The mechanization of agricultural activities has led to indiscriminate deposition of toxic xenobiotics, including organophosphates in the biomes, and this has led to intoxication characterized with deleterious oxidative and neuronal changes. This study investigated the consequences of oxidative and neurogenic disruptions that follow exposure to two organophosphates, chlorpyrifos (CPF) and dichlorvos (DDVP) on neuro-cognitive performance and anxiety-like behaviors in rats Thirty-two adult male Wistar rats (150 – 170g) were randomly divided into 4 groups, orally exposed to normal saline (NS), DDVP (8.8mg/kg), CPF (14.9mg/kg) and DDVP+CPF for 14 consecutive days. On day 10 of exposures, anxiety-like behaviors and amygdala dependent fear learning were assessed using Open Field and Elevated Plus Maze paradigms respectively, while spatial working memory was assessed on day 14 in the Morris water maze paradigm, following 3 training trials each on days 11, 12 and 13. On day 15, the rats were euthanized, and their brains excised, hippocampus and amygdala removed, 5 of which were homogenized and centrifuged to analyze nitric oxide (NO) metabolites, total reactive oxygen species (ROS), and acetylcholinesterase (AChE) activity, and the other three processed for histology (cresyl violet stain) and proliferative marker (Ki67 immunohistochemistry). Marked (p≤0.05) loss in body weight, AChE depletion, and overproduction of both NO and ROS were observed after repeated exposure to individual and combined doses of CPF and DDVP. Insults from DDVP exposure appeared more severe owing to the observed greater losses in the body weights of exposed rats. There was also a significant (p≤0.05) effect on the cognitive behaviors recorded from the exposed rats, and these deficits were related to the oxidative damage and neurogenic cell loss in the hippocampus and the amygdala of the exposed rats. Taken together, these results provided an insight that oxidative and neurogenic damages are central to the severity of neuro-cognitive dysfunction and increased anxiety-like behaviors that follow organophosphate poisoning.

Regarding number of vehicles, forest roads are characterized by low traffic intensity, but on the other hand great values of ground pressure between wheels of timber truck units and forest road surface occur, often with pressures values above 80 kN which additionally causes damage of the upper and lower forest road layer. There are currently several methods for assessing condition of a forest road surface which are mainly used for assessing state of public roads, but can be used in forestry as well. Assessing condition of forest road surface was done by measuring vibrations with a specially developed software for Android OS installed on a Huawei MediaPad 7 Lite. Software measured vibrations in all three axes, coordinates of device, speed of the vehicle and time. Aim of this research was to determine accuracy of collected data so that this method can be used for scientific and practical purposes. Research was carried out on the segment of a forest road during driving a vehicle equipped with a measuring device. Tests were performed in both driving direction of the forest road segment with different measuring frequencies, tyre inflation pressures and driving speeds. Values of vibrations were classified and translated on a map of forest road together with devices’ measured coordinates. Vibration values were compared with places of recorded forest road surface damages. Research results show no significant difference in vibration values between 1 Hz and 10 Hz of measurement frequencies. Based on the analysis of collected data and obtained results, it is clear that it is possible to assess the condition of a forest road surface by measuring vibrations. The greatest values of vibrations were recorded on the most damaged parts of the forest road. Vibrations do not depend on tyre inflation pressure, but ranges of vibrations are decreasing with decreasing driving speed. Accuracy of collected data depends on GPS signal quality, so it is recommended that each segment of forest road is recorded twice so that location of damages on forest road can be confirmed with certainty.

The effect of low cycle fatigue (LCF) pre-damage on the subsequent very high cycle fatigue (VHCF) behavior is investigated in TC21 titanium alloy. LCF pre-damage is applied under 1.8% strain amplitude up to various fractions of the expected life and subsequent VHCF properties are determined using ultrasonic fatigue tests. Results show that 5% of LCF pre-damage insignificantly affects the VHCF limit due to the absent of pre-crack, but decreases the subsequent fatigue crack initiation life estimated by Pairs’ law. Pre-cracks introduced by 10% and 20% of LCF pre-damage significantly reduce the subsequent VHCF limits. The crack initiation site shifts from subsurface-induced fracture for undamaged and 5% of LCF pre-damage specimens to surface pre-crack for 10% and 20% of LCF pre-damage specimens in very high cycle region. The fracture mechanism analysis indicate that LCF pre-crack will re-start to propagate under subsequently low stress amplitude when stress intensity factor of pre-crack is larger than its threshold. Furthermore, the predicted fatigue limits based on EI Haddad model for the LCF pre-damage specimens well agree with the experimental results.

The information of seismic damage of buildings in SAR images of different time phase, especially in SAR images after earthquake, is easily disturbed by other factors, which affects the accuracy of information discrimination. In order to identify and evaluate the distribution information of the seismic damage accurately and make full use of the abundant texture features in the SAR image. The conventional method of change detection based on texture features usually takes the pixel as the calculating unit. In this paper, a method of texture feature change detection of SAR images based on watershed segmentation algorithm is proposed. Based on the optimization of texture feature parameters, the feature parameters are segmented by the watershed segmentation algorithm, and the feature object image is obtained. This method introduces the idea of object oriented, and carries out the calculation of the difference map at the object level, Finally, the classification threshold value of different types of seismic damage types is selected, and the recognition of building damage is achieved. Taking the ALOS data before and after the earthquake in Yushu as an example to verify the effectiveness of the method, the overall accuracy of the building extraction is 88.9%, Compared with pixel-based methods, it is proved that the proposed method is effective.

Background: Intestinal helminthiases and schistosomiasis are among the neglected tropical diseases targeted by the World Health Organization (WHO) for elimination as a public health issue by 2030. For this, it is important to determine their distribution and predicting factors, after a decade of mass deworming campaigns. In particular, such information is scarce among pre-school aged children who have not been the target for epidemiological studies and schistosomiasis deworming activities. This cross-sectional study and secondary data analysis focused on preschool-aged children and was aimed to determine the prevalence of intestinal helminthiases (Ascaris, ankylostoma, trichirus trichura, taenia) and Schistosomiasis, and identify the factors associated with them in Rwanda. Methods: Data from 4,675 preschool-aged children randomly selected from 17 districts endemic to Schistosoma mansoni were analyzed. Parasitological assessment was performed using the Kato Katz technique. Having at least one intestinal helminthiasis or schistosomiasis case was considered a positive outcome. A structured questionnaire for childcare guardians, literature, and GIS were used to collect information regarding environmental factors. Data were aggregated at village level to calculate village prevalence used in depicting the distribution of intestinal helminthiases and schistosomiasis. Descriptive analysis was performed, and prevalence was assessed as a measure of frequency. The chi-square test was used for bivariate analysis whereas logistic regression was used for multivariable analysis. The confidence level was set at 95%, and the decision was made based on the P-value. Odds ratios (ORs) were assessed as a measure of association. STATA 15 and ArcGIS software were used in this study. Results: The prevalence of intestinal helminthiases and schistosomiasis among preschool-aged children was 20.3%. Ascaris was the most prevalent parasite in this study (15%). Being older than 24 months, having self-employed parents, residence, fetching water into the lake or water body, land cover, clay soil, and high LST are predictors of intestinal helminthiases and schistosomiasis among preschool-aged children in Rwanda. Conclusion: The prevalence of 20.3% is moderate and in the march towards the elimination of these parasitic infections, deworming activities should be coupled with water supply, reinforcement of the use of Early Child Development (ECD), relocating people living in proximity of wetlands and water bodies, and health education are key interventions in preventing preschool-aged children to get intestinal helminthiases and Schistosomiasis.

Background: Early diagnosis of postoperative complications is an urgent task, allowing timely prescribing of appropriate therapy and reducing the cost of patient treatment. Prognostic models based on various data could help in the early diagnosis of postoperative complications after cardiac surgery. Objectives: The purpose of the study was to determine whether an integrated approach based on clinical data along with metabolites and biomarkers had greater predictive value than the models built on less data. Methods: The study included patients (n=62) admitted for planned cardiac surgery (coronary artery bypass grafting with cardiopulmonary bypass), who were retrospectively divided into two groups depending on the presence (n=26) or absence (n=36) of postoperative complications of all types. Clinical and laboratory data on the first day after surgery were analyzed. Additionally, patients' blood samples were collected before and on the first day after surgery to determine biomarkers (interleukin-6, procalcitonin, NT-proBNP, high-sensitivity troponin T) and metabolites (8 aromatic and 2 dicarboxylic acids were detected using gas chromatography-mass spectrometry). Results: Patients before surgery, compared with healthy donors, differed in the concentration of metabolites (p < 0.05), and had concentrations of a number of biomarkers exceeding the corresponding reference values. Multivariate PLS-DA models, predicting the presence or absence of postoperative complications, were built using clinical data (ROC-AUC=0.71), concentrations of metabolites and biomarkers (ROC-AUC=0.60), and the entire data set (ROC-AUC=0.75). For comparison we built univariate models using the EuroScore2 (ROC-AUC=0.59) and SOFA (ROC-AUC=0.76) scales; concentrations of lactate (ROC-AUC=0.71), the dynamic changes of 4-hydroxyphenyllactic acid (ROC-AUC=0.69), and the sum of three sepsis-associated metabolites (ROC-AUC=0.70). The proposed complex model using entire data set was comparable to the SOFA scale, which confirms the expediency of searching for new predictive models based on a variety of factors.

Healthcare-Associated infections (HAIs) affect more than 100 million patients each year worldwide. These infections are mainly caused by multi-resistant bacterial strains (MDR) such as Acinetobacter Baumanii which is responsible of high mortality rate in immunocompromised individuals. However, the treatment is further aggravated by the abuse of antibiotics, the lack of vaccine and the emergence of resistance posing a huge challenge for the discovery of new therapeutic drugs to overcome this nosocomial infection. In this context, antimicrobial peptides with potential antibacterial proprieties could be an alternative. In this research, we describe the synthesis and the bioactivity of dermaseptins and their derivatives against Acitenobacter baumanii. The cytotoxicity of these DS was investigated on the HEp-2 cell line by the MTT cell viability assay. Thereafter, we studied morphological alterations caused by the action of one of the active peptides on the bacterial membrane using Atomic Force Microscopy (AFM). The cytotoxicity of dermaseptins was concentration-dependent at microgram concentrations. It was observed that all tested analogs exhibit antibacterial activity with MICs ranging from 3.125 to 12.5 μg/mL and MBCs ranging from 6.25 to 25 μg/mL. Microscopic images obtained by AFM revealed morphological changes on the surface of treated bacteria caused by K4S4(1-16), as well as significant surface alterations. Overall, these findings demonstrate that DS might constitute new lead structures for the development of potent antibacterial agents against Acinetobacter infections.

Injured peripheral nerves regenerate their axons in contrast to those in the central nervous system. However, functional recovery after surgical repair is often disappointing. The basis for the poor recovery is the progressive deterioration with time and distance, of the growth capacity of the neurons that lose their contact with targets (chronic axotomy) and the growth support of the chronically denervated Schwann cells (SC) in the distal nerve stumps. This is despite the retained capacity of chronically denervated and atrophic muscle to accept reinnervation. Progressive decline in regeneration associated genes in both axotomized neurons and denervated SCs accounts for the decline in regenerative success in association with silencing of neural activity in sensory neurons due to their disconnection from their sense organs and, in motoneurons due to loss of their synaptic contacts in the spinal cord. Whilst exogenous neurotrophic factors promote nerve regeneration, the profuse axonal outgrowth and difficulties in delivery are avoided by promoting their endogenous expression with brief (1 hour) low frequency (20Hz) electrical stimulation (ES) proximal to the injury site. ES accelerates axon outgrowth and in turn, target reinnervation in both animals and human subjects. Applying ES to intact nerve days prior to nerve injury, conditional ES (CES) increases axonal outgrowth and regeneration rate with the potential for application in nerve transfer surgeries and end-to-side neurorrhaphies. However, the additional surgery for applying CES electrodes may be a hurdle. ES is applicable in all surgeries with excellent outcomes.

Classic Hodgkin lymphoma (cHL) is a lymphoid neoplasm composed of rare neoplastic Hodgkin and Reed-Sternberg (HRS) cells surrounded by a reactive tumor microenvironment (TME) with suppressive properties against anti-tumor immunity. TME is mainly composed of T-cells (CD4 helper, CD8 cytotoxic and regulatory), and tumor-associated macrophages (TAMs) but the impact of these cells on the natural course of the disease is not absolutely understood. TME contributes to the immune evasion of neoplastic HRS cells through production of various cytokines and/or aberrant expression of immune checkpoint molecules, in ways that have not been fully understood yet. Herein, we present a comprehensive review of findings regarding the cellular components and the molecular features of the immune TME in cHL, its correlation with treatment response and prognosis as well as the potential targeting of the TME with novel therapies. Among all cells, macrophages appear to be a most appealing target for immunomodulatory therapies, based on their functional plasticity and antitumor potency.

Kaposi’s sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus-8, is the causative agent of Kaposi’s sarcoma, Castleman’s disease, and primary effusion lymphoma. Although the functions of the viral thymidine kinases (vTK) of herpes simplex virus-1/2 and varicella zoster virus are well understood, that of KSHV ORF21 (an ortholog of vTK) is largely unknown. Here, we investigated the role of ORF21 in lytic replication and infection by generating two ORF21-mutated KSHV BAC clones: ORF21-kinase activity deficient-KSHV (21KD) and stop codon-induced ORF21-deleted-KSHV (21del). The results showed that both ORF21-mutations did not affect viral genome replication, lytic genes transcription, or the production of viral genome-encapsidated particles. ORF21 molecule-dependent function, other than the kinase function of ORF21, was involved in the infectivity of progeny virus. ORF21 was expressed at 36 h after induction of lytic replication, and endogenously expressed ORF21 was localized in the whole cytoplasm and decreased on the cell surface area. Moreover, the effects of ORF21 expression on signaling pathways and proliferation were analyzed. The results showed that ORF21 upregulated the MEK phosphorylation and anchorage-independent cell growth. These findings indicate that ORF21 plays key roles in both infection and oncogenesis of KSHV through the manipulation of cellular function.

Leptospirosis remains an important worldwide zoonotic disease caused by Leptospira spp affecting human and animals. This research aims to study the virulent-associated secreted proteins (protein secretome) of pathogenic Leptospira interrogans serovar Icterohemorrhagiae strain RGA (Leptospira RGA) transition from the environment to mammalian physiological osmolarity, temperature (37 °C) and carbon dioxide concentration (5% CO2) conditions for 24 h. Mass Spectrometry and bioinformatics approaches, we identified 69 potential secreted proteins from the culture supernatant of the Leptospira RGA isolate. We discovered transporters and porins such as phosphate porin, outer membrane efflux, ompA family protein, and polymer-forming cytoskeletal family protein under hyperosmotic condition. Under heat stress, degradation enzymes included zinc metallopeptidase, M23 family (LA3456, LA0709), Rhs family protein (LA1765), thermolysin metallopeptidase; / hydrolase family (LA1345, LA2501). Oxidative stress response proteins induced by osmolarity and temperature shifts included chaperon GrpE, DnaK (LA3705), antioxidants, i.e., thiol-specific redoxin, and peroxiredoxin (LA2809). In response to the in vivo transition, metabolic and other enzymes involved in energy production (COG:C), amino acid metabolism and transport (COG:E), and lipid metabolism and transport (COG:I), as well as moonlighting proteins functionally binding to plasminogen and fibronectin and regulating transcription, were also discovered. An overview of secreted proteins will supplement our understanding of Leptospira biology and pathogenesis during infection and also in response to environmental stimuli and their potential virulent determinants have the potential for developing leptospirosis vaccines and diagnosis.

One of the most striking findings in biogerontology in the 2010s was the demonstration that elimination of senescent cells delays many late-life diseases and extends lifespan in mice. This implied that accumulation of senescent cells promotes late-life diseases, particularly through action of senescent cell secretions (the senescence-associated secretory phenotype or SASP). But what exactly is a senescent cell? Subsequent to the initial characterization of cellular senescence it became clear that, prior to aging, this phenomenon is in fact adaptive. It supports tissue remodeling functions in a variety of contexts, including embryogenesis, parturition and acute inflammatory processes that restore normal tissue architecture and function, such as wound healing, tissue repair after infection, and amphibian limb regeneration. In these contexts such cells are normal and healthy, and not in any way senescent in the true sense of the word, as originally meant by Hayflick. Thus, it is misleading to refer to them as “senescent”. Similarly, the common assertion that senescent cells accumulate with age due to stress and DNA damage is no longer safe, particularly given their role in inflammation - a process that becomes persistent in later life. We therefore suggest that it would be useful to update some terminology, to bring it into line with contemporary understanding, and to avoid future confusion. To open a discussion of this issue, we propose replacing the term cellular senescence with remodeling activation, and SASP with RASP (remodeling-associated secretory phenotype).

The cytosolic PNGase (peptide:N-glycanase; Png1 in yeast; NGLY1/Ngly1 in human/mice), also known as peptide-N4-(N-acetyl-beta-glucosaminyl)-asparagine ami-dase, is a well-conserved deglycosylation enzyme (EC 3.5.1.52) which catalyzes the non-lysosomal hydrolysis of an N(4)-(acetyl-β-D-glucosaminyl) asparagine residue into N-acetyl-β-D-glucosaminylamine and a peptide containing an aspartate residue. This enzyme (NGLY1) plays essential roles in clearance of misfolded or unassembled gly-coproteins through a process named ER-associated degradation (ERAD). Accumulating evidence also points out that NGLY1 deficiency can cause an autosomal recessive hu-man genetic disorder associated with abnormal development and congenital disorder of deglycosylation. In addition, the loss of NGLY1 can affect multiple cellular pathways, including but not limited to NFE2L1 pathway, Creb1/Atf1-AQP pathway, BMP path-way, AMPK pathway, and SLC12A2 ion transporter, which might be the underlying reasons for a constellation of clinical phenotypes of NGLY1 deficiency. The current comprehensive review indeed uncovers the detailed NGLY1’s structure and its im-portant roles for participation in ERAD, involvement in CDDG and potential treatment for NGLY1 deficiency.

In the context of the COVID-19 pandemic, thousands of healthcare workers (HCWs) infected with COVID-19 have lost their lives worldwide. At the early stage of the epidemic, when COVID-19 was still not considered as a pandemic, a large number of Chinese HCWs were infected. Officials reported that more than 3,000 HCWs in Hubei contracted the virus at the early stage of the outbreak due to limited knowledge of the virus. Following reports of overloaded local hospitals, more than 42,000 medical staff, including those from the military, were dispatched to Hubei from across the country. At the peak of the fight, one in 10 intensive care medics in China were working in Wuhan. During fighting against COVID-19 in China, although a large number of HCWs were infected by SARS-CoV-2 in the early stages of the epidemic, the timely adoption of measures indicated that, a faster rate of diagnosis could be achieved, patients were isolated in-time, HCWs’ safety was prioritized, training on basic protective knowledge and unified management of HCWs was strengthened, and effective protective measures were implemented. This resulted in the accomplishment of zero SARS-CoV-2 infection among the 42,632 members of the national medical teams sent to Hubei, and the number of COVID-19 cases among HCWs in local hospitals also significantly decreased, thereby indicating that hospital-acquired infections of SARS-CoV-2 among HCWs are fully preventable.

Suboptimal health status (SHS) is a state between health and disease, has several associated factors, although, its underlying mechanism is still unclear. This study aimed to investigate the status of SHS and its associated factors of high school students in three areas of China (Shanxi, Guangzhou, and Tibet). A multidimensional sub-health questionnaire of adolescent (MSQA) is used to evaluate SHS. Among 1461 respondents, females proportion 56.47% was higher than males 43.53% where SHS was higher in Shanxi followed by Tibet and then Guangzhou. The rural area, grade, lack of sleep, home visit in a week, lack of exercise, a heavy burden of study, smoking, drinking, and fewer friends were the risk factors of SHS, while, families living status, seeking help and extroversion were the protective factors. SHS is significantly associated with different influencing factors. For comprehensive prevention and control measures, reduce the risk factors and enhance the protective factors.

Sonoran felids are threatened by drought and habitat fragmentation. Vector range expansion and anthropogenic factors such as habitat encroachment and climate change are altering viral evolutionary dynamics and exposure. However, little is known about the diversity of viruses present in these populations. Small felid populations with lower genetic diversity are likely to be most threatened with extinction by emerging diseases, as with other selective pressures, due to having less adaptive potential. We used a metagenomic approach to identify novel circoviruses, which may have a negative impact on the population viability, from confirmed bobcat (Lynx rufus) and puma (Puma concolor) scats collected in Sonora, Mexico. Given some circoviruses are known to cause disease in their hosts, such as porcine and avian circoviruses, we took a non-invasive approach using scat to identify circoviruses in free-roaming bobcats and puma. Three circovirus genomes were determined, and, based on the current species demarcation, they represent two novel species. Phylogenetic analyses reveal that one circovirus species is more closely related to rodent associated circoviruses and the other to bat associated circoviruses, sharing the highest genome-wide pairwise identity of approximately 70% and 63%, respectively. At this time, it is unknown whether these scat-derived circoviruses infect felids, their prey, or another organism that might have had contact with the scat in the environment. Further studies should be conducted to elucidate the host of these viruses and assess health impacts in felids.

Oral cancer cells (TYS) and the signalling pathways involved in metastasis, in response to cancer-associated fibroblasts (CAFs, COM) and normal oral mucosal fibroblasts (MM1) was studied. Metastatic cell behaviour was observed by cell-scatter, 3D-collagen gel migration and 3D-spheroid invasion assays. Akt, MAPK, EGFR, TGFβRii and CXCR4 inhibitors were used to identify the signalling pathways involved. Signalling pathway protein expression and activation were assessed by SDS-PAGE and Western Blotting. COM-CM (conditioned medium) and MM1-CM stimulated cancer cell scattering, which was blocked only by the Akt inhibitor. COM-CM induced scattered cancer cells showed higher levels of Akt phosphorylation than the negative control and MM1-CM. Migration and invasion of TYS cells into the collagen gels from the spheroids was stimulated by CM from both sources, compared to the negative control. COM cells stimulated TYS, cancer cell invasion into the collagen more than MM1 and the control. Akt and EGFR inhibitors effectively blocked CM and COM cell-induced invasion. Akt-silenced cancer cells were not stimulated to migrate and invade by fibroblast-CM and did not survive addition of the EGFR inhibitor. This suggests that CAFs stimulate oral cancer cell migration and invasion in an Akt- dependent manner. EGFR and Akt are potential therapy targets in metastatic oral cancer.

Since the first description of bisphosphonate-related osteonecrosis of the jaw (BRONJ) numerous research groups have focused on possible pathological mechanisms including the suppression of the bone turnover of the jaw, antiangiogenic effects and soft tissue toxicity. In our review we focused on summarizing the role of the soft tissues in the development and progression of BRONJ. The biological behavior of fibroblasts can be significantly influenced by bisphosphonates (BP) such as a concentration dependent reduction of cell viability. High concentrations of BP can induce apoptosis and necrosis of the cells. Comparable effects could be detected for keratinocytes. Compared to non-nitrogen containing bisphosphonates nitrogen-containing BP have worse effects on cell biology by blocking the mevalonate pathway. Next to this the cell architecture and the expression levels of several genes and proteins are significantly disturbed by BP. These inhibitory effects of BP are in accordance with BP related reduced angiogenesis and neovascularization and could underline the hypothesis that inhibition of fibroblasts and keratinocytes results in delayed wound healing and can induce and trigger BRONJ.

The central reason behind emergence of clinically-detectable tumors is evasion from immune surveillance due to lack of cancer cells surface membrane expression of tumor-specific peptides in association with MHC class I molecules, concealment of natural killer cells-activating molecules, and absence of inflammation resulting from inefficient stimulation of innate immunity receptors and co-stimulatory molecules. The tumor microenvironment (TME) also contributes to tumor initiation, progression and resistance to therapeutic interventions because of its dense, fibrogenic, barrier-like composition, aberrant vasculature, and production of cytokines and chemokines responsible for recruitment of immune suppressive cells, notably myeloid-derived suppressor cells, M2 macrophages, regulatory T cells, extracellular trap-forming neutrophils, and cancer-associated fibroblasts. We herein show that the relentless efforts and strategies to overcome the TME elusive tumor-promoting impact produced contrasting, opposed, controversial effects, characterized by limited efficacy and proven adversity, and most importantly deterred from attempts to discover and counteract the fundamental inherent mechanisms initiating, and not consequent to, carcinogenesis.

In the United States, the Federal Aviation Administration has officially classified flight crew (FC) consisting of commercial pilots, cabin crew or flight attendants as “radiation workers” since 1994 due to the potential for cosmic ionizing radiation (CIR) exposure at cruising altitudes originating from solar activity and galactic sources. Several epidemiological studies have documented elevated incidence and mortality for several cancers in FC, but it has not yet been possible to establish whether this is attributable to CIR. CIR and its constituents are known to cause a myriad of DNA lesions, which can lead to carcinogenesis unless DNA repair mechanisms remove them. But critical knowledge gaps exist with regard to CIR dosimetry, the role of other genotoxic exposures among FC, and possible biological mechanisms underlying higher cancer rates observed in FC exist. This review summarizes our understanding of the role of DNA damage and repair responses relevant to CIR exposure in FC. We aim to stimulate new research directions and provide information that will be useful for guiding regulatory, public health, and medical decision-making to protect and mitigate risks for those who travel by air.

The paper presents the problem of damage detection in steel girders. Static displacements at the selected point of the structure play the role of measured variables. Structural response signal decomposition is performed according to the Mallat pyramid algorithm, which is used to perform the discrete wavelet transform (DWT). This procedure allows us to quite well determine the location of structural damage. The geometry and the placement of any defective part of the structure may have a random character. It can be assumed that the random processes occurring in the broadly understood structure mechanics are Gaussian in nature. The first four probabilistic moments are estimated using three approaches independent: semi-analytical (SAM), perturbative (SPT), and Monte-Carlo simulations (MCS). The semi-analytical random approach seems to be the most optimal due to the necessary computation time. The incorporation of the mathematical stochastic apparatus into the classical (deterministic) analysis of the statics of the structure makes it possible to estimate the reliability measures of the analyzed girder.

Various wood fibres, including pine and flax, are used in wood–plastic composites (WPCs). This paper studies the effect of the lignin content on the morphological and thermal degradation and damage due to the ultraviolet (UV) aging of polypropylene/flax (PP-flax) and polypropylene/pine (PP-pine) fibres composites. Flax and pine fibres exhibited distinct densities of 1.51 and 1.47 g/cm³, respectively, potentially influenced by growth factors and varying compositions of light substances, such as hemicellulose, lignin, and impurities. The thermal decomposition mass loss increased proportionally with the percentage of lignin in the fibre. From 238°C to 390°C, the pine fibre exhibited a 72% mass loss compared to flax fibre, which showed a 54% mass loss, owing to the higher lignin content in pine fibres. Based on differential scanning calorimetry (DSC), the fibre composition affected the material melting temperature. Moreover, DSC curves revealed a higher degree of crystallinity in the case of the PP-flax biocomposite (12%) compared to pure polypropylene (9%) and PP-pine (6%). This result can be attributed to the high content of crystalline components in flax fibres, such as cellulose. Acoustic emissions analysis confirmed that the high lignin content delays degradation and mitigates the appearance of microcracks on the surface of the PP-pine biocomposite. Overall, the study provides valuable data for understanding the UV degradation phenomenon in biocomposites and highlights the influence of fibre composition on material performance.

The degree of ore rock fragmentation of mine blasting is an important index for evaluating the effect of engineering blasting. In order to study the effect of millisecond delayed blasting on the internal fragmentation of the ore rock, LS-DYNA numerical simulation software was used to obtain the damage characteristics of the ore rock in the blasting area using the RHT model. The Mohr-Coulomb strength damage criterion was applied to analyze the internal stress state of the ore rock, and the effects of 25ms, 50ms and 75ms delay time conditions on ore rock fragmentation were studied. The results show that, within a certain range of delay time, the degree of rock fragmentation increases with the increase of delay time. The stress state in the ore rock due to blasting is strengthened with the increase of delay time in the direction of the blast hole, which shows that the stress concentration is strengthened from the excavation face to the interior of the ore rock. The damage and the degree of fragmentation show a characteristic relationship of 25ms＜50ms＜75ms, which is verified by carrying out blasting experiments on site.

In rock blasting for mining production, stress waves play a major role in rock fracturing along with explosion gases. Better energy distribution improves fragmentation and safety, lowers production costs, increases productivity, and controls ore losses and dilution. Blast outcomes vary significantly with the choice of the explosive and the properties of the rock mass encountered. This study analyzes the effects of rock mass and explosives properties on the blast outcomes through numerical simulation using data from the case study and later validates the simulation results from the field blast fragmentation. The outcomes suggest that, for a given set of rock properties, the choice of explosive has a major influence on the resulting fragmentation. Strong explosives favor large fracture extents in hard rocks, while less strong explosives offer a better distribution of explosive energy and fractures. The presence of rock structures such as rock con-tacts and joints influences the propagation of stress waves and fractures depending on the structures' material properties, intensity and orientations, and the direction and strength of the stress wave. To achieve effective fragmentation, the blast design should mitigate the effect of variability in the rock mass by ensuring adequate energy distribution within the limits of geo-metrical design.

The saltmarsh plant Halimione portulacoides was shortly exposed to realistic levels of inorganic mercury (iHg), aiming to investigate adaptative processes of the roots and leaves regarding re-dox homeostasis, physiology, and Hg accumulation. Plants were collected at a contaminated (CONT) and a reference (REF) site, addressing the interference of contamination background. The influence of major abiotic variables (i.e., temperature and light) was also examined. Total Hg lev-els, antioxidant enzymes, lipid peroxidation (LPO), and photosynthetic activity were analyzed after 2 and 4 hours of exposure. Accumulation of iHg in the roots was noticed poorly, and no translocation to stems and leaves was found, but plants from CONT seemed more prone to iHg uptake (in winter). Despite that, antioxidant modulation in roots and leaves was found, disclos-ing, in winter, higher thresholds for the induction of enzymatic antioxidants in CONT leaves compared to REF, denoting that the former are better prepared to cope with iHg redox pressure. Consistently, CONT leaves exposed to iHg had remarkably lower LPO levels. Exposure did not impair the photosynthetic activity, pinpointing H. portulacoides ability to cope with iHg toxicity under a very short-term exposure. Biochemical changes were noticed before enhancements in ac-cumulation, reinforcing the relevance of these responses in precociously signaling iHg toxicity.

Background: Uncontrolled hemorrhage is a major preventable cause of death in patients with trauma. However, the majority of large animal models of hemorrhage have utilized controlled hemorrhage rather than uncontrolled hemorrhage to investigate the impact of immunopathy and coagulopathy on multi-organ failure (MOF) and mortality. This study evaluates these alterations in a severe porcine-controlled and uncontrolled hemorrhagic shock (HS) model. Methods: Anesthetized female swine underwent controlled hemorrhage (22 ml/kg) and uncontrolled hemorrhage by partial splenic resection followed with or without lactated Ringer solution (LR) or Voluven® resuscitation. Blood chemistry, physiologic variables, systemic and tissue levels of complement proteins and cytokines, coagulation parameters, organ function, and damage were recorded and assessed. Results: HS resulted in systemic and local complement activation, cytokine release, metabolic acidosis, hyperkalemia, MOF, and no animal survival. Resuscitation with LR and Voluven® after HS improved hemodynamic parameters (MAP and SI), metabolic acidosis, hyperkalemia, and survival but resulted in increased complement activation and worse coagulopathy. Compared with the LR group, the HS animal treated with Voluven® had worse dilutional anemia, coagulopathy, renal and hepatic dysfunction, increased myocardial complement activation and renal damage, and decreased survival rate. Conclusions: Hemorrhagic shock triggers early immunopathy and coagulopathy that appear associated with MOF and death. This study indicates that immunopathy and coagulopathy are therapeutic targets that may be addressed with a high-impact adjunctive treatment to conventional resuscitation.

The open hole tensile and flexural test of composites holds immense importance in aerospace and structural engineering. These tests provide critical insights into how composites perform under real-world conditions, allowing for the development of materials that meet rigorous standards, thereby ensuring the safety and durability of aircraft and other applications. This study investigates the influence of hole size on the open hole tensile (OHT) and flexural properties (OHF) of plane woven aramid/epoxy (AFRP), basalt/epoxy (BFRP), and aramid-basalt/epoxy (ABFRP) sandwiched laminates. Specimens with three different hole sizes viz., 4 mm, 6 mm, 8 mm were prepared and tested according to ASTM D5766 and ASTM D7264 for OHT and OHF performance respectively. Results indicated that the hybridization of aramid-basalt layers in a sandwich lay up significantly improved the mechanical performance when compared to only aramid laminate. However, with the increase in hole size the mechanical properties declined irrespective of the material. Basalt fibres showed higher hole sensitivity under tensile loading due to its brittle fracture mechanism while aramid fibres exhibited higher hole sensitivity under flexural loading which can be attributed to its the poor compressive strength. The effect of hole size on the damage mechanism has also been highlighted through scanning electron microscope (SEM). Major failure modes observed are delamination around the hole edges, ductile and brittle fibre fractures, and delamination.

Recent successes in the field of evolutionary cancer cell biology (ECCB) have brought to a head two of the most important controversies regarding cancer origin. The first concerns the question of whether carcinogenesis is initiated only by genetic alterations, mutations, and driver genes, as the mutational theory teaches. The ECCB, claims that a large number of polyploidy-related cancers (PGCC cancers) are not due to mutations, but rather to inadequate ancient repair mechanisms used by DNA-damaged stem cells for their repair. Somatic mutations are merely secondary. The second controversy, described in the previous article, concerns the non-mutational theory itself: Are non-mutational polyploid cancers an atavism - as previously thought - or rather the effect of an ancient gene regulatory network aGRN that controls genome reprogramming in precancerous DNA-damaged cells as well in the transformed cells. Finally, the unicellular gene module of cancer, of which the aGRN is a part, has evolved along with the multicellular genome during the last 1000 My of evolution. and non-mutated cancer cell systems are under the control of the aGRN. The atavistic theory relies on phylostratigraphic evidence to determine the age of cancer genes. It states that most cancer-like genes arose during the transition period from unicellularity to multicellularity, but also during the early metazoan era. In our opinion, the atavistic theory is flawed and suffers from many misunderstandings. It provides little insight into the origin and coevolution of the cancer cell system and its control by the ancient gene regulatory network aGRN.

Brainstem auditory evoked potentials (BAEPs) testing is very important when microvascular decompression (MVD) is performed with hemifacial spasm (HFS). The reason for this is that the vestibulocochlear nerve is located right next to the facial nerve, so the vestibulocochlear nerve may be affected by manipulation by surgery. The BAEPs test method for detecting vestibulocochlear nerve damage during surgery has been developed a lot and is helping a lot during surgery. In most HFS patients with normal vestibulocochlear nerve, the degree of vestibulocochlear nerve damage caused by surgery is reflected very well in the BAEPs test waveforms. Therefore, a real time test is the best way to minimize the damage to the vestibulocochlear nerve. The purpose of this study was to review the most recently published BAEPs test used in MVD surgery and to find out in detail the relationship between the vestibulocochlear nerve damage and the BAEPs waveforms.

Polymethyl methacrylate (PMMA) polymer is widely used in various fields today. In order to thoroughly reveal the structural impact performance of PMMA materials, this paper is based on the comprehensive Johnson-Cook constitutive model and damage failure model, and accurately confirm the J-C constitutive and damage failure model parameters of PMMA through material test data, The dynamic process of steel bullet impacting PMMA plate structure is analyzed by finite element software ABAQUS. The calculation results show that the numerical simulation results in this paper are in good agreement with the experimental test data. Therefore, the feasibility and accuracy of the impact analysis of PMMA structures based on J-C constitutive and damage failure models in this paper are studied. Finally, based on the J-C constitutive model and damage failure model, the variation of the residual velocity of the bullet with the PMMA plate thickness is analyzed in depth, that is, the results show that the residual velocity of the bullet has a certain linear relationship with the plate thickness.

A Fall armyworm (FAW) is a major pest of maize and causes huge losses. Chemical control is the commonly used strategy FAW among farmers. Efficacy of baculovirus against FAW has been proven, however, farmers may not afford the products. The use of farmer produced baculovirus mixtures could provide an opportunity for a nature-based solution for FAW at low cost. This study evaluated the potential of virus extracted from FAW larvae treated with a commercial baculovirus (Littovir) for the management of FAW under laboratory and field conditions. In Laboratory, the virus extracted from 25, 50, 75 and 100 FAW larvae caused varied mortality on FAW instars. The highest mortality (45%) on 1st-3rd instars was caused by Littovir followed by virus extract from 100 FAW larvae (36%). Under field conditions, even though virus extracts did not offer adequate protection against the FAW damage, the maize yield was comparable to commercial insecticides treated plots. This study has shown the potential of use of virus extracts for management of FAW. This would offer the farmers a sustainable and affordable option for management of FAW as it would require the farmers to purchase the commercial baculovirus once and collect larvae from treated plots for repeat applications.

Water damage is one of the main causes of roads’ deterioration throughout their service life. This effect harms the adhesion and cohesion parameters of the asphalt mix, which leads to a decrease in the structural and functional characteristics of the road surface. This research focuses on studying the water susceptibility of hot mix asphalt mixtures using three different procedures: (1) UNE-EN 12697-12, (2) ASTM D4867, and (3) AASHTO T-283. The tests are carried out on reference mixtures and mixtures modified with polyethylene terephthalate (PET) particles as an additive. The results indicate that the incorporation of 6% PET allows the limits established by the UNE-EN 12697-12 standards to be exceeded, reaching 86% of the tensile strength ratio (TSR). However, for the ASTM D4867 and AASHTO T-283 standards, the results obtained concerning the water susceptibility of the bituminous mixtures were not as satisfactory because the established minimum limits were not reached (< 75%), which indicates that the procedure applied in a test can significantly modify the results of a later application.

Nonlinear catastrophes caused by geological fluids are a fundamental issue in rock mechanics and the geoengineering hazard field. For the consideration of hydrodynamic force on red-bed mudstone softening damage, X-ray visualization test on the fissure flow in mudstone block failure under hydrodynamic force was performed in this study based on block scale and the physical phenomena of fissure seepage and nonlinear diffusion were further explored. A new method for evaluating the hydro-damage degrees of rocks using an X-ray image analysis was proposed, and the quantitative relation of diffusion coefficients of hydro-damage and seepage was established. The research results revealed that the hydrodynamic force promoted the fluid-filled fissure behavior in mudstone specimen failure. Also, the seepage and diffusion phenomena of fluid in rocks during failures were indicated using X-ray imaging. A dual mechanical behavior was presented in the nonlinear seepage and abnormal diffusion of a red mudstone geological body under hydrodynamic conditions. The damaged degree of mudstone was aggravated by the effect of hydrodynamic force, and the initial seepage–diffusion coefficient with respect to lower hydro-damage was larger than the final seepage–diffusion coefficient with respect to higher hydro-damage of rocks with a decreasing nonlinear trend.

High temperature (HT) significantly affects the crop physiological traits and reduces the 12 productivity in plants. To increase yields as well as survival of crops under HT, developing heat13 tolerant plants is one of the main targets in crop breeding programs. The present study attempted 14 to investigate the linkage of the heat tolerance between the seedling and the reproductive growth 15 stages of tomato cultivars ’Dafnis‘ and ’Minichal’. This research was undertaken to evaluate heat 16 tolerance under two experimental designs such as screening at seedling stage and screening from 17 reproductive traits in greenhouses. Survival rate and physiological responses in seedlings of 18 tomatoes with 4-5 true leaf were estimated under HT (40 °C, RH 70%, day/night, respectively) and 19 under two control and HT greenhouse conditions (day time 28 °C and 40 °C, respectively). Heat 20 stress significantly affected physiological-chemical (photosynthesis, electrolyte conductivity, 21 proline) and vegetative parameters (plant height, shoot fresh weight, root fresh weight) in all 22 tomatoes seedlings. The finding revealed that regardless of tomato cultivars the photosynthesis, 23 chlorophyll, total proline and electrical conductivity parameters were varied in seedlings during the 24 heat stress period. The heat tolerance rate of tomatoes in the seedling stage might not be associated 25 always with reproductive parameters. HT reduced the fruit parameters likeas fruit weight (31.9%), 26 fruit length (14.1%), fruit diameter (19.1%) and fruit hardness (9.1%) in compared to NT under HT 27 in heat susceptible tomato cultivar ‘Dafnis’, while in heat tolerant cultivar ‘Minichal’ fruit length 28 (7.1%) and fruit diameter (12.1%) was decreased by the affect of HT but on the contrary fruit weight 29 (3.6%) and fruit hardness (8.3%) were increased. In conclusion, screening and selection for tomatoes 30 should be evaluated at the vegetative and reproductive stages with consideration of reproductive 31 parameters.

The enterohemorrhagic Escherichia coli (EHEC) O157: H7 EspF is known to be a multifunctional effector that triggers several damage processes in the host cells. However, in the process of EHEC O157: H7 infection, the interactions between EspF, its N- or C-terminus, and host proteins are still unclear. In this work, we use co-immunoprecipitation combined with mass spectrometry (CoIP-MS) to screen the interactions between EspF/EspF-N/EspF-C terminus and host proteins. A total of 311 host proteins are analyzed. The N-terminus of EspF is found to interact with 192 proteins, whereas 205 proteins interact with the C-terminus. These proteins are mainly involved in RNA splicing, endoplasmic reticulum stress, and a variety of metabolic signaling pathways. Surprisingly, MS results reveal that EspF can also phosphorylate H2AX, suggesting that EspF may directly mediate DNA damage. Here, by western blot and immunofluorescence (IF), we verified that EspF can cause phosphorylation of H2AX and mediates cell multi-nuclearation and cell hypertrophy. Furthermore, we verify here for the first time that SMC1 interacts with EspF -C-terminus, and provide evidence that EspF increases p-SMC1 levels. p-SMC1 is known to influence S-phase cell cycle arrest and usually increases during periods of DNA damage. Our work revealed a novel interaction between EspF and the host protein SMC1 and lays a foundation for further research on EspF-mediated host DNA damage, apoptosis, and even colorectal carcinogenesis.

COVID-19 pandemic represents an unprecedented sanitary threat: antiviral and host-directed medications to treat the disease are still urgently needed.A great effort has been paid to find drugs and treatments for hospitalized, severely ill patients. However, medications used for the domiciliary management of initial symptoms, notwithstanding their importance, have not been and are not presently regarded with the same attention. In analogy with other respiratory viral infections, COVID-19 patients in the early phase require specific antivirals (still lacking) and non-etiotropic drugs to lower pain, fever and control inflammation. Non-steroidal antinflammatory drugs (NSAIDs) and paracetamol (PAC) are widely used as non-etiotropic agents in these conditions and hence are both theoretically repurposable for COVID-19. However, a warning from some research reports and National Authorities raised NSAIDs safety concerns because of the supposed induction of ACE2 protein levels (the receptor used by SARS-CoV2 to enter host airways cells), the risk of bacterial superinfections and masking of disease symptoms. As a consequence, the use of NSAIDs was, and is, strongly discouraged while the alternative adoption of paracetamol is still preferred.On the basis of novel data and hypothesis on the possible role of scarce glutathione (GSH) levels in the exacerbation of COVID-19 and of the GSH depleting activity of PAC, this commentary raises the question of whether PAC may produce an oxidative imbalance which could be detrimental in COVID-19 clinical outcomes.

This article proposes a monitoring system that allows to track transitions between different stages in the berry harvesting process (berry picking, waiting for transport, transport, and arrival to the packing) solely using information from temperature and vibration sensors located in the basket. The monitoring system assumes a characterization of the process based on Hidden Markov Models and uses the Viterbi algorithm to perform inference and estimate the most likely state trajectory. The obtained state trajectory estimate is then used to compute a potential damage indicator in real-time. The proposed methodology does not require information about the weight of the basket to identify each of the different stages, which makes it effective and more efficient than other alternatives available in the industry.

In intermediary metabolism, enzymes are mainly for the specific provision of one small molecule from another, B from A, for its further use. But there are also decades of work relating to another evolved purpose, which is to prevent untoward effects of odd compounds of various origins, and of ordinary intermediates, whose improper concentrations may be avoided by hydrolases and other activities of metabolic correction.

Marine mortar was the goal material and its multi-scale physical-chemical-mechanical characteristics were the principal interest in this study. The on-line multi-scale damage detection experiments art was designed to quantify the characteristics mathematically and graphically. The normal cylinder specimen with 70-day age was produced and investigated by dynamically global MSHCT scan and local detection of EDS, SEM and XRD. The experiments results indicated that the marine mortar offered the appreciable strength at the early age at least, although some saline minerals were generated during the preparation. The micro-interfacial behavior and the parental foci controlled the damage development of the marine mortar the performance of which was still the adjustable one by the composition optimization.

Impact of Nitrogen Foamed Stimulation Fluids Stabilized by Nanoadditives on Reservoir Rocks of Hydrocarbon Deposits

Reliable fatigue design rules affect the proactive identification of safety parameters in aerospace industry. Numerous fatigue crack initiation and propagation models, linear and nonlinear, have been developed for designing purposes or estimation of the remaining life of aging airplanes. Depending on the adopted assumptions, the accuracy varies for different loading histories, loading types, and materials. Semi empirical models are simple but yield significant inaccuracies. Models with better theoretical basis provide better accuracy, but implementation in real conditions is problematic. In the present work, a review of author’s recent fatigue crack initiation and propagation models based on physical mechanisms is presented and improvements are proposed. Verification of the models on test results is provided and discussed.

Maintenance of the human chromosomes stability requires a tight regulation of DNA replication to duplicate once and only once the entire genome of a single cell. In mammalians cells, origin activation is controlled in space and time by a cell specific and robust program called replication timing. About 100 000 of potential origins are loaded onto the chromatin at the G1 phase but only 20-30% are selected and active during the replication of a given cell. When the replication fork is slowed down by exogenous or endogenous sources, the cell need to activate more origins to complete the replication on time. Thus, the large choice of origins that can be activated may be a key player in the protection of the genome. The aim of this review is to discuss about the role of these dormant origins as housekeepers of the human genome in response to replicative stress.

In the lowland forests of south-western Poland, the effect of the fencing of forest regeneration stages, aged up to 20 years, upon the level of damage inflicted by red deer (Cervus elaphus), fallow deer (Dama dama), and roe deer (Capreolus capreolus) in non-fenced patches of this age class of forest was studied. In the studied forest districts (n=4), there was the highest proportion of the mixed coniferous‑deciduous forest types, where the main forest‑forming tree species were pine (Pinus sylvertris), birch (Betula sp.), oak (Quercus sp.), beech (Fagus sylvatica), and spruce (Picea abies). At the forest district level, the percentage of fenced areas in young forest plantations (1‑10‑year old) ranged, on average, from 9.1-30.9%, and that in tickets (11-20‑year old) ranged from 0.0%-10.2%. The percentage of areas of severely damaged young plantations fluctuated between 5.7 and 14.2%, and that of tickets fluctuated between 0.3-12.9%. For young plantations, a statistically significant correlation (“r” ranged from 0.51-0.75) was obtained between percentage of area in fenced plots and the level of damage caused by deer. For thickets, this correlation was obtained solely in Pieńsk Forest District (r = 0.646). In the studied forest districts, the fencing of young plantations and thickets resulted in the reduction of average potential food base for cervids, from 2.9 to 10.0 %. An attempt was made to interpret the level of deer damage on the basis of an index, taking into account the standing crop of deciduous browse and forbs, and the population density of cervids.

The correlation and comorbidity between depression and chronic pain have been observed for a long time. Generally, it is considered that the two conditions reinforce each other, whereas the causal relationship between them is not clear. However, some evidence suggested that chronic pain may reverse the progression of depression in some cases. This article presents a selective review of clinical and pharmacological relationship between depression and pain, and their interactions at neurochemical and neurobiological levels. In addition, we open a discussion on a recent case report of repeated success of using short but continuous pain (SCP) during meditation as the only treatment for depression, compared to initial success but no remission with other conventional antidepressants on the same patient. Together this review proposes an updated model for depression and its various treatments that is based on synaptic and system homeostasis. More importantly, it suggests that SCP may benefit depression recovery through its properties that are different from either acute or chronic pain and represents a novel research area that has been largely neglected to date.

TGF-β signaling transduces immunosuppressive biochemical and mechanical signals in the tumor microenvironment. In addition to canonical SMAD signaling, TGF-β can promote tumor growth and survival by inhibiting proinflammatory signaling and extracellular matrix remodeling. In this article, we will review how TAK1 activation lies at the intersection of proinflammatory signaling by immune receptors and anti-inflammatory signaling by TGF-β receptors. Additionally, we will discuss the role of TGF-β in the mechanobiology of cancer. Understanding how TGF-β dampens proinflammatory responses and induces pro-survival mechanical signals throughout cancer development will be critical in designing therapeutics which inhibit tumor progression while bolstering the immune response.

Aiming at the damage detection and continuous monitoring of high efficiency composite structure, the method of carbon nano sensor embeded in the 3-D braided composite material specimen was put forward and the method of damage location for 3-D braided composite material was described. In this paper, the mechanical and electrical characteristics of carbon nano-fiber were analyzed. Considering the massive data of the health monitoring of composite processing, to ensure that the system has good real-time performance, quaternary matrix Singular Value Decomposition algorithm is proposed to simplify data and improve the efficiency of the algorithm. The existence of injury is determined and the damage location is calculated by comparing with key features of healthy specimen. Experimental results prove the method is feasible and effective.

Adeno-associated viral (AAV) vectors can be used for gene delivery. AAV.CAP-Mac was recently developed; it can cross the blood-brain barrier and transduce cells throughout the CNS. However, some brain regions were not transduced in adult rhesus monkeys. Additionally, AAV vectors can only package 5 kb of DNA. Also, AAV vectors may be genotoxic and cytotoxic, especially at high doses. Finally, AAV vectors are very expensive to produce at sufficiently high titers for treatment. Off-the-shelf cell-based delivery systems wherein the cells can infiltrate the target tissue and be hyper-motile would be ideal. Also, mRNA-based gene editing would be a transient treatment, and thus be much safer.

Ferroptosis, a form of regulated cell death characterized by lipid peroxidation and iron accumulation, has been implicated in the progression of metabolic dysfunction-associated steatohepatitis (MASH) in obesity. This study investigated the role of ferroptosis in the development of hepatic steatosis and MASH in obese mice and assessed the therapeutic potential of ferrostatin-1, a ferroptosis inhibitor. C57BL/6J wild-type mice (n = 8) and ob/ob (n = 16) were maintained on a standard chow diet. Mice were divided into three groups that included C57BL/6 (n = 8), ob/ob (n = 8), and ob/ob + ferrostatin-1 (FER) (n = 8), with the latter group receiving an intraperitoneal injection of 5 μM/kg ferrostatin three times per week for eight weeks. Following treatment, serum and tissue samples were collected for analysis. Significant hepatic steatosis and increased lipogenesis markers were observed in ob/ob mice, and this was normalized in the ob/ob + FER group treated with ferrostatin-1. Elevated oxidative stress was indicated by increased reactive oxygen species (ROS) and Malondialdehyde (MDA) levels in the ob/ob group, while glutathione peroxidase 4 (GPX4) activity was significantly reduced. Ferrostatin-1 treatment decreases MDA levels and restores GPX4 activity. Additionally, ferrostatin mitigates iron overload and promotes macrophage polarization from M1 to M2, thereby reducing liver inflammation and fibrosis. Ferrostatin treatment reversed mitochondrial dysfunction in ob/ob mice Our findings revealed that ferroptosis plays a significant role in the progression of obesity to hepatic steatosis and MASH. Inhibiting ferroptosis using ferrostatin-1 effectively improves liver histology, reduces oxidative stress, normalizes lipogenesis, and modulates macrophage polarization. This study highlights the potential of targeting ferroptosis as a therapeutic strategy for obesity-related liver diseases, warranting further investigation in clinical settings.

Objective: To evaluate the value of otolith‑associated protein otoconin‑90 (OC90) and otolin-1 in the pathogenesis research and clinical treatment of benign paroxysmal positional vertigo (BPPV). Material and Method: The study included 50 patients with BPPV admitted to neurology and otorhinolaryngology departments and 30 healthy subjects with no history of dizziness as control group. Results: BPPV and controls were similar in terms of gender and age. Otolin-1 level was significantly greater in the BPPV group than controls (710.44 vs 280.45 ; p<0.001). No statistical significance was found although OC90 were higher in the BPPV group than controls. There was a strong positive correlation between otolin-1 and OC90, a moderate negative correlation between otolin-1 and vitamin D, and a strong negative correlation between OC90 and vitamin D in BPPV patient group. Otolin-1 had high specificity and AUC values for BPPV (AUC: 0.933; 95% CI: 0.881-0.986, 79.2% sensitivity, 100% specificity with a cutoff greater than 525). Conclusion: High serum levels of otolin-1 were associated with an increased risk of BPPV, but not CO90. Serum levels of otolin-1 can potentially be used as a biomarker for acute onset of inner ear disorders due to its significant increase in patients with BPPV. Vitamin D has high specificity and sensitivity in the patients with BPPV patients. It also provides evidence that BPPV patients with vitamin D deficiency may improve their complaints with replacement therapy. More large-scale prospective studies is required to confirm these association and clarify the exact mechanism.

Adeno-associated viruses (AAV) are widely used as viral vectors for gene delivery in mammalian cells. We focused on the efficacy of transduction of AAV 2/5, 2/6, 2/8 and 2/9 expressing GFP in 3T3-L1 murine preadipocyte cells by live imaging microscopy using IncuCyte S3 and flow cytom-etry. Three transduction modes were assessed: AAV transduction in 3T3-L1 preadipocyte cells with or without further differentiation into mature adipocyte-like cells and injection of AAVs in differ-entiated adipocyte-like cells. AAV2/6 demonstrated the highest transduction efficiency in 3T3-L1 preadipocytes, as it was 1.5–2-fold more effective than AAV2/5, and AAV2/8 in the range of viral concentrations from 2×104 to 1,6×105 VG/cell. AAV2/5 and AAV2/8 showed transduction effi-ciencies similar to each other. The expression of GFP under the CMV promoter remained stable for up to 20 days. The induction of 3T3-L1 differentiation in three days after AAV transduction did not alter the GFP expression level, and AAV2/6 showed the best transduction efficiency. AAV2/6 demonstrated the ability to transduce mature adipocytes. These results were confirmed by in vivo studies on C57BL6 mice AAV2/6 had the highest transducing activity on both inguinal and inter-scapular adipose tissue. Thus, AAV2/6 has demonstrated higher transduction efficacy compared to AAV2/5, AAV2/8 and AAV2/9 both in 3T3-L1 adipocytes and adipose tissue in vivo, which proves its usability along with AAV8 and AAV9 for gene delivery to adipocytes.

Background: The incidence of metabolic dysfunction-associated steatohepatitis (MASH)-related hepatocellular carcinoma (HCC) is increasing annually with a rise in the incidence of obesity and metabolic syndrome. Based on preliminary reports regarding the potential association of HCC and periodontitis, this study aimed to analyze the involvement of periodontal bacteria as well as the oral and intestinal bacterial flora in MASH-related HCC (MASH-HCC). Methods: Forty-one patients with MASH and 19 with MASH-HCC who completed survey questionnaires, underwent periodontal examinations, and subjected to sample collection (saliva, mouth-rinsed water, feces, and peripheral blood) participated in the study. Bayesian network analysis was used to analyze the causation between various factors, including MASH-HCC, examinations, and bacteria. Results: The occupancy rate of the genus Fusobacterium in the intestinal bacterial flora was significantly higher in in the MASH-HCC group than in the MASH group (p = 0.002), whereas that of Butyricicoccus (p = 0.022) and Roseburia (p &lt; 0.05) was significantly lower. Bayesian network analysis revealed the absence of periodontal pathogenic bacteria and enteric bacteria affecting HCC. However, HCC directly affected the periodontal bacterial species Porphyromonas gingivalis, Tannerella forsythia, Fusobacterium nucleatum, and Prevotella intermedia in the saliva, as well as the genera Lactobacillus, Roseburia, Fusobacterium, Prevotella, Clostridium, Ruminococcus, Trabulsiella, and SMB53 in the intestine. Furthermore, P. gingivalis in the oral cavity directly affected the genera Lactobacillus and Streptococcus in the intestine. Conclusion: MASH-HCC directly affects periodontal pathogenic and intestinal bacteria, and P. gingivalis may affect the intestinal bacteria associated with gastrointestinal cancer.

.Background: Negative outcomes associated with medications (NOM) and drug-related problems (DRP) significantly impact individuals with kidney replacement therapy (KRT) given the complexities of managing kidney disease and associated comorbidities. The present study aims to assess the frequency of NOMs/DRPs among KRT patients and identify contributing factors. Methods: A cross-sectional study was conducted at the Virgen de las Nieves University Hospital (Granada, Spain), involving 117 outpatient adults with KRT. Data were collected from February 2021 to July 2023 using electronic records, semi-structured interviews (Dáder Method), and discussions with nephrology specialists. NOMs/DRPs were identified following treatment guidelines. Binary logistic regression determined associated factors (p-value < 0.05). Results: Across 117 patients, 2,436 NOMs and 3,303 DRPs were identified, averaging 20.82 NOMs and 28.23 DRPs per patient. Prevalent NOMs included untreated conditions (58.95%), quantitative ineffectiveness (35.43%), and non-quantitative safety problems (5.13%). Dominant DRPs were undertreated conditions (37.63%), wrong dose/posology/length (33.00%), risk of adverse drug reactions (ADR) (16.14%), and non-adherence (6.87%). Patients with ADR, undertreated condi-tions, and anemia were associated with quantitative ineffectiveness. Risk of ADR and vitamin D deficiency/insufficiency correlated with non-quantitative safety problems. Conclusions: KRT pa-tients exhibited a substantial prevalence of NOMs/DRPs. Further research is needed to deepen our understanding of these complexities for improved patient care.

Distal Sensory Peripheral Neuropathy (DSP) is a common complication in HIV-infected individ-uals, leading to chronic pain and reduced quality of life. Despite antiretroviral therapy (ART), DSP persists, often prompting the use of opioid analgesics, which can paradoxically worsen symptoms through opioid-induced microbial dysbiosis. This study employs the HIV Tg26 mouse model to investigate HIV-DSP development and assess gut microbiome changes in response to chronic morphine treatment and ART using 16s rRNA sequencing. Our results reveal that chronic morphine and ART exacerbate HIV-DSP in Tg26 mice, primarily through mechanical pain path-ways. As the gut microbiome may be involved in chronic pain persistence, microbiome analysis indicated distinct bacterial community changes between WT and Tg26 mice as well as morphine and ART-induced microbial changes in the Tg26 mice. This study reveals the Tg26 mice model to be a relevant system that can help elucidate the pathogenic mechanisms of opioid and ART-induced exacerbation of HIV-associated pain. Our results shed light on the intricate inter-play between HIV infection, ART, opioid use, and the gut microbiome in chronic pain development. They hold implications for understanding the mechanisms underlying HIV-associated pain and microbial dysbiosis, with potential for future research focused on prevention and treatment strategies.

Background: Identifying genetic mutations that lead to spermatogenic impairment is essential for offering patients informed genetic counseling and preventing the transmission of genetic defects to their offspring, often through the use of advanced reproductive technologies. Objectives: The purpose of this study was to identify potential single nucleotide polymorphisms (SNPs) associated with male infertility. Methods and Materials: Genetic variants that may cause infertility are identified by combining targeted next generation sequencing (NGS) panel and whole exome sequencing (WES). The validation step of Sanger sequencing adds confidence to the identified variants. Results: Our analysis revealed five distinct affected genes covering seven SNPs: based on targeted NGS panel and WES data, namely SPATA16 (rs16846616, 1515442, 1515441), CFTR (rs213950), KIF6 (rs2273063), STPG2 (r2903150) and DRC7 (rs3809611). Infertile men have a higher mutation rate than fertile men, especially those with azoospermia. Discussion and Conclusions: These findings strongly support the hypothesis that dysfunction of microtubule-related and spermatogenesis-specific genes contributes to idiopathic male infertility. The SPATA16, CFTR, KIF6, STPG2 and DRC7 mutations are associated with male infertility, specifically azoospermia, further examination of this genetic function is required.

Sepsis-associated encephalopathy (SAE) is a common brain dysfunction following sepsis that often results in severe cognitive and neurological sequelae and increases the mortality rate in patients with sepsis. Microglia are resident macrophages in the brain that play essential roles in the pathological and physiological processes of SAE. Depending on the nature of the stimulus, microglia can adopt two polarization states (M1/M2), which correspond to altered microglial morphology, gene expression, and function. Therefore, we systematically described the pathogenesis, morphology, function, and phenotype of microglial activation in SAE. We demonstrated that microglia are closely related to occurrence and development of SAE and concomitant cognitive impairement. Finally, we outlined some potential therapeutic approaches that can prime microglia and neuroinflammation towards the beneficial restorative microglial phenotype in SAE.

Microglial dysfunction is one of the hallmarks and leading causes of common neurodegenerative diseases (NDD), including Alzheimer’s disease (AD) and Parkinson’s disease (PD). All these pathologies are characterized by aberrant aggregation of disease-causing proteins in the brain, which can directly activate microglia, trigger microglia-mediated neuroinflammation, and increase oxidative stress. Inhibition of glial activation may represent a therapeutic target to alleviate neurodegeneration. Recently, 3-iodothyronamine (T1AM), an endogenous derivative of thyroid hormone (TH) able to interact directly with a specific GPCR known as trace amine-associated receptor 1 (TAAR1), gained interest for its ability to promote neuroprotection in several models. Nevertheless, T1AM’s effects on microglial disfunction remain still elusive. In the present work we investigated whether T1AM could inhibit the inflammatory response of human HMC3 microglial cells to LPS/TNFα or β-amyloid peptide 25-35 (Aβ25-35) stimuli. The results of ELISA and qPCR assays revealed that T1AM was able to reduce microglia-mediate inflammatory response by inhibiting the release of proinflammatory factors, including IL-6, TNFα, NF-kB, MCP1 and MIP1, while promoting the release of anti-inflammatory mediators, such as IL-10. Notably, T1AM anti-inflammatory action in HMC3 cells resulted to be a TAAR1-mediated response, further increasing the relevance of the T1AM/TAAR1 system in the management of NDD.

Background: The objective of the present study was to evaluate the formation of biofilm in bone patellar tendon bone grafts (BPTB grafts) and to compare it to the formation of biofilm formation in quadrupled hamstring anterior cruciate ligament grafts (4xHt graft). Methods: A descriptive in vitro study was conducted. One 4xHt graft and one BPTB graft were prepared. They were then contaminated with a strain of S. epidermidis. Later, a quantitative analysis was carried out by means of microcalorimetry and sonication with plating. Additionally, a qualitative analysis was carried out by means of electron microscopy. Results: No significant differences were found between the bacterial growth profiles of 4xHt graft and BPTB graft in microcalorimetry and colony counting. In the samples analyzed with electron microscopy, no specific biofilm growth pattern was identified upon comparing BPTB graft to 4xHt graft. Conclusions: There were no significant differences at either the quantitative or qualitative level when comparing bacterial growth in BPTB graft to that in 4xHt graft. Therefore, the presence of sutures in 4xHt graft cannot be established as a predisposing factor for increased biofilm growth in this in vitro study.

The tumor microenvironment (TME) surrounding tumor cells is a complex and highly dynamic system that promotes tumorigenesis. Cancer-associated fibroblasts (CAFs) are key elements in TME playing a pivotal role in cancer cells’ proliferation and metastatic spreading. Considering the high expression of the fibroblast activation protein (FAP) on cell membrane, CAFs emerged as appealing TME targets, namely for molecular imaging, leading to a pan-tumoral approach. Therefore, FAP inhibitors (FAPis) have been recently developed for PET imaging and radioligand therapy, exploring the clinical application in different tumor sub-types. The present review aimed to describe recent developments on radiolabeled FAP inhibitors and evaluate the possible translation of this pan-tumoral approach in clinical practice. At present, the application of FAPi-PET has been explored mainly in single-center studies, generally performed in small and heterogeneous cohorts of oncological patients. However, preliminary results were promising, in particular in low FDG-avid tumors such as primary liver and gastro-entero-pancreatic cancer, or in regions with unfavorable tumor-to-background ratio at FDG-PET/CT (i.e. brain), as well as in radiotherapy planning of head and neck tumors. Further promising results have been obtained in the detection of peritoneal carcinomatosis, especially in ovarian and gastric cancer. Data regarding the theranostics approach are still limited at presents, and definitive conclusion about its efficacy cannot be drawn at present. Nevertheless, the use of FAPi-based radio-ligand to treat the TME has been evaluated in first-in-human studies and appears feasible. Although the pan-tumoral approach in molecular imaging showed promising results, its real impact in day-to-day clinical practice has yet to be confirmed, and multi-center, prospective studies powered for efficacy are needed.

Nucleoid-associated proteins (NAPs) play an architectural role by bending, bridging, and wrapping the DNA along with a regulatory role of controlling various transcriptional units in the cell. Previews reviews have highlighted the role of HU and its paralog IHF plays in intracellular function as a transcriptional regulator, nucleoid bending protein and sometimes also moonlights in other functions. This review highlights along with the canonical functions of HU and IHF which affects genes responsible for translational machineries, cell wall biosynthesis, aerobic respiration and virulence ; other non-canonical roles which HU plays outside the cellular milieu, notably in acting as an adhesin and playing role in host-cell adhesion, its role in biofilm architecture and its association with cationic low complexity region, resembling histone like H1 proteins. HU and IHF thus has evolved as a hub protein performing a vast type of functions which makes it a important drug target for antibacterial therapy.

The function of the endoplasmic reticulum (ER) can be impaired by the alternation of the extra- and intracellular environment such as disruption of calcium homeostasis, expression of mutated proteins and oxidative stress. In response to disruptions to ER homeostasis, eukaryotic cells activate canonical branches of signal transduction cascades, collectively termed the unfolded protein response (UPR). The UPR attempts to recover the protein folding capacity and avoid irreversible cellular damage. Additionally, the UPR has been shown to play unique physiological roles in the regulation of diverse cellular events, including cell differentiation and development and lipid biosynthesis. Recent studies have indicated that these important cellular events are also regulated by contact and communication among organelles. These reports suggest strong involvement among the UPR, organelle communication and regulation of cellular homeostasis. However, the precise mechanisms for the formation of contact sites and the regulation of its dynamics by UPR remain unresolved. In this review, we summarized the current understanding of how the UPR regulates morphological changes to the ER and the formation of contact sites between the ER and other organelles. We also review how UPR-dependent connections between the ER and other organelles affect cellular and physiological functions.

The function of the endoplasmic reticulum (ER) can be impaired by the alternation of the extra- and intracellular environment such as disruption of calcium homeostasis, expression of mutated proteins and oxidative stress. In response to disruptions to ER homeostasis, eukaryotic cells activate canonical branches of signal transduction cascades, collectively termed the unfolded protein response (UPR). The UPR attempts to recover the protein folding capacity and avoid irreversible cellular damage. Additionally, the UPR has been shown to play unique physiological roles in the regulation of diverse cellular events, including cell differentiation and development and lipid biosynthesis. Recent studies have indicated that these important cellular events are also regulated by contact and communication among organelles. These reports suggest strong involvement among the UPR, organelle communication and regulation of cellular homeostasis. However, the precise mechanisms for the formation of contact sites and the regulation of its dynamics by UPR remain unresolved. In this review, we summarized the current understanding of how the UPR regulates morphological changes to the ER and the formation of contact sites between the ER and other organelles. We also review how UPR-dependent connections between the ER and other organelles affect cellular and physiological functions.

The excited-state lifetimes of the anticoagulant drug warfarin (W) in water and in the absence and presence of methyl-β-cyclodextrins (Me-β-CD) were recorded using time-resolved fluorescence measurements. Selective excitation of the open and cyclic protonated isomers of W were acquired with laser emitting diodes (LED) producing 320 and 280 nm excitation pulses, respectively. Formation of the inclusion complex was checked by UV–visible absorption spectroscopy, and the values of binding constants (2.9 × 10³ M^–1 and 4.2 × 10² M^–1 for protonated and deprotonated forms, respectively) were extracted from the spectrophotometric data. Both absorption and time-resolved fluorescence results established that the interior of the macromolecular host binds preferentially the open protonated form, red shifts the maximum of its absorption of light at ~305 nm, extends its excited-state lifetime, and decreases its emission quantum yield (ФF). Collectively, sequestration of the open guest molecules decreases markedly their radiative rate constants (kr), likely due to formation of hydrogen-bonded complexes in both the ground and excited states. Due to lack of interactions, no change was observed in the excited-state lifetime of the cyclic form in the presence of Me-β-CD. The host also increases the excited-state lifetime and ФF of the drug deprotonated form (W¯). These later findings could be attributed to the increased rigidity inside the cavity of Me-β-CD. The pKa values extracted from the variations of the UV–visible absorption spectra of W versus the pH of aqueous solution showed that the open isomer is more acidic in both ground and excited states. The positive shifts in pKa values induced by three derivatives of cyclodextrins: HE-β-CD, Ac-β-CD, and Me-β-CD supported the preferential binding of these hosts to open isomers over cyclic.

Some of the most promising small molecule toxins used to generate antibody drug conjugates (ADCs) include anti-mitotic agents (e.g auristatin and its derivatives) which are designed to attack cancerous cells at their most vulnerable state during mitosis. We were interested to identify a human cystostatic protein eventually showing comparable activities and allowing the generation of corresponding targeted fully human cytolytic fusion proteins. Recently, we identified the human microtubule associated protein tau (MAP tau) which binds specifically to tubulin and modulates the stability of microtubules thereby blocking mitosis and presumably vesicular transport. By binding and stabilizing polymerized microtubule filaments, MAP tau-based fusion proteins skew microtubule dynamics towards cell cycle arrest and apoptosis. This biological activity makes rapidly proliferating cells (e.g cancer and inflammatory cells) an excellent target for MAP tau-based targeted treatments. Their superior selectivity for proliferating cells confers additional selectivity towards upregulated tumor-associated antigens at their surface, thereby preventing off-target related toxicity against normal cells bearing tumor-associated antigens at physiologically normal to low levels. In this review, we highlight recent findings on MAP tau-based targeted cytolytic fusion proteins reported in preclinical immunotherapeutic studies.

In metropolitan regions, which are particularly vulnerable to seismic damage, numerous reinforced concrete (RC) buildings are being constructed. Public safety has been an important consideration to safeguard and protect people, buildings, and infrastructure from the potential effects of earthquakes. The assessment of seismic vulnerability within urban areas encompassed an analysis of both building vulnerability and the scale of seismic hazards prevalent in the locality. This assessment aimed to ascertain the likelihood of building damage resulting from ground motion induced by an earthquake of a specific magnitude. In recent decades, considerable efforts have been made to develop and improve methods for assessing earthquake damage to reinforced concrete (RC) buildings. These efforts included the creation of seismic hazard and seismic risk indices that were used to quantify the potential destruction of individual building components or the entire building. This scholarly review article presents an in-depth analysis and concise summary of the primary techniques (including qualitative or empirical, quantitative, analytical, and experimental test methods) devised for appraising the seismic vulnerability of reinforced concrete frame buildings, pre- and post-earthquake occurrences. It is a valuable reference for policymakers, engineers, researchers, and specialists engaged in earthquake risk mitigation efforts.

We examine worldwide Property and Casualty and Life and Health insurance companies from 2004 until 2023, implementing panel regression models and mediation analysis to show that insurers raise their reserves when they face increasing costs for their potential environmental damages, ultimately reducing their profitability and underwriting capacity. Our findings extend to the insurance sector the previous evidence on banks, demonstrating that environmental damages could affect profits and solvency of financial intermediaries. These insights are important especially for insurance managers and regulators.

The Sustainable Development Center of the University of Brasilia is one of the modernist buildings that make up the Darcy Ribeiro campus. The architectural project contains several recommendations for the execution of the flat roof waterproofing system, as well as details for rainwater runoff and drainage, which reveals a certain concern with watertightness. The research seeks to identify the relationship between the pathological manifestations recognized on the roof and the semicircular shape of the building, assessing the state of conservation through the use of damage maps as an analysis tool. The article is based on a field survey using aerophotogrammetry with a drone, the application of vector drawing software for graphic representation and discussion of the possible causes, agents and mechanisms of degradation at work. The results show the importance of mechanical protection for the good performance of the waterproofing system, as well as the need for correct sizing of expansion joints in order to absorb and relieve the stresses caused by hygrothermal variations. The methodology incorporated proved to be effective and economical in diagnosing and monitoring pathological manifestations, making it possible to plan maintenance actions that extend the useful life and preserve the intrinsic characteristics of building systems.

There are few results about the internal damping ratio of normal and high strength concretes. Hence, this paper presents the expansion of the investigation about internal damping ratio under undamaged and damaged conditions, for usual concretes (NSC) and high strength concretes (HSC). In this way, the study cover a strength range of 42 to 83 MPa. Cyclic load was employed by a servo-controlled hydraulic testing machine and for each cyclic step the dynamic elastic modulus (Ed) and internal damping ratio (ξ) were determinate by acoustic tests. Normal strength concretes (fc = 42MPa) presented undamaged internal damping ratio ξ = 0.5% and achieved the maximum value of ξ = 2.5 for a damage index equal to 0.8. High strength concretes mixtures (fc = 83MPa) presented an undamaged internal damping of ξ=0.29% and maximum internal damping equal to ξ=0.93% (under damage index of 0.32). Porosity and the transition zones were the responsible to the initial internal damping values and how the material behavior under each cyclic load. The progressive damage generates the increase of coulomb damping. There are few studies allowing the quantification and comprehension of internal damping ratio under damage cyclic loading and this approach will lead to improve the understanding of NSC and HSC under dynamical excitation subject to damage evolution, mainly in impact situations.

Preterm birth accounts for about 10% of births worldwide. Studying risk factors for perinatal brain damage is essential, as findings suggest that almost 20% of disabilities are linked to risks in the early stages of development. This research aimed to study longitudinal changes in intelligence from 6 to 8 years of age in a sample of 39 preterm children with a history of risk of brain damage and a control group of 35 children born at term. The Wechsler Intelligence Scale (WISC-IV) was used for cognitive measurement. The results showed that the preterm group obtained significantly lower scores than the control group. The working memory indicator significantly affected the interaction between age and prematurity. We consider that it is crucial to expand the knowledge we have about the neurocognitive development of premature infants both in specific cognitive domains and in age ranges so that the information obtained helps to predict the probability of presenting cognitive alterations from early stages and, therefore, to implement intervention strategies and programs based on scientific evidence and complemented in their design by clinical experience, empirical and theoretical knowledge of the different professionals involved in infant cognitive intervention.

In this paper, the mechanism of combined process of ion beam sputtering (IBS) and HF acid etching on the chemical structure defects of fused silica and its laser damage resistance perfor-mance were investigated. During the removal process of surface material, the sputtering effect causes lattice atoms to detach from their original positions, forming a large number of unsaturated structures on silica surface, which improves the chemical activity of Si and O atoms, accelerates the chemical reaction process between surface atoms and water molecules, increases the content of hydroxyl (OH-) groups in the shallow layer, and enhances the photothermal weak absorption intensity. However, the presence of OH- groups reduces the bonding strength of Si-O, destroys the spatial network structure of silica bulk, and reduces the mechanical strength of silica surface, resulting in a decrease in its laser damage resistance performance. The paper reveals for the first time the mechanism of IBS to change the structure characteristics of silica material, accelerate the surface hydroxylation process, and thereby reduces the laser damage resistance performance. This work provides technical guidance for effectively suppressing chemical structure defects on silica surface and improving laser damage resistance performance of optical components under high-flux laser irradiation.

The liver diseases are posing serious threat to human health associated with abusive use of allopathy medicines, especially in developing economies like Pakistan. The strengthening of detoxification system using natural products might be a suitable option to minimize the liver problems. In this current research, Zingiber officinale and Azadirachta indica were evaluated for their hepatoprotective role. For the purpose, 20 Sprague Dawley rats were equally divided into four groups i.e., negative control, paracetamol positive control, 2.5% ginger and 2% neem powder, respectively. During 42 days study, the levels of bilirubin and liver enzymes significantly elevated due to liver damage. Although, the values dropped (20-25%) in treatment group. Serum glucose and serum lipid profile increased in positive control group, but reduced (5-10%) in both ginger and neem groups. The serum protein profile declined in liver damage group, however, improved (~5%) in treatment groups. The hematological parameters slightly declined in liver damage group, but increased in ginger and neem groups. Moreover, the white blood cells differential count and renal parameters showed abnormal values in liver damage group, but improved after treatment. This study is promising and highlighted the hepato-protective role of neem and ginger that may open several avenues of research.

Growing mushrooms is meeting challenges while aiming for sustainability and circularity. Wherever the producer is located, commercial strains are the same originating from several producers. Following the harvest, enormous quantities of spent mushroom substrate containing spores are disposed presenting a type of foreign material pressure on the ecosystem in the form of the loss of genetic diversity in wild mushroom populations. This challenge can be mitigated by bioprospecting local strains and using them to generate commercial inoculum. Accordingly, the mycoceutical potential of five polypore mushroom species from Serbia was evaluated: secondary metabolite composition, oxidative damage prevention, anti-tyrosinase, and anti-angiotensin converting enzyme (ACE) properties. The phenolic pattern was comparable in all samples, but the amounts of specific chemicals varied. Hydroxybenzoic acids were the primary components. All samples had varying quantities of ascorbic acid, carotene, and lycopene, and showed a pronounced inhibition of lipid peroxidation (LPx) and ability to scavenge HO•. Extracts were more potent tyrosinase inhibitors but unsuccessful when faced with ACE. Fomitopsis pinicola had the strongest anti-tumor efficacy while Ganoderma lucidum demonstrated strong selectivity in anti-tumor effect in comparison to healthy cells. The evaluated species provided a solid foundation for commercial development while keeping the local ecology in mind.

Appropriate diagnosis, treatment and care contributes to better service engagement, improvements to wellbeing, cost savings, reductions in morbidity and mortality for people with Alcohol Related Brain Damage. In the North-East of England large amounts of alcohol are consumed, reflected in the number of alcohol-related deaths in the region. However, the pathway for people with Alcohol Related Brain Damage to receipt of diagnosis, treatment and care is unknown and could be unwittingly influenced by stigma. Qualitative in-depth semi-structured interviews were completed with 25 health and social care professionals from organisations involved with people with Alcohol Related Brain Damage recruited via snowball-sampling. Interviews were recorded, transcribed verbatim, coded, and analysed. People with Alcohol Related Brain Damage were stigmatised both by society and professionals which inhibited entry into services therefore Alcohol Related Brain Damage remained underdiagnosed and misdiagnosed. There was no dedicated service but silos with revolving doors and underfunded generic care with long waiting lists typically excluding those with alcohol or neurological problems. Professionals need to be challenged on the assumption that Alcohol Related Brain Damage is self-inflicted via training aimed at challenging unconscious bias. Reducing stigmatising processes associated with Alcohol Related Brain Damage could counteract professionals’ reluctance to provide care.

With demand for the long-term continued use of existing building facilities, structural health monitoring and damage detection are attracting interest from society. Sensors of various types have been practically applied in the industry to satisfy this need. Among the sensors, piezoelectric sensors are an extremely promising technology by virtue of their cost advantages and durability. Although they have been used in aerospace and civil engineering, their application for building engineering remains limited. Remarkably, recent catastrophic seismic events have further rein-forced the necessity of rapid damage detection and quick judgment about the safe use of facilities. Faced with these circumstances, this study was conducted to assess the applicability of piezoelectric sensors to evaluate building components. Specifically, this study emphasizes structural damage caused by earthquakes. After first applying to cyclic loading tests to composite beam component specimens and steel frame subassemblies with a folded roof plate, the prospective damage posi-tions were also found using finite element analysis. Crack propagation and buckling locations were predicted adequately. The piezoelectric sensors provided output when the concrete slab showed tensile cracks, or when the folded roof plate experienced local buckling. Furthermore, damage expansion and progression were detected multiple times during loading tests. Results showed that the piezoelectric sensors can detect structural damage of building components, demonstrating their potential for use in inexpensive and stable monitoring systems.

To achieve sustainable development during urbanization, construction waste is recycled for use as an aggregate in recycled concrete (RC). To determine the influence of the brick content in coarse recycled aggregates on the damage sustained by the resultant RC, the RC was first divided into seven phases: natural crushed stone, old gravel inside waste concrete, bricks, new mortar, old mortar on waste concrete surfaces, and new and old interface transition zones. The Monte Carlo method was then applied to establish a two-dimensional random aggregate model of the RC made with coarse brick aggregates. The ABAQUS software package was used to simulate a uniaxial compression test, the results of which were combined with those of a macro-test to determine the internal damage change rule of brick-containing RC. The stress–strain curves obtained from the simulation coincided well with that of the macroscopic tests. As the brick content increased, the damage zone inside the specimen and the number of microcracks increased. The stress concentration area decreased, as indicated by a lower compressive strength in the macro-test. The results indicate that higher brick contents in RC yield more initial damage inside the concrete and a lower compressive strength.

Biocontrol strategies are gaining tremendous attention with the growing awareness of the irreparable harm caused by the continuous use of synthetic pesticides. This study examines the proteolytic and chitinolytic activities of Bacillus velezensis CE 100 and its termiticidal effect through cuticle degradation. The proteolytic and chitinolytic activities of B. velezensis CE 100 systematically increased with cell growth to the respective peak of 68.3, and 128.3 units/mL after seventh days of inoculation, corresponding with the highest cell growth of 16 x 107 colony forming units (CFU)/mL. The in vitro termiticidal assay showed that B. velezensis CE 100 caused a rapid and high rate of termite mortality with the median lethal time (LT50) of &gt; 1h, and the highest mortality rate of 91.1% and 92.2% recorded at 11h and 12h in the bacterial broth culture and crude enzyme fraction, respectively. In addition to broken setae and deformed sockets, termites treated with the bacterial broth culture exhibited degraded epicuticles, while the crude enzyme fraction caused severe disintegration of both the epicuticle and endocuticle. These results indicate a tremendously higher prospect of B. velezensis CE 100 in the biological control of subterranean termites compared to the previously used entomopathogenic bacteria.

In the current manuscript, a novel software application for Rapid Damage Assessment of RC buildings subjected to earthquake excitation is presented based on Artificial Neural Networks. The software integrates the use of a novel deep learning methodology for Rapid Damage Assessment into modern software development platforms, while the developed graphical user interface promotes the ease of use even from non-experts. The aim is to foster actions both in the pre- and post- earthquake phase. The structure of the source code permits the usage of the application either autonomously as a software tool for Rapid Visual Inspections of buildings prior to or after a strong seismic event or as a component of Building Information Modelling systems in the framework of digitizing building data and properties. The methodology implemented for the estimation of the RC buildings’ damage states is based on the theory and algorithms of Pattern Recognition problems. The effectiveness of the developed software is successfully tested using an extended, numerically generated database of RC buildings subjected to recorded seismic events

Previously, we reported that MTH1 inhibitors TH588 and TH1579 selectively induce oxidative damage and kill Ras expressing or transforming cancer cells, as compared to non-transforming immortalized or primary cells. While this explains the impressive anti-cancer properties of the compounds, the molecular mechanism remains elusive. Oncogenes induce replication stress, re-sulting in under replicated DNA and replication continuing into mitosis, where TH588 and TH1579 treatment cause toxicity and incorporation of oxidative damage. Hence, we hypothesized that oncogene-induced replication stress explains the cancer selectivity. To test this, we overex-pressed c-Myc in human epithelial kidney cells (HA1EB), resulting in increased proliferation, polyploidy and replication stress. TH588 and TH1579 selectively kill c-Myc overexpressing clones, enforcing the cancer cell selective killing of these compounds. Moreover, the toxicity of TH588 and TH1579 in c-Myc overexpressing cells is rescued by transcription, proteasome or CDK1 inhibitors, but interestingly not by nucleoside supplementation. This suggest that cancer selectivity is unrelated oncogene-induced replication stress. We conclude that the molecular toxi-cological mechanisms how TH588 and TH1579 kill c-Myc overexpressing cells have several com-ponents and involves MTH1-independent proteosomal degradation of c-Myc itself, c-Myc driven transcription and CDK activation, and is likely unrelated to oncogene-induced replication stress.

Management approaches inspired by the variability of natural disturbances are expected to produce forests in the future that will be significantly more resilient and better adapted to local environmental conditions. Due to climate change, windstorms are becoming increasingly common resulting in the destruction not only of extensive forest areas but, quite often, of small-sized and scattered forest lands that can ultimately become home to insects and disease dissemination sites. In the present study, an attempt is made to identify and record areas in the northeastern forests of Greece covered by mixed stands of conifers and broadleaves that experienced massive windthrow following local storms. Based on tree-level data, local topographic features, forest characteristics and the mechanical properties of green wood, a reliable model, to be used for the prediction of similar disturbances in the future, has been created after a thorough comparative study of the most well-known intelligent machine learning algorithms.

Current bridge inspection practices rely on paper-based data acquisition, digitization, and multiple conversions in between incompatible formats to facilitate data exchange. This practice is time-consuming, error-prone, cumbersome, and leads to information loss. One aim for future inspection procedures is to have a fully digitized workflow that achieves loss-free data exchange, which lowers costs and offers higher efficiency. On the one hand, existing studies proposed methods to automatize data acquisition and visualization for inspections. These studies lack an open standard to make the gathered data available for other processes. On the other hand, several studies discuss data structures for exchanging damage information through out different stakeholders. However, those studies do not cover the process of automatic data acquisition and transfer. This study focused on a framework that incorporates automatic damage data acquisition, transfer, and a damage information model for data exchange. This enables inspectors to use damage data for subsequent analyses and simulations. The proposed framework shows the potentials for a comprehensive damage information model and related (semi-)automatic data acquisition and processing.

The work is devoted to the study of the mechanisms of damage accumulation in a polymer composite material (PCM) during fatigue loading. Mechanical testing of a fiberglass sample was carried out by cyclic tension accompanied by registration of acoustic emission (AE). For the recorded AE signals, the Fourier spectra were calculated and used for clustering with Kohonen self-organizing map. Relations between clusters and types of damage in the PCM structure were established. The analysis of the peak frequencies of the Daubechies D14-wavelet components of AE signals was carried out. Obtained results has allows one to describe the processes of destruction in the PCM sample. It has been established that, on the base of local formation of microdamages in the matrix and the fracture of the fibers detected during recording of the AE data, it is possible to predict the destruction of the polymer composite material, while the beginning of a material destruction can be registered if the damage identified as an adhesion failure is observed. Perspectives of application of adaptive fiber-optic AE sensors for structural monitoring of PCMs on the base of preliminary experimental results are considered and discussed.

Long-haul COVID-19 illness first gained widespread recognition among social support groups and later in scientific and medical communities. This illness is mysterious as it affects COVID-19 survivors at all levels of disease severity, even younger adults and children. While the precise definition may be lacking, the defining symptoms are fatigue, dyspnea, and headache that last for months after hospital discharge. The less typical symptoms may include cognitive impairments, chest and joint pains, myalgia, smell and taste dysfunctions, cough, mood changes, and gastrointestinal and cardiac issues. Presently, there is limited literature discussing the possible pathophysiology, risk factors, and treatments in long-haul COVID-19, which the current review aims to address. In brief, long-haul COVID-19 may be driven by long-term lung and brain damage and unresolved inflammation from multiple sources. The associated risk factors may include female sex, more than five early symptoms, early dyspnea, and specific biomarkers like D-dimer. While only rehabilitation training has been useful for long-haul COVID-19, therapeutics repurposed from mast cell activation syndrome, myalgic encephalomyelitis/chronic fatigue syndrome, and pulmonary fibrosis also hold potential. In sum, this review hopes to provide the current understanding of what is known about long-haul COVID-19.

Wenchuan earthquake that occurred in China in 2008 caused severe damage to a large number of electric substations. In this paper, Kriging interpolation method was used to calculate the impact area of the instrumental seismic intensity in Wenchuan earthquake, and to compare the intensities based on strong motion observation against the instrumental seismic intensities at locations where the observation data is available. The instrumental seismic intensities were calculated for the Wenchuan Earthquake at substations in the national power grid with voltage of 110kV or higher in areas of Mianyang, Deyang, Guangyuan and Chengdu. The cumulative Gaussian distribution function was then used to fit the relationship of the curves of the damage probabilities of high-voltage electrical equipment such as transformers, voltage mutual inductors, current mutual inductors, circuit breakers, isolating switches and lightning arrester with their instrumental seismic intensities. The damage probability density distribution curve of high-voltage electrical equipment based on the instrumental seismic intensities was obtained. The results showed that: (1) In the lower seismic intensity region, the mean instrumental seismic intensity was in good agreement with the traditional seismic intensity, but there was noticeable dispersion; in regions of intensity IX and above, the instrumental intensity was lower than the seismic intensity, but there was a lower degree of dispersion. (2) Among high-voltage electrical equipment, the transformers were most vulnerable to damage and they had some damage even under lower instrumental intensity. More damage would be produced when the instrumental intensity reached VIII or above; the second most vulnerable equipment was the circuit breaker, and the damage was most likely to occur when the instrument intensity was IX or above . (3) The damage rate curves of lightning arresters, current mutual inductors, voltage mutual inductors and isolating switches were relatively close to each other and the damage probability was the highest when the instrumental intensity was about X.

Wenchuan earthquake that occurred in China in 2008 caused severe damage to a large number of electric substations. In this paper, Kriging interpolation method was used to calculate the impact area of the instrumental seismic intensity in Wenchuan earthquake, and to compare the intensities based on strong motion observation against the instrumental seismic intensities at locations where the observation data is available. The instrumental seismic intensities were calculated for the Wenchuan Earthquake at substations in the national power grid with voltage of 110kV or higher in areas of Mianyang, Deyang, Guangyuan and Chengdu. The cumulative Gaussian distribution function was then used to fit the relationship of the curves of the damage probabilities of high-voltage electrical equipment such as transformers, voltage mutual inductors, current mutual inductors, circuit breakers, isolating switches and lightning arrester with their instrumental seismic intensities. The damage probability density distribution curve of high-voltage electrical equipment based on the instrumental seismic intensities was obtained. The results showed that: (1) In the lower seismic intensity region, the mean instrumental seismic intensity was in good agreement with the traditional seismic intensity, but there was noticeable dispersion; in regions of intensity IX and above, the instrumental intensity was lower than the seismic intensity, but there was a lower degree of dispersion. (2) Among high-voltage electrical equipment, the transformers were most vulnerable to damage and they had some damage even under lower instrumental intensity. More damage would be produced when the instrumental intensity reached VIII or above; the second most vulnerable equipment was the circuit breaker, and the damage was most likely to occur when the instrument intensity was IX or above . (3) The damage rate curves of lightning arresters, current mutual inductors, voltage mutual inductors and isolating switches were relatively close to each other and the damage probability was the highest when the instrumental intensity was about X.

There is a confusion in the original design concept for the tensioning of longitudinally connected reinforcement of CRTSII slab ballastless track. In order to clarify the effect of tension value of longitudinal reinforcement on mechanical characteristics of ballastless track, a three dimensional finite element model considering the nonlinear interaction between the track slab and CA mortar of CRTSII slab ballastless track was established. The mechanical characteristics of the track structure under longitudinal tension load and temperature gradient load of the longitudinal joint were calculated. A method of applying pre-stress to post-pouring concrete was proposed according to the concept of pre-stress loss of pretensioning pre-stressed concrete, reasonable tensile force value was proposed after the crack width and the reinforcement stress of the ballastless track in the operation stage were checked and calculated according to the concrete design principle. When the tension force is greater than 300 kN, it’s harmful to the bonding between the slab and mortar layer, which is prone to interlayer damage. In order to adding pre-stress to concrete of wide joints to ensure the longitudinal stability of ballastless track and the reinforcement stress and crack width to meet the design requirements. It is suggested that the tension force value should be 230 kN, and the temperature difference between reinforcement and concrete should be 30 °C before the initial curdle of wide joint concrete.

Lightning strike can cause a considerable damage in aircraft parts made from semiconducting materials such as Carbon Fiber Reinforced Plastics (CFRPs). Therefore, in recent years, the lightning strike phenomenon has attracted the interest of the academic community and the aircraft industry. Until now, the problem has been addressed mainly experimentally, while the reported numerical works are very limited. In the present work, a coupled electro-thermal FE model has been developed using the ANSYS commercial FE code to simulate the lightning strike damage in unidirectional CFRP laminates due to the Joule heat flux phenomenon. The model is based on the SOLID69 thermoelectric element and applies a non-linear, time-transient analysis. The main input to the model is the thermal-electrical properties of the composite material which vary with temperature. Using the model, a parametric study on the effect of mesh density and peak intensity on the thermal damage has been performed. Three electrical lightning strikes of low (10 kA), medium (30 kA) and high peak intensity (40 kA) have been applied according to the SAE ARP 5412 standard. The electro-thermal model has been validated against a numerical model from the literature. The numerical results reveal that the increase of peak intensity leads to the increase of the area and penetration depth of matrix thermal damage (pyrolysis) as well as to the increase of the area of fiber damage (deterioration and ablation). Through progressive damage modeling, the residual tensile strength of the CFRP plate after being subjected to lightning strike of different peak intensity has been predicted. Lightning strike initial damage has been simulated by translating the thermal field into degradation of elastic properties of the lamina. The results show an increase in the accumulated matrix damage and a decrease of tensile strength due to the initial lightning strike damage. For the maximum peak intensity of 40 kA, a decrease in tensile strength of 4.8% has been predicted

Macromolecular crystallography at cryogenic temperatures has so far provided the majority of the experimental evidence that underpins the determination of the atomic structures of proteins and other biomolecular assemblies by means of single crystal X-ray diffraction experiments. One of the core limitations of the current methods is that crystal samples degrade as they are subject to X-rays, and two broad groups of effects are observed: global and specific damage. While the currently successful approach is to operate outside the range where global damage is observed, specific damage is not well understood and may lead to poor interpretation of the chemistry and biology of the system under study. In this work, we present a phenomenological model in which specific damage is understood as the result of a single process, the steady excitation of crystal electrons caused by X-ray absorption, which acts as a trigger for the bulk effects that manifest themselves in the form of global damage and obscure the interpretation of chemical information from XFEL and synchrotron structural research.

With forty years of developments, bio-macromolecule cryo-electron microscopy has met its revolution of resolution and is playing a very important role in structural biology study. According to different specimen states, cryo-electron microscopy (cryo-EM) involves three specific techniques, single particle analysis (SPA), electron tomography and sub-tomogram averaging, and electron diffraction. All these three techniques have not realized their full potentials of solving structures of bio-macromolecules and therefore need to be developed in the future. In this review, the current existing bottlenecks of cryo-EM SPA are discussed with theoretical analysis, which includes air-water interface during specimen cryo-vitrification, bio-macromolecular conformational heterogeneity, focus gradient within thick specimen, and electron radiation damage. Besides, potential solutions of these bottlenecks are proposed and discussed, which are worthy of further investigations in the future.

Internal and mesoscopic variables differ from each other fundamentally: both are state space variables, but mesoscopic variables are additional equipped with a distribution function introducing a statistical item into consideration which is missing in connection with internal variables. Thus, the alignment tensor of liquid crystal theory can be introduced as an internal variable or as one generated by a mesoscopic background using the microscopic director as mesoscopic variable. Because the mesoscopic variable is part of the state space, the corresponding balance equations change into mesoscopic balances, and additionally an evolution equation of the mesoscopic distribution function appears. The flexibility of the mesoscopic concept is not only demonstrated for liquid crystals, but is also discussed for dipolar media and flexible fibers.

This case study investigates the effects of ventilation intervention on measured and perceived indoor air quality (IAQ) in a repaired school where occupants reported IAQ problems. Occupants´ symptoms were suspected to be related to the impurities leaked indoors through the building envelope. The study’s aim was to determine whether a positive pressure of 5-7 Pa prevents the infiltration of harmful chemical and microbiological agents from structures, thus decreasing symptoms and discomfort. Ventilation intervention was conducted in a building section comprising 12 classrooms and was completed with IAQ measurements and occupants´ questionnaires. After intervention, the concentration of total volatile organic compounds (TVOC) and fine particulate matter (PM_2.5) decreased, and occupants´ negative perceptions became more moderate compared to those for other parts of the building. The indoor mycobiota differed in species composition from the outdoor mycobiota, and changed remarkably with the intervention, indicating that some species may have emanated from an indoor source before the intervention.

Surface damage on honeycomb aircraft panels is often measured manually, and is therefore subject to variation based on inspection personnel. Eddy current testing (ECT) is sensitive to variations in probe-to-specimen spacing, or lift-off, and is thus promising for high resolution profiling of surface damage on aluminum panels. Lower frequency testing also allows inspection through the face sheet, an advantage over optical 3D scanning methods. This paper presents results from the ECT inspection of surface damage on an approximately flat aluminum honeycomb aircraft panel, and compares the measurements to those taken using optical 3D scanning technology. An ECT C-Scan of the dented panel surface was obtained by attaching the probe to a robotic scanning apparatus. Data was taken simultaneously at four frequencies of 25, 100, 400 and 1,600 kHz. A reference surface was then defined that approximated the original, undamaged panel surface, which also compensated for the effects of specimen tilt and thermal drift within the ECT instrument. Data was converted to lift-off using height calibration curves developed for each probe frequency. A damage region of 22,550 mm² area with dents ranging in depth from 0.13-1.01 mm was analyzed. The method was accurate at 1,600 kHz to within 0.05 mm (2s) when compared with 231 measurements taken via optical 3D scanning. Testing at 25 kHz revealed a 3.2 mm cell size within the honeycomb core, which was confirmed via destructive evaluation. As a result, ECT demonstrates potential for implementation as a method for rapid in-field aircraft panel surface damage assessment.

There are currently no effective treatments for retinal pigment epithelial (RPE) cell loss in atrophic AMD (aAMD). However, our research on Prom1, a known structural protein in photoreceptors (PRs), has revealed its distinct role in RPE and offers promising insights. While pathogenic Prom1 mutations have been linked to macular diseases with RPE atrophy, the broader physiological impact of dysfunctional Prom1 in RPE loss is unclear. We have shown that Prom1 plays a crucial role in regulating autophagy and cellular homeostasis in human and mouse RPE (mRPE) cells in vitro. Nevertheless, a comprehensive understanding of its in vivo expression and function in mRPE remains to be elucidated. To characterize Prom1 expression in RPE in situ, we used RNAscope assays and immunogold electron microscopy. Our use of chromogenic and fluorescent RNAscope assays in albino and C57BL/6J mice retinal sections has revealed Prom1 mRNA expression in perinuclear regions in mRPE in situ. Immunogold imaging showed Prom1 expression in RPE mitochondria. To confirm Prom1 expression in RPE, we interrogated human RPE single-cell RNA-sequencing datasets using an online resource, Spectacle. Our analysis showed Prom1 expression in human RPE. To investigate Prom1's function in RPE homeostasis, we performed RPE-specific Prom1-knockdown (KD) using subretinal injections of AAV2/1.CMV.saCas9.U6.Prom1gRNA in male and female mice. Our data show that RPE-specific Prom1-KD in vivo resulted in abnormal RPE morphology, sub-retinal fluid accumulation, and secondary PR loss. These changes were associated with patchy RPE cell death and reduced a-wave amplitude, indicating retinal degeneration. Our findings underscore the central role of Prom1 in cell-autonomous mRPE homeostasis. The implications of Prom1-KD in causing aAMD-like RPE defects and retinal degeneration in a mouse model are significant and could lead to novel treatments for aAMD.

This review aims to describe the role of Limbic System-Associated Membrane Protein (LSAMP) in normal and pathophysiology and its potential implications in oncogenesis. We have summarized research articles reporting the role of LSAMP in the development of a variety of malignancies such as clear cell renal cell carcinoma, prostatic adenocarcinoma, lung adenocarcinoma, osteosarcoma, neuroblastoma, acute myeloid leukemia, and epithelial ovarian cancer. We also examine current understandings of how defects in LSAMP gene function may contribute to oncogenesis. Finally, this review discuss-es the implications of future LSAMP research and clinical applications. Recent Findings LSAMP has been originally described as a surface adhesion glycoprotein expressed on cortical and subcortical neuronal somas and dendrites during the development of the limbic system. It is categorized as part of the IgLON immunoglobulin superfamily of cell-adhesion molecules and is involved in regulating neurite outgrowth and neural synapse generation. LSAMP is both aberrantly expressed and implicated in the development of neuropsychiatric disorders due to its role in the formation of specific neuronal connections within the brain. Additionally, LSAMP has been shown to support brain plasticity via the formation of neuronal synapses and is involved in modulating the hypothalamus in anxiogenic environments. In murine studies, loss of LSAMP expression was associated with decreased sensitivity to amphetamine, increased sensitivity to benzodiazepines, increased hyperactivity in new environments, abnormal social behavior, decreased aggressive behavior, and decreased anxiety. Findings have suggest-ed that LSAMP plays a role in attuning serotonergic activity as well as GABA activity. Given its importance to limbic system development, LSAMP has also been studied in the context of suicide. In malignancies, LSAMP plays a significant role as a putative tumor suppressor, the loss of which leads to more aggressive phenotypes and mortality from metastatic disease. Loss of the LSAMP gene facilitates epithelial-mesenchymal transition, or EMT, where epithelial cells lose adhesion and gain the motile properties associated with mesenchymal cells. Additionally, LSAMP and the function of the RTK pathway have been implicated in tumorigenesis through the modulation of RTK expression in cell membranes and the activation of second messenger pathways and β-catenin.

Glioma is the most common primary malignant brain tumors. Despite advances in surgical techniques and treatment regimens, the therapeutic effects remain unsatisfactory. Immunotherapy has brought new hope to glioma patients, but the immunosuppressive nature of the tumor microenvironment (TME) has limited the therapeutic outcomes. This study aims to reveal the subpopulations and functional characteristics of tumor-associated macrophages (TAMs), to explore the regulatory effects of chlorogenic acid on the immune microenvironment, and investigate its potential for clinical application. In this study, Chlorogenic acid slowed tumor growth in the mouse model and extended the survival time of the mice. ScRNA-seq analysis elucidated the differentiation trajectories and functional characteristics of BMDMs and microglia, revealing the regulatory effects of chlorogenic acid on these two populations. It enhanced the antigen-presenting function of macrophages and the gene expression related to T-cell immune activation, activated microglia through the JAK-STAT pathway, and improved antitumor functions. Using the target prediction database, a PPI and molecular docking model were constructed, confirming the good affinity of chlorogenic acid with STAT1. A case of a patient treated with chlorogenic acid was reviewed, who survived for 5 years and 6 months, achieved partial remission (PR) after 9 months of treatment, and remains alive with no new symptoms or toxic side effects. Our study revealed the subtypes and differentiation trajectories of tumor-associated macrophages. Chlorogenic acid significantly improved the immune microenvironment of glioma by modulating the function of bone marrow-derived mono-macrophages (BMDMs) and microglia, demonstrating good antitumor effects. This study provides new insights for targeting the regulation of the TME and offers theoretical and practical support for the clinical application of chlorogenic acid.

Trichoderma has been widely studied for its potential as a biocontrol agent against plant pathogenic organisms. Trichoderma's biological control mechanisms include competition, modification of environmental conditions, antibiosis, induction of plant defensive mechanisms, and mycoparasitism. Trichoderma species are known to produce a variety of secondary metabolites that have antifungal activity. These metabolites include peptaibols, gliotoxin, and trichokonins. Trichoderma also produces chitinases and β-1,3-glucanases that can degrade the cell walls of fungal pathogens. In addition to direct antagonism against fungal pathogens, Trichoderma can also induce systemic or localised resistance in plants, which is achieved through the production of elicitors such as chitin oligosaccharides and β-glucans that activate plant defence responses. Trichoderma can also form mutualistic associations with plants. In these associations, Trichoderma colonises the roots of plants and promotes plant growth by increasing nutrient uptake and inducing systemic resistance. Using Trichoderma as a biocontrol agent has several advantages over conventional crop protection techniques based on applying synthetic pesticides.

Graft injury affects over 50% of liver transplant (LT) recipients, but non-invasive biomarkers to diagnose and guide treatment are currently limited. We aimed to develop a biomarker of graft injury by integrating serum metabolomic profiles with clinical variables. Serum from 55 LT recipients with biopsy confirmed metabolic-dysfunction associated steatohepatitis (MASH), T-cell mediated rejection (TCMR) and biliary complications was collected and processed using a combination of LC-MS/MS assay. The metabolomic profiles were integrated with clinical information using a multi-class Machine Learning (ML) classifier. The efficacy of the model was assessed through the evaluation of the Out-of-Bag (OOB) error estimate. Our ML model yielded an overall accuracy of 79.66% with an OOB estimate of the error rate at 19.75%. The model exhibited a maximum ability to distinguish MASH, with an OOB error estimate of 7.4% compared to 22.2% for biliary and 29.6% for TCMR. The metabolites serine and serotonin emerged as the topmost predictors. When predicting binary outcomes using 3 models: Biliary (biliary vs. rest), MASH (MASH vs. rest) and TCMR (TCMR vs. rest), the AUCs were 0.882, 0.972 and 0.96 respectively. Our ML tool integrating serum metabolites with clinical variables shows promise as a non-invasive, multi-class serum biomarker of graft pathology.

C. auris is a newly emerging yeast, raising public health concerns due to its outbreak potential, lack of protocols for decontamination and isolation of patients or contacts, increased resistance to common antifungals and associated high mortality. This research aimed to describe the challenges related to identifying the outbreak, limiting further contamination, and treating affected individuals. We retrospectively analysed all cases of C. auris detected between October 2022 and August 2023, but our investigation focused on a three-month-long outbreak in the department of cardio-vascular surgery and the related intensive care unit. Along with isolated cases in different wards, we identified 13 patients who became infected or colonized in the same area and time, even though the epidemiological link could be traced only in 10 patients, according to the epidemiological investigation. In conclusion, our study emphasizes the substantial challenge encountered in clinical practice when attempting to diagnose and limit the spread of an outbreak. Therefore, it is crucial to promptly apply contact precaution measures and appropriate environmental cleaning, from the first case detected positive.

Growth environment greatly alters many facets of pathogen physiology, including pathogenesis and antimicrobial tolerance. The importance of host-mimicking environments for attaining an accurate picture of pathogen behaviour is widely recognised. Whilst this recognition has translated into the extensive development of artificial cystic fibrosis (CF) sputum medium, attempts to mimic the growth environment in other respiratory disease states have been completely neglected. The composition of the airway surface liquid (ASL) in different pulmonary diseases is far less well characterised than CF sputum, making it very difficult for researchers to model these infection environments. In this review we discuss the components of human ASL, how different lung pathologies affect ASL composition, and how different pathogens interact with these components. This will provide researchers interested in mimicking different respiratory environments with the information necessary to design a host-mimicking medium, allowing for better understanding of how to treat pathogens causing infection in these environments.

Dystonias, characterized by excessive muscle contractions resulting in involuntary postures and movements, impact 3 million people globally, making them the third most common movement disorder. Often accompanied by tremors, dystonias have epidemiological links and non-motor features shared with isolated tremor, such as essential tremor. Both dystonia and tremor present with balance dysfunction and abnormal involuntary movements, potentially linked to abnormal cerebellar function. This study explores the perception of one’s own linear movement, heading, particularly discrimination of heading direction, in isolated cervical dystonia, isolated tremor, and their combination. The focus is on the perception of heading direction during isolated visual star-cloud movement (visual heading perception) and en bloc body movement (vestibular heading perception). Nineteen participants underwent a two-alternative forced-choice task in the vestibular and visual domains. Results reveal elevated vestibular heading perception thresholds in cervical dystonia with or without tremor, and isolated tremor compared to healthy controls. Vestibular heading perception threshold was comparable in cervical dystonia with tremor and isolated tremor, but it was even worse in isolated cervical dystonia. Visual heading perception, however, remained less affected all three conditions – isolated cervical dystonia, isolated tremor, and their combination. These findings indicate shared deficits and distinctions in the perception of linear translational heading across movement disorders, such as isolated cervical dystonia, tremor, or their combination, offering insights into their pathophysiology, particularly the involvement of cerebellum regions responsible for vestibular processing.

Aim. The analysis of incidence, clinical and morphological manifestations, and the prognosis of IgA nephropathy in the Northeastern Europe (NEE). Materials and methods. We enrolled cases with primary IgA nephropathy (IgAN) from 2005 to 2020 in the single-center retrospective study. Demographic and clinical parameters, histology data, and the treatment were analyzed. The outcomes were the occurrence of complete (PR) or partial remission (CR), renal replacement therapy (RRT), eGFR<15 ml/min/1.73m² and eGFR decrease ≥ 50%. The composite endpoint included all renal outcomes and was used to evaluate the risk of IgAN progression and associated factors. Results. The incidence of IgAN cases was 23.6% of all indication biopsies and 41.2% of primary immune glomerulopathies. At the time of the kidney biopsy, the proteinuria was 2.5 (1.5-5.0) g/24h, eGFR - 69 ± 32 ml/min/1.73 m². Proportions of cases with arterial hypertension and eGFR <60 ml / min / 1.73 m² were 75% and 36%, respectively. The prevalence of histological changes in accordance with the Oxford (MEST-C) classification was M1 - 40.5%, E1 -22.9%, S1-70.2%, T1-22%, T2 - 9%, C1-16.7%, C2 - 4.4%. In the follow-up of 27 (11; 61) months, 6 deaths occured (1.7%). The 10-year cumulative dialysis-free survival was 80% and progression-free survival was 56%. Remissions registered in 50% of cases, being more frequent in patients who received immunosuppression vs renoprotection (60% vs. 40%, p = 0.001). In multivariable Cox regression, the independent factors associated with the increased probability of IgAN progression were male gender, a younger age, higher blood pressure and hematuria, lower eGFR, interstitial fibrosis/ tubular atrophy (≥50%), the presence of peritubular capillaritis and any crescents. Compared to the cohorts of other ethnic or geographical origin, IgAN in the studied cohort were found to have more severe clinical and morphological presentations and faster progression rate. Conclusion. Being the most common glomerulopathy in the NEE population, IgAN has more pronounced clinical and morphological presentations. Considering the distinctive features of the disease, further research is warranted in order to establish approaches for enhancing risk stratification and treatment efficacy.

Background: Data on the benefits of rapid microbiological testing on antimicrobial consumption (AC) and antimicrobial resistance patterns(ARP) are scarce. We evaluated the impact of a protocol based on rapid techniques on AC and ARP in intensive care (ICU) patients. Methods: Retrospective pre(2018) and post-intervention(2019-21) study in ICU patients. A rapid diagnostic algorithm was applied from 2019 in patients with lower respiratory tract infection. Incidence of nosocomial infection, ARP, and AC as DDD(defined daily dose) were monitored. Results: A total of 3635 patients were included, 987(pre-intervention) and 2648(post-intervention). A median age was 60 years, 64% male, with APACHE II of 19 points and SOFA of 3 points. Overall ICU mortality of 17.2% without differences between the periods. An increase in the number of infections was observed in the post-intervention period(44.5% vs 17.9%, p<0.01), especially due to an increase in ventilator-associated pneumonia(44.6% vs 25%,p<0.001). AC decreased from 128.7 DDD in 2018 to 66.0 DDD in 2021(Rate Ratio=0.51). A recovery of P.aeruginosa susceptibility of 23% for Piperacillin/tazobactam and 31% for Meropenem was observed. Conclusion: The implementation of an algorithm based on rapid microbiological diagnostic techniques allowed a significant reduction in AC and ARP without affecting the prognosis of critically ill patients.