Direct intercellular communication, mediated by gap junctions formed by the connexin transmembrane protein family, is frequently dysregulated in cancer. Connexins have been described as tumour suppressors, but emerging evidence suggests that they can also act as tumour promoters. This feature is connexin- and tissue-specific and may be mediated by complex signalling pathways through gap junctions or hemichannels or by completely junction-independent events. Lung cancer is the number one cancer in terms of mortality worldwide, and novel biomarkers and therapeutic targets are urgently needed. Our objective was to gain a better understanding of connexins in this setting. We used several in silico tools to analyse TCGA data in order to compare connexin mRNA expression between healthy lung tissue and lung tumours and correlated these results with gene methylation patterns. Using Kaplan-Meier plotter tools, we analysed a microarray dataset and an RNA-seq dataset of non-small cell lung tumours in order to correlate connexin expression with patient prognosis. We found that connexin mRNA expression is frequently either upregulated or downregulated in lung tumours. This correlated with both good and poor prognosis (overall survival) in a clear connexin isoform-dependent manner. These associations were strongly influenced by the histological subtype (adenocarcinoma versus squamous cell carcinoma). We present an overview of all connexins but particularly focus on four isoforms implicated in lung cancer: Cx26, Cx30.3, Cx32 and Cx43. We further analysed the protein expression and localization of Cx43 in a series of 72 human lung tumours. We identified a subset of tumours that exhibited a unique strong nuclear Cx43 expression pattern that predicted worse overall survival (p=0.014). Upon sub-stratification, the prognostic value remained highly significant in the adenocarcinoma subtype (p=0.002) but not in the squamous carcinoma subtype (p=0.578). This finding highlights the importance of analysis of connexin expression at the protein level, particularly the subcellular localization. Elucidation of the underlying pathways regulating Cx43 localization may provide for novel therapeutic opportunities.

The anti-inflammatory effect of ginsenoside Rh2 (GRh2) is one of the most important ginsenosides. The purpose of this study is to identify the anti-inflammatory and antioxidant effects of GRh2 after LPS challenge lung injury animal model. GRh2 reduced LPS-induced NO, TNF-α, IL-1, IL-4, IL-6 and IL-10 productions in lung tissues. GRh2 treatment decreased the histological alterations in the lung tissues and BALF protein content and total cells number also diminished in LPS-induced lung injury mice. Moreover, GRh2 blocked iNOS, COX-2, the phosphorylation of IκB-α, ERK, JNK, p38, Raf-1 and MEK protein expression which is corresponded to the growth of HO-1, Nrf-2, catalase, SOD and GPx expressions in LPS-induce lung injury. An experimental study has suggested that GRh2 has provided with anti-inflammatory effects in vivo, and its potential therapeutic efficacy in major anterior segment lung diseases.

In our continuous search for selective anticancer treatments, we have screened 65 extracts from 45 plants collected in several areas of Western Andalusia (Spain) for cytotoxic activity against lung cancer cells and lung normal cells. Active extracts were also tested against 11 cell lines from other tissues. An extract from the leaves of Tetraclinis articulata (Vahl) Mast. (Cupressaceae) showed a marked cytotoxicity (IC₅₀ = 0.37 ± 0.03 µg/mL) and selectivity (selectivity index = 378.3) against the lung cancer cells; cisplatin, 5-fluorouracil and an extract from the leaves of Taxus baccata L. (Taxaceae) were less cytotoxic and selective.

Fasudil, a potent Rho kinase (ROCK) inhibitor, can ameliorate LPS-induced acute lung injury (ALI) in mice, but the mechanism remains obscure. In this study, a mice model of ALI was established by intra-tracheal instillation of LPS. Histological changes, cytokine levels, lung permeability, and endothelial apoptosis were determined to evaluate the effects of fasudil on lung injury. The cellular and molecular biological mechanisms were explored by culturing human pulmonary microvascular endothelial cells (PMECs). The results showed that fasudil reduced LPS-induced lung inflammation, pulmonary hyperpermeability, and endothelial apoptosis in mice. In cultured human PMECs, fasudil inhibited LPS-induced caspse-3 cleavage and cell apoptosis. It also decreased LPS-induced hyperpermeability of human PMECs monolayer by reversing the down-regulation of intercellular junctions. Moreover, fasudil inhibited LPS-induced overexpression of chemokines and intercellular adhesion molecule (ICAM)-1 in human PMECs, which in turn suppressed neutrophil chemotaxis and neutrophil-endothelial adhesion. Further molecular researches showed fasudil inhibited LPS-induced activation of ROCK, NF-κB, and p38 in human PMECs. Our findings demonstrated that fasudil alleviated LPS-induced ALI by protecting endothelial function via inhibiting endothelial apoptosis, maintaining endothelial barrier integrity, and reducing endothelial inflammation. These effects of fasudil could be attributed to the inhibition of ROCK and its downstream NF-κB and p38 signaling pathways.

The açaí (Euterpe oleracea Mart.) is a native fruit of the Amazon that is well-known due to its commercial value. Its production chain is centered in the state of Pará, largely supplied by extractivism. The processing of açaí fruits in nature generates huge amount of solid waste, which can pose serious risks to the environment if not used and managed properly. Due to a small number of systhematic studies on the effect of chemical activation by pyrolysis of açaí seeds and fibers, and with the aim of providing a basis for future applications of the waste generated by processing of açaí fruits, the present work proposes a study of the pyrolysis of açaí seeds and fibers and the physicochemical and compositional characterization of the aqueous phase products. In this way, açaí seeds were collected from a local artisan processing facility in the city of Belém, PA. The seeds were dried at 105°C until constant weight, and subsequently, the fibers were separated from the seeds in a rotating drum. The seeds and fibers were impregnated with NaOH solutions at 0.5M, 1.0M, and 2.0M, and then pyrolyzed at a laboratory scale at 450 °C and 1 atm. The liquid products from pyrolysis were characterized through acidity index analysis, Fourier-transform infrared spectroscopy, and gas chromatography. The increase in the concentration of the impregnating agent resulted in an increase in bio-oil yield from both the seeds and fibers, rising from 3.3% (raw seeds) to 6.6% (seeds impregnated with 2M NaOH) and from 1.2% (raw fibers) to 3.7% (fibers impregnated with 2M NaOH). The yield in the aqueous phase after biomass pyrolysis showed an inverse behavior to the bio-oil yield, decreasing from 33.7% (raw fibers) to 21.2% (fibers impregnated with 2M NaOH) and from 41% (raw seeds) to 37.5% (seeds impregnated with 2.0M NaOH). High acidity levels were found in the aqueous phase samples and bio-oils derived from the seeds and fibers, which decreased as the concentration of the impregnating agent increased. The increase in the concentration of the impregnating agent (NaOH) influenced the chemical composition of the obtained liquid products, leading to a decrease in oxygenated compounds and an increase in nitrogenous compounds in both experimental matrices, which was also evidenced by the reduction in acidity.

Gastric cancer is a challenging public health concern worldwide and remains a leading cause of cancer-related mortality. The primary risk factor implicated in gastric cancer development is infection with Helicobacter pylori. H. pylori induces chronic inflammation affecting the gastric epithelium, which can lead to DNA damage and promotion of precancerous lesions. Disease manifestations associated with H. pylori are attributed to virulence factors with multiple activities and its capacity to subvert host immunity. One of the most significant H. pylori virulence determinants is the cagPAI gene cluster, which encodes a type IV secretion system and the CagA toxin. This secretion system allows H. pylori to inject the CagA oncoprotein into host cells, causing multiple cellular perturbations. Despite the high prevalence of H. pylori infection, only a small percentage of affected individuals develop significant clinical outcomes, while most remain asymptomatic. Therefore, understanding how H. pylori triggers carcinogenesis and its immune evasion mechanisms is critical in preventing gastric cancer and miti-gating the burden of this life-threatening disease. This review aims to provide an overview of our current under-standing of H. pylori infection, its association with gastric cancer and other gastric diseases, and how it subverts the host immune system to establish persistent infection.

The nutrient absorption and utilization efficiency in the roots of seedlings are beneficial for increasing crop yield. Creating marker assisted selection for wheat root traits can assist wheat breeders in choosing robust roots to maximize nutrient uptake. Exploring and identifying the effect of different nitrogen applications on RSA is of great significance for breeding nitrogen efficient wheat varieties. In this study, A total of 243 wheat varieties native to the Yellow and Huai Valley regions of China were utilized for genome-wide association studies (GWAS). Furthermore, a recombinant inbred line (RIL) population of 123 lines derived from the cross between Avocet and Chilero was utilized for linkage examination and confirmation of the hereditary loci distinguished by GWAS. Five RSA traits include the relative number of root tips (RNRT); relative total root length (RTRL); relative total root surface area (RTRS); relative total root volume (RTRV) and relative average root diameter (RARD) where evaluated under two N conditions—normal N (NN) supply and low N (LN)—to characterize the NUE of each accession. GWAS and linkage analysis were performed by integrating data from the wheat 660k single nucleotide polymorphism (SNP) chip and diversity arrays technology (DArT) to identify genetic loci associated with RSA. The results showed that based on the ratio of RSA related traits under two N supply conditions, a total of 598 SNP markers, which are significantly associated with RSA related traits, were detected at 160 genetic loci by GWAS. A total of 10 QTL loci related to RSA were dis-covered and identified by linkage mapping. In which, three significant RSA related Quantitative Trait Locus (QTL) were identified, namely qRtrl-3D, qRnrt-3D, and qRtrl-7D. The study has the potential to enhance the effectiveness of selecting root traits in wheat breeding programs, offering valuable insights into the genetic underpinnings of nitro-gen use efficiency (NUE) in wheat. This could lead to the creation of NUE wheat varieties by implementing focused breeding strategies.

Neuromorphic computing, a brain inspired non-Von Neumann computing system, addresses the challenges posed by the Moore’s law memory wall phenomenon. It has the capability to increasingly enhance performance while maintaining power efficiency. Neuromorphic chip architecture requirements vary depending on the application and optimizing it for large-scale applications remains to be a challenge. Neuromorphic chips are programmed using spiking neural networks which provide them with important properties such as parallelism, asynchronism, and on-device learning. Widely used spiking neuron models include the Hodgkin-Huxley Model, Izhikevich model, integrate-and-fire model and spike response model. Hardware implementation platforms of the chip follow three approaches: analog, digital, or a combination of both. Each platform can be implemented using various memory topologies which interconnects with the learning mechanism. Current neuromorphic computing systems typically use the unsupervised learning spike timing-dependent plasticity algorithms. However, algorithms such as voltage-dependent synaptic plasticity have the potential to enhance performance. This review summarizes the potential neuromorphic chip architecture specifications and highlights which applications they are suitable for.

The electronic cigarette or e-cigarette is the new alternative method to deliver nicotine. In 2007, the United States introduced vaping devices on the market. Due to their attractive taste and lack of adverse effects, these vaping devices have gained popularity among youth and adults. However, there has been increasing evidence that vaping can cause severe lung injury, and these devices release toxic chemicals into the body. E-cigarettes are recognized as a global threat to public health. Nicotine, the most prevalent chemical in vaping devices, is associated with neurological problems and cognitive decline. Long-term use of e-cigarettes can cause adverse health problems, including respiratory illnesses, asthma, bronchitis, and lung inflammation. In 2019, the Centers for Disease Control and Prevention (CDC) officially declared vaping-associated illness EVALI (e-cigarette or Vaping Product Associated Lung Injury). The US Surgeon General published an alarm in December 2016 that e-cigarette consumption among adolescents and teens in the US is a "major public health concern" and that more young people are now vaping than smoking traditional cigarettes and cigars. Since its commercial introduction in 2003, modern electronic cigarettes (or E-cigarette s) have become increasingly popular with smokers, non-smokers, and those who used to smoke who have switched to them. With such a rise in consumption, people are becoming more aware of the irritating, harmful, and perhaps cancer-causing effects on the lungs. (Chadi et al., 2019; Dinardo & Rome, 2019; Lyzwinski et al., 2022; Marrocco et al., 2022; O’Callaghan et al., 2022)

KThe promising possibility of organic photodetector (OPD) is emerging in the field of sensing applications for its tunable absorption range, flexibility, and large-scale fabrication abilities. In this work, we fabricated bulk heterojunction OPD with a device structure of glass/ITO/PEDOT:PSS/ P3HT:PC61BM/Al by spin coating process and characterized the dark and photocurrent at different applied bias conditions for red, green, and blue incident LED light. OPD photocurrent density exhibited up to 2.5–3 orders higher magnitude compared to the dark current density at -1 V bias while it increased up to 3–4 orders at zero bias conditions for red, green, and blue lights showing an increasing trend higher voltage applied in the negative direction. Different OPD inner periphery shapes, OPD to LED distance, and OPD area were also considered to bring the variation in OPD dark and photocurrent, which can affect the on/off ratio of the OPD–LED hybrid system and is a critical phenomenon for any sensing application.

Large language models (LLMs) have shown impressive performance and versatility. However, their billions of parameters and high computational costs hinder the development of personalized and privacy-preserving AI assistants operating locally on user devices. In this work, we explored the potential of pruning LLMs to create lightweight models suitable for user devices, using the moderate-sized Llama-2 7B model as an example. By adopting a simple yet effective pruning method, we found that up to 60% of the weights in the Llama-2 7B model could be pruned without significantly impairing its language modeling capabilities. Furthermore, despite occasional factual inaccuracies, the pruned model at the sparsity limit generated fluent and helpful answers to daily queries, demonstrating its feasibility of on-device AI assistants. These inaccuracies might originate from forgetting or hallucination due to pruning. We proposed a simple protocol to distinguish between the two mechanisms, as well as future directions to improve the pruned models for local AI assistants.

A low cost, scalable and robust process has been proposed as innovative method for coating solar mirrors with a self-cleaning, transparent in the full solar range and versatile material based on auxetic aluminium nitrides, previously obtained on the laboratory scale. This work presents the scaling-up of fabrication process from laboratory to prototypal scale and pre-liminary results of outdoor self-cleaning solar mirror prototypes testing in the demonstrative CSP plant ENEASHIP located in Casaccia (Rome) ENEA research centre. Prototypes 50x40cm have shown stability in external conditions: no degradation occurs during the test campaign. Their washing restores the initial reflectance affected by soiling and the self-cleaning performance allows the utilization of a reduced quantity of water for cleaning operations with respect to uncoated glass of back surface mirrors. A similar self-cleaning AlN coating could be utilized on other solar components affected by soiling, such as glass envelopes of heat collecting elements, PV panels and everywhere are required self-cleaning performance combined to optical ones.

With the increase in technological advancements, architects and engineers over the past couple of decades have been trying to achieve high efficiency within construction projects. Their goals also include reducing global warming effects from construction and building new construction faster for the growing population in urban cities. This requires using a construction method that is less harmful to the environment and faster than other traditional methods. Modular construction, also known as modular construction, is the method that has the potential to make this happen. This review paper discusses what modular construction is and how it is different from the traditional on-site construction. Environmental impacts of using modular construction and what leads to it being more efficient and faster than on-site construction. The study doesn’t suggest that modular construction is the solution to all the problems being faced in the construction industry today, but it is a potential solution that if used in the right situation and correct manner, can have a huge positive impact on the construction industry.

(1) Background: Since the pandemic, adolescent girls have increasingly faced mental health challenges. We examined prevalence trends and associated risk factors for depression among adolescent girls. 2) Methods: Data for girls aged 12 to 17 years (N=4346) from the 2021 cross-sectional National Survey on Drug Use and Health were analyzed. Factors associated with depression were examined using multiple regression analysis. (3) Results: Rates of severe depression were significantly higher (p<.001) in older girls (adjusted odds ratio [AOR]: 1.63, 1.61, those who did not have authoritative parents (AOR: 3.40), and those with negative school experiences (AOR: 4.03). Black and Asian/Native Hawaiian or other Pacific Islanders were less likely to report severe depression than white girls. As previously reported, non-White girls were significantly less likely to receive treatment for depression (p<.05). Parents’ characteristics and school experiences had no effect on the likelihood of receiving mental health treatment. (4) Conclusion: Depression has become increasingly common among American adolescent girls, who are now three times as likely as adolescent boys to have had recent experiences with depression. Our results show that family structure, parenting style, and negative school experiences significantly contribute to the rate of depression and that treatment disparities exist with regard to race and ethnicity.

This proposed research explores a novel approach to image classification by deploying a complex-valued neural network (CVNN) on a field-programmable gate array (FPGA), specifically for classifying 2D images transformed into polar form. The aim of this research is to address the limitations of existing neural network models in terms of energy and resource efficiency, by exploring the potential of FPGA-based hardware acceleration in conjunction with advanced neural network architectures like CVNNs. The methodological innovation of this research lies in the Cartesian to polar transformation of 2D images, effectively reducing the input data volume required for neural network processing. Subsequent efforts focused on constructing a CVNN model optimized for FPGA implementation, emphasizing the enhancement of computational efficiency and overall performance. The experimental findings provide empirical evidence supporting the efficacy of the image classification system developed in this study. One of the developed models, CVNN_128, achieves an accuracy of 88.3% with an inference time of just 1.6ms and a power consumption of 4.66mW for the classification of the MNIST test dataset consists of 10,000 frames. While there is a slight concession in accuracy compared to recent FPGA implementations that achieve 94.43%, our model significantly excels in classification speed and power efficiency—surpassing existing models by more than a factor of 100. In conclusion, the paper demonstrates the substantial advantages of FPGA-implementation of CVNNs for image classification tasks, particularly in scenarios where speed, resource, and power consumption are critical. The study’s reproducible results and corresponding code are available on GitHub at the following link: https://github.com/mahmad2005/CVNNonFPGA

Influence of reaction time on silver nanoparticles-catalyzed oxidation of 3,3’,5,5’-tetramethylbenzidine (TMB) was evaluated via probing the oxidation process by recording the UV-Visible absorbance of the resulting colored products of TMB oxidation by hydrogen peroxide in the presence of silver nanoparticles as peroxides mimics. The time curve of the oxidation process was constructed, revealed that the concentration of the oxidation product was increased by increasing the reaction time and then levled off because the nanozyme active nodes were saturated after a certain reaction time and consequently the steady-state condition can be observed. The maximal activity of the silver nanozymes was achieved after a very short reaction time as short as 3.0 min and after this time, the color intensity of the oxidation products remained constant, revealing saturation of active nodes of nanoparticles with nanozyme-substrate.

Keywords: Kenaf; liquid cultivation; solid cultivation; in vitro propagation, life on land

The idea of an extension of life for CubeSats is proposed to reduce space debris in a low-earth orbit. In this work, a gripper is designed for geometry-based grasping in berthing tasks. The grasping operation is outlined for square- and rectangle-profiled CubeSats. Equilibrium conditions are used to choose fingertips shape and parameters for grasping the CubeSat body. A design scheme is proposed to provide the required accuracy. A design concept is developed into a lab prototype by using low-cost 3D printing technique, and a mock-up grasping task that is representative of the berthing operation is evaluated with the lab prototype. Center-mass hanging setup for the prototype and grasped body is used to evaluate the impact of grasping, partially replicating the conditions in space by reducing the effect of gravity on the system.

MultiCal is an affordable, high-precision measuring device designed for the on-site calibration of industrial robots. Its design features a long measuring rod with a spherical tip that is attached to the robot. By restricting the rod’s tip to multiple fixed points under different rod orientations, the relative positions of these points are accurately measured beforehand. A common issue with MultiCal is the gravity deformation of the long measuring rod, which introduces measurement errors into the system. This problem becomes especially serious when calibrating large robots, as the length of the measuring rod needs to be increased to enable the robot to move in a sufficient space. To address this issue, we propose two improvements in this paper. Firstly, we suggest the use of a new design of the measuring rod that is lightweight yet has high rigidity. Secondly, we propose a deformation compensation algorithm. Experimental results have shown that the new measuring rod improves calibration accuracy by 20% to 39%, while by using the deformation compensation algorithm, the accuracy increases by 6% to 16%. In the best configuration, the calibration accuracy is similar to that of a measuring arm with a laser scanner, producing an average positioning error of 0.274 mm and a maximum positioning error of 0.838 mm. The improved design is cost-affordable, robust, and has sufficient accuracy, making MultiCal a more reliable tool for industrial robot calibration.

This article aims to reflect upon the relevance of Decolonization methodologies with the Theses on Feuerbach. Somehow, all the Indigenous scholars started from new Marxist like Paulo Freire, Frantz Fanon, but not from classic Marx. To us, the German Ideology of young Marx only resembles the pioneering sources of Indigenous methodology. This discussion is thus a reflection of our studies and a philosophic endeavor to talk about the marginal people of the world, and the scholars who engaged in and with the oppressed. However, we are not prepared to turn our attention away from all the vastness of Marx to a collection of potentially equally relevant to Indigenous methodology. This article concludes that the Theses on Feuerbach is the core of Marxist archaeology of knowledge or philosophy as a whole and has been wading in the Indigenous paradigm.

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.

This study was aimed to investigate the effect of capital structure on firms’ profitability with special emphasis on Ethiopian Large Private Manufacturing Firms using panel data of five consecutive years (2006/07-2010/11G.C). The secondary data sources (audited financial statements) have been collected from the randomly selected thirty three large private manufacturing firms in Ethiopia. Linear regression model has been employed to analyze the relationship between firms’ profitability and capital structure. Specifically, Random-effect Generalized Least Square of panel data regression model has been selected to empirically test the literature driven hypotheses. Finally, the findings of this study revealed that a significant positive relationship between firms’ profitability and total debt ratio which indicate firm’s capital structure.

Lipopeptides are bioactive compounds produced by Bacillus spp. This work provides insight into de antifungal activity of lipopeptides through a meta-analysis of published studies, in addition following PCR (polymerase chain reaction) technique, the presence of lipopeptides genes in 20 Bacillus strains were also analyzed. The meta-analysis of published studies showed that iturin, fengycin and surfactin significantly reduced the growth of phytopathogenic fungi. Similarly, when applied to plant tissues, the lipopeptides reduced the severity of damage in plant tissues caused by phytopathogenic fungi. As for the lipopeptides genes detection, we used 20 Bacillus strains reported to have antagonistic activity against various fungal plant pathogens. The PCR amplification study was carried out to detect the genes involved in the synthesis of lipopeptides: ituA for iturin A, fenD for fengycin and srfA for surfactin. Comparative sequence analysis showed a range of 98 to 100% identity with the corresponding genes in several Bacillus species. We observed at least one Bacillus gene in the strains: CBRF5, CBRF15, CBSN67, and CBRM9. In the strain CBRF6, we detected the presence of the fabD and srfAD genes. For the development of natural fungicides to control phytopathogenic fungi, lipopeptides produced by Bacillus spp. could be a useful tool.

The increasing frequency and severity of phytoplankton blooms worldwide highlight the need for advancements in monitoring technologies. Optical remote sensors, such as Landsat, have proven to be a cost-effective method for large-scale, near-real-time assessments of phytoplankton biomass in lakes. However, its effectiveness is often compromised by atmospheric interferences like clouds, dust, and wildfire smoke, which can obscure the clear-sky conditions essential for accurate remote sensing. While partial atmospheric correction (removing only the Rayleigh effect) is commonly applied to address these interferences, it remains inadequate for mitigating the impact of wildfire smoke. This study investigates the potential of Landsat's coastal/aerosol band (B1) for assessing wildfire smoke interference effects on Chlorophyll-a (Chl-a) retrieval models, which serve as proxies for phytoplankton biomass. We employed cluster analysis of B1 values to create a screening system based on aerosol reflectance, categorizing smoke interference into low, moderate, and high levels. Subsequently, we applied both partial (Rayleigh-corrected reflectance) and full (Landsat 8 Level 2 surface reflectance) atmospheric corrections before developing the Chl-a retrieval models. Excluding high wildfire smoke interference (B1 > 0.07) from the Chl-a calibration dataset significantly enhanced model performance, increasing the r-squared value from approximately 0.55 to 0.80. Moderate smoke interference (0.05 < B1 < 0.07) yielded results comparable to low-interference conditions. Notably, Rayleigh-corrected reflectance, even without additional aerosol band filtering, achieved higher r-squared values for the Chl-a retrieval model than full atmospheric correction. B1 thus proves to be a valuable tool for identifying low smoke-impacted observations, offering an effective method to monitor phytoplankton biomass amid increasing wildfire activity and improving the capacity to monitor aquatic environments in a changing global landscape.

Mathematical algorithms relate satellite data of ocean color with the surface Chlorophyll–a con-centration (Chl-a), a proxy of phytoplankton biomass. These mathematical tools work best when they are adapted to the unique bio-optical properties of a particular oceanic province. Ocean color algorithms should also consider that there are significant differences between datasets derived from different sensors. Common solutions are to provide different parameters for each sensor or use merged satellite data. In this paper we use satellite data from the Copernicus merged product suite and in situ data from the southernmost part of the California Current System to test two widely used global algorithms, OCx and CI, and a regional algorithm, CalCOFI2. The OCx al-gorithm gave the best result, therefore, it was regionalized and, again, tested. The database was then separated according to (a) dynamic boundaries in the area, (b) bio-optical properties and (c) climatic condition (El Niño/La Niña). Regional algorithms were obtained and tested for each partition. The Chl-a retrievals for each model were tested and compared. The best fit for the data was for the regional algorithms that considered the climatic conditions (El Niño/La Niña). These results will allow the construction of consistent regionally adapted time-series and, therefore, demonstrates the importance of El Niño/La Niña events on the bio-optical properties of the area.

The objective of this study was to evaluate the occurrence of Clostridium perfringens in stool samples and swabs collected from wild mammals in the Amazon biome. Sixty-five faecal and swab samples were collected in situ and ex situ from 16 species and three genera of wild mammals, some of which were in good health and some of which had diarrhoea. After pre-enrichment, the samples were plated on selective agar for C. perfringens. Characteristic colonies were subjected to multiplex PCR for the detection of genes encoding the main C. perfringens toxins (alpha, beta, epsilon, and iota toxin and enterotoxin). Among the 65 samples, 40 (61.5%) were positive for the gene encoding the alpha toxin and were classified as type A. Faecal samples were more than four times more likely to be positive for C. perfringens than were swab samples. No other toxinotypes were found. The findings of this study suggest that C. perfringens type A is commonly found as a commensal in mammal species of the Amazon biome. This seems to be the first study to identify C. perfringens type A in species such as B. variegatus (common ground sloth), C. didactylus (two-toed sloth), P. flavus (Jupará), T. tetradactyla (anteater), S. collinsi (squirrel monkey), S. niger (black marmoset), and S. apella (Guyana capuchin) and in the genus Didelphis sp. (opossum).

IgA nephropathy (IgAN) is a kidney disease that is characterized by the deposition of IgA (immunoglobulin A) in the kidney tissue, leading to inflammation and damage. This disease is a common chronic glomerulopathy that affects people worldwide (1). Therefore, it is crucial to identify factors that worsen the disease, monitor its activity, and predict appropriate treatments. Complement component 4d (C4d) is a protein that is involved in the activation of the complement system, which is a part of the immune system.

The microglia, displaying diverse phenotypes, play a significant regulatory role in the development, progression, and prognosis of Parkinson's disease. Research has established that glycolytic reprogramming serves as a critical regulator of inflammation initiation in pro-inflammatory macrophages. Furthermore, the modulation of glycolytic reprogramming has the potential to reverse the polarized state of these macrophages. Previous studies have shown that levetistilide A (LA), a phthalide component derived from Angelica sinensis, possesses a range of pharmacological effects, including anti-inflammatory, antioxidant, and neuroprotective properties. In our study, we have examined the impact of LA on inflammatory cytokines and glucose metabolism in microglia induced by lipopolysaccharide (LPS). Furthermore, we explored the effects of LA on the AMPK/mTOR pathway and assessed its neuroprotective potential both in vitro and in vivo. The findings revealed that LA notably diminished the expression of M1 pro-inflammatory factors induced by LPS in microglia, while leaving M2 anti-inflammatory factor expression unaltered. Additionally, it reduced ROS production and suppressed IκB-α phosphorylation levels as well as NF-κB p65 nuclear translocation. Notably, LA exhibited the ability to reverse microglial glucose metabolism reprogramming and modulate the phosphorylation levels of AMPK/mTOR. In vivo experiments further corroborated these findings, demonstrating that LA mitigated the death of TH-positive dopaminergic neurons and reduced microglia activation in the ventral SNpc brain region of the midbrain and the striatum. In summary, LA exhibited neuroprotective benefits by modulating the polarization state of microglia and altering glucose metabolism, highlighting its therapeutic potential.

Proximal tubular epithelial cells (PTEC) are constantly exposed to potentially toxic metabolites and xenobiotics. The regenerative potential of the kidney enables the replacement of damaged cells either via the differentiation of stem cells or the regain of proliferative properties of the PTEC. Nevertheless, it is known that renal function declines, suggesting that the deteriorated cells are not replaced by fully functional cells. To understand the possible causes of this loss of kidney cell function, it would be beneficial to understand the role of toxins during the regeneration process. Therefore, we investigated the sensitivity and function of human induced pluripotent stem cells (hiPSC), hiPSC differentiating, and hiPSC differentiated into proximal tubular epithelial-like cells (PTELC) to known nephrotoxins. hiPSC were differentiated into PTELC, exhibiting a similar morphology to PTEC, expressing prototypical PTEC markers and performing albumin endocytosis. When treated with two nephrotoxins, hiPSC and differentiating hiPSC were more sensitive to cisplatin than differentiated PTELC, whereas all stages were equally sensitive to cyclosporin A. Both toxins also had an inhibitory effect on albumin uptake. Our results suggest a high sensitivity of differentiating cells towards toxins, which could have an unfavorable effect on regenerative processes. To study this, our model of hiPSC differentiating into PTELC appears suitable.

Neuroendocrine tumors (NETs) of duodenal origin are an unusual subset among all NETs, comprising only about 3% of this neoplasm class. In general, NETs are characterized by overexpression of somatostatin receptors and carry an excellent prognosis with early diagnosis and intervention. Chromogranin A (CgA), a protein originating in secretory vesicles of neurons and endocrine cells, has gained wide usage in NET diagnosis and surveillance. Lanreotide is a synthetic octapeptide somatostatin analog with potent anti-proliferative action which has been approved by the FDA (U.S.) and EMA (E.U.) for NET treatment. It is known for its inhibitory effects on growth hormone, serotonin, CgA, and other markers. Here we describe a 56yr-old female with functional NET of duodenal origin, where serum CgA was successfully reduced from 3636 to <100 ng/mL after multidose lanreotide within five months. Of note, no metastatic spread was identified on positron emission tomography/computed tomography with 64Cu-labeled somatostatin analog tracer. Surgical resection of distal antrum, pylorus, and proximal duodenum followed without complication. Histology revealed several foci of well-differentiated tumor cells with characteristic neuroendocrine features and clear surgical margins; low proliferation index (2%) was noted on Ki-67 staining. While select laboratory and imaging modalities are available for diagnosis and monitoring of duodenal NET, this is the first reported therapeutic use of lanreotide in this NET setting. The observed serum CgA attenuation, even before surgery, supports its effectiveness in management of primary nonmetastatic duodenal NET.

In this paper, MnO2 nanowire (MnO2-NW) modified carbon paper (CP) electrode was developed as a novel electrochemical sensor for sensitive determination of tetrabromobisphenol A (TBBPA). MnO2 nanowire was prepared by a hydrothermal synthesis method, and the morphology and structure of MnO2 were characterized using scanning electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy. Electrochemical performance of TBBPA on MnO2-NW/CP was investigated by cyclic voltammetry, and the result confirmed that MnO2-NW/CP exhibited excellent sensitive for the determination of TBBPA due to the high specific surface area and good electrical conductivity of the nanowire-like MnO2. Moreover, the important electrochemical factors such as pH value, incubation time and modified material proportion were systematically studied to improve the determination sensitivity. The interferences from similar structure compounds on TBBPA have also been investigated. Under the optimal conditions, MnO2-NW/CP displayed the linear range of 70 500 nM for TBBPA with the detection limit of 3.1 nM, which was superior to some electrochemical methods in references. The work presents a novel and simple method for the determination of TBBPA.

This study aimed to assess the variations in the nutritional attributes of thirteen Moringa oleifera cultivars. Leaves from six-month-old plants were harvested and tested for various nutritional attributes. There were significant (p ≤ 0.05) differences in the carbohydrates, energy, some of the sugars and fibre amongst the cultivars. The levels of moisture in the cultivars ranged from 7.10% to 8.20%. Additionally, there were significant (p ≤ 0.05) differences across the cultivars in microelements studied except for zinc (Zn). These data revealed that plants from different geographical provenances differed in their adapting to varied environments. In general, under the same cultivation, management and environmental conditions, the main reasons for these differences occurred in cultivars could be associated with the genetic background of each M. oleifera germplasm. However, the study cautions on the differences of nutritional properties, as some of the cultivars have been reported not to be pharmacological potent.

A sensitive electrochemical sensor based on AuPtPd trimetallic nanoparticles functionalized multi-walled carbon nanotubes coupled with chitosan modified glassy carbon electrode (GCE/CS/MWCNTs-AuPtPd) for the rapid detection of bisphenol A (BPA) was proposed. AuPtPd trimetallic nanoparticles were first assembled on MWCNTs to obtain MWCNTs-AuPtPd nanocomposite. Then the MWCNTs-AuPtPd was further dispersed on the surface of chitosan modified electrode surface to fabricate the GCE/CS/MWCNTs-AuPtPd sensor. Due to the superior catalytic properties of MWCNTs-AuPtPd and the good film formation of chitosan, the constructed sensor displayed good performances for BPA detection. The structural morphology of CS/MWCNTs-AuPtPd was characterized by many methods, such as SEM, UV-vis and TEM. Under the optimal conditions, the designed sensor showed a linear range from 0.05 to 100 µM for BPA detecting with a low detection limit of 1.4 nM. The designed sensor was further used to realize the determination of BPA in real samples and the recoveries ranged from 94.4% to 103.6%. The results demonstrated that the electrochemical sensor designed by CS/MWCNTs-AuPtPd nanocomposites was reliable and could be a useful tool for the monitoring of food safety.

Glioblastoma (GBM) is a major type of primary brain tumors without ideal prognosis and it’s necessary to find novel compound possessing therapeutic effect. Chrysomycin A (Chr-A) has been reported to inhibit the proliferation, migration and invasion of U251 and U87-MG cells, but the mechanism of Chr-A against glioblastoma in vivo and whether Chr-A modulates apoptosis of neuroglioma cells is unclear.The present study was to elucidate the potential of Chr-A against glioblastoma in vivo and how Chr-A modulates apoptosis of neuroglioma cells. Briefly, The an-ti-glioblastoma activity was assessed in human glioma U87 xenografts nude mice. Chr-A-related targets were identified by RNA-seq. Apoptotic ratio and caspase 3/7 activity of U251 and U87-MG cells were assayed by flow cytometry. Apoptosis-related proteins and possible molecular mecha-nism were validated via Western blotting. The results showed that Chr-A treatment significantly inhibits glioblastoma progression in xenografts nude mice, and enrichment analysis suggested that apoptosis, PI3K-Akt and Wnt signaling pathway were involved in the possible mechanism. Chr-A increased apoptotic ratio and the activity of caspase 3/7 in U251 and U87-MG cells. Western blot revealed that Chr-A broke the balance between Bax and Bcl-2 activating caspase cascade re-action and downregulated the expression of p-Akt and p-GSK-3β, suggesting that Chr-A may contribute to glioblastoma regression modulating Akt/GSK-3β signaling pathway to promote apoptosis of neuroglioma cells in vivo and in vitro. Therefore, Chr-A may hold therapeutic promise for glioblastoma.

Due to increased energy intensive human activities resulting accelerated demand for electric power coupled with occurrence of natural disasters with increased frequency, intensity, and duration, it becomes essential to explore and advance renewable energy technology for sustainability of the society. Addressing the stated problem and providing a radical solution has been attempted in this study. To harvest the renewable energy, among variety of solar cells reported, a composite a-Si/CZTS photovoltaic devices has not yet been investigated. The calculated parameters for solar cell based on the new array of layers consisting of a-Si/CZTS are reported in this study. The variation of i) solar cell efficiency as a function of CZTS layer thickness, temperature, acceptor, and donor defect concentration; ii) variation of the open circuit current density as a function of temperature, open circuit voltage; iii) variation of open circuit voltage as a function of the thickness of the CZTS layer has been determined. There has been no reported study on a-Si/CZTS configuration-based solar cell, analysis of the parameters, and study to address the challenges imped efficiency of the photovoltaic device and the same has been discussed in this work. The value of the SnO2/a-Si/CZTS solar cells obtained from the simulation is 23.9 %.

Mobility as a Service (MaaS) is an innovative transport concept, anticipated to provide travelers with different kinds of travel services, more sustainable than a private car, in a simpler, packaged way. It combines different transport modes to offer a tailored mobility package, like a monthly mobile phone contract. The rapid development of intelligent transportation system and the shared economy has speeded up the development of MaaS in these years. In this paper, we aim at classifying the existing research on MaaS and the characteristics of MaaS into different categories, in order to answer the following questions after reviewing the existing literature: What is MaaS? Who are the main actors in MaaS? How can MaaS be implemented? Why should it be implemented? Where will MaaS end up in this wave of disruption? When we talk about MaaS, what are we focusing on? What is the future leading frequency of MaaS? Finally, based on the existing literature, we envision the leading future of MaaS.

Streptococcus pneumoniae causes invasive infections such as otitis media, pneumonia and meningitis. It produces pneumolysin (Ply) toxin, which forms a pore to host cell membrane and has multiple functions in S. pneumoniae pathogenesis. The Ply C-terminal domain 4 mediates binding to membrane cholesterol and induces the formation of pores composed of up to 40 Ply monomers. Ply has a key role in the establishment of nasal colonization, pneumococcal transmission from host to host and pathogenicity. Altogether, 27 hydrolyzable tannins were tested for Ply inhibition in hemolysis assay and tannin-protein precipitation assay. Pentagalloylglucose (PGG) and gemin A showed nanomolar inhibitory activity. Ply oligomerization on the erythrocyte surface was inhibited with PGG. PGG also inhibited Ply cytotoxicity to A549 human lung epithelial cells. Molecular modelling of Ply interaction with PGG suggested that it binds to the pocket formed by domains 2, 3 and 4. In this study, we reveal the structural features of hydrolyzable tannins that are required for interaction with Ply. Monomeric hydrolysable tannins containing a sufficient number of polyvalent and flexible galloyl groups have highest inhibitory power to Ply cytotoxicity, and are followed by oligomers. Of the oligomers, macrocyclic and C-glycosidic structures were weaker in their inhibition than the glucopyranose-based oligomers. Accordingly, PGG-type monomers and certain oligomers might have therapeutic value in the targeting of S. pneumoniae infections.

Preeclampsia (PE) is characterized by a series of clinical features such as hypertension and proteinuria associated with endothelial dysfunction and the impairment of placenta vascular endothelial integrity. This study aimed to investigate the effect of serum copper (Cu) level on some angiogenesis-related factors including vascular endothelial growth factor-A (VEGF-A), soluble Fms-like tyrosine kinase-1 (sVEGF-R1), soluble endoglin (sEng) and cerruloplasmin (Cp) in Iraqi women with preeclampsia (PE) and control pregnant women. Therefore, 60 women with PE in addition to 30 healthy pregnant women were enrolled in the study. Serum concentration of sEng, VEGF-A, sVEGF-R1, and Cu in PE group significantly increased (p<0.05) in the PE group compared with that in the control group. Increased production of antiangiogenic factors, soluble VEGF-A and sEng contribute to the pathophysiology of PE, indicating the involvement of these parameters in the angiogenic balance in patients with PE. Tests for between-subject effects showed that the circulating angiogenesis factors and Cu were significantly associated with the presence of PE. Serum Cu level was significantly correlated with VEGF- A and VEGF-R1 levels but not with sEng. Multiple regression analysis revealed that only Cp and BP can significantly predict the complications in women with PE. In conclusion, serum Cu has a role in the angiogenesis in women with PE and may be a new drug target in the prevention or treatment of PE.

Dewetting transition - a concept borrowed from fluid mechanics - is a physiological process which takes place inside the hydrophobic pores of ion channels. This transient phenomenon causes a metastable state which forbids water molecules to cross the microscopic receptors’ cavities. This leads to a decrease of conductance, a closure of the hole and, subsequently, severe impairment of cellular performance. We suggest that artificially-provoked dewetting transition in ion channels’ hydrophobic pores could stand for a molecular candidate to erase detrimental organisms, such as viruses, bacteria and cancer cells. We describe a novel type of high-affinity monoclonal antibody, which: a) targets specific trans-membrane receptor structures of harmful or redundant cells; b) is equipped with lipophilic and/or hydrophobic fragments that prevent physiological water flows inside ion channels. Therefore, we achieve an artificial dewetting transition inside receptors’ cavities which causes transmembrane ionic flows discontinuity, channel blockage and subsequent damage of morbid cells. As an example, we describe dewetting monoclonal antibodies targeting the M2 channel of the Influenza A virus: they might prevent water to enter the pores, thus leading to virion impairment.

A novel virus with distinct genome features was discovered by high throughput sequencing in a symptomatic blackcurrant plant. The virus tentatively named as blackcurrant virus A (BCVA) has distinct genome organization and molecular features bridging genera in the order Tymovirales. The genome consists of 7106 nucleotides excluding the poly(A) tail. Five open reading frames were identified with the first encoding a putative viral replicase with methyl transferase (MTR), AlkB, helicase and RNA dependent RNA polymerase (RdRp) domains. The other four putative proteins exhibit no significant homology to other virus proteins. The genome organization downstream of the replicase resembles that of members of the order Tymovirales with an unconventional triple gene block (TGB) movement protein arrangement. Phylogenetic analysis using replicase conserved motifs loosely placed BCVA within the Betaflexiviridae whereas it was evolutionarily distant to existing members of the family when using the putative TGBp 1-like and coat protein sequences. Our analysis strongly suggests that BCVA is a novel virus that should be classified as a species in a new genus in the Betaflexiviridae or a new family in the order Tymovirales.

HER2/neu positive breast tumors predict a high mortality and comprise 25-30% of breast cancer. We have shown that Flavokawain A (FKA) preferentially reduces the viabilities of HER2 overexpressing breast cancer cell lines (i.e. SKBR3 and MCF7/HER2) versus those with less HER2 expression (i.e. MCF7 and MDA-MB-468). FKA at cytotoxic concentrations to breast cancer cell lines also has minimal effect on the growth of non-malignant breast epithelial MCF10 cells. FKA induces G2M arrest in cell cycle progression of HER2 overexpressing breast cancer cell lines through inhibition of Cdc2 and Cdc25C phosphorylation and down-regulation of Myt1 and Wee1expression leading to increased Cdc2 kinase activities. In addition, FKA induces apoptosis in SKBR3 cells by increasing the protein expression of Bim and BAX and decreasing expression of Bcl₂, Bcl_x/L , XIAP and survivin. FKA also down-regulates the protein expression of HER-2 and inhibits AKT phosphorylation. Herceptin plus FKA treatment leads to enhanced growth inhibitory effect on HER-2 overexpressing breast cancer cell lines through down-regulation of Myt1, Wee1, Skp2, Survivin and XIAP. Our results suggest the promise of FKA as a novel apoptosis inducer and G2 checkpoint abrogating agent in combination with Herceptin for treatment of HER2 overexpressing breast cancer.

Hypercytokinemia, or cytokine storm, is one of the severe complications of viral and bacterial infections, involving the release of abnormal amounts of cytokines, resulting in a massive inflammatory response. Cytokine storm is associated with COVID-19 and sepsis high mortality rate by developing epithelial dysfunction and coagulopathy, leading to thromboembolism and multiple organ dysfunction syndrome. The anticoagulant therapy is an important tactic to prevent thrombosis in sepsis and COVID-19, but recent data show the incompatibility of modern direct oral anticoagulants and antiviral agents. It seems relevant to develop dual-action drugs with antiviral and anticoagulant properties. At the same time it was shown that azolo[1,5-a]pyrimidines are heterocycles with a broad spectrum of antiviral activity. We have synthesized a new family of azolo[1,5-a]pyrimidines and their condensed polycyclic analogs by cyclocondensation reactions and direct CH-functionalization and studied their anticoagulant properties. Five compounds among 1,2,4-triazolo[1,5-a]pyrimidin-7-ones and 5-alkyl-1,3,4-thiadiazolo[3,2-a]purin-8-ones demonstrated higher anticoagulant activity than the reference drug, dabigatran etexilate. Antithrombin activity of lead compounds was confirmed using lipopolysaccharide (LPS) treated blood to mimic conditions of cytokine release syndrome. The studied compounds affected only the thrombin time value, reliably increasing it 6.5–15.2 times as compared to LPS-treated blood.

Objectives: Imaging exams are requested in intensive care units as a diagnostic, evaluation, and clinical monitoring method. While Chest Computed Tomography is the gold standard, Chest X-ray is the exam usually performed in routine care. Lung ultrasound has been gaining ground as it is a reliable exam performed at the bedside without exposure to radiation and at a low cost. This study aimed to evaluate the accuracy of bedside lung ultrasounds performed by pediatric intensivists as a diagnostic method. Methods: A prospective, diagnostic test-type study comparing bedside lung ultrasound performed by a pediatric intensivist with the evaluation of chest X-ray and lung ultrasound performed by a radiologist. Result: 48 patients on mechanical ventilation, aged from 1 month to 14 years, were analyzed, corresponding to 95 chest X-ray exams and 95 lung ultrasound exams. The Kappa agreement coefficients between the pediatric intensivist and the radiologist, both analyzing the lung ultrasound, were: normal report (1.0), atelectasis (1.0), pneumothorax (1.0), consolidation (0.97), pleural effusion (0.95), and pulmonary edema (0.90). Sensitivity, specificity, and accuracy of lung ultrasound were, respectively, normal report (50%; 91.8%; 82.1%), consolidation (88.3%; 57.1%; 76.8%), atelectasis (11.1%; 90.7%; 83.2%), edema (0; 70.2%; 70.5%), pneumothorax (83.3%; 94.4%; 93.7%), and pleural effusion (71.4%; 73%; 72.6%). Conclusion: The pediatric intensivist was skilled in examining and diagnosing lung injuries. Lung ultrasound showed good sensitivity, specificity, and accuracy when the pediatric intensivist performed when diagnosing consolidation, pleural effusion, and pneumothorax. Furthermore, lung ultrasound demonstrated better accuracy in evaluating pulmonary edema when compared with chest X-ray.

Epigenetic changes regulate gene expression through histone modifications, chromatin remod-eling and proteins interpreter of these modifications. The PRC1 and PRC2 complexes shape gene repression via histone modifications. Specifically, the CBX protein family aids PRC1 recruitment to chromatin, impacting the progressive multistep process driving chromatin silencing. Among family members, CBX3 is a complex protein involved in aberrant epigenetic mechanisms that drive lung cancer progression. CBX3 promotes lung tumorigenesis by interacting with key pathways such as PI3K/AKT, Ras/KRAS, Wnt/β-catenin, MAPK, Notch, and p53, leading to in-creased proliferation, inhibition of apoptosis, and enhanced resistance to therapy. Given our current lack of knowledge, additional research is required to uncover the intricate mechanisms underlying CBX3 activity, as well as its involvement in molecular pathways and its potential biomarker evaluation. Specifically, the dissimilar roles of CBX3 could be reexamined in order to gain a greater insight into lung cancer pathogenesis. This review aims to provide a clear overview of the context-related molecular profile of CBX3, which could be useful for addressing clinical challenges and developing novel targeted therapies based on personalized medicine.

ABSTRACT: Background: Virtual Reality (VR) emerges as a promising non-pharmacological intervention for managing symptoms and providing distraction during chemotherapy. This study aims to assess VR's effectiveness on cancer-related symptoms, vital signs, and patients' perception of the chemotherapy in lung cancer patients. Methods: A quasi-experimental study was conducted on 100 patients. Participants were allocated into an intervention group (n = 55), which experienced immersive VR, and a comparison group (n = 45), which received usual care. Data were collected through questionnaires and checklists, including feedback on the VR experience, pain, vital signs, and common cancer symptoms, assessed through the Edmonton Symptom Assessment Scale. Results: VR had a significant impact on reducing the perception of the chemotherapy length. Patients reported high levels of satisfaction and tolerability. No adverse events were observed. VR did not have significant influence on pain intensity and vital signs. The only exceptions were oxygen saturation, where a significant difference (p = 0.02) was reported, and perception of chemotherapy duration. Conclusions: As a non-pharmacological intervention, VR proves beneficial in minimizing the perceived length of chemotherapy session for lung cancer patients, enhancing their overall treatment experience. The intervention showed to be a safe, feasible, and well-accepted distraction technique. Future research should explore VR's potential effects on a wider range of symptoms and evaluate its impact on long-term outcomes.

Lung cancer is the leading cause of cancer-related deaths globally, with non-small cell lung cancer (NSCLC) accounting for over 85% of cases and poor prognosis in advanced stages. This study explored shifts in circulating metabolite levels in NSCLC patients versus healthy controls and examined the effects of conventionally fractionated radiation therapy (CFRT) and stereotactic body radiation therapy (SBRT). We enrolled 91 NSCLC patients (38 CFRT and 53 SBRT) and 40 healthy controls. Plasma metabolite levels were assessed using semi-targeted metabolomics, revealing 32 elevated and 18 reduced metabolites in patients. Key discriminatory metabolites included ethylmalonic acid, maltose, 3-phosphoglyceric acid, taurine, glutamic acid, glycocolic acid, and d-arabinose, with a combined Receiver Operating Characteristics curve indicating perfect discrimination between patients and controls. CFRT and SBRT affected different metabolites, but both changes suggested a partial normalization of energy and amino acid metabolism pathways. In conclusion, metabolomics identified distinct metabolic signatures in NSCLC patients with potential as diagnostic biomarkers. The differing metabolic responses to CFRT and SBRT reflect their unique therapeutic impacts, underscoring the utility of this technique in enhancing NSCLC diagnosis and treatment monitoring.

Background: The aim of this study was to investigate a series of complete blood cell count – based biomarkers of systemic inflammation as predictors of clinical outcomes in patients who underwent first-line chemoimmunotherapy for advanced NSCLC. Methods: Consecutive patients with pathologically diagnosed stage III/IV NSCLC who underwent first-line chemoimmunotherapy were retrospectively enrolled. The clinical outcomes used for biomarker evaluation were Objective Response Rate (ORR) and Overall Survival (OS). Results: Non-responders had significantly higher values of neutrophil to lymphocyte ratio (NLR, median: 5.36; IQR: 2.78–10.82 vs. 3.31; IQR: 2.15–4.12, p = 0.019), neutrophil to monocyte ratio (NMR, median: 14.00; IQR: 8.82–21.20 vs. 9.20; IQR: 7.45–11.20, p = 0.013), and systemic inflammation index (SII, median: 1,395; IQR: 929–3,334 vs. 945; IQR: 552–1,373, p = 0.025), but only NLR and NMR remained independently related with clinical response in multivariate logistic regression. In univariate analysis white blood cells (OR:1.2202; 95% CI: 1.0339 - 1.4400, p=0.019), neutrophils (OR:1.2916; 95% CI: 1.0692 - 1.5604, p=0.008), NLR (OR:1.3601: 95% CI: 1.0949 - 1.6896, p=0.005) and NMR (OR:1.2159; 95% CI: 1.00396 - 1.4221, p=0.015) were significantly associated with survival; Cox regression models confirmed that neutrophils, NLR and MLR were independently associated with survival; NLR at a cut-off value of 4.0 showed the better AUC (0.749) in predicting survival. Conclusions: Baseline complete blood cell count biomarkers, especially the NLR, can predict clinical outcomes in patients with advanced NSCLC treated with first-line chemoimmunotherapy.

Abstract: Delayed initiation of effective antifibrotic therapy in patients with interstitial lung diseases (ILD) may influence the progression and outcome of the disease. This study analyzes the differences in the journey of patients with ILD in the Brazilian and Mexican health systems. An evaluative study was conducted in reference centers for interstitial lung diseases in Brazil and Mexico with a panel of four specialists. The patient's journey in both countries begins when the patient seeks medical care after observing a chronic respiratory symptom. In both countries, due to diagnostic complexity, these patients arrive at ILD referral centers at an advanced stage of the disease. Once diagnosis is established, the treatment onset differs between Mexico and Brazil. Antifibrotic drugs are not yet available by SUS in Brazil, and the purchase is unfeasible for most of the population, which forces specialists to only offer support to patients until the treatment can get the drug. In Mexico, antifibrotics have been available in health sectors since 2018. Brazil and Mexico have several similarities regarding the initial journey of the patient due to diagnosis difficulties, but the outcome tends to be different due to a difference in access to treatment with antifibrotics. For this reason, advancing health policies that ensure proper treatment for patients with ILD is crucial for the sustainability and reliability of the health system.

Background: Asthma is a widespread chronic respiratory disease that poses a significant public health challenge. The current study investigated the associations between air pollution and asthma severity among individuals residing near the Sohar industrial port (SIP) in Oman. Despite the presence of multiple major industrial complexes in Oman, limited knowledge regarding their impact on respiratory health is accredited. Hence, the primary objective of this study is to offer valuable insights into the respiratory health consequences of industrial air pollution in Al Batinah North. Methods: The state health clinics' records for patient visits related to asthma were collected for the timeframe spanning 2014 to 2022. Exposure was defined as the distance from SIP, Majan Industerial Area (MIA) and Sohar Industerial Zone (SIZ) to determine high, intermediate, and low exposure zones (12 km, respectively). Exposure effect modifications by age, gender, and smoking status were also examined. Results: The conducted cross-sectional study of 410 patients (46.1% males and 53.9% females) living in over 17 areas around SIP revealed that 73.2% of asthmatics were under 50 years old, with severity significantly associated with closeness to the port. Risk ratios were estimated to be (RR:2.42; CI95%: 1.01–5.78), (RR:1.91; CI95%: 1.01–3.6), and (RR:1.68; CI95%: 0.92–3.09) for SIP, MIP and SIZ areas, respectively, compared to the control area. Falaj Al Qabail (6.4 km) and Majees (6 km) had the highest number of asthma patients (N. 69 and N. 72), and highest percentages of severe asthma cases among these patients (28% and 24%) with significant risk ratios (RR:2.97; CI95%: 1.19–7.45 and RR:2.55; CI95%: 1.00–6.48), correspondingly. Moreover, severe asthma prevalence peaked in the 25-50 age group (RR:2.05; CI95%: 1.26–3.33), and this linkage between asthma and age was much more pronounced in males than females. Smoking and exposure to certain contaminant (dust and smoke) increased also the risk of severe asthma symptoms, but their effects were less important in the high risk zone, suggesting much more important risk factor. A neural network model accurately predicted asthma risk (94.8% accuracy), with proximity to Sohar Industrial Port as the most influential predictor. Conclusion: The study highlights the High asthma burden near Sohar Industrial Port, linked to port proximity and smoking and wind direction as major risk factors. These findings inform vital public health policies to reduce air pollution and improve respiratory health in the region, prompting national policy review.

Mutations in epidermal growth factor receptor (EGFR) occur in about 48% of Asian and 19% of Western patients with lung adenocarcinoma (LUAD), leading to its constitutive activation and subsequent uncontrolled cell proliferation. To counteract this, tyrosine kinase inhibitors (TKIs) have been developed, targeting EGFR activity. However, the emergence of metastases and resistance mutations often undermines the durability of the treatment response. Knowledge-based mechanistic models that replicate existing clinical trial outcomes, tailored to specific population characteristics, provide invaluable assistance in designing future clinical trials. These models are particularly effective in identifying optimal responders to specific treatments, thereby enhancing therapeutic efficacy. We have developed physiologically based pharmacokinetic (PBPK) models for gefitinib and osimertinib, representing two distinct generations of EGFR TKIs, to accurately simulate the drugs’ distribution within the primary tumor and metastatic sites following oral administration. These models were integrated with a pathophysiological mechanistic model of EGFR-mutant LUAD, enabling the representation of the effects of both gefitinib and osimertinib on EGFR activation-induced signaling pathways. This comprehensive model outputs detailed evolutions of the primary tumor and each metastatic site, facilitating the evaluation of patient progression in alignment with RECIST guidelines (version 1.1). Notably, the model encapsulates the heterogeneity within the tumor, through the representation of various subclones, each characterized by unique mutation profiles, thereby reflecting differential responses to treatment. Calibration of the model was achieved using publicly available data from the NEJ002 and FLAURA clinical trials. Rigorous visual predictive checks and statistical tests were employed to ensure the proper behavior of the model. The model adeptly replicated the time to progression observed in real clinical trials in EGFR-mutant LUAD patients receiving gefitinib or osimertinib as first-line therapy. In addition, the model was able to reproduce the results from a retrospective study comparing gefitinib and osimertinib, a study that was not used to inform the model. With a consistent virtual population as a reference, the combined model facilitated a comparative analysis of the efficacy of both treatments, thereby underscoring its utility in evaluating therapeutic strategies. The faithful replication of real-world data significantly enhances the credibility of our model, rendering it a vital investigational tool for deriving pertinent insights and informing treatment strategies, particularly in identifying optimal responders to various generations of EGFR TKIs. Following its consecutive prospective validations in the FLAURA2 and MARIPOSA trials, the model is poised to facilitate the generation of synthetic control arms in future clinical trials. This advancement promises a more nuanced analysis of covariate relationships, especially when comparing investigational treatments to established standards of care. Additionally, it potentially reduces the required patient cohort size in such trials, optimizing resource utilization.

Purpose: The aim of the study is an approach to a nanocomposite with copper nanoparticles, constituting a bacteriostatic surface for maintaining the human lung cells' function. Methods: The polyelectrolyte layer coating with copper nanoparticles incorporated was designed. As a bacteriostatic factor, copper nanoparticles were applied as a colloidal solution of copper nanoparticles (ColloidCuNPs) and solution of copper nanoparticles (CuNPs). The influence of polyelectrolytes on selected Gram(+) and Gram(-) strains was examined. The function of the human adenocarcinoma A549 cell line of epithelial human lung cells cultured in the presence of nanocomposite layer coatings was analyzed, as well as their morphology using flow cytometry, fluorescence microscopy, and scanning electron microscopy. In addition, the material of layer coating was assessed using AFM and SEM-EDX characterization. Results: It was observed that polyelectrolytes polyethylenimine and poly-L-lysine do not induce proliferation of E.coli strain. On the other hand, it induces the proliferation of S. aureus strain. Due to CuNPs effectiveness against E.coli strain, CuNPs were selected for further research. The designed coatings at proper NPs share sustained the function of human lung cells cultured within 10 days of culture. The AFM and EDX characterization confirmed copper presence in the layer coating nanomaterial. The presence of CuNPs in polyethyleneimine-based nanocomposite deepens the bacteriostatic effect on E. coli compared with PEI alone. Meanwhile, incorporating CuNPs in PLL at share allowed A549 cell maintenance, did not exert a bacteriostatic influence on the examined strain.Conclusion: The platform based on polyelectrolytes incorporated with copper nanoparticles ensuring the growth and morphology of the human lung epithelial cells can be considered an element of the system components for medical devices for maintaining the human lung cells' function.

Research has shown the role of growth factors in lung cancer angiogenesis. Angiogenesis promotes lung cancer progression by stimulating tumor growth, enhancing tumor invasion, contributing to metastasis, and modifying immune system responses within the tumor microenvironment. As a result, new treatment techniques based on the anti-angiogenic characteristics of compounds have been developed. These compounds selectively block the growth factors themselves, their receptors, or the downstream signaling pathways activated by these growth factors. The EGF and VEGF families are the primary targets in this approach, and several studies are being conducted to propose anti-angiogenic drugs that are increasingly suitable for the treatment of lung cancer, either as monotherapy or as combined therapy. The efficacy results are encouraging, but a caution must be placed on the higher risk of toxicity, outlining the importance of personalized follow-up in the management of these patients.

Green products have excellent potential for discovering and producing new medicinal products. In recent years, there is a growing interest towards the green synthesis of metal nanoparticles, particularly from plants sources. This eco-friendly approach was used in the recent research to biosynthesize zinc oxide nanoparticles (ZnO NPs) from Cissus antractica plant. The present study aims to examine the cell cytotoxicity, cell death, and pathways of apoptosis in lung cancer cells (A549) and inflammation properties treated with biosynthesized ZnO NPs. Additionally, synthe-sized ZnO nanoparticles were characterized using UV–vis spectroscopy, X-ray diffraction (XRD), Transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FT-IR), and Energy-dispersive X-ray spectroscopy (EDS). The XRD and TEM analyses exhibited 31 nm as the size of synthesized nanoparticles, the pure crystal form of ZnO NPs, and the shape of the NPs as nearly spherical and hexagonal quartzite. The MTT assay used for cytotoxicity evaluation de-picted the significant toxic effect of CA-ZnONPs against the A549 lung cancer cells at concentra-tions up to 20 µg/mL than non-cancerous cells. Furthermore, we observed an elevated ROS level in cancer cells. These NPs also demonstrated dose-dependent ability to suppress colony for-mation and cell migration, which increases their potential as a lung cancer treatment. Further-more, The NPs formulation's ability to induce apoptosis in cancer cells was further supported by Hoechst and propidium iodide dye. Further, CA ZnO NPs increased the gene expression of BAX, Cyto-c, Caspase 3 and 9, but decreased the expression of Bcl-2, indicating that the nanoformulation triggered mitochondrial-mediated apoptosis. Besides, this study showed that NPs suppressed in-flammatory responses by subsequently decreasing reactive oxygen species (ROS) generation, downregulating the expression of the pro-inflammatory cytokines TNF-α, iNOS, COX-2, IL-6, IL-8, and NO. Moreover, the study's findings imply that Cissus antractica are a potential source with biosynthesize nanoparticles that can might be further investigated for the progress of an-ti-inflammatory and anti-cancer drugs with further study.

Little is known about the effect of statin use in lung cancer development in idiopathic pulmonary fibrosis (IPF). We analyzed the database of the National Health Insurance Service to further investigate the clinical impacts of statin on lung cancer development and overall survival (OS) in IPF patients. The analysis included 9,182 individuals diagnosed with IPF, of which 3,372 (36.7%) were statin users. Compared to statin non-users, the time from diagnosis of IPF to lung cancer development and OS were longer in statin users in IPF patients. In Cox proportional hazard regression models, higher statin compliance, statin use, and being female had an inverse association with lung cancer risk, while older age at diagnosis of IPF and smoking history were associated with higher risk of lung cancer in IPF patients. For OS, statin use, female sex, higher exercise frequency, and diabetes were associated with longer survival. In contrast, older age at diagnosis of IPF and smoking history were associated with shorter OS in IPF patients. These data from a large population indicate that statin had an independent protective association with lung cancer development and mortality in IPF patients.

Airway epithelial cells (AECs) play a key role in maintaining lung homeostasis, epithelium regeneration and the initiation of pulmonary immune responses. To isolate and study murine AECs investigators have classically used short and hot (1h 37°C) digestion protocols. Here, we present a workflow for efficient AECs isolation and culture, utilizing long and cold (20h 4°C) dispase II digestion of murine lungs. This protocol yields a greater number of viable AECs compared to an established 1h 37°C dispase II digestion. Using a combination of flow cytometry and immunofluorescent microscopy, we demonstrate that compared to the established method, the cold digestion allows for recovery of a 3-fold higher number of CD45-CD31-EpCAM+ cells from murine lungs. Their viability is increased compared to established protocols, they can be isolated in larger numbers by magnetic-activated cell sorting (MACS), and they result in greater numbers of KRT5+p63+ colonies in vitro. Our findings demonstrate that temperature and duration of murine lung enzymatic digestion have a considerable impact on AEC yield, viability, and ability to form colonies in vitro. We believe this workflow will be helpful for studying lung AECs and their role in the biology of lung.

Currently, large cell neuroendocrine carcinoma of the lung (LCNEC) is classified as a rare lung cancer subtype, but given the high incidence of lung cancer, the overall number of cases is considerable. The pathologic diagnosis is based on the microscopic appearance of the tumor cells, the amount of intra-tumoral necrosis, the mitotic rate, and the presence of positive neuroendocrine markers identified by immunohistochemistry. Recently, a subdivision into two main categories was proposed based on mutation signatures involving the RB1, TP53, KRAS, and STK11/LKB1 genes, into SCLC-like (small cell lung cancer-like) and NSCLC-like (non-small cell lung cancer-like) LCNEC. In terms of treatment, surgery remains the best option for resectable, stage I–IIIA cases. Chemotherapy and radiotherapy have conflicting evidence. Etoposide/platinum remains the standard chemotherapy regimen. However, based on the newly proposed LCNEC subtypes, some retrospective series report better outcomes using a pathology-driven chemotherapy approach. Encouraging outcomes have also been reported for immunotherapy and targeted therapy, but the real impact of these strategies is still being determined in the absence of adequate prospective clinical trials. The current paper scrutinizes the epidemiology, reviews the reliability of pathologic diagnosis, discusses the need for molecular subtyping, and reviews the heterogeneity of treatment algorithms in LCNEC.

Long non-coding RNAs (LncRNAs) are mRNA-like molecules that do not encode for proteins and that are longer than 200 nucleotides. LncRNAs play important biological roles in normal cell physiology and organism development. Therefore, deregulation of their activities is involved in disease processes such as cancer. Lung cancer is the leading cause of cancer-related deaths due to late stage at diagnosis, distant metastasis, and high rates of therapeutic failure. LncRNAs are emerging as important molecules in lung cancer for their oncogenic or tumor suppressive functions. LncRNAs are highly stable in circulation, presenting an opportunity for use as non-invasive and early-stage cancer diagnostic tools. Here, we summarize latest works providing in vivo evidence available for LncRNAs role in cancer development, therapy-induced resistance, and their potential as biomarkers for diagnosis and prognosis, with a focus on lung cancer. Additionally, we discuss current therapeutic approaches to target LncRNAs. The evidence discussed here strongly suggests that investigation of LncRNAs in lung cancer in addition to protein-coding genes will provide a holistic view of molecular mechanisms of cancer initiation, development, and progression, and could open a new avenue for cancer treatment.

This review brings together the current knowledge regarding the risk factors, and the clinical, radiologic and histological features of both post-COVID-19 interstitial pul-monary fibrosis (PCPF) and Idiopathic Pulmonary Fibrosis (IPF) with a particular fo-cus on describing the similarities and the disparities between the fibrotic changes in these two diseases. It is important to highlight the common points of PCPF and IPF to observe if they are some targetable changes to improve patient outcomes. The litera-ture review was performed using numerous databases to identify relevant articles published in English through October 2022. This review would help clinicians, pathologists and researchers to make an accurate diagnosis, which can be useful in identifying the group of patients who can be selected for antifibrotic therapies, and future therapeutic perspectives.

COVID-19 is a pandemic triggered by the coronavirus SARS-CoV-2 whose peak occurred in the years 2020 and 2021. The main target of the virus is the lung and infection is associated to an accentuated inflammatory process involving mainly the innate arm of the immune system. Here, we described the induction of a pulmonary inflammatory process triggered by the intranasal (IN) instillation of UV-inactivated SARS-CoV-2 in C57BL/6 mice and then the evaluation of vitamin D (VitD) ability to control this process. The assays used to estimate the severity of lung involvement included total and differential number of cells in the BALF, histopathological analysis, quantification of T cell subsets and inflammatory mediators by RT-PCR, cytokine quantification in lung homogenates and flow cytometric analysis of cells recovered from lung parenchyma. IN instillation of inactivated SARS-CoV-2 triggered a pulmonary inflammatory process, consisting of various cell types and mediators, resembling the typical inflammation found in COVID-19 patients. This inflammatory process was significantly decreased by IN delivery of vitD, but not by its IP administration, suggesting that this hormone has therapeutic potential in COVID-19 if locally applied.

Metabolic changes are an important component of tumor cell progression. Tumor cells adapt to environmental stresses via changes to carbohydrate and lipid metabolism. Autophagy, a physiological process in mammalian cells that digests damaged organelles and misfolded proteins via lysosomal degradation is closely associated with metabolism in mammalian cells acting as a meter of cellular ATP levels. In this review, we discuss the changes in glycolytic and lipid biosynthetic pathways in mammalian cells and their impact on carcinogenesis via the autophagy pathway. Also, we discuss the impact of these metabolic pathways on autophagy in lung cancer.

BACKGROUND: The National Lung Screening Trial (ILST) and the NELSON study showed that lung cancer-specific mortality can be reduced by 20-24% using low-dose computed tomography (LDCT) screening in high-risk populations, due to an increase in early-stage diagnoses. RESEARCH QUESTION: How much lung cancer-related direct costs may be reduced using a LDCT screening programme based on the ILST protocol in a public healthcare system?STUDY DESIGN AND METHODS: Cost analysis of lung cancer screening (LCS) vs. usual care in the framework of the retail price of the Catalan public healthcare system. The LCS group included costs of screening (ILST protocol), treatment cost according to weighted average distribution of TNM staging in the NLST and NELSON trials, lung cancer detection rate (CDR) and smoking cessation intervention. The usual care group included treatment costs based on distribution of TNM staging registered in the Spanish index hospital. RESULTS: In the usual care group, treatment costs were €91,959. In the 5-year duration of the LCS programme, the average expected costs per subject were €1,342 (range €1,054-1,832 depending on malignancy in detected nodules) for screening and €32,431 for treatment, with an expected reduction of €952 based on an average CDR of 1.6%. The decrease in cost resulting from stage shift offsets 70.6% of the costs of the screening programme. INTERPRETATION: Baseline 5-year LCS costs are low according to the ILST protocol. In the Catalan public healthcare system, the expense reduction from the stage shift due to the LCS programme compensates a substantial part of its costs.

Background. In a cannot ventilate cannot intubate situation, careful preoxygenation with high FiO₂ allowing subsequent apneic oxygenation can be life-saving. The best position for an oxygen supply line within the human airway at which oxygen insufflation is more effective than standard preoxygenation with a face mask, or comparably effective as intratracheal insufflation, is unknown. Methods. In this experimental study, we compared effectiveness of preoxygenation by placing an oxygen cannula at the nose entrance, through the nose at the soft palatine, or at the base of tongue; as control we used ambient air. We connected a fully preoxygenated test lung on one side to an oximeter with a flow rate of 200ml/min simulating oxygen consumption of a normal adult, and on the other side to the trachea of an anatomically correctly shaped airway manikin over a 20 min observation period five times for each cannula placement in random order. Results. Oxygen percentage in the test lung dropped from 100% in all groups to 53±1% in the ambient air control group, to 87±2% in the nasal cannula group, to 96±2% in the soft palatine group, while it remained at 99±1% in the base of tongue group (p=0.003 for soft palatine vs base of tongue; and p<0.001 between all other groups). Conclusions. When simulating apneic oxygenation in a preoxygenated manikin, oxygen insufflation at the base of tongue kept oxygen percentage at baseline values of 99% demonstrating a complete block for ambient air flowing into the manikin’s airway. Oxygen insufflation at the soft palatine or insufflation via nasal cannula were less effective in regard of this effect.

Malignant growth is the most widely recognized repulsive infections winning around the world, and the patients with disease are saved just when the malignant growth is distinguished at the beginning phase. Each kind of disease is interesting, with its own arrangement of development properties and hereditary changes. This paper presents the lung knob division and disease characterization by proposing an enhancement calculation. The general technique of the created approach includes four stages, such as pre-processing, division, highlight extraction, and the order. From the outset, the CT picture of the lung is taken care of to the division. When the division is done, the highlights are extricated through morphological and measurable and surface highlights like LOOP and LGP. At long last, the extricated highlights are given to the order step. Here, the characterization is done dependent on the Deep Belief Network (DBN) which is prepared by utilizing the proposed Chicken-Sine Cosine Algorithm (CSCA) which distinguish the lung tumor, giving two classes in particular, knob or non-knob. The presentation assessment of lung knob division and malignant growth grouping dependent on CSCA is figured utilizing three measurements to be specific, precision, affectability, and the explicitness.

Dry powder inhalers are used by a large number of patients worldwide to treat respiratory diseases. The objective of this work is to experimentally investigate changes in aerosol particle diameter and particle number concentration of pharmaceutical aerosols generated by five dry powder inhalers under realistic inhalation and exhalation conditions. The active respiratory system model (xPULM™) was used as a model of the human respiratory system and to simulate a patient undergoing inhalation therapy. A mechanical upper airway model was developed, manufactured and introduced as a part of the xPULM™ to represent the human upper respiratory tract with high fidelity. Integration of optical aerosol spectrometry technique into the setup allowed for evaluation of pharmaceutical aerosols. The results show that the upper airway model increases the resistance of the overall system and act as a filter for bigger particles (>3 µm). Furthermore, there is a significant difference (p < 0.05) in mean particle diameter between inhaled and exhaled particles with the majority of the particles depositing in the lung. The minimum deposition is reached for particle size of 0.5 µm. The mean particle number concentrations exhaled are 2.94% (BreezHaler®), 2.66% (Diskus®), 10.24% (Ellipta®) 2.13% (HandiHaler®) and 6.22% (Turbohaler®). In conclusion, the xPULM™ active respiratory system model is a viable option for studying interactions of pharmaceutical aerosols and the respiratory tract in terms of applicable deposition mechanisms. The model can support the reduction of animal experimentation in aerosol research and provide an alternative to experiments with human subjects.

Aim: To establish, through molecular modelling, safe and clinically acceptable putative antagonists of E571K-mutated exportin-1 among the bioactive compounds in various parts of Juglans mandshurica. Methods: The bioactive compounds were subjected to compendium of druglikeness and lead-likeness filter workflows prior to docking of the resultant compounds into E571K exportin-1 active site using PyRx AutoDock vina to establish their binding affinity and interaction profile. The evolutionary algorithm of Osiris property explorer DataWarrior software as well as lead-likeness filter were employed for generation of novel non-promiscuous analogues of the lead compound with better putative selectivity and clinical acceptability as E571K Exportin-1 antagonists.Results: The findings of this study present taxifolin as the putatively effective and lead-like E571K Exportin-1 inhibitor with high potential of qualifying for clinical evaluation but is associated with high promiscuity tendency in high throughput screening. The evolutionary derivation of novel analogues of the compound, however, results in the generation of putatively non-promiscuous, non-toxic, and lead-like E571K Exportin-1 antagonists with high synthetic accessibility and clinical developability for evaluation in the strategy for treatment of drug-resistant KRAS-mutant lung adenocarcinoma condition.

For the first time, it is shown that inhaled ambient air-dust particles settled in the human lower respiratory tract induce lung calcification. Chemical- and mineral compositions of pulmonary calcium precipitates in the lung right lower-lobe (RLL) tissues of 12 individuals who lived in Upper Silesia Conurbation in Poland and who had died from causes not related to lung disorder were determined by transmission- and scanning electron microscopy. Whereas calcium salts in lungs are usually reported as phosphates, calcium salts precipitated in RLL are almost exclusively carbonates, i.e. Mg-calcite and calcite. These constitute 37% of 1652 mineral particles examined. Mg-calcite predominates in the submicron size range with the MgCO3 content up to 50 mol%. Magnesium plays a significant role in the lung mineralization, a fact so far overlooked. The calcium phosphate (hydroxyapatite) content in RLL is negligible. The predominance of carbonates is explained by increased CO2 fugacity in RLL. Carbonates enveloped inhaled mineral-dust particles, including uranium-bearing oxides, quartz, aluminosilicates, and metal sulfides. Three possible pathways for the carbonates precipitation on the dust particles are postulated: (1) precipitation of amorphous calcium carbonate (ACC) followed by its transformation to calcite; (2) precipitation of Mg-ACC followed by its transformation to Mg-calcite; (3) precipitation of Mg-free ACC causing a localized relative enrichment in Mg ions and subsequent heterogeneous nucleation and crystal growth of Mg-calcite. The actual number of inhaled dust particles may be significantly greater than observed because of the masking effect of the carbonate coatings. There is no simple correlation between smoking habit and lung calcification.

The incidence of lung cancer has increased in recent years and causes major mortalities across the globe. Besides, the availability of the several chemotherapeutics modalities in the management, there is still a challenge to find out an efficient remedy with lesser or no toxic effects. Hence, there is a necessity to employ complementary research to establish effective management for lung cancer. In this study, we have implemented a novel herbal informatics model to find out the alternative remedy in the treatment of lung cancer. This model utilizes five major steps of the bioprospection process based on the classical surge followed by the binary index and rationale-based selection of herbal products targeting the cancer-causing factors which are explained in detail in the methodology section of this model. This study revealed 07 herbals such as Withania somnifera (Ws), Berberis vulgaris(Bv), Glycyrrhiza glabra(Gg), Andrographis paniculate(Ap), Azadirachta indica(Ai), Cinnamomum Verum(Cv), Piper longum(Pl) based on the fuzzy set optimization scoring(0.6-1) that could be further studied in vitro and in vivo level for utilization in the management of lung cancer.

Exportin-1, the ubiquitous nuclear protein transporter, is widely confirmed as an active chemotherapeutic target in non-small cell lung cancer condition while Juglans mandshurica is a well-studied anticancer plant in some lung cancer cell lines. We intend to find novel exportin-1 inhibitor from Juglans mandshurica with better potential tolerability and pharmaco-dynamo-kinetic properties than the current selective inhibitors of nuclear export in non-small cell lung cancer treatment. Osiris property explorer DataWarrior, Glide standard precision docking, quantum mechanics polarized ligand docking, MMGBSA binding free energy calculations, Jaguar density functional theory analysis, and the online web-based SwissADME were employed respectively in this study to filter the retrieved compounds based on tolerability, toxicity, and Lipinsky’s rule of five violation potential, determine their druggability, establish relative stability of the lead compound in water solvation model, and evaluates druglikeness, lead-likeness, as well as synthetic accessibility of the lead compound. This study reveals eriodictyol as having higher binding free energy (-40 kcal/mol) than that of standard (-39.56 kcal/mol) in exportin-1 active site, better synthetic accessibility score (3.15 versus 3.29), high GI absorption, non-blood brain barrier permeant, lacks Brenk and PAINS alert, obeying Lipinski’s, Ghose’s, Veber’s, Egan’s, and Muegge’s rule of druglikeness and lead-likeness as well as non-cytotoxic to HepG2 cells. We therefore found eriodictyol as a lead-like, non-toxic exportin-1 inhibitor with good predictive stability and pharmacokinetic potential and thus provided data for further validation of eriodictyol as a candidate exportin-1 inhibitor in both preclinical and clinical studies involving lung cancer therapy.

Epigenetic aging has been found associated with a number of phenotypes and diseases. Few studies investigated its effect on lung function in relatively older people. However, this effect has not been explored in younger population. This study examines whether lung function at adolescent can be predicted with epigenetic age accelerations (AAs) using machine learning techniques. DNA methylation based AAs were estimated in 326 matched samples at two time points (at 10 years and 18 years) from the Isle of Wight Birth Cohort. Five machine learning regression models (linear, lasso, ridge, elastic net, and Bayesian ridge) were used to predict FEV1 (Forced Expiratory Volume in one second) and FVC (Forced Vital Capacity) at 18 years from feature selected predictor variables (based on mutual information) and AA changes between the two time points. The best models were ridge regression (R2 = 75.21% ± 7.42%; RMSE = 0.3768 ± 0.0653) and elastic net regression (R2 = 75.38% ± 6.98%; RMSE = 0.445 ± 0.069) for FEV1 and FVC, respectively. This study suggests that the application of machine learning in conjunction with tracking changes in AA over life span can be beneficial to assess the lung health in adolescence.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an RNA virus, is responsible for coronavirus disease 2019 (COVID-19) pandemic of 2020. Experimental evidence suggests that microRNA can mediate an intracellular defence mechanism against some RNA viruses. The purpose of this study was to identify microRNA with predicted binding sites in the SARS-CoV-2 genome, compare these to their microRNA expression profiles in lung epithelial tissue and make inference towards possible roles for microRNA in mitigating coronavirus infection. We hypothesize that high expression of specific coronavirus-targeting microRNA in lung epithelia may protect against infection and viral propagation, conversely low expression may confer susceptibility to infection. We have identified 128 human microRNA with potential to target the SARS-CoV-2 genome, most of which have very low expression in lung epithelia. Six of these 128 microRNA are differentially expressed upon in vitro infection of SARS-CoV-2. Twenty-eight and 23 microRNA also target the SARS-CoV and MERS-CoV, respectively. In addition, 48 and 32 microRNA are commonly identified in two other studies. Further research into identifying bona fide coronavirus targeting microRNA will be useful in understanding the importance of microRNA as cellular defence mechanism against pathogenic coronavirus infections.

EGFR mutations are heterogenous but all carry the same weighting in the Lung-molGPA. The aim of this study was to elucidate the different prognostic implications of molecular subtypes and frontline TKIs in EGFR-mutated lung adenocarcinoma with synchronous brain metastases (BM) using the Lung-molGPA. Medical records were searched in hospital databases from 2011 to 2015. Patients with EGFR-mutated adenocarcinoma and brain metastases who received TKIs were included. The Kaplan-Meier method was used to estimate survival, and multivariate Cox proportional hazard models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 256 patients were included with a median overall survival (OS) of 17.2 months. In multivariate analysis of OS, only age (70 versus &lt;70 years, HR:1.71, 95% CI:1.25-2.35, p&lt;0.001), KPS (&lt;70 versus 70, HR:1.71, 95% CI:1.26-2.31, p&lt;0.001), and rare mutations (other versus exon 19 deletions, HR:1.78, 95% CI:1.04-3.05, p=0.037) remained statistically significant. In patients with a Lung-molGPA score 2.5, EGFR molecular subtypes had different median OS (exon 19 deletions versus Leu858Arg versus other, 18.8 vs 12.4 vs 12.1 months, p=0.021). In conclusion, different molecular subtypes treated with frontline TKIs have different prognostic implications in the Lung-molGPA. Further prospective studies are warranted to validate these findings.

It has been suggested that particle size plays an important role in determining the genotoxicity of gold nanoparticles (GNPs). The purpose of this study was to compare the potential radio-sensitization effects of two different sized GNPs (3.9 and 37.4 nm) fabricated and examined in vitro in Lewis Lung carcinoma (LLC) as a model of non-small cell lung cancer through use of comet and clonogenic assays. After the treatment of 2Gy X-ray irradiation, both particle sizes demonstrated increased DNA damage when compared to treatment with particles only and radiation alone. This radio-sensitization was further translated into a reduction in cell survival demonstrated by clonogenicity. This work indicates that GNPs of both sizes induce DNA damage in LLC cells at the tested concentrations, whereas the 37.4 nm particle size treatment group demonstrated greater significance in vitro. The presented data aids in the evaluation of the radiobiological response of Lewis Lung carcinoma cells treated with gold nanoparticles.

The new pandemic coronavirus disease 2019 (COVID-19) is a worldwide threatening health issue. Early progression of this disease starts in the lung airways with an exaggerated inflammation, triggered by the viral infection and characterized by a “cytokine storm” that can lead to lethal lung injuries. In the absence of an effective anti-viral molecule and until the formulation of a successful vaccine, anti-inflammatory drugs might offer a complementary tool for controlling the associated complications and thus decreasing the subsequent fatalities. Drug repurposing for several molecules has emerged as a rapid temporary solution for COVID-19. Among these drugs, Thalidomide, a historically emblematic controversial molecule that harbors an FDA approval for treating Erythema Nodosum Leprosum (ENL) and multiple myeloma (MM). Based on only one-case report of positive outcomes in a patient treated amongst others with Thalidomide, two clinical trials on the efficacy and safety of Thalidomide in treating severe respiratory complications in COVID-19 patients were registered. Conversely, the absence of any substantial, promising evidence on Thalidomide usage in that context along with the discontinued studies on the efficiency of this drug in similar pulmonary diseases might cause a significant obstacle for carrying on clinical studies. In this review, we will discuss the theoretical effectiveness of this drug in attenuating inflammatory complications that are encountered in patients with COVID-19 while pinpointing the lack of evidence that is needed to move forward with this drug.

Both lung adenocarcinoma and SARS-CoV-2 infection could cause pulmonary inflammation. Angiotensin-converting enzyme 2, not only as the functional receptor of SARS-CoV-2 but also play key role in lung adenocarcinoma. To study the risk of SARS-CoV-2 infection in lung adenocarcinoma patients, mRNA and miRNA profiles were obtained from TCGA and GEO databases followed by bioinformatics analysis. A regulatory network which regards angiotensin-converting enzyme 2 as the center would be structured. In addition, via immunological analysis about key factors in lung adenocarcinoma patients, to explore the essential reasons for the susceptibility of SARS-CoV-2. Compared with normal tissue, angiotensin-converting enzyme 2 was increased in lung adenocarcinoma patients. Furthermore, a total of 7 differently expressed correlated mRNAs (ACE2, CXCL9, MMP12, IL6, AZU1, FCN3, HYAL1 and IRAK3) and 5 differently expressed correlated miRNAs (miR-125b-5p, miR-9-5p, miR-130b-5p, miR-381-3p and miR-421) were screened followed by enrichment analysis. Interestingly, toll-like receptor signaling pathway with the most frequent occurrence was enriched by mRNA (IL6) and miRNA (miR-125b-5p) sets simultaneously. Finally through comprehensive analysis, it was assumed that miR-125b-5p-ACE2-IL6 axis in the structured regulatory network could alter risk of SARS-CoV-2 infection in lung adenocarcinoma patients.

Background: Lung cancer is one of the leading causes of morbidity and mortality worldwide with 25% of deaths due to lung cancer occurring in Europe. This study therefore sought to assess the burden of lung cancer by country and to evaluate the magnitude of fine Particulate Matter (PM2.5) and cigarette smoking by country in Europe. Methods: An ecological study nested on the World Health Organization air pollution database 2016 was conducted. We sampled 30 European Countries, with a total of 1625 mean annual samples of Particulate Matter (PM2.5) collected from 1625 designated sites (n = 1625). We further used the ‘World Health Disease Rankings’ database to extract Lung Cancer Morbidity and Mortality Rate by country. We used SAS version 9.4 to indicate the distribution of PM2.5 and Lung Cancer Mortality Rate. Results: Lung cancer Relative Risk (RR) was 1.0 in all never- smokers. RR for Ex-smokers for Adeno carcinoma was 3.5 in males and 1.1 in females, small cell carcinoma was 16.2 in males and 3.8 in females. RR for current smokers for Adeno carcinoma was 8.0 in males and 4.1 in females, small cell carcinoma was 57.9 in males and 18.2 in females. Mean annual PM2.5 by country ranged from 6.01 to 37.28µg/m3 whereas lung cancer mortality rate by country ranged from 19.67 to 54.26 deaths per 100,000 population. Conclusion: Cigarette smoking and exposure to both second hand smoke and high concentration of PM2.5 resulted into increased burden of lung cancer in Europe. Countries should re-strategize to reduce the burden of lung cancer in Europe.

Cachexia is a complex metabolic syndrome characterized by loss of skeletal muscle, leading to a significant weight loss that impacts patient morbidity and mortality. Given the complexity of gene regulatory networks that control gene expression, our objective was to perform an integrative mRNA and miRNA profiling to identify genetic programs that capture essential mechanistic details that promote muscle atrophy in cancer cachexia. Here, we used RNA sequencing to analyze miRNAs and mRNAs expression profiles in tibialis anterior (TA) muscles of the Lewis lung carcinoma model of cancer cachexia. In addition, we compared these findings with RNA-Seq data from C2C12 myotubes treated in vitro with the cachectic factors tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ). Extracellular matrix (ECM) alterations were validated by picrosirius staining, western blot, and fractal dimension analyses. We found 1,008 mRNAs and 18 miRNAs differentially expressed in cachectic mice. This set of genes was associated with the ECM, proteolysis, and inflammatory response. Enrichment analysis of transcriptional factor binding sites revealed activation of the atrophy-related transcriptional factors: NF-κB, Stat3, AP-1, and FoxO. Furthermore, the integration of mRNA and miRNA expression profiles identified post-transcriptional regulation by miRNAs of genes involved in ECM organization, cell migration, transcription factors binding, ion transport, and FoxO signaling pathway. C2C12 myotubes treated with TNF-α and IFN-γ similarly down-regulate subsets of ECM genes, including collagens. Our integrative analysis of miRNA-mRNA co-profiles comprehensive characterized regulatory relationships of molecular pathways and revealed miRNAs targeting ECM-associated genes in cancer cachexia. We also confirmed in C2C12 myotubes that changes in ECM-associated genes are dependent on inflammatory signaling of the cytokines TNF-α and IFN-γ.

The present study aims to investigate radiation doses from Computed Tomography Pulmonary Angiography (CTPA) examinations based on the patient’s size and to estimate the probability of cancer risk induced from the examination. Data from 100 patients who had undergone CTPA examinations, such as scanning acquisition parameters, patient demography, as well as radiation dose exposure, were collected and analysed. All subjects which aged above 18 y/o were scanned using a Philips Brilliance 128 multi-detector CT (MDCT) scanner. The mean dose value for Volume Computed Tomography Dose Index (CTDI_vol), Dose-Length Product (DLP) and effective dose (E) were 11.06 ± 7.17 mGy, 400.38 ± 259.10 mGy.cm and 8.68 ± 5.47 mSv respectively. In addition, with respective of patient’s effective diameter, the mean SSDE value for Group 1, Group 2 and Group 3 were 9.93 ± 3.89, 13.70 ± 9.04 and 22.29 ± 7.35, respectively. Cancer risk per million procedure was calculated based on te recommendation by the International Commission on Radiological Protection Publication 103 report. The organ dose and cancer risk attained for breast, lung and liver were 17.05 ± 10.40 mGy (194 per one million procedure), 17.55 ± 10.86 mGy (192 per one million procedure) and 15.04 ± 9.75 mGy (53 per one million procedure), respectively. In conclusion, CTDI_vol underestimated, and SSDE was more accurate in describing the radiation dose. Lung and breast with larger lung effective diameter received the highest dose exposure which increase the probability of the cancer risk. Therefore, it is important to apply optimised protocols in order to reduce patient’s exposure during CTPA examination.

Bird Fancier’s Syndrome is a rare, non-atopic immunologic response to repeated or intense inhalation of avian (bird) proteins/antigens found in the feathers or droppings of many species of birds, which leads to an immune mediated inflammatory reaction in the respiratory system. Although this is the most common type of hypersensitivity pneumonitis reported in adults, it is one of the classification of a rare subtype of interstitial lung disease that occurs in the pediatric age group of which few case reports are available in the literature. The pathophysiology of hypersensitivity pneumonitis is complex; numerous organic and inorganic antigens can cause immune dysregulation, leading to an immune related antigen-antibody response (immunoglobulin G–IgG- against the offending antigen). Diagnosing Bird Fancier’s disease in the pediatric age group is challenging, history of exposure is usually missed by health care providers, symptoms and clinical findings in such cases are nonspecific and often misdiagnosed during the acute illness with other common diseases such asthma, or acute viral lower respiratory tract infection, and the lack of standardization of criteria for diagnosing such condition, or sensitive radiological or laboratory test. Treatment, on the other hand, is also controversial. Avoidance of the offending antigen could be the sole or most important part of treatment, particularly in acute mild and moderate cases. Untreated cases can result in irreversible lung fibrosis. In this case report, we highlight how children presenting with an acute viral lower respiratory tract infection can overlap with hypersensitivity pneumonitis. Early intervention with pulse steroids markedly improves the patient’s clinical course.

Aims TRAIL is a promising anticancer agent that has the potential to sensitize a wide variety of cancer or transformed cells by inducing apoptosis. However, resistance to TRAIL is a growing concern. Current manuscript aimed to employing combination treatment to investigate resveratrol induced TRAIL sensitization in NSCLC. Method A549 and HCC-15 cells were used in experimental design. Cell viability was determined by morphological image, crystal violet staining and MTT assay. Apoptosis was evaluated by LDH assay, Annexin V and DAPI staining. Autophagy and apoptosis indicator protein were examined by western blotting. TEM and puncta assay were carried out to evaluate the autophagy. MTP and ROS activity were evaluated by JC-1 and H₂DCFDA staining. Findings Resveratrol is a polyphenolic compound capable of activation of tumor suppressor p53 and its pro-apoptotic modulator PUMA. Herein, we showed the p53-independent apoptosis by decrease the expression of phosphorylated Akt-mediated suppression of NF-κB that is also substantiated with the downregulation of anti-apoptotic factors Bcl-2 and Bcl-xl in NSCLC, resulting in an attenuation of TRAIL resistance in combined treatment. Furthermore, apoptosis was induced in TRAIL-resistant lung cancer cells with a co-treatment of resveratrol and TRAIL assessed by the loss of MMP, ROS generations which resulting the translocation of cytochrome c from the mitochondria into the cytosol due to mitochondrial dysfunction. Moreover, autophagy flux was not affected by resveratrol-induced TRAIL-mediated apoptosis in NSCLC. Significance Overall, targeting the NF-κB (p65) pathway via resveratrol attenuates TRAIL resistance and induces TRAIL-mediated apoptosis which could be the effective TRAIL-based cancer therapy regimen.

Lung cancer is almost the most common cause of cancer death in the world. Clinically, the conventional therapy to eradicate the cancer cells is chemotherapy but a better drug remains required. In this study, the effects of three bufadienolides, kalantuboside B, kalantuboside A and bryotoxin C, isolated from Kalanchoe tubiflora (Harvey) were evaluated and characterized in CL1-5 highly metastatic human lung cancer cells. Contrary to the apoptosis-promoting activity in other cancer cells, these three bufadienolides did not induce apoptosis in CL1-5 cancer cells. Instead, they activated an autophagy pathway, as indicated by the increase of autophagosomes formation. The induction of autophagy by these three bufadienolides was demonstrated to link to down-regulation of p-mTOR as well as up-regulation of LC3-II, ATG5, ATG7, Beclin-1. Moreover, among these three compounds, kalantuboside B in which a monosaccharide is attached at the bufadienolide aglycon, exhibited a better autophagy induction. Our findings revealed an alternative mechanism of drug action by bufadienolides in lung cancer cells and provided evidence for the possibility of treating highly metastatic human lung cancer through an autophagy pathway.

A novel five-surface phosphor-in-glass (FS-PiG) for high illumination and excellent color uniformity in larger-scale LEDs for sensor light source application is demonstrated. YAG phosphor (Y3Al5O12:Ce3+) was uniformly mixed with ceramic and sintered at 680°C to form a phosphor wafer. A sophisticated laser engraving was employed on the phosphor wafer to form a saddle-shaped large-scale FS-PiG LEDs. The performance of the FS-PiG LEDs exhibited the illumination of 401lm, average color temperature (CCT) of 5488K±110K, and color coordinates (CIE) of (0.3179±0.003, 0.3352±0.003). In contrast to convention single-surface phosphor-in-glass (SS-PiG) LEDs, the performance exhibited the illumination of 380lm, average CCT of 5830K±758K, and CIE of (0.3083±0.07, 0.3172±0.07). These indicated that the performance of the FS-PiG LEDs was higher than the SS-PiG LEDs for illumination, CCT, and CIE of 1.7, 7, and 23 times, respectively. Furthermore, the FS-PiG LEDs demonstrate lower lumen loss of 2% and less chromaticity shift of 5.4x10-3 under accelerated aging at 350°C for 1008 hours, owing to the high ceramic melting temperature of up to 510°C. In this study, the proposed FS-PiG larger-scale LEDs having excellent optical performance and high reliability may be the promising candidates to replace the convention phosphor-in-organic silicone material used in high-power LEDs for the next generation of sensor light sources, display, and headlight applications.

A novel five-surface phosphor-in-ceramic (FS-PiC) for high illumination and excellent color uniformity in larger-scale LEDs for sensor light source application is demonstrated. YAG phosphor (Y3Al5O12:Ce3+) was uniformly mixed with ceramic and sintered at 680°C to form a phosphor wafer. A sophisticated laser engraving was employed on the phosphor wafer to form a saddle-shaped large-scale FS-PiC LEDs. The performance of the FS-PiC LEDs exhibited the illumination of 401lm, average color temperature (CCT) of 5488K±110K, and color coordinates (CIE) of (0.3179±0.003, 0.3352±0.003). In contrast to convention single-surface phosphor-in-ceramic (SS-PiC) LEDs, the performance exhibited the illumination of 380lm, average CCT of 5830K±758K, and CIE of (0.3083±0.07, 0.3172±0.07). These indicated that the performance of the FS-PiC LEDs was higher than the SS-PiC LEDs for illumination, CCT, and CIE of 1.1, 7, and 23 times, respectively. Furthermore, the FS-PiC LEDs demonstrate lower lumen loss of 2% and less chromaticity shift of 5.4x10-3 under accelerated aging at 350°C for 1008 hours, owing to the high ceramic melting temperature of up to 510°C. In this study, the proposed FS-PiC larger-scale LEDs having excellent optical performance and high reliability may be the promising candidates to replace the convention phosphor-in-organic silicone material used in high-power LEDs for the next generation of sensor light sources, display, and headlight applications.

Blood image intensity has been used to detect erythrocyte sedimentation rate (ESR). However, it does not give an information on biophysical properties of blood sample under continuous ESR. In this study, three physical properties, including, τ₀, ESR_τ, and AI_I, are suggested to quantify mechanical variations of blood under continuous ESR. To demonstrate the proposed method, blood sample is loaded into a driving syringe. The blood flow rate is set in a periodic on–off pattern. Blood sample is then supplied into a capillary chip, and microscopic blood images are captured at specific intervals. Blood shear stress is quantified from the interface of blood stream in the coflowing channel. Both τ₀ and ESR_τ are then obtained by analyzing the blood shear stress. Simultaneously, the AI_I is evaluated by analyzing the image intensity of blood flow. According to the experimental results, the τ₀ exhibits consistent trends with respect to hematocrit as well as diluent. The ESR_τ and AI_I showed a reciprocal relationship each other. Three suggested properties represented substantial differences for suspended blood samples (i.e., hardened red blood cells, different concentration of dextran solution and fibrinogen). In conclusion, the present method can detect variations of blood sample under continuous ESR effectively.

Psyllids (Hemiptera: Psylloidea) can transmit the phloem restricted bacterium ‘Candidatus Liberibacter solanacearum’ (Lso). In Europe, Lso causes severe losses to carrot and represents a threat to the potato industry. A rising concern of Lso transmission from carrot to potato and within potato has driven the need for monitoring populations of psyllid species that could serve as vectors on both crops, which would provide a fundamental understanding of the epidemiology of this pathogen. Different sampling methods were used to survey populations of psyllid species in commercial carrot and potato fields in Central and Eastern mainland Spain from 2015 to 2017. Two psyllid species, Bactericera trigonica and Bactericera nigricornis were found to be mainly associated with carrot and potato crops. In carrot fields the most abundant species was B. trigonica occurring from crop emergence to harvest, whereas in potato crops the most abundant psyllid species was B. nigricornis. The maximum psyllid population occurred between June and October its timing depending on the field location. Since B. nigricornis was found on both carrot and potato and is the only psyllid species able to feed and breed on both these crops in Europe, there is the potential risk of Lso transmission from carrot to potato

Promoter is a small region of DNA sequence in response to various transcription factors, which initiates a particular gene expression. The promoter-engineered bio-sensor can activate or repress gene expression through transcription factor recognizing specific molecules, such as polyamine, sugars, lactams, amino acids, organic acids or redox molecule, however, the reported applications of promoter enhanced bio-sensor are not too much. This review paper highlights the strategies of construction of promoter-gene engineered bio-sensor with human and bacteria’s genetic promoter array for high-throughput screening (HTS) molecular drugs, study of membrane protein’s localization and nucleocytoplasmic shuttling mechanism of regulating factor, enzyme activity, detection of the toxicity of intermediate chemicals, and probing bacteria density to improve value-added product titer. These bio-sensors’s sensitivity and specificity can be further improved by proposed approaches of Mn²⁺ and Mg²⁺ added random Error-prone PCR and site-directed mutagenesis which is applied for construction of bacteria’s “mutant library”. It is expected to establish flexible HTS platform (Bio-sensor array) to large-scale screen transcription factor-acting drugs, reducing the toxicity of intermediate compounds, and constructing gene dynamic regulatory system in “push and pull” mode to effectively regulate the valuable medicinal product production. This proposed novel promoter-engineered biosensors aided synthetic genetic circuit construction will maximize the efficiency of bio-synthesis of medicinal compound, which will greatly promote the development of microbial metabolic engineering and biomedical science.

Emulsion stabilisation of base layers surfaced with chip seals often proves problematic with chips punching into the base and early distress. This can be aggravated by the use of modified binders that restricts the evaporation of moisture from pavement layers. The introduction of New-age (Nano) Modified Emulsion (NME) stabilisation has the advantage that water is chemically repelled from the stabilised layer resulting in an accelerated development of strength. A need was identified to evaluate the early life performance of selected chip seals, together with identified binders. Three different chip seal surfacings with unconventional modified binders were constructed and evaluated using Accelerated Pavement Testing (APT) with the MMLS3. The objectives of the experimental design and testing were to evaluate binder performance, early loss of chips before chip orientation at low temperatures, punching of the chips into the NME stabilised base, deformation characteristics of a Cape seal and the effect of the use of a standard normal modified binder. This paper contains details of the NME base layer, the binder and seal selection and the test results. It is shown that a cost-effective thin chip seal in combination with a suitable binder can be used on a NME stabilised base with confidence.

It is well known that the photon trajectories follow a curved path in a gravitational field. We explore here the gravitational bending of electric field lines. It seems that the electric field lines of a charge, supported in a gravitational field, follow exactly the trajectories of photons emitted isotropically from a source situated at the charge location. From a detailed examination of the electrostatic field of a charge accelerated uniformly in the instantaneous rest frame, exploiting the strong principle of equivalence, one can determine the bending of the electric field lines of a charge in a gravitational field. The fraction of electric field lines crossing a surface, stationary above or below the charge in the gravitational field, is shown to be exactly similar to the fraction of photon trajectories, emitted from a source placed at the charge location, intersecting that surface. On the other hand, for a freely falling charge in the gravitational field there is no such bending of electric field lines. The field lines continue to extend in radial straight lines from the instantaneous 'present' position of the charge, as do the trajectories of photons streaming away from the instantaneous position of a freely falling source in the gravitational field. The electric field configuration of a freely falling charge in the gravitational field is shown to be exactly the same as that of a charge moving uniformly in an inertial frame with velocity equal to the instantaneous ``present'' velocity of the freely falling charge.

The main channel for disseminating information is now the Internet. Users have different expectations for the calibre of websites regarding the posted and presented content. The WEB site's quality is influenced by up to 120 factors, each represented by two to fifteen attributes. A major challenge is quantifying the features and evaluating the quality of a website based on the feature counts. One of the aspects that determines a website's quality is its completeness, which focuses on the existence of all the objects and their connections with one another. It isn’t easy to build an expert model based on feature counts to evaluate website quality, so this paper has focused on that challenge. Both a methodology for calculating a website's quality and a parser-based approach for measuring feature counts are offered. We provide a multi-layer perceptron model that is an expert model for forecasting website quality from the "Completeness" perspective. The accuracy of the predictions is 98%, whilst the accuracy of the nearest model is 87%.

It is discovered that the gravitational field on the surface of a neutron star is with a relativistic mass density of 2.65*10¹⁶~5.87*10¹⁸kgm^-3 which can be larger than the mass density of the neutron star (~10¹⁷kgm^-3). And, the total relativistic mass of the gravitational field of the Sun is ~10⁷ times the mass of the Sun. For different stars, the relativistic mass of the gravitational field is larger as the mass density of the star is larger. In the Milky Way, the total relativistic mass of the gravitational fields is much larger than the total mass of the stars, planets and gas. And, the relativistic mass density of the observed strongest magnetic field is 2.17*10⁸kgm^-3. This discovery should be a new frame to understand the fundamental problem of physics.

The phenylpropanoid pathway is a major secondary metabolite pathway that helps plants overcome biotic and abiotic stress and produces various by-products that promote human health. Its byproduct, chloroquinic acid (CQA), is a soluble phenolic compound present in many angiosperms. Hy-droxycinnamate-CoA shikimate/quinate transferase(BAHDs superfamily enzyme) is a significant en-zyme that plays a role in accumulating CQA biosynthesis. This study analyzed transcriptome-wide identification of the phenylpropanoid to chloroquinic acid biosynthesis candidate genes in A. spathulifolius flowers and leaves. Transcriptomic analyses of the flowers and leaves showed a differential expression of the PPP and CQA biosynthesis regulated unigenes. An analysis of PPP captive unigenes revealed the following: the major duplication of the key enzyme, PAL, 120 unigenes in leaves and 76 in flowers; the gene encoding C3’H, 169 unigenes in leaves and 140 unigenes in flowers; duplicated unigenes of 4CL, 41 in leaves and 27 in flowers. In addition, C4H unigenes had 12 unigenes in the leaves of A. spathulifolius and four in the flowers. The characterization of the BAHDs superfamily members identified 82 in leaves and 72 in flowers. Among them, phylogenetic analysis showed that five unigenes encoded HQT and three en-coded HCT in A. spathulifolius. The three HQT are common to both leaves and flowers, whereas the two HQT were specialized for leaves. The pattern of HQT synthesis was upregulated in flowers, whereas HCT was expressed strongly in the leaves of A. spathulifolius. Overall, 4CL, C4H, and HQT are expressed strongly in flowers, and caffeic acid and HCT show more expression in leaves. Therefore, CQA biosynthesis occurs in the flowers of A. spathulifolius rather than leaves.

The study of localized surface plasmons (LSPs) in nanoscale structures is an essential step towards identifying optimal plasmonic modes that can facilitate robust optomechanical coupling and deepen our understanding of light-matter interactions at the nanoscale. This paper investigates numerically, using the finite element method, LSPs modes in a design comprising two coupled nano-ridges deposited on a gold layer, with an interposing polymer spacer layer. Such a structure, usually referred to as particles-on-mirror, shows exquisite optical properties at the nanoscale. We first examine the LSPs modes of a single nano-ridge through the analysis of its scattering cross-section in the visible and infrared range. To enhance the plasmonic response, a thin polymer layer is placed at the middle of the ridge, which introduces additional LSPs modes confined within the former. Then, we extend the analysis to the dimer configuration, which exhibits more complex and enhanced plasmonic behavior compared to a single nano-ridge. In particular, the dimer configuration yields LSPs resonances with a quality factor enhancement of approximately threefold relative to single nano-ridge. Furthermore, the presence of the polymer layer within the ridges significantly improves plasmon field localization and quality factor. These findings underscore the potential of nano-ridge-based structures in advancing optomechanical coupling and plasmon-phonon interaction studies, offering valuable insights for the development of high-performance acousto-plasmonic devices. In particular, the proposed device could help significantly improve the design of nano-acousto-optic modulators operating in the visible or in the near infrared, that require enhanced light-photon coupling rate.

Heating stage accounts for the largest proportion of building carbon emissions. In order to figure out heating situations of rural residential building in Gansu Province, Gannan region was selected to carry out on-site survey on heating condition including heating mode, energy used for heating, heating fees, residents’ satisfaction on heating and thermal environment of typical building. The results showed that local rural residents burnt scattered coal for heating with primitive heating stove with high heating cost and low efficiency, causing low air temperature and high heating fees. Besides carbon emissions caused by heating reached 5743.28 kgCO2em-2, Several strategies for improving the heating effect and reducing carbon were proposed taking economic benefits into consideration limited by rural economic development. A parameter of reduced carbon emissions per investment input was proposed to evaluate the carbon reduction strategies. Results showed that Biomass was the most economical way to reduce the carbon emissions, followed by thermal insulation design, natural gas furnace and air source heat pumps for heating, and it was not reasonable to blindly increase building insulation to reduce building carbon emissions. The optimum energy efficiency was 55% in Gannan. The results provided reference for building low-carbon design in rural areas, helped achieving low carbon goal with low investment.

Background: The safety and effectiveness of factor-Xa (FXa) inhibitors for nonvalvular atrial fibrillation (NVAF) remains inconclusive. We investigated the current dosing of rivaroxaban, apixaban and edoxaban by monitoring drug plasma concentration (PC) and coagulation activity. Methods and Results: This multicenter clinical study monitored the drug PC levels and two coagulation biomarkers (fibrinogen: FIB, and fibrin monomer complex: FMC) at peak and trough timing in 268 outpatients receiving rivaroxaban (n = 72), apixaban (n = 71), and edoxaban (n = 125) for NVAF. Doses were adjusted according to the dose adjustment criteria of each drug. Based on our previous study, each peak drug PC remained below the cut-off level for predicting bleeding events except in eight patients (three on rivaroxaban, two on apixaban and three on edoxaban) in whom bleeding events occurred; among them, two (one each on rivaroxaban and edoxaban) had a peak drug PC below the cut-off level. Drug PCs widely varied from peak to trough, whereas FMC levels remained within the normal range (< 6.1 µg/ml) regardless of PC variation. These finding suggested that the anticoagulant effects of these drugs persisted throughout the day regardless of the drug PC levels, dosage, and frequency of dosing. Regarding the change in peak drug PC levels over time, rivaroxaban tended to accumulate more than edoxaban (p

Aeromagnetic compensation plays a vital role in geomagnetic navigation and has received considerable attention throughout last few decades. Classical aeromagnetic compensation methods based on the Tolles–Lawson (T-L) model are mainly aimed at permanent, induced, and eddy-current magnetic interferences of aircraft platform, which ignores other stray magnetic field interference on the platform including the interferences caused by on-board electronic (OBE) systems. In order to cooperate with TL model, magnetometers are usually required to be installed on the extension rod outside the cabin, which is widely applied to geophysical magnetic survey. In order to ensure safety and reduce the cost of platform modification in geomagnetic navigation, it’s necessary to place magnetometers inside the cabin. It also further exacerbates the magnetic interferences and improves the difficulty of magnetic compensation. In this paper, a modified aeromagnetic compensation method is proposed, and the in-cabin OBE interferences are respectively modelled to be proportional to the currents and their temporal variations of different electronic devices. To ensure that modified model adapts to strong OBE interference in the cabin, a cut-off frequency determination method based on curvature calculation and a feature selection method based on correlation calculation are proposed. The cut-off frequency determination method helps to select passband filter which suitable for in-cabin OBE interference. The feature selection method can help to effectively select current and voltage inputs for modified model. In addition, principal component analysis (PCA) is adopted to reduce multicollinearity which is intensified by the extension of OBE interferences in coefficient-estimating. Experiments on public dataset are conducted to illustrate the effectiveness of the proposed method, and the best compensation result achieved 1.71nT of root mean square error (RMSE).

This study sought to evaluate the awareness, comprehension, and practices concerning Forensic Odontology among dental students and faculty at a Dental School in Cyprus. An online, cross-sectional, descriptive survey was disseminated to the entirety of dental students and faculty of the School of Dentistry, European University Cyprus, in November 2022. Of those surveyed, 47 faculty members and 304 students responded, yielding response rates of 66.2% and 80%, respectively. The survey revealed that 87% of faculty and 65% of students were familiar with Forensic Odontology. A noteworthy 94% of faculty and 85% of students recognized teeth as DNA repositories. A high percentage, 98% of faculty and 89% of students, acknowledged the role of Forensic Odontology in the identification of criminals and deceased individuals. Awareness of age estimation through dental eruption patterns was evident in 85% of faculty and 81.6% of students. A substantial proportion (80% of faculty) maintained dental records, while 78% of students recognized the importance of dental record-keeping in ensuring quality care. Interestingly, 57% of students and 64% of faculty were aware of the possibility of dentists testifying as expert witnesses. The majority, 95.7% of faculty and 85% of students, concurred that physical harm, scars, and behavioral alterations predominantly indicate child abuse. The survey underscored a robust awareness of Forensic Odontology among respondents. Despite faculty's comprehensive understanding, there's a pronounced need to bolster their inclination towards attending relevant seminars. Emphasis on improved record-keeping practices for potential forensic applications is paramount.

This study investigates the complex interplay between public sentiment, as captured through news titles and descriptions, and the stock prices of three major tech companies: Microsoft (MSFT), Tesla (TSLA), and Apple (AAPL). Leveraging advanced analytical methods including Pearson correlation, wavelet coherence, and regression analysis, this research probes the degree to which stock price fluctuations can be attributed to the polarity of media sentiment. The methodology combines statistical techniques to assess sentiment's predictive power on stock opening and closing prices, while wavelet coherence analysis unveils the temporal dynamics of these relationships. Results demonstrate a significant correlation between sentiment polarity and stock prices, with description polarity affecting Microsoft's opening prices, title polarity influencing Tesla's opening prices, and a positive impact of title polarity on Apple's closing prices. However, Tesla's stock showed no significant coherence, indicating a potential divergence in how sentiment affects stock behavior across companies. The study highlights the importance of sentiment analysis in forecasting stock market trends, revealing not only direct correlations but also lagged influences on stock prices. Despite its focus on large-cap tech firms, this research provides a foundational understanding of sentiment's financial implications, suggesting further investigation into smaller firms and other market sectors.

This work investigates the influence of ground albedo on the solar radiation obtained by surfaces mounted on fixed-tilt to south, one-axis, and two-axis systems. To do this, estimation of the solar radiation difference is performed by applying real albedo and zero albedo. This is done within Saudi Arabia, at 82 selected sites. Annual, seasonal, and monthly mean solar energy differences are computed as function of the site’s number, latitude, and local near-real ground albedo. The great variation in the ground-albedo values at the 82 sites (0.1 - 0.46) could be thought as having a significant effect on the solar radiation levels received on the 3 tracking modes. The analysis shows quite the opposite; a zero-albedo ground diminishes solar radiation levels by 1.43%, 3.50%, and 3.20%, respectively for the 3 modes. Therefore, in most solar engineering applications a ground albedo of 0.2 (considered as reference) can be used without losing accuracy. This is the main conclusion of the study, which must, however, be applied with caution in areas with snow cover, especially for mode-III tracking systems. In such situations the increase in solar radiation levels may be up to 15% (but ≈3.5% for mode-I and -II systems instead).

In this work, we present an analytical model of dynamic power losses for enhancement-mode AlGaN/GaN high-electron-mobility transistor power devices (eGaN HEMTs). To build this new model, the dynamic on-resistance (Rdson) is first accurately extracted by our ex-traction circuit based on a double-diode isolation (DDI) method for a high operating frequency up to 1 MHz and a large drain voltage up to 600 V, thus the unique problem of an increase in the dynamic Rdson is presented. Then the impact of the current operation mode on the on/off transi-tion time is evaluated by a dual-pulse-current-mode test (DPCT) which including a discontinu-ous conduction mode (DCM) and a continuous conduction mode (CCM), thus the transition time is revised for different current mode. Afterward the discrepancy between the drain current and the real channel current is qualitative investigated by an external shunt capacitance (ESC) meth-od, thus the losses due to device parasitic capacitance are also taken into account. After these improvements, the dynamic model will be more compatible for eGaN HEMTs. Finally, the dynamic power losses calculated by this model are verified to be in good agreement with experimental results. Based on this model, we propose a superior solution with qua-si-resonant mode (QRM) to achieve lossless switching and accelerate switching speed.

Access and Benefit Sharing (ABS) is a framework which refers to a relatively recent type of legal requirements for access to and/or use of “genetic resources”. They are based on diverse national and regional laws and regulations, which mostly result from the implementation of the United Nations’ Convention on Biological Diversity (CBD) and its supplementary agreement, the Nagoya Protocol. Their ambition is to achieve fair and equitable sharing of benefits arising out of the use of genetic resources as an incentive to conserve and sustainably use them. This paper describes the experiences, practical constraints and complexities encountered by users of genetic resources when dealing with ABS legislation, with a focus on users from the private sector. We provide insights on how ABS laws have fundamentally changed the way of working with genetic resources in the hope that it inspires re-thinking of the ABS framework, to better support the overall objectives of the CBD.

The outdoor field test of the 4-terminal on Si tandem photovoltaic module (specifically, InGaP/GaAs on Si) was investigated and performance model, considering spectrum change affected by fluctuation of atmospheric parameters, was developed and validated. The 4-terminal on Si tandem photovoltaic module had about 40 % advantage in seasonal performance loss compared with standard InGaP/GaAs/InGaAs 2-terminal tandem photovoltaic module. This advantage is expanded in (subarctic zone) < (temperate zone) < (subtropical zone). The developed and validated model used all-climate spectrum model and considered fluctuation of atmospheric parameters, and can be applied every type of on-Si tandem solar cells.