical procedures are described here for analysis of the VIV response of a long flexible cylinder subjected to uniform and sheared current profiles. The methods include weighted waveform analysis (WWA), proper orthogonal decomposition (POD), modal phase reconstruction (MPR), a modified WWA procedure, and a hybrid method which combines MPR and the modified WWA method. Fatigue damage rates estimated using these different empirical methods are compared and cross-validated against measurements. Detailed formulations for each method are presented and discussed with examples. Results suggest that all the empirical methods, despite different underlying assumptions in each of them, can be employed to estimate fatigue damage rates quite well from limited strain measurements.

Background: KDM5 enzymes are H3K4 specific histone demethylases involved in transcriptional regulation and DNA repair. These proteins are over-expressed in different kinds of cancer, including breast, prostate and bladder carcinoma, with positive effects on cancer proliferation and chemo-resistance. For these reasons, these enzymes are potential therapeutic cancer targets. Methods: In the present study, we analyzed the effects of three different inhibitors of KDM5 enzymes in MCF-7 breast cancer cells over-expressing JARID1B. In particular we tested H3K4 demethylation (western blot); target gene transcription (RNAseq and real time PCR); radio-sensitivity (citoxicity and clonogenic assays) and damage accumulation (kinetics of H2AX phosphorylation). Results: we show that two compounds with completely different chemical structure can selectively inhibit KDM5 enzymes and that both compounds are capable of increasing sensitivity of breast cancer cells to ionizing radiation and H2AX phosphorylation. Conclusions: These findings confirm the involvement of H3K4 specific demethylases in DNA damage signaling and repair and suggest new strategies for the therapeutic use of their inhibitors.

New corrosion inhibitor derived from coumarin-3-amine namely 3-((2-chlorobenzylidene)amino)coumarin was synthesized and characterized by CHN elemental analysis in addition to Fourier transform infrared and nuclear magnetic resonance techniques. The anti-corrosion ability of 3-((2-chlorobenzylidene)amino)coumarin to inhibit the impacts of corrosion has been demonstrated and damage reduction of the mild steel also. 3-((2-chlorobenzylidene)amino)coumarin, has been employed as a good corrosion inhibitor for mild steel in HCL solution. The efficiency of the inhibition was figured according to weight loss method and it was 74.6%.

Understanding and predicting damage progression within thin plain-woven CFRP components is an essential issue for scheduling maintenance intervals and structural inspections, and typically require extensive test series. However, uncertainties always remain and result in conservative design and unnecessary downtimes due to the repeated inspections of a healthy structure. SHM can be used to reduce these uncertainties, as it allows to evaluate the condition of a mechanical structure during operation. Numerous SHM methods are developed , that achieve different levels of damage identification but are often investigated at small coupons with non-realistic structural damages and loading conditions on both, structure and sensor. The present research investigates the electrical impedance tomography (EIT) featuring an elastoresistive thin-film sensor to evaluate damage that propagates from a circular hole in a large plate under cyclic tensile-tensile multi-block loading. Applied fatigue loads were increased multiple times up to a total number of two million cycles. During the loading damage initiated at the hole and continuously propagated into the plate. Repeated EIT evaluations of the applied sensor and validating evaluations by means of digital image correlation clearly revealed the robustness of the hardware and the potential of the SHM method for damage evaluation of plain-woven CFRP components.

DNA is frequently damaged by genotoxic stresses such as ionizing radiation, reactive oxygen species, and nitrogen species. DNA damage is a key contributor to cancer initiation and progression, and thus the precise and timely repair of these harmful lesions is required. Recent studies revealed transcription as a source of genome instability, and transcription-coupled DNA damage has been a focus in cancer research. Impaired mRNA export is closely related to DNA damage through R-loop formation. The molecular machineries of transcription-coupled DNA damage have been extensively analyzed in Saccharomyces cerevisiae. However, the molecular basis of these phenomena in higher eukaryotes remains elusive. In this review, we focus on the relationship between deregulated mRNA export, especially through the transcription-export-2 (TREX-2) complex, and cancer development. The expression of GANP, a key molecule in the TREX-2 complex, is highly associated with tumorigenesis in mouse and human. Additionally, we describe recent evidence for medical application that downregulation of the other components may be a good candidate for chemotherapeutic target in terms of reducing the side effects, although the involvement of R-loop is still ambiguous.

Radiotherapy remains a cornerstone in cancer treatment, leveraging ionizing radiation to eradicate malignant cells. Its efficacy, however, is frequently challenged by the heterogeneous sensitivity of tumors and surrounding tissues to radiation. Therefore, understanding the molecular mechanisms underlying radiosensitivity is crucial for improving treatment outcomes. Among the myriad of molecular players involved, the tumor suppressor protein p53 stands out as a central regulator with significant implications for radiosensitivity. Known as the “guardian of the genome,” p53 plays a pivotal role in maintaining genomic stability and orchestrating cellular responses such as cell cycle arrest, DNA repair, apoptosis, and senescence in response to various stress signals, including radiation-induced DNA damage. Activation of p53 triggers the transcription of target genes involved in DNA repair pathways, such as p21, MDM2, and GADD45, facilitating the repair of radiation-induced DNA damage or the elimination of irreparably damaged cells. This, in turn, influences the overall radiosensitivity of tissues. Mutations in the TP53 gene, which encodes p53, are among the most frequent genetic alterations in human cancers. Loss or dysfunction of p53 can compromise the cellular response to radiation, leading to increased resistance to therapy and poorer clinical outcomes. Conversely, intact p53 function is associated with enhanced radiosensitivity due to its ability to promote cell cycle arrest and apoptosis in response to radiation-induced DNA damage. In conclusion, elucidating the molecular mechanisms by which p53 influences radiosensitivity is essential for advancing our understanding of radiation response in cancer cells and developing more effective therapeutic approaches in cancer treatment. This review provides a comprehensive overview of the multifaceted role of p53 in modulating cellular responses to radiation, emphasizing its influence on radiosensitivity.

Carbon fiber reinforced polymers (CFRP) are extensively employed in the aerospace industry due to their excellent properties. Delamination damage occurring at critical locations in CFRP can seriously reduce the safety of in-service components. The detection and localization of delamination damage using Lamb waves hold significant potential for widespread application in non-destructive testing. However, the choice of damage localization algorithm may produce different delamination damage localization results. This research presented an IRAPID (improved reconstruction algorithm for probabilistic inspection of defects) method derived from the ORAPID (original reconstruction algorithm for probabilistic inspection of defects) method, aiming to improve the accuracy and reliability of delamination damage localization. Three CFRP bending plates, including a healthy bending plate and two bending plates with delamination damage sizes of Φ20 mm and Φ40 mm, were prepared in the experiment, respectively. The detection experiment of the CFRP bending plate using lead zirconate titanate (PZT) as a transducer to excite and receive Lamb waves was conducted, and the influence of excitation signal frequency on the performance of the proposed method was discussed. Under the condition of excitation signal frequency of 220 ~ 320 kHz and step size of 10 kHz, the accuracy of the delamination damage localization method proposed in this paper was compared with that of the existing methods. The experimental results indicate that the IRAPID algorithm exhibits good stability in the localization of delamination damage across the frequency variations range considered. The localization error of the IRAPID algorithm for delamination damage is significantly lower than that of the DaS (delay-and-sum) algorithm and the ORAPID algorithm. As the size of the delamination damage increases, so does the localization error. The accuracy of delamination damage localization is lower in the X-axis direction than in the Y-axis direction. By averaging the localization results across various frequencies, we can mitigate the potential localization errors associated with single-frequency detection to a certain extent. For the localization of delamination damage, Lamb waves at multiple frequencies can be employed for detection, and the detection results at each frequency are averaged to enhance the reliability of localization.

Alzheimer's Disease (AD) presents a significant challenge in the wake of its multifaceted nature, characterized by cognitive decline, memory impairment, and neuroinflammation. Despite extensive research, effective pharmacological interventions remain elusive, prompting exploration into non-pharmacological approaches. Microcurrent therapy (MC), utilizing imperceptible currents, has emerged as a potent clinical protocol. While previous studies have focused on its therapeutic effects, this study investigates its impact on neuronal damage and neuroinflammation in an AD mouse model, specifically addressing potential side effects. Utilizing 5xFAD transgenic mice, we examined the effects of MC therapy on neuronal integrity and inflammation. Our findings suggest that MC therapy attenuates memory impairment and reduces neurodegeneration, as evidenced by improved performance in memory tests and preservation of neuronal structure. Additionally, MC therapy significantly decreases amyloid-beta (Aβ) plaque deposition and inhibits apoptosis, indicating its potential to mitigate AD pathology. Our study discovered that MC therapy effectively reduces glial activation by inhibiting the TLR4-MyD88-NFκB pathway, consequently leading to decreased levels of inflammatory factors TNF-α, IL-1β, and IL-6, thus implicating TLR4 in neurodegenerative disease-related neuroinflammation. Furthermore, while our study did not observe significant adverse effects, further clinical trial into potential side effects and neuroinflammatory responses associated with MC therapy is warranted.