Topoisomerases, common targets for anti-tumor therapeutics, are crucial enzymes for DNA replication, transcription, and many other aspects of DNA metabolism. The potential anti-cancer effect of thiosemicarbazones (TSC) and metal-TSC complexes has been demonstrated by targeting several biological processes, including DNA metabolism. Human topoisomerases were discovered among the molecular targets for TSCs, and metal-chelated TSCs specifically displayed significant inhibition. The processes by which metal-TSCs or TSCs inhibit topoisomerases are still being studied. In this brief review, we summarize the TSCs and metal-TSCs that inhibit various types of human topoisomerases.

Phenotypes are necessary for genomic evaluations and management. Sometimes genomics can be used to measure phenotypes when other methods are difficult or expensive. Prolificacy of bulls used in multiple-bull pastures for commercial beef production is an example. A retrospective study of 79 bulls aged 2-year-old and older used 141 times in 4-5 pastures across 4 years was used to estimate repeatability from variance components. Traits available before each season’s use were tested for predictive ability. Sires were matched to calves using individual genotypes and evaluating exclusions. A lower cost method of measuring prolificacy was simulated for 5 pastures using the bulls’ genotypes and pooled genotypes to estimate average allele frequencies of calves and of cows. Repeatability of prolificacy was 0.62 ± 0.09. A combination of age-class and scrotal circumference accounted for less than 5 % of variation. Simulated estimation of prolificacy by pooling DNA of calves was accurate. Adding pooling of cow DNA or actual genotypes both increased accuracy about the same. Knowing a bull’s prior prolificacy would help predict future prolificacy for management purposes and could be used in genomic evaluations and research with coordination of breeders and commercial beef producers.

The ability to predict physical characteristics from DNA presents significant opportunities for forensic science. Giving scientists an ability to make predictions about the donor of genetic material at a crime scene can then give investigators new intelligence leads for cold cases where DNA evidence has not identified any person of interest. However, the interpretation of this new form of intelligence requires careful analysis. The responses to an online survey, conducted in 2018-19, were used to examine how actors in the criminal justice system assess and interpret different types of DNA evidence and intelligence. The groups of focus for the survey were investigators, legal practitioners and the general public (as potential jurors). Several statistically significant effects were identified based on occupation and whether an individual had prior exposure to new DNA technology. Monitoring how those involved in interpreting reports from different types of DNA evidence and intelligence interpret them helps to ensure that decisions are made based on a sound understanding of their capabilities and limitations and may inform broader training and awareness strategies.

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.

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.

A fully analytical treatment of the base-pair and codon dynamics in double-stranded DNA molecules is introduced, by means of a realistic treatment which considers different mass values for G, A, T, and C nucleotides and takes into account the intrinsic three-dimensional, helicoidal geometry of DNA in terms of a Hamitonian in cylindrical coordinates. Within the framework of the Peyrard-Dauxois-Bishop model we consider the coupling between stretching and stacking radial oscillations as well as the twisting motion of each base pair around the helix axis. By comparing the linearized dynamical equations for the angular and radial variables when going from the bp local scale to the longer triplet codon scale, we report an underlying hierarchical symmetry. The existence of synchronized collective oscillations of the base-pairs and their related codon triplet units are disclosed from the study of their coupled dynamical equations. The possible biological role of these correlated, long-range oscillation effects in double standed DNA molecules containing mirror-symmetric codons of the form XXX, XX’X, X’XX’, YXY, and XYX is discussed in terms of the dynamical equations solutions and their related dispersion relations.

There is a major clinical need for accurate biomarkers for prostate cancer prognosis, to better inform treatment strategies and disease monitoring. Current clinically recognised prognostic factors, including prostate-specific antigen (PSA) levels, lack sensitivity and specificity in distinguishing aggressive from indolent disease, particularly in patients with localised intermediate grade prostate cancer. There has therefore been a major focus on identifying molecular biomarkers that can add prognostic value to existing markers, including investigation of DNA methylation, which has a known role in tumorigenesis. In this review, we will provide a comprehensive overview of the current state of DNA methylation biomarker studies in prostate cancer prognosis, and highlight the advances that have been made in this field. We cover the numerous studies into well-established candidate genes, and explore the technological transition that has enabled hypothesis-free genome-wide studies and the subsequent discovery of novel prognostic genes.

Background: The presence of HIV residual replication markers was investigated among distinct subgroups of individuals on antiretroviral treatment (ART). Methods: One hundred sixteen patients were distributed into 5 treatment groups: first-line suppressive ART with a non-nucleoside analog reverse-transcriptase inhibitor (NNRTI) (n = 26), first-line suppressive ART with boosted protease inhibitors (PI-r) (n = 25), suppressive salvage therapy using PI-r (n = 27), suppressive salvage therapy with PI-r and raltegravir (n = 22) and virologic failure (n = 16). Episomal and total DNA quantitation was evaluated. HIV antibody and LPS quantitation was performed. Results: Episomal DNA was positive in 26% to 38% of individuals under suppressive ART, and it was higher among ART virologic failure group (p = 0.04). HIV proviral load was higher among patients with detectable episomal DNA (p = 0.01). Individuals receiving initial PI-r treatment presented lower HIV antibody (p = 0.027) and LPS (p = 0.029) levels than individuals receiving NNRTI. There was a negative correlation between episomal DNA quantitation and the duration of suppressive ART (p = 0.04), CD4+ T-cell count (p = 0.08), and CD8+ T-cell count (p = 0.07). Conclusions: Residual HIV replication has been inferred among individuals under suppressive ART according to episomal DNA detection. Residual replication may decrease with longer periods of suppressive ART and higher levels of CD4+ and CD8+ T cells. The relationship between episomal DNA and total DNA suggests there is a replenishment of the proviral reservoir. Lower antibody and LPS levels among patients with initial PI-r ART suggest these regimens may more effectively suppress HIV, more effectively decreasing HIV antigenic component.

High concentrations of Na⁺ or [Co(NH₃)₆]³⁺ can induce the B to Z conformational transition in alternating (dC-dG) oligo and polynucleotides. The use of short DNA oligomers (dC-dG)₄ and (dm⁵C-dG)₄ as models can allow a thermodynamic characterization of the transition. Both form right handed double helical structures (B-DNA) in standard phosphate buffer with 115 mM Na⁺ at 25 ^oC. However, at 2.0 M Na⁺ or 200 mM [Co(NH₃)₆]³⁺, (dm⁵C-dG)₄ assumes a left handed double helical structure (Z-DNA) while the unmethylated (dC-dG)₄ analogue remains right handed under those conditions. We have previously demonstrated that the enthalpy of the transition at 25 ^oC for either inducer can be determined using isothermal titration calorimetry (ITC) [Ferreira, J. M. & Sheardy, R. D., Biophys. J. 2006, 91, 1–7]. Here, ITC is used to investigate the linkages between temperature, water activity and DNA conformation. We found that the determined enthalpy for each titration varied linearly with temperature allowing determination of the heat capacity change (DC_p) between the initial and final states. As expected, the DC_p values were dependent upon the cation (i.e. Na⁺ vs [Co(NH₃)₆]³⁺) as well as the sequence of the DNA oligomer (i. e., methylated vs unmethylated). Osmotic stress experiments were carried out to determine the gain or loss of water by the oligomer induced by the titration. The results are discussed in terms of solvent accessible surface areas, electrostatic interactions and the role of water.

Oxidative and nitrosative stress are a common problem when manipulating gametes in vitro. In vitro development in mammalian embryos is highly affected by culture conditions, especially by reactive oxygen species (ROS) and reactive nitrogen species (RNS), because its absence or over production causes embryo arrest and changes in gene expression. Melatonin in gamete co-incubation during IVF has deleterious or positive effects depending on the concentration used in culture medium, demonstrating the delicate balance that must exist between antioxidant and pro-oxidant activity. Further research is needed to better understand the possible impact of melatonin on the different IVP steps in domestic animals, especially in seasonal breeds where this neuro-hormone system highly regulates its reproduction physiology.

In E. coli DNA replication forks stall on average once per cell cycle. When this occurs, replisome components disengage from the DNA, exposing an intact, or nearly intact fork. Consequently, the fork structure must be regressed away from the initial impediment so repair can occur. Regression is catalyzed by the powerful, monomeric DNA helicase, RecG. During this reaction, the enzyme couples unwinding of fork arms to rewinding of duplex DNA resulting in the formation of a Holliday junction. RecG works against large opposing forces enabling it to clear the fork of bound proteins. Following subsequent processing of the extruded junction, the PriA helicase mediates reloading of the replicative helicase DnaB leading to the resumption of DNA replication. The single-strand binding protein (SSB) plays a key role in mediating PriA and RecG functions at forks. It binds to each enzyme via linker/OB-fold interactions and controls fork loading sites in a substrate-dependent manner that involves helicase remodeling. Finally, it is displaced by RecG during fork regression. The intimate and dynamic SSB-helicase interactions play key roles in ensuring fork regression and DNA replication restart.

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.

The study titled "Molecular Choreography of DNA: Insights and Innovations" explores the intricate dance of DNA, shedding light on its structure, function, and regulation. This comprehensive review delves into the historical significance of DNA research, from Watson and Crick's double helix discovery to recent innovations in genomics and molecular biology. The review highlights DNA's roles in replication, repair, gene regulation, and chromatin dynamics, emphasizing the precision and complexity of its molecular choreography. Innovations like CRISPR-Cas9 gene editing and advanced sequencing technologies have revolutionized our understanding of DNA, opening new avenues for scientific exploration. This study aims to provide readers with a deeper appreciation of DNA's central role in life's choreographed processes.

In our work, using the analysis of DNA barcodes and morphology (wing color, male genitalia, sphragis shape in females), we show that the group of species close to P. mnemosyne is represented by two phylogenetic lineages, the western and eastern ones. The eastern lineage includes P. stubbendorfii, P. glacialis and P. hoenei. The western lineage includes three morphologically similar species, P. mnemosyne (Western Eurasia), P. turatii (southwestern Europe) and P. nubilosus stat. nov. (Turkmenistan and NE Iran), as well as P. ariadne (Altai). The latter species differs from the rest of the group in the presence of red spots on the wings. Parnassius mnemosyne s.s. is represented by four differentiated mitochondrial clusters that show clear association with specific geographic regions. We propose to interpret them as subspecies: P. mnemosyne mnemosyne (Central and Eastern Europe, N Caucasus, N Turkey), P. mnemosyne adolphi (the Middle East), P. mnemosyne orientalis (Tian Shan) and P. mnemosyne gigantea (Gissar-Alai in Central Asia). We demonstrate that in P. ariadne the red spots on the wing evolved as a reversion to the ancestral wing pattern. This reversion is observed in Altai, where the distribution areas of the western lineage, represented by P. ariadne, and the eastern lineage, represented by P. stubbendorfii, overlap. These two species hybridize in Altai, and we hypothesize that the color change in P. ariadne is the result of reinforcement of prezygotic isolation in the contact zone. Lectotype of Parnassius mnemosyne var. nubilosus Christoph, 1873 is designated.

Relative contribution of different repair pathways to the radiation-induced DNA damage responses remains a challenging issue of studying the radiation injury endpoints. Comparative manifestation of homologous recombination (HR) after application of different radiation doses greatly determines an overall effectiveness of recovery in dividing cell after irradiation, since HR is an error-free mechanism intended for repair of DNA double strand breaks (DSB) during S/G2 phases of cell cycle. In this article, we present an experimentally observed evidence of dose-dependent shift in relative contribution of HR in human fibroblasts after X-ray exposure at doses 20-1000 mGy, which is also supported by quantitative modeling of DNA DSB repair. Our findings indicate that the radiation dose increase leads to dose-dependent decrease in relative contribution of HR into the entire repair process.

Although the APOBEC3 family of single-stranded DNA cytosine deaminases are well-known as antiviral factors, these enzymes are rapidly gaining attention as prominent sources of mutation in cancer. APOBEC3 signature single base substitutions, C-to-T and C-to-G in TCA and TCT motifs, are evident in over 70% of human malignancies and dominate the mutational landscape of numerous individual tumors. Recent murine studies have established cause-and-effect relationships, with both human APOBEC3A and APOBEC3B proving capable of promoting tumor formation in vivo. Here, we investigate the molecular mechanism of APOBEC3A-driven tumor development using the murine Fah liver complementation and regeneration system. First, we show that APOBEC3A alone is capable of driving tumor development (without Tp53 knockdown as in prior studies). Second, we show that the catalytic glutamic acid residue of APOBEC3A (E72) is required for tumor formation. Third, we show that an APOBEC3A separation-of-function mutant with compromised DNA deamination activity and wildtype RNA editing activity is defective in promoting tumor formation. Collectively, these results indicate that APOBEC3A is a “master driver” that fuels tumor formation through a DNA deamination-dependent mechanism.

The aggregate aftermath of persistent inflammation in patients with inflammatory bowel disease (IBD) places them at increased risk for the advancement to colitis-associated colorectal cancer (CACRC). CACRC is preceded by IBD, the highly heterogenous, pharmacologically incurable, pertinacious, reverting/worsening, and immune-mediated inflammatory pathologies of the colon and rectum. The molecular and immunological basis of CACRC is highly correlated with the length/duration and stringency/severity of colon inflammation predisposed by the exogenous/free hemoglobin alpha chain (HbαC) the byproduct of infiltrating immune cells, extravasated erythrocytes, and macrophage erythrophagocytosis. The exogenous free HbαC prompts oxygen-free radical-arbitrated DNA damage (DNAD) through increased cellular reactive oxygen species (ROS) exacerbated by decreased tissue antioxidant defenses. Mitigation of Fenton reaction via pharmaceutical therapy would attenuate the ROS, promote apoptosis, DNAD repair, and subsequent prevent the incidence of CACRC. Three pharmaceutical options that attenuate hemoglobin toxicity include haptoglobin, deferoxamine, and flavonoids (vitamins C/E). Haptoglobin’s clearance rare from plasma is inversely correlated with its size; the smaller the size, the faster the clearance. Thus, the administration of Hp1-1 may prove to be beneficial. Furthermore, deferoxamine’s hydrophilic structure limits its ability to cross cell membranes. Thus, it may be beneficial if administered intracellularly to avoid the higher plasma concentrations and longer incubation periods associated with extracellular administration. Finally, the effectiveness of flavonoids and natural herb antioxidants is associated with high reactivity of hydroxyl substituents. Multiple analyses are currently underway to assess the clinical context of CACRC and outline the molecular basis of HbαC-induced ROS pathogenesis by exposing colonocytes and/or colonoids to HbαC. These cells are then treated with haptoglobin, deferoxamine (DFO), and flavonoids in order to separate free HbαC and measure their impact on hydroxyl radical formation therapies. The molecular pathogenesis of sporadic colorectal cancer (SCRC) i.e., “inflammation-dysplasia-carcinoma” progression sequence is well described, but the immunopathogenesis of CACRC herein reviewed is broadly still in prodromal stage/phase to be validated and understood. Therefore this timely review outlines the molecular and immunological basis of disease pathogenesis and the pharmaceutical intervention as a protective measure for CACRC.

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.

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.

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.

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.

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.

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.

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.

The sperm heads of frozen/thawed horse spermatozoa were injected into ovulated mouse oocytes where they decondensed and formed paternal pronuclei in which the DNA damage has been evaluated. The motile spermatozoa exhibit none or minor level of DNA damage and the xenogenic zygotes cleave to the two-cell embryonic stage with regular nuclei and no micronuclei (MNs). On the other hand, the immotile spermatozoa exhibit typically high levels of DNA damage and blastomeres in two-cell stage embryos contain multiple MNs. Moreover, extremely high sperm DNA damage prevents even the cleavage to the two-cell stage.Keywords: keyword 1; keyword 2; keyword 3 (List three to ten pertinent keywords specific to the article yet reasonably common within the subject discipline.)

Dried blood spot (DBS) testing on confetti is one of the most common methods used to collect and extract DNA from field samples for molecular epidemiology of malaria studies. Here, we investigated whether ethanol or other solutions used to clean scissors are a source of sample contamination. DBS were prepared from 3 drops of blood from two Plasmodium falciparum cultures spotted on confetti, and 3 solutions (water, ethanol and DNase) were used to clean scissors between spots during DNA extraction. For each cleaning solution, two blank confetti were used as negative controls. Samples were analyzed by PCR-based genotyping of merozoite surface proteins 1 & 2 (msp-1 and msp-2), and P. falciparum chloroquine resistance transporter (Pfcrt). A total of 15 samples were analyzed. Based on msp-1 and msp-2 amplification, P. falciparum was detected on blank confetti when scissors were washed with ethanol. Based on Pfcrt amplification, DNA of P. falciparum was detected on blank confetti when scissors were cleaned with ethanol or water. No P. falciparum genes were detected on blank confetti when scissors were cleaned with DNase. Scissors cleaned with DNase prevented cross-contamination between samples during processing of dried blood spots, whereas ethanol (which is commonly used) fails to avert cross-contamination.

Two novel sizable multicharged cationic complexes, of the formulae [(η6-[12]CPP)[Ru(η5-Cp)]12]Χ12 and [(η6-[11]CPP)[Ru(η5-Cp)]11]Χ11, CPP= cycloparaphenylene, Cp = cyclopentadienyl, X = [PF6]-, (1), (3) and [Cl]-, (2), (4), were synthesized and characterized using NMR techniques, high-resolution mass spectrometry, and elemental analyses. The complexes, (1) and (3) were stable in acetone and acetonitrile solutions over 48 h. In contrast, the water-soluble, (2) and (4), begins to decompose in aqueous media after 1h, due to the [Cl]- tendency for nucleophilic attack on ruthenium of the {Ru(η5-Cp)} units. Fluorescence quenching experiments conducted during the stability window of (2) with the d(5′-CGCGAATTCGCG-3′)2-EtBr adducts, revealed remarkably high values for Ksv = 1.185 × 104 ± 0.025 M-1 and Kb = 3.162 × 105 ± 0.001 M-1. Furthermore, the cytotoxic activity of (2) against A2780, A2780res, and MCF-7 cancer cell lines shows that it is highly cytotoxic with IC50 values in the range of 4.76 ± 1.85 to 16 ± 0.81 μΜ.

Apurinic/apyrimidinic endonuclease 1 (APE1), also known as redox factor-1 (Ref-1), is a multifunctional protein which is widely existing in living organisms. It can specifically recognize and cleave the DNA in apurinic/apyrimidinic (AP) site in the base excision repair (BER) pathway, as well as regulate the expression of genes to activate some transcription factors. The abnormal ex-pression and disruptions in the biological functions of APE1 are linked to a number of diseases, including inflammation, immunodeficiency, and cancer. Hence, it is extremely desired to monitor the activity of APE1, acquiring a thorough understanding of the healing process of damaged DNA and making clinical diagnoses. Thanks to the advent of DNA nanotechnology, some nanodevices are used to image the activity of APE1 with great sensitivity and simplicity. In this review, we will summarize DNA nanotechnology-empowered fluorescence imaging in the past years for APE1 activity according to the types of DNA probe, which are classified into linear DNA probes, composite DNA nanomaterials and three-dimensional (3D) DNA nanostructures. We also highlight the future research directions in the field of APE1 activity imaging.

To activate gene expression, the initiation of transcription is a highly regulated process involving the interaction of proteins and DNA nucleotides at the promoter site, which consists of a small number of base pairs. As it involves interactions at the atomic scale, it is challenging to determine the mechanism of binding responsible for the great specificity between the amino acid residuals comprising the transcription binding protein and the DNA nucleotides comprising the promoter. Here, a new approach to characterize the transcription initiation process is developed and verified from analysis of comparative pharmacological efficacy data and elemental modeling. The newly developed description of a mechanism for transcription initiation involves the direct binding of small molecule ligands of approximately twenty carbon atoms, which are both structurally symmetric to DNA nucleotides, and also chemically complementary in its functional groups for interaction with the oxygen element at the carbon two position of thymine and with the phosphodiester chain. The results indicate that the activating ligands are transported to the DNA nucleotide promoter site by protein transcription factors, which serve as delivery vectors, for transfer of the ligand to the DNA nucleotide pairs. The ligands examined in this study include the steroid hormones, synthetic steroid molecules, derivatives of vitamin D, and prostaglandins, particularly PGJ2 and 15d-PGJ2. The transcription factors evaluated include glucocorticoid receptors, VDR, PPAR, and TBP. Through the developments, it is shown that because of the chemically complementary binding of the ligand to DNA nucleotide pairs, the resultant intermolecular complex produces three hydrogen bonds for the A-T and T-A configurations, which matches that of G-C and C-G. The orientation of the nucleotide base pairs is also seen to adjust as an inversion of the nominal position of the nucleobases to a dimer configuration presented via TBP transcription factor. The developments comprise a new approach to characterizing the initiation of the transcription process comprising the direct binding and interaction of ligands with DNA nucleotides as verified through comparative analysis of pharmacological activity and through perfect structural correspondence between the steroid hormone class as ligands with Watson-Crick DNA nucleotide pairings.

We apply hierarchical clustering (HC) of DNA k-mer counts on multiple Fastq files. The tree structures produced by HC may reflect experimental groups and thereby indicate experimental effects, but clustering of preparation groups indicates the presence of batch effects. Hence, HC of DNA k-mer counts may serve as an unspecific diagnostic device. In order to provide a simple applicable tool we implemented sequential analysis of Fastq reads with low memory usage in an R package (seqTools) available on Bioconductor. The approach is validated by analysis of Fastq file batches containing RNAseq data. Analysis of three Fastq batches downloaded from ArrayExpress indicated experimental effects. Analysis of RNAseq data from two cell types (dermal fibroblasts and Jurkat cells) sequenced in our facility indicate presence of batch effects. The observed batch effects were also present in reads mapped to the human genome and also in reads filtered for high quality (Phred > 30). We propose, that hierarchical clustering of DNA k-mer counts provides an unspecific diagnostic tool and a quality criterion and for RNAseq experiments.

This review article delves into the pivotal role of DNA in advancing criminal investigations, presenting a comprehensive analysis of its impact on modern justice systems. DNA, as the genetic blueprint of individuals, has revolutionized forensic science, augmenting the accuracy and reliability of criminal investigations. This study explores the historical evolution of DNA analysis, from its initial discovery to the development of sophisticated techniques like polymerase chain reaction (PCR), short tandem repeat (STR) profiling, and next-generation sequencing (NGS). The article elucidates the intricate process of DNA collection, preservation, and analysis, highlighting its significance in establishing identity, proving guilt or innocence, and resolving cold cases. The utilization of DNA databases and international cooperation in cross-border investigations are also examined, emphasizing their contributions to solving complex criminal cases. Moreover, the ethical, legal, and privacy considerations surrounding DNA usage in criminal justice are critically evaluated. Through a comprehensive literature review, this article synthesizes empirical evidence showcasing how DNA evidence has exonerated wrongfully convicted individuals and provided closure to victims' families. It further elucidates how technological advancements have extended DNA analysis to trace evidence, touch DNA, and forensic genealogy, thereby broadening its application in criminal investigations.

Background: Despite recent advances in epithelial ovarian carcinoma (EOC) treatment, recur-rence and mortality rates have not improved significantly. DNA hypermethylation has generally been associated with ominous prognosis and chemotherapy resistance, but the role of DNMTs in EOC remains to be investigated. Methods: In the current study, we systematically retrieved gene expression data from patients with EOC and studied the immunohistochemical expression of DNMTs in 108 primary and 26 relapsed tumors. Results: Our results showed that DNMT1, DNMT3A, DNMT3B and DNMT3L RNA levels were higher and DNMT2 lower in tumors compared to non-neoplastic tissue, and DNMT3A and DNMT2 expression decreased from Stage II to Stage IV carcinomas. Proteomic data also suggested that DNMT1 and DNMT3A levels were increased in tumors. Similarly, DNMT1, DNMT3A and DNMT3L protein levels were overex-pressed and DNMT2 expression was reduced in high grade carcinomas compared to non-neoplastic tissue and low-grade tumors. Moreover, DNMT1 and DNMT3L were increased in relapsed tumors compared to their primaries. DNMT3A, DNMT1 and DNMT3B mRNA lev-els were correlated with overall survival. Conclusions: Our study demonstrates that DNMT1 and DNMT3L are upregulated in primary high grade EOC and further increase in relapses, whereas DNMT3A is upregulated only in the earlier stages of cancer progression. DNMT2 downregulation highlights a presumptive tumor-suppressor activity of this gene in ovarian car-cinoma.

Transcription factors must scan genomic DNA, recognize the cognate sequence of their control element(s), and bind tightly to them. The DNA recognition process is primarily carried out by their DNA binding domains (DBD), which interact with the cognate site with high affinity and more weakly with any other DNA sequence. DBDs are generally thought to bind to their cognate DNA without changing conformation (lock-and-key). Here we used nuclear magnetic resonance and circular dichroism to investigate the interplay between DNA recognition and DBD conformation in the Engrailed homeodomain (EnHD), as model case for the homeodomain family of eukaryotic DBDs. We found that the conformational ensemble of EnHD is rather flexible and becomes more structured as ionic strength increases following a Debye-Hückel’s dependence. Our analysis indicates that EnHD’s response to ionic strength is mediated by a built-in electrostatic spring-loaded latch that operates as conformational transducer. We also found that, at moderate ionic strengths, EnHD changes conformation upon binding to cognate DNA. This change is of larger amplitude and somewhat orthogonal to the response to ionic strength. As a consequence, very high ionic strengths (e.g. 700 mM) block the electrostatic-spring-loaded latch and binding to cognate DNA becomes lock-and-key. However, the interplay between EnHD conformation and cognate DNA binding is robust across a range of ionic strengths (i.e. 45 to 300 mM) that covers the most physiologically-relevant conditions. Therefore, our results demonstrate the presence of a mechanism for the conformational control of cognate DNA recognition on a eukaryotic DBD. This mechanism can function as a signal transducer that immediately locks the DBD in place upon encountering the cognate site during active DNA scanning. The electrostatic-spring-loaded latch of EnHD can also enable the fine control of DNA recognition in response to local/temporal changes in ionic strength induced by variate physiological processes.

The idea of CUAD (contact unmodified antisense DNA) biotechnology and the use of oligonucleotide insecticides (briefly, olinscides, or DNA insecticides) was proposed on lepidopterans and gradually disseminated on hemipteran pests. As the next-generation platform for creation of insecticides, it has a number of unique characteristics (short unmodified antisense DNA as contact insecticide, insect rRNAs as target, DNA containment as mechanism of action) that distinguish it from existing classes of chemical insecticides. Oligonucleotide insecticides possess low carbon footprint, high safety for non-target organisms, rapid biodegradability, avoidance of target-site resistance, ensuring prosperity for agricultural countries that will implement this innovation. As the next-generation class of insecticides olinscides create opportunities that have never existed before in crop protection. Using flexible CUAD platform, any farmer, botanical garden or pest control company is capable of creating its own unique arsenal of insecticides, well-tailored for a particular population of insect pest. Most technological innovations start out very expensive and don't work well, but eventually start working well and become very cheap. CUAD biotechnology has come a long way for 16 years and is very close to the point to be implemented on a large scale against certain groups of pests. In this article we provide basic knowledge of use of oligonucleotide pesticides and list pests (mainly from suborder Sternorrhyncha, Hemiptera) which were successfully controlled by us recently.

The classical human satellite DNAs, also referred to as human satellites 1, 2 and 3 (HSat1, HSat2, HSat3, collectively HSat1-3) constitute the largest individual arrays of tandemly repeated DNA sequences in the genome. Even though they were among the first human DNA sequences to be isolated and characterized at the dawn of molecular biology, HSat1-3 have been left behind in the genomics era and remain among the most enigmatic sequences in the human genome. Although HSat1-3 total roughly 3% of the genome on average, they were almost entirely missing from the human genome reference assembly for 20 years. Recently, the Telomere-to-Telomere Consortium produced the first truly complete assembly of a human genome, including the enormous HSat1-3 arrays, opening them up for a new wave of discovery. Towards this end, here, I provide an account of the history and current understanding of HSat1-3 genomics, evolution, and roles in disease.

The identification of floral visitation by pollinators provides an opportunity to improve our understanding of the fine-scale ecological interactions between plants and pollinators, contributing to biodiversity conservation and promoting ecosystem health. In this review we outline the various methods which can be used to identify floral visitation, providing a comparison between molecular and non-molecular methods. We review the literature covering the ways in which DNA metabarcoding has been used to answer ecological questions relating to plant use by pollinators and discuss the findings of this research. We present detailed methodological considerations for each step of the metabarcoding workflow, from sampling through to amplification and finally bioinformatic analysis. Detailed guidance is provided to researchers for utilization of these techniques, emphasizing the importance of standardization of methods and improving the reliability of results. Future opportunities and directions of using molecular methods to analyze plant-pollinator interactions are then discussed.

Since 1970s, a great deal of attention has been paid to the development of semiconductor–based biosensors because of the numerous advantages they offer, including high sensitivity, faster response time, miniaturization, and low–cost manufacturing for quick biospecific analysis with reusable features. Commercial biosensors have become highly desirable in the fields of medicine, food, environmental monitoring as well as military applications (e.g., Hoffmann–La Roche, Abbott Point of Care, Orion High technologies, etc.), whereas increasing concerns on the food safety and health issues have resulted in the introduction of novel legislative standards for these sensors. Numerous devices have been developed for monitoring of biological–processes such as nucleic–acid hybridization, protein–protein interaction, antigen–antibody bonds and substrate–enzyme reactions, just to name a few. Since 1980s scientific interest moved to the development of semiconductor–based devices which also include integrated front–end electronics, such as the extended–gate–field–effect–transistor biosensor which is one of the first miniaturized chemical sensors. This work is intended to be a review of the state of the art focused on the development of biosensors based extended–gate–field–effect–transistor within the field of bioanalytical applications, which will highlight the most recent research works reported in the literature. Moreover, a comparison among the diverse EGFET devices will be presented giving particular attention to the materials and technologies.

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.

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

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.

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.

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.

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%.

There is no routine approach to identify patients with gynecologic malignancies at high risk for chemotherapy-resistance. Circulating tumor DNA (ctDNA) tumor fraction (TFx) represents a minimally-invasive approach to tumor profiling, with as yet limited data on utility in gynecologic malignancies. The objective was to investigate the use of ctDNA TFx in a cohort of patients with ovarian and endometrial cancer. Plasma samples from patients with biopsy-proven ovarian or endometrial cancer collected between 4/2018 and 4/2020 were subjected to shallow whole genome sequencing with determination of TFx via ichorCNA package. The association of TFx to continuous and categorical baseline clinicopathologic factors and progression-free survival was assessed. 210 plasma samples from 78 patients with gynecologic cancers were analyzed. Mean TFx for ovarian cancer was 5.5% and endometrial cancer 2.4% and there was no significant difference in TFx among histology either for endometrial or ovarian cancers. Grade was associated with significant difference in ‘sentinel’ TFx among ovarian cancers but not endometrial cancers. ctDNA TFx dynamics over time demonstrated rapid clearance of ctDNA in most patients with ovarian cancer, while endometrial cancer had consistently low TFx. ctDNA TFx is feasible in ovarian and endometrial cancers and may be a valuable important tool for prognostication.

The European white birch, scientifically known as Betula pendula, and its variant, B. pendula 'Dalecarlica' are characterized by a serrated leaf margin that enhances their aesthetic appeal. However, the lobed leaf trait can undergo random and spontaneous reversion to the typical ovoid or cordate shape during asexual reproduction. Investigating and elucidating the molecular mechanisms underlying this unpredictable reversion mutation is essential for comprehending the birch leaf development process. In this research, we employed a non-lobed-leaf mutant derived from a lobed-leaf birch clone during plant tissue culture. We adopted a multi-omics approach, including whole-genome resequencing, transcriptome sequencing, and methylation profiling, to analyze and compare genomic variations and gene expression modifications. The study revealed that the 24 variant genes affected by 1464 SNP/InDel sites in the genome of the non-lobed-leaf mutant are not associated with leaf development. While the overall methylation level in the mutant's genome closely resembles that of the serrated-leaf birch, ten genes exhibit differential methylation accompanied by differential expression. Transcriptome sequencing demonstrated that the differentially downregulated genes in the mutant are significantly enriched in the GO:0009733 (response to auxin) and GO:0009734 (auxin-activated signaling) pathways. Validation through McrBC-PCR and qRT-PCR confirmed differential methylation and expression of BpIAA9 in the reversion mutant. The elevated methylation level in the BpIAA9 promoter leads to reduced expression, resulting in changes in the expression of auxin-responsive genes. This, in turn, leads to a transcriptional downregulation enrichment effect in auxin-related pathways in the reversion mutant, ultimately inhibiting the regulation of leaf veins by auxin during their development.

Pediatric brain tumors are the leading cause of cancer-related death in children. Diagnosis cur-rently relies on surgical biopsy to obtain tumor tissue for histological analysis. There is a great need for less invasive approaches to molecularly profile tumors and monitor therapeutic response. Liquid biopsy analysis of circulating tumor biomarkers in biofluids like cerebrospinal fluid (CSF) and blood offers a promising minimally invasive strategy. This review discusses recent advances in developing liquid biopsy assays using next-generation sequencing, digital PCR, and emerging techniques to detect circulating tumor DNA (ctDNA), cells (CTCs), and exosomes in pediatric brain tumors. The ability to use these circulating biomarkers for non-invasive diagnosis, thera-peutic targeting, tracking response to therapy, and understanding resistance mechanisms is ex-amined. Technical and clinical validation challenges to translate liquid biopsies into routine clin-ical practice are also discussed.

Pharmacogenetics and DNA methylation influence therapeutic outcomes and provide insights into potential therapeutic targets for brain-related disorders. To understand the effect of genetic polymorphisms on drug response and disease risk, we analyzed the relationship between global DNA methylation, drug-metabolizing enzymes, transport genes, and pathogenic gene phenotypes in serum samples from two groups of patients: Group A, which showed increased 5-methylcytosine (5mC) levels during clinical follow-up, and Group B, which exhibited no discernible change in 5mC levels. We identified specific SNPs in several metabolizing genes, including CYP1A2, CYP2C9, CYP4F2, GSTP1, and NAT2 that were associated with differential drug responses. Specific SNPs in CYP had a significant impact on enzyme activity, leading to changes in phenotypic distribution between the two patient groups. Group B, which contained a lower frequency of normal metabolizers and a higher frequency of ultra-rapid metabolizers compared to patients in Group A, did not show an improvement in 5mC levels during follow-up. Furthermore, there were significant differences in phenotype distribution between patient Groups A and B for several SNPs associated with transporter genes (ABCB1, ABCC2, SLC2A9, SLC39A8, and SLCO1B1) and pathogenic genes (APOE, NBEA, and PTGS2). These findings appear to suggest that the interplay between pharmacogenomics and DNA methylation has important implications for improving treatment outcomes in patients with brain-related disorders.

Background: Oxygen exists in two gaseous (dioxygen and ozone) and six solid allotropic modifications. An additional allotropic modification of oxygen, the cyclooctaoxygen, was predicted to exist in 1990. The first synthesis and characterization of cyclooctaoxygen as its sodium crown complex, isolated in the form of three cytosine nucleoside hydrochloride complexes, was reported in 2016.Results: The sperminium hydrogen phosphate/cyclooctaoxygen sodium complex is calculated to cover the actively transcribed regions (2.6%) of bovine lymphocyte interphase genome. Cyclooctaoxygen seems to be naturally absent in hypoxia-induced highly condensed chromatin, taken as a model for eukaryotic metaphase/anaphase/early telophase mitotic chromatin. Hence, it is proposed that the cyclooctaoxygen sodium-bridged sperminium hydrogen phosphate and selenite coverage serves as an epigenetic shell of actively transcribed gene regions in eukaryotic ‘open’ euchromatin DNA. Cyclooctaoxygen sodium-bridged sperminium hydrogen selenite was calculated to serve as a marker shell component at ATG start codons in human euchromatin DNA mRNA genes, both at the translation initiation triplet and at 5'-untranslated region upstream ATGs. The total herbicide glyphosate (ROUNDUP®) and its metabolite (aminomethyl)phosphonic acid (AMPA) are proved to represent ‘epigenetic poisons’, since they both selectively destroy the cyclooctaoxygen sodium complex. This definition is of reason, since the destruction of cyclooctaoxygen is certainly sufficient to bring the protection shield of human euchromatin into collateral epigenetic collapse.Conclusions: The total herbicide glyphosate and its environmental metabolite (aminomethyl)phosphonic acid (AMPA) can be associated in vitro with catalytic detoriation of eukaryotic euchromatin genetic information.General Significance: The epigenetic shell of eukaryotic euchromatin is susceptible to decay induced by catalytic epigenetic poisons threatening eukaryotic genomic heritage.

Background: Strongyloidiasis, a neglected disease caused by intestinal nematodes of the genus Strongyloides, is endemic to tropical and subtropical areas such as Vietnam. The morphological diagnosis of larvae by Hara Mori culture technique and microscopicare are considered the standard diagnostic procedures in the endemic areas of Strongyloides spp. However, they could only identify the genus, not the species of Strongyloides. DNA-molecular techniques which are highly sensitive and more cost-effective have been increasingly utilized in detection of Strongyloides species. This study aims to determine prevalence and the species of Strongyloides among resident population in Duc Hoa district, Long An province, Southern Vietnam. Methods: A cross-sectional study was conducted using 1,190 stool samples collected in Duc Hoa district, Long An province, Vietnam, from July, 2017 to November 2018. The stool specimens were transported to the Laboratory of Medical Parasitology, Pham Ngoc Thach University of Medicine within two hours of collection at an appropriate temperature of 25 oC. All samples were stored at 2 - 8°C and processed within 48 hours for microscopic examination. Molecular detection was carried out at Laboratory of Molecular Biology, Pham Ngoc Thach University of Medicine, Hochiminh city, VietNam. Results: Of the 1,190 samples tested, Strongyloides spp. larvae were detected in 79 specimens (6.6%) by two classical parasitological methods, namely direct microscopy and the modified Harada-Mori filter paper culture. DNA was extracted from 70 of the 79 samples of Strongyloides spp. larvae, which was subsequently characterized by real-time PCR amplification of the 18S and 28S regions of the rDNA gene. The results showed that 97.1% of the DNA samples were S. stercoralis, 2.9% were co-infections with S. ratti and S. stercoralis, and 2.9% belonged to S. ratti. For all 14 isolates, nucleotide sequencing was compared with other human pathogenic species of Strongyloides whose sequences are available in GenBank. The identity of 12/14 sequences were confirmed as S. stercoralis with a high level of similarity (91.3% - 100%) and over 98% for S. ratti. Between the two co-infection samples, the higher similarity belonged to S. stercoralis. Conclusion: A molecular amplification of small subunit ribosome RNA followed by sequence analysis has been proved to be a suitable method for discrimination of Strongyloides spp. retrieved from stool samples.

Gastric cancer (GC) is one of the most common malignancies around the world, and the incidence of GC is increasing in the past decades. In addition to genetic modifications, epigenetic alterations catalyzed by DNA methyltransferases (DNMTs) are a well-characterized epigenetic hallmark in gastric cancer. Nowadays, DNA methylation landscape is essential for maintaining the silence of tumor suppressor genes (TSGs). As an important group of peptide, TFF family has been confirmed to function as a TSG in various kinds of cancers. However, whether TFFs could be modified by DNA methylation in gastric cancer remains unknown. In this study, we initially screened out two expression profiles about GC from Gene Expression Omnibus (GEO) database. The higher expressions of TFF1 and TFF2 were observed in GC tumor tissues than normal tissues. Additionally, we illustrated that the expressions of TFF1/TFF2 were associated to the overall survival (OS) and tumor free survival (TFS) of GC patients via through the Kaplan-Meier analysis. Subsequently, the integrative analysis was performed to estimate the DNA methylation level of each site in TFF1/TFF2 CpG islands. Importantly, our findings indicated that hyper-methylation of cg01886855 and cg26403416 were separately responsible for the downregulation of TFF1 and TFF2 in GC samples. Besides, utilizing the gain of function assay, we demonstrated that TFF1/TFF2 could suppress the proliferation of GC cells. Based on these results, We identified that TFF1 and TFF2 acted as the putative tumor suppressors in gastric cancer, which suggested that TFFs could be two candidate biomarkers for predicting tumor recurrence in gastric cancer patients. Furthermore, these findings highlight a potential therapeutic approach in targeting the TFFs for the treatment of gastric cancer.

Wildfires have continued to increase in frequency and severity in Southern California due in part to climate change. To gain a further understanding of microbial soil communities’ response to fire and functions that may enhance post-wildfire resilience, soil fungal and bacterial microbiomes were studied from different wildfire areas in the Gold Creek Preserve within the Angeles National Forest using 16S, FITS, 18S, 12S, PITS, and CO1 amplicon sequencing. Sequencing datasets from December 2020 and June 2021 samplings were analyzed using DNA Subway, ranacapa, stats, vcd, EZBioCloud, and mixomics. Significant differences were found among bacterial and fungal taxa associated with different fire areas in the Gold Creek Preserve. There was evidence of seasonal shifts in the alpha diversity of the bacterial communities. In the sparse partial least squares analysis, there were strong associations (r>0.8) between longitude, elevation, and a defined cluster of Amplicon Sequence Variants (ASVs). The Chi-square test revealed differences in fungi:bacteria (F:B) proportions between different trails (p=2*10^-16). sPLS results focused on a cluster of Green Trail samples with high elevation and longitude. Analysis revealed the cluster included the post-fire pioneer fungi Pyronema, and Tremella. Chlorellales algae, and pathogenic Fusarium sequences were elevated. Bacterivorous Corallococcus, which secretes antimicrobials, and bacterivorous flagellate Spumella, were associated with the cluster. There was functional redundancy in clusters that were differently composed, but shared similar ecological functions. These results implied a set of traits for post fire resiliency. These included photo-autotrophy, mineralization of pyrolyzed organic matter and aromatic/oily compounds, pathogenicity and parasitism, antimicrobials, and N-metabolism.

The deadliest disease in the world, cancer, kills many people every year. The early detection is the only hope for the survival of malignant cancer patients. As a result, in the preliminary stages of , the diagnosis of cancer biomarkers at the cellular level is critical for improving cancer patient survival rates. For decades, scientists have focused their efforts on the invention of biosensors. Biosensors, in addition to being employed in other practical scenarios, can essentially function as cost effective and highly efficient devices for this purpose. Traditional cancer screening procedures are expensive, time-consuming, and inconvenient for repeat screenings. Biomarker-based cancer diagnosis, on the other hand, is rising as one of the most potential tools for early detection, disease progression monitoring, and eventual cancer treatment. As Biosensor is an analytical device, it allows the selected analyte to bind to the biomolecules being studied (– for example RNA, DNA, tissue, proteins, cells). They can be divided based on the kind of biorecognition or transducer elements on the sensor. Most biosensor analyses necessitate the analyte being labeled with a specific marker. In this review article, the application of distinct variants of biosensors against cancer has been described.

Two-dimensional silicon allotrodes– also called Sinicene– have recently experienced intensive scientific research interest due to their unique electrical, mechanical, and sensing characteristics. A novel silicene based nano-material has been enticed great amenities, partially because of its uniformity with graphene. Silicene is a highly sensitive for numerous sensors based on molecular sensing as pH sensor, gas sensor, ion sensor and biosensing are Deoxyribonucleic acid (DNA) nucleobase sensor, photonic sensor, cell-based biosensor, glucose sensor, and bioelectric nose sensor. Nowadays genetic research based on DNA hybridization, which is a vital tools for sensing material and it has various detection methods. Among of them, the detection method is frequency readout used to a label-free detection of DNA hybridization. In this paper we have compared the graphene and silicene quantum capacitance that has been proposed for a DNA hybridization detection method on wireless readout. These method shows, the strands of mismatched and complementary DNA have in different range of frequency to identify output efficiency. With respect to DNA concentration the output of silicene is almost sharply linear than graphene. In addition of field effect transistor, silicene opens a new opportunities due to its band gap whereas graphene indicates zero band gap. It can be stated that silicene is much more reliable as well as much stronger than multi-layered graphene.

This review article offers an in-depth look at DNA, its discovery, structure, functions, and the significant role it plays in modern biomedical research. It begins by revisiting the landmark discovery of the DNA double helix by scientists Watson and Crick, a structure resembling a twisted ladder that forms the blueprint of life. The review explains the basic processes of DNA replication (copying DNA), transcription (converting DNA to RNA), and translation (turning RNA into proteins), which are fundamental to understanding how genetic information is passed on and used by living organisms. The article then explores gene regulation and epigenetics, which involve how genes are turned on or off and how environmental factors can affect gene expression without changing the DNA sequence itself. It examines how DNA interacts with various proteins and modifiers, which play crucial roles in these processes. A major focus is on the advancements in DNA sequencing technologies. From the initial Sanger sequencing method, which was labor-intensive and time-consuming, to the highly efficient next-generation sequencing (NGS) and the latest single-molecule sequencing techniques, the review covers how these technologies have revolutionized genomics and personalized medicine. It also highlights the importance of computational genomics and bioinformatics, fields that deal with analyzing and interpreting the vast amounts of data generated by DNA sequencing. The review discusses DNA's crucial role in understanding human diseases. It covers DNA-based research in cancer, rare genetic disorders, infectious diseases, and pharmacogenomics (how genes affect a person's response to drugs). It emphasizes studies that have led to new ways of diagnosing and treating diseases. The article looks at the future of DNA research. It talks about emerging technologies like CRISPR-Cas9, a revolutionary gene-editing tool that allows scientists to modify DNA with high precision. Synthetic biology, an interdisciplinary field that combines biology and engineering for designing and constructing new biological parts and systems, is also discussed. Furthermore, DNA nanotechnology, which involves designing DNA molecules for technological uses, is explored. Finally, the review addresses ethical issues in DNA research, such as privacy concerns and debates over genome editing.

Tdp1 and Tdp2 are DNA repair enzymes that repair DNA damages caused by various agents, including anticancer drugs. Thus, these enzymes resist anticancer therapy and could be the reasons of resistance to such widely used drugs as topotecan and etoposide. In the present work, we found compounds capable of inhibiting both enzymes among derivatives of (-)-usnic acid. Both (+)- and (-)-enantiomers of compounds act equally effectively against Tdp1, and only (-)-enantiomers inhibited Tdp2. Surprisingly, the compounds protect HEK293FT wild type cells from the cytotoxic effect of etoposide but potentiate it against Tdp2 knockout cells. We assume that the sensitizing effect of the compounds in the absence of Tdp2 is associated with effective inhibition of Tdp1, which could take over the functions of Tdp2.

This article is devoted to the results of in-depth analysis of the system of binary-oppositional structures in DNA n-plet alphabets and their algebraic-matrix representations. These results show that the molecular complementary replication of DNA strands is accompanied by the presence of an algebraic version of the principle "like begets like" in matrix representations of DNA alphabets having internal structures. This algebraic version is based on binary-oppositional structures in the genetic molecular system, which can be represented by binary numbers and corresponding matrices of DNA alphabets. The received results allow thinking that the phenomenon "like begets like" (or a complementary replication in a wide sense) is systemic in the genetic organization and is connected with algebraic features of biological organization. Correspondingly, the biological principle "like begets like" can be additionally modeled by algebraic-matrix methods and approaches. Such algebra-matrix modeling of the genetic coding system gives new ways for studying and understanding the key role of the named principle in genetic and other inherited physiological complexes. On this way, the author discovered general rules of stochastic organization of information binary sequences of genomic DNAs of eukaryotes and prokaryotes. The presented rules are connected with information dichotomies of probabilities and corresponding fractal-like trees of probabilities, which fundamentally differ from constructional dichotomies in biological bodies. The received phenomenological data and rules lead to new biological ideas.

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.

Chromothripsis is a mutational mechanism leading to complex and relatively clustered chromosomal rearrangements resulting in diverse phenotypic outcomes depending on the involved genomic landscapes. It may occur both in the germ and the somatic cells resulting in congenital and developmental disorders and cancer, respectively. Asymptomatic individuals may be carriers of chromotriptic rearrangements and experience recurrent reproductive failures when two or more chromosomes are involved. Several mechanisms are postulated to underly chromothripsis. The most attractive hypothesis involves chromosome pulverization in micronuclei followed by incorrect reassembly of fragments through DNA repair to explain the clustered nature of the observed complex rearrangements. Moreover, exogenous or endogenous DNA damage induction and dicentric bridge formation may be involved. Chromosome instability is commonly observed in the cells of patients with DNA-repair disorders, such as ataxia telangiectasia, Nijmegen breakage syndrome and Bloom syndrome. In addition, germline variations of TP53 have been associated with chromothripsis in Sonic-Hedgehog medulloblastoma and acute myeloid leukemia. In the present review, we focus on the underlying mechanisms of chromothripsis and the involvement of defective DNA-repair genes resulting in chromosome instability and chromothripsis-like rearrangements.

The presence of mutated genes strongly correlates with the incidence of cancer. Decades of research, however, has not yielded any specific causative gene or set of genes for the vast majority of cancers. The Cancer Genome Atlas program was supposed to provide clarity but it only gave much more data without any accompanying insight into how the disease begins and progresses. It may be time to notice that epidemiological studies consistently show that the environment, not genes, has the principal role in causing cancer. Since carcinogenic chemicals in our food, drink, air and water are the primary culprits, we need to look at the biochemistry of cancer, with a focus on enzymes which invariably facilitate transformations in a cell. In particular, attention should be paid to the rate-limiting enzyme in DNA synthesis, ribonucleotide reductase (RnR) whose activity is tightly linked to tumor growth. Besides circumstantial evidence that cancer is induced at this enzyme’s vulnerable free-radical-containing active-site by various carcinogens, its role in initiating retinoblastoma and HPV-related cervical cancers is well documented. Blocking the activity of malignant RnR is a certain way to arrest cancer.

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.

Existing studies often lack a systematic solution for Unmanned Aerial Vehicles (UAV) inspection system, which hinders their widespread application in crack detection. To enhance its practicality, this study proposes a formal and systematic framework for UAV inspection systems, specifically designed for automatic crack detection and pavement distress evaluation. The framework integrates UAV data acquisition, deep learning based crack identification, and road damage assessment in a comprehensive and orderly manner. Firstly, the flight control strategy is presented, and road crack data is collected using the DJI Mini 2 UAV imagery, establishing a high-quality UAV crack image datasets with ground truth information. Secondly, a validation and comparison study is conducted to enhance the automatic crack detection capability and provide an appropriate deployment scheme for UAV inspection systems. This study develops automatic crack detection models based on mainstream deep learning algorithms(namely, Faster-RCNN, YOLOv5s, YOLOv7-tiny, and YOLOv8s) in urban road scenarios. The results demonstrate that the Faster-RCNN algorithm achieves the highest accuracy and is suitable for online data collection of UAV and offline inspection at work stations. Meanwhile, the YOLO models, while slightly lower in accuracy, are the fastest algorithm and are suitable for lightweight deployment of UAV with online collection and real-time inspection. Quantitative measurement methods for road cracks are presented to assess road damage, which will enhance the application of UAV inspection systems and provide factual evidence for maintenance decisions made by road authorities.

In order to study the strength changes of concrete specimens under different loading conditions, based on the principle of minimum energy dissipation and from the Angle of concrete failure energy per unit area, the finite element numerical simulation software was applied to concrete specimens with different failure modes of tension, compression, bending and torsion, and the double-broken line damage constitutive model was adopted to simulate and analyze the failure forms of concrete specimens under different loading conditions. The failure area and failure energy of each specimen during loading were quantitatively calculated under each failure mode, and the relationship between the failure area and failure energy consumed under different failure modes was analyzed. The results show that under different failure modes, the failure area of concrete specimens is different, the energy consumed during failure is different, and the strength is different. However, in the process of failure, no matter how the failure mode changes, the failure energy W per unit area remains unchanged and is a constant, which is related to the physical properties of concrete itself.

The flavor, aroma and color of coffee may change due to mechanical damage, reducing its qual-ity. To measure the mechanical response of materials, compression tests can be performed, de-termining the effect of force application on the mechanical behavior of the fruit at different stages of ripeness. In this context, this study aimed to analyze the deformation, strain energy and equivalent von Mises stress of coffee fruits at mature, semi-mature and immature maturation stages and compressed by collapse forces. Compression in three directions (x, y and z) was sim-ulated on coffee fruit models using the finite element method, with a compression support in the direction opposite to the force application axis. The numerical simulation of the compression process allowed to verify that the more mature the fruit, the greater the associated mean defor-mation (2.20 mm mm-1, 0.78 mm mm-1 and 0.88 mm mm-1), the lower the mean strain energy (0.07 mJ, 0.21 mJ and 0. 34 mJ) and the lower the mean equivalent von Mises stress (0.25 MPa, 1.03 MPa and 1.25 MPa), corresponding to ripe, semi-ripe and immature fruits; and these proper-ties may be used to analyze how processes in the production chain affect the amount of mechan-ical damage.

This work demonstrates the antimycotic activity and structural damage of stingless bee propolis against Malassezia pachydermatis,causative agent of canine otitis.Two propolis ethanolic extracts(EEP) derived from the stingless bees, Scaptotrigona mexicana and Tetragonisca angustula were tested against three clinical strains of Malassezia pachydermatis and one of reference (ATCC 14522). Each ethanolic extract of propolis was analyzed by Gas Chromatography – Mass Spectrometry(GC-MS). Antimycotic activity was evaluated by plate microdilution. To evaluate the induced changes in yeasts, by fluorescence microscopy, stains were performed with chalcofluor white and propidium iodide. For both propolis, sesquiterpenes were the main components determined by GC-MS. Minimum inhibitory concentration (MIC) of 32 mg/mL and a minimum fungicidal concentration of 64 mg/Ml were determined in both extracts. EPP of Scaptotrigona mexicana and Tetragonisca angustula caused significant damage to yeast morphology. Propidium iodide penetration was observed, indicating damage to the yeast and with calcofluor-white stain, only morphology deformation was observed..The antimycotic activity and structural damage of propolis from Scaptotrigona mexicana and Tetragonisca angustula against Malassezia pachydermtais was demonstrated .This probably being the first scientific report that demonstrates structural damage in Malassezia pachydermatis of Mexican stingless bee propolis

The azimuth wheel-rail of large aperture radio telescope is the key component, it not only sup-ports the whole weight of the antenna, but also directly affects the pointing performance of the antenna with its surface accuracy. The whole weight of the radio telescope is hundreds or even thousands of tons, its azimuth frame rollers have great contact stress with the wheel-rail surface, repeated rolling can cause rolling contact fatigue on the wheel-rail surface, resulting in wear, cracks and other damage to the wheel-rail, and even lead to failure or fracture of the wheel-rail in serious cases, so it is very important to monitor the damage of the antenna wheel-rail. In order to visually detect the use of antenna wheel-rail surface, this paper proposed the method using electromagnetic ultrasonic detection to detect the damage of antenna wheel-rail surface for the first time. Based on the electromagnetic ultrasonic nondestructive testing principle, the simplified wheel-rail model containing wear, corrosion and crack damage is simulated. The results show that this method can effectively detect the surface damage of the antenna wheel-rail surface, and it can provide an important reference for the research of wheel-rail damage detection of large radio telescope.

The damage evolution rules of coal under true triaxial combined static-dynamic loads are important to understand and reveal the mechanism of rockburst in coal mines. The numerical simulation was carried out using FLAC3D to explore the coupling effect of static and dynamic stress, especially the influence of dynamic load parameters. The results show that the increase of dynamic load amplitude not only makes the plastic zone grow exponentially and shorten the damage development time, but also decreases the residual strength of the coal sample, which leads to a much more violent of the dynamic failure. The stress wave can propagate more stable in the coal sample with the increase of dynamic load frequency and the development time of the plastic zone also show synchronous fluctuating features, and when the frequency is like the intrinsic frequency of the coal sample, the dynamic load has a significant stimulate effect. The static and dynamic loads have different damage effect to the coal sample under true triaxial stress path, the weight decreases in order of the minimum principal stress, the maximum principal, the amplitude of the dynamic load and at last the dynamic stress frequency by the entropy weight method analysis.

Damage assessment is one of the most crucial issues for bridge engineers, especially for existing steel bridges. Among several methodologies, the vibration measurement test is a typical approach in which the natural frequency variation of the structure is monitored to detect the existence of damage. However, locating and quantifying the damage is still a big challenge. In this regard, the artificial intelligence (AI)-based approach seems a potential way to accomplish those obstacles. This study deploys a comprehensive campaign to determine all dynamic parameters of a pre-damage steel truss bridge structure. Based on the results of mode shape, natural frequency, and damping ratio, a finite element model (FEM) is created and keeps updating. The artificial intelligence network's input data will be analyzed and evaluation from damage cases. The trained artificial neural network model will be curated and evaluated to confirm the approach's feasibility. During the actual operational stage of the steel truss bridge, this damage assessment system is showing good performance in terms of monitoring the structural behavior of the bridge under some unexpected accidents.

Excessive extracellular histones can damage cells despite their importance in DNA structure and gene regulation. We previously showed the harmful effect of histone 3.3 (H3.3) and its acetylated form (AcH3.3) in chronic obstructive pulmonary disease (COPD), but further research is needed to understand the in vivo underlying mechanisms. To investigate this, we administered a single dose of recombinant histones via intra-tracheal instillation in C57BL/6 mice and analyzed the outcomes after 48 hours. Both rH3.3 and rAcH3.3 effectively reached the bronchial and alveolar space. Lung histology revealed severe immune cell infiltration, rupture, damage, and thickening of many alveolar walls. Micro-CT scans showed macroscopic structure changes with a decreased tissue volume to total volume ratio. The administration of rH3.3 and rAcH3.3 induced lung apoptotic activity, as indicated by increased levels of cleavage caspase 3 and 9. Moreover, elevated plasma levels of pro-inflammatory cell mediators, including TNF-alpha, IL-6, MCP-3, and CXCL-1, were observed. The pathological changes and pro-inflammatory cytokine response were more pronounced in animals treated with rAcH3.3, which also exhibited leukocytosis and lymphocytosis. These findings emphasize the crucial role of extracellular H3.3 acetylation in inducing cytotoxicity and a robust, acute inflammatory response similar to what occurs in the lungs of COPD patients.

Understanding the effect of staking sequences and identifying the damage occurring within a structure using a structural health monitoring system are the keys to an efficient design of composite-based parts. In this research, a combination of digital image correlation (DIC) and acoustic emission (AE) is used to locate and classify the type of damage depending on the stacking sequence of the laminate during flexural loading. A comparison of the strain field results for unidirectional, cross-ply, and quasi-isotropic laminates was made in a first attempt to discuss their global behavior and to correlate the different damage patterns with the possible failure mechanisms. The damage was then addressed using a comprehensive interpretation of the acoustic emission signatures using the K-means classification of the acoustic events. The development of each damage mechanism was correlated to the applied load and expressed as a function of the loading rate to highlight the effect of the stacking sequence. Finally, the results of DIC and AE were combined to improve the reliability of the damage investigation without limiting the failure mechanism to matrix cracking, interfacial failure, and fiber breakage, as expected by the unsupervised event clustering.