The RV144 trial represents the only vaccine trial to demonstrate any protective effect against HIV-1 infection. While the reason(s) for this protection are still being evaluated, it serves as justification for widespread efforts aimed at developing new, more effective HIV-1 vaccines. Advances in our knowledge of HIV-1 immunogens and host antibody responses to these immunogens are crucial to informing vaccine design. While the envelope (Env) protein is the only viral protein present on the surface of virions, it exists in a complex trimeric conformation and is decorated with an array of variable N-linked glycans, making it an important but difficult target for vaccine design. Thus far, efforts to elicit a protective humoral immune response using structural mimics of native Env trimers have been unsuccessful. Notably, the aforementioned N-linked glycans serve as a component of many of the epitopes crucial for the induction of potentially protective broadly neutralizing antibodies (bnAbs). Thus, a greater understanding of Env structural determinants, most critically Env glycosylation, will no doubt be of importance in generating effective immunogens. Recent studies have identified the HIV-1 Env signal peptide (SP) as an important contributor to Env glycosylation. Further investigation into the mechanisms by which the SP directs glycosylation will be important, both in the context of understanding HIV-1 biology and in order to inform HIV-1 vaccine design.

The urgent need to improve performance in the construction industry has led to the adoption of many innovative technologies. 3D laser scanners are amongst the leading technologies being used to capture and process assets or construction project data for use in various applications. Due to its nascent nature, many questions are still unanswered about 3D laser scanning, which in turn contribute to the slow adaptation of the technology. Some of these include the role of 3D laser scanners in capturing and processing raw construction project data. How accurate is the 3D laser scanner or point cloud data? How does laser scanning fit with other wider emerging technologies such as Building Information Modelling (BIM)? This study adopts a proof-of-concept approach, which in addition to answering the afore-mentioned questions, illustrates the application of the technology in practice. The study finds that the quality of the data, commonly referred to as point cloud data is still a major issue as it depends on the distance between the target object and 3D laser scanner’s station. Additionally, the quality of the data is still very dependent on data file sizes and the computational power of the processing machine. Lastly, the connection between laser scanning and BIM approaches is still weak as what can be done with a point cloud data model in a BIM environment is still very limited. The aforementioned findings reinforce existing views on the use of 3D laser scanners in capturing and processing construction project data.

Type 1 diabetes (T1D) is an autoimmune condition where the body’s immune cells destroy their insulin-producing pancreatic beta-cells leading to dysregulated glycaemia. Individuals with T1D control their blood glucose through exogenous insulin replacement therapy, often using multiple daily injections or pumps. However, failure to accurately mimic intrinsic glucose regulation results in glucose fluctuations and long-term complications impacting key organs such as the heart, kidneys, and/or the eyes. It is well-established that genetic and environmental factors contribute to the initiation and progression of type 1 diabetes, but recent studies show that epigenetic modifications are also important. Here, we discuss key epigenetic modifications associated with type 1 diabetes pathogenesis and discuss how recent research is finding ways to harness epigenetic mechanisms to prevent, reverse, or manage type 1 diabetes.

Western Anatolia comprises a vast amount of various volcanic successions spanning from Eocene to Upper Miocene periods. These units mainly display southward younging in broad sense and display large amounts of chemical variation that spanned from basalt to rhyolite. The southward younging of magmatism and chemical variations have been largely attributed to the retreat and roll-back of the Hellenic slab and the western escape of the Anatolian microplate. However, there is still a lack of high precision data to pinpoint the exact nature of the magmatism and lithospheric tectonics. In this contribution we investigated a poorly known region along the Western Anatolia along Manisa district called Karakılıçlı volcanic field. We investigated two different volcanic sections (Kalpakkaya and Çamlık hill) that display the best volcano-sedimentary features in terms of geochronology and geochemistry. Samples acquired from the bottom, middle and upper portions of these sections display Early-Middle Miocene ages of 17.64±0.20, 17.22±0.15, 16.16±0.17 and 16.36±0.13, 15.79±0.71 and 13.61±0.20 Ma respectively. The results indicate that the volcanism in the region generated by the melting of the mantle and/or lithospheric mantle by slab retreat and roll-back of the Hellenic slab and evolved in the shallow magma chambers/mushes by fractional crystallization, magma mixing and crustal assimilation.

Molecular analysis is an easier means to identify and isolate a specific gene which has imperative function for growth, body composition , fat deposition, metabolic and skeletal traits as well as the molecular genetics selection on individual genes is a very efficient method to genetically improve economically important traits in chickens. Insulin- like growth factor 1 ( IGF-1)is a member of a heterogeneous group of peptides with important growth.Transforming growth factorβ ( TGF-β) belongs to a large family of growth and differentiation factors that play a pivotal role in a great variety of biological activities including morphogenesis, development and differentiation. DNA was extracted from 48 chickens sampled from three strains Lohman (17) , Sinai (24) and Gimmizah (7) IGF-1 gene and TGFβ2 gene were amplified using PCR protocol. Electrophoresis was carried out on the products of PCR , bands viewed on transilluminator. The size of IGF-1 gene was 675 bp while the size of TGFβ2 gene was 188bp. Sharp bands were purified and sequenced and used the dendrogram to show the relationships between other vertebrate species

Novel severe acute respiratory syndrome coronavirus 2 infection (SARS-Cov-2) is an acute respiratory and infectious disease. This perspective aims to provide the basic understanding of the inflammation caused by SARS-Cov-2 and relation to trigeminal ganglion (TG). Virus enters through the mucous membranes of orofacial region and reach the TG where it resides and take control of its peptides including Substance P (SP).SP is the main neuropeptide, neuromodulator and neuro-hormone of TG, associated with nociception and inflammation under noxious stimulus. SP release is triggered and consequently, it affects the immune cells, blood vessels to release the mediators for inflammation. Cytokine storming is initiated and cause respiratory distress, bronchoconstriction and death in complicated cases. Neurokinin-1 Receptor (NK-1R) antagonist and glucocorticoids may be used to alleviate the symptoms and treat this infection. SP is the main culprit seem to be involved in the triggering of inflammatory pathways in SARS-Cov-2 infection. It has direct association with cardiorespiratory rhythm, sleep-wake cycle, nociception, ventilator responses and regulates many important physiological and pathological roles. Its over-secretion should be blocked by NK-1R antagonist. However, experimental work leading to clinical trials are mandatory for further confirmation.

Background: Barleria lupulina Lindl. (Hop-headed) is a small shrub, possess potent anti-inflammatory, analgesic, anti-leukemic, antitumor, anti-hyperglycemic, anti-amoebic, virucidal, diuretic, bactericidal and antibiotic properties. Methods: Cytotoxicity, bioactive assay and genetic analysis of B. lupulina were investigated in the present communication. The leaf extract was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), Neutral red uptake (NRU), DNA fragment, reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP) assay, gene expression analysis and cDNA synthesis to evaluate anti-cancerous potency using cancerous THP-1 cell lines in vitro and in vivo. Results: HPTLC analysis reveals four spots and GC-MS analysis displayed the presence of eleven bioactive compounds among which benzofuranon, hexadecanoic acid, ethyl 9,12,15-octadecatrienoate, and 3,7,11,15-tetramethyl-2-hexadecanoic acid were the most prominent compounds. The ethanolic extract showed significant cytotoxicity (P<0.5) against THP-1 cell line at a concentration of 1mg/mL. The cells were also observed for apoptosis through DNA fragmentation in B. lupulina treated cells. Conclusions: It can be concluded that if the dose range was further refined within the range of 100-1000 µg/mL there could be dose at which the entire population of the THP-1 cell line would be apoptosis induced. The extract induced ROS in the cells after 30 minutes of exposure displaying cytotoxic effects and DNA fragmentation assay.

The recent outbreak of Coronavirus Disease 2019 (COVID-19) is a major threat to human health and the global economy. In addition to the development of vaccines there is an urgent need for preventive and therapeutic strategies towards severe COVID-19. Key to this would be a better understanding of the molecular mechanismsoiuuuu affected by SARS-COV-2. To address this, we performed a systems biology approach by integrating available RNA-seq datasets from post-mortem lung tissue of COVID-19 patients and cell culture models infected with SARS-COV-2, Respiratory Syncytial virus or influenza virus. We identified two gene-expression modules that are commonly regulated by the three viral diseases and one that is specific to COVID-19. All 3 gene-expression modules represent key inflammatory processes. We identified several proteins within these networks that can be targeted by FDA approved drugs. Key examples are TNF, NFkB, INTERLEUKIN-1 and ALOX5 signaling pathways. Our data also suggest that Vitamin D supplementation and a ketogenic diet should be further analyzed as preventive strategies. In conclusion, our data highlights the potential of transcriptomics to unravel the pathological processes related to COVID-19 and guide the initiation of clinical trials.

Pre-implantation horse conceptuses require nutrients and signals from histotroph, the composition of which is regulated by luteal progesterone and conceptus-secreted factors. To distinguish progesterone and conceptus effects we shortened the period of endometrial progesterone-priming by asynchronous embryo transfer. Day 8 embryos were transferred to synchronous (day 8) or asynchronous (day 3) recipients, and RNA sequencing was performed on endometrium and conceptuses recovered 6 and 11 days later (embryo days 14 and 19). Asynchrony resulted in many more differentially expressed genes (DEGs) in conceptus membranes (3473) than endometrium (715). Gene ontology analysis identified upregulation in biological processes related to organogenesis and preventing apoptosis in synchronous conceptuses on day 14, and in cell adhesion and migration on day 19. Asynchrony also resulted in large numbers of DEGs related to ‘extracellular exosome’. In endometrium, genes involved in immunity, the inflammatory response, and apoptosis regulation were upregulated during synchronous pregnancy and, again, many genes related to extracellular exosome were differentially expressed. Interestingly, only 14 genes were differentially expressed in endometrium recovered 6 days after synchronous versus 11 days after asynchronous transfer (day 14 recipient in both). Among these, KNG1 and IGFBP3 were consistently up-regulated in synchronous endometrium. Furthermore bradykinin, an active peptide cleaved from KNG1, stimulated prostaglandin release by cultured trophectoderm cells. The horse conceptus thus responds to a negatively asynchronous uterus by extensively adjusting its transcriptome, whereas the endometrial transcriptome is modified only subtly by a more advanced conceptus.

PD-1/PD-L1 axis is one key therapeutic target against tumor cell immune escape. Structurally essential to the PD-1/PD-L1-linked immune escape is the binding interface of the PD-1/PD-L1 complex structure. Incorporating currently available PD-1/PD-L1-related experimental structures, this article unveils two sets of experimentally observed inter-molecular electrostatic interactions which stabilize the binding interface of the PD-1/PD-L1 complex structure. For the first time, this article proposes an evolutionary structural hypothesis that, as a result of natural selection, PD-1 is able to genetically mutate itself to structurally disrupt the PD-1/PD-L1 axis towards the restoration of T cell-mediated anti-tumor immunity.

We show that the Einstein field equations for a five-dimensional warped spacetime, where only gravity can propagate into the bulk, determine the dynamical evolution of the warp factor of the four-dimensional brane spacetime. This can be explained as a holographic manifestation. The warped 5D model can be reformulated by considering the warp factor as a dilaton field ($\omega$) conformally coupled to gravity and embedded in a smooth $M_4 \otimes R$ manifold. On the brane, where the U(1) scalar-gauge fields live, the dilaton field manifests itself classically as a warp factor and enters the evolution equations for the metric components and matter fields. We write the Lagrangian for the Einstein-scalar-gauge fields in a conformal invariant setting. However, as expected, the conformal invariance is broken (trace-anomaly) by the appearance of a mass term and a quadratic term in the energy-momentum tensor of the scalar-gauge field, arising from the extrinsic curvature terms of the projected Einstein tensor. These terms can be interpreted as a constraint in order to maintain conformal invariance. By considering the dilaton field and Higgs field on equal footing on small scales, there will be no singular behavior, when $\omega\rightarrow 0$ and one can deduce constraints to maintain regularity of the action. Our conjecture is that $\omega$, alias warp factor, has a dual meaning. At very early times, when $\omega \rightarrow 0$, it describes the small-distance limit, while at later times it is a warp (or scale) factor that determines the dynamical evolution of the universe. We also present a numerical solution of the model and calculate the (time-dependent) trace-anomaly. The solution depends on the mass ratio of the scalar and gauge fields, the parameters of the model and the vortex charge $n$.

Single-particle tracking with quantum dots (QDs) constitutes a powerful tool to track the nanoscopic dynamics of individual cell membrane components unveiling their membrane diffusion characteristics. Here we tested the possibility of extracting from the nano-resolved (16 ms and 30 nm) population dynamics of several quantum dots, time-binned at the second time-scale, the rapid structural changes of the cell membrane surface. We used for this proof-of-concept study bright, small and stable biofunctional QD nanoconstructs recognizing the neuronal cannabinoid type 1 (CB1) receptor and a commercial point-localization microscope to reconstruct in 3D the dynamics of the plasma membrane surface of cultured cells with a spatial resolution of tens of nanometers. CB1 receptor was chosen because it’s a highly expressed and fast diffusing membrane protein. Therefore, rapid QD diffusion on the axonal plasma membrane of cultured hippocampal neurons allowed highly precise reconstruction of the membrane surface in less than one minute. QD nanoconstructs diffused into the membrane of synaptic clefts allowing the entire topological reconstruction of the presynaptic component. In addition, we demonstrated successful reconstruction of the remarkably high dynamics of membrane surface topology at the second time-scale both in HEK-293 cell filopodia and axons. Our results show that this novel technique, which we named nanoPaint, is a powerful precision tool for the study of the structural plasticity of cell membrane surfaces.

This paper describes the use of the Chinese Gaofen-1 (GF-1) satellite imagery to automatically extract tertiary Linear Archaeological Traces of Tuntian Irrigation Canals (LATTICs) located in the Miran site. The site is adjacent to the ancient Loulan Kingdom at the eastern margin of the Taklimakan Desert in western China. GF-1 data was processed following atmospheric and geometric correction, and spectral analyses were carried out for multispectral data. The low values produced by SSI indicate that it is difficult to distinguish buried tertiary LATTICs from similar backgrounds using spectral signatures. Thus, based on the textual characteristics of high-resolutionGF-1 panchromatic data, this paper proposes an automatic approach that combines joint morphological bottom and hat transformation with a Canny edge operator. The operator was improved by adding stages of geometric filtering and gradient vector direction analysis. Finally, the detected edges of tertiary LATTICs were extracted using the GIS-based draw tool and converted into shapefiles for archaeological mapping within a GIS environment. The proposed automatic approach was verified with an average accuracy of 95.76% for 754 tertiary LATTICs in the entire Miran site and compared with previous manual interpretation results. The results indicate that GF-1 VHR PAN imagery can successfully uncover the ancient tuntian agricultural landscape. Moreover, the proposed method can be generalized and applied to extract linear archaeological traces such as soil and crop marks in other geographic locations.

Increased access to highly active antiretroviral therapy (HAART) by HIV⁺ individuals has become a reality worldwide. In Brazil, ART currently reaches over half of the HIV-infected subjects. In the context of a remarkable HIV-1 genetic variability, highly related variants, called quasispecies, are generated. HIV quasispecies generated during infection can influence virus persistence and pathogenicity, representing a challenge to treatment. However, the clinical relevance of minority quasispecies is still uncertain. For this study, we have determined the archived proviral sequences, viral subtype and drug resistance mutations from a cohort of HIV⁺ patients with undetectable viral load undergoing HAART as first-line therapy using next-generation sequencing for near full-length virus genome (NFLG) assembly. HIV-1 consensus sequences representing NFLG were obtained for eleven patients, while for another twelve varying genome coverage rates were obtained. Phylogenetic analysis showed the predominance of subtype B (83%; 19/23). Considering the minority variants, 18 patients carried archived virus harboring at least one mutation conferring antiretroviral resistance; for six patients, the mutations correlated with the current ARVs used. These data highlight the importance of monitoring HIV minority drug resistant variants and their clinical impact, to guide future regimen switches and improve HIV treatment success.

Herpes simplex virus type 1 (HSV-1) is a lifelong pathogen characterized by asymptomatic latent infection in the trigeminal ganglia (TG) with periodic outbreaks of cold sores caused by virus reactivation in the TG and subsequent replication in the oral mucosa. While antiviral therapies can provide relief from cold sores, they are unable to eliminate HSV-1. We provide experimental results that highlight non-thermal plasma (NTP) as a new alternative therapy for HSV-1 infection that would resolve cold sores faster and reduce the establishment of latent infection in the TG. Additionally, this study is the first to explore the use of NTP as a therapy that can both treat and prevent human viral infections. We investigated the antiviral effect of NTP using an in vitro model for HSV-1 cold sores, involving the application of NTP from two separate devices to cell-free HSV-1, HSV-1-infected cells, and uninfected cells. We found NTP reduced the infectivity of cell-free HSV-1, reduced viral replication in HSV-1-infected cells, and diminished the susceptibility of uninfected cells to HSV-1 infection. This triad of antiviral mechanisms of action suggest the potential of NTP as a therapeutic agent effective against HSV-1 infection.

BTB domain and CNC homology 1 (BACH1) is a highly expressed transcription factor in tumors including breast and lung, relative to their non-tumor tissues. BACH1 is known to regulate multiple physiological processes including heme homeostasis, oxidative stress response, senescence, cell cycle, and mitosis. In a tumor, BACH1 promotes invasion and metastasis of cancer cells, and the expression of BACH1 presents a poor outcome for cancer patients including breast cancer patients. Recent studies identified novel functional roles of BACH1 in the regulation of metabolic pathways in cancer cells. BACH1 inhibits mitochondrial metabolism through transcriptional suppression of mitochondrial membrane genes. In addition, BACH1 suppresses activity of pyruvate dehydrogenase (PDH), a key enzyme that converts pyruvate to acetyl-CoA for the citric acid (TCA) cycle through transcriptional activation of pyruvate dehydrogenase kinase (PDK). Moreover, BACH1 increases glucose uptake and lactate secretion in aerobic glycolysis through the expression of metabolic enzymes involved such as hexokinase 2 (HK2) and glyceraldehyde 3- phosphate dehydrogenase (GAPDH). Pharmacological or genetic inhibition of BACH1 could reprogramme metabolic pathways, subsequently rendering metabolic vulnerability of cancer cells. Furthermore, inhibition of BACH1 decreased antioxidant-induced glycolysis rates as well as reduced migration and invasion of cancer cells, suggesting BACH1 as a potentially useful cancer therapeutic target.

The sexual reproduction of ascomycetes is controlled by the mating-type(MAT) locus. (Pseudo)homothallic reproduction has been hypothesized based on genetic data from Hirsutella sinensis (Genotype #1 of Ophiocordyceps sinensis). In this study, the differential occurrence of the mating-type genes in the MAT1-1 and MAT1-2 idiomorphs, which constitute the genetic control of O. sinensis reproduction, was analyzed in 237 strains and 5 genomes of H. sinensis. The mating-type genes were differentially transcribed in H. sinensis Strain L0106, and the MAT1-2-1 transcript in H. sinensis Strain 1229 was alternatively spliced, with an unspliced intron I containing stop codons; these findings constitute O. sinensis reproduction controls at the transcriptional and coupled transcriptional-translational levels. The occurrence of the mating-type genes and a-/α-pheromone receptor genes differed among the 5 H. sinensis genomes. The differential occurrence and transcription of these genes are inconsistent with self-fertilization under (pseudo)homothallism but suggest self-sterility of H. sinensis, which therefore needs a mating partner to achieve sexual outcrossing under heterothallism or hybridization. Consistent occurrence and transcription of the mating-type genes of both the MAT1-1 and MAT1-2 idiomorphs have been reported in natural and cultivated Cordyceps sinensis, but these findings are insufficient to determine the reproduction mode(s) because of the co-occurrence of >90 fungal species and multiple genomically independent genotypes of O. sinensis. The mutant MAT1-1-1 and α-pheromone receptor transcripts in natural C. sinensis result in the N-terminus or middle-truncated proteins, with changes in hydrophobicity and secondary structures of the proteins, suggesting heterogeneous fungal source(s) of the proteins and hybridization reproduction.

Background and Objectives: Fibrillinopathies have different phenotypic expression: Marfan- like skeleton features, MLSF; mitral valve prolapse syndrome, MVPS; MASS phenotype, M= mitral valve prolapse, MVP, A= aortic root dilation, S= skeletal features, and the second S= (cutaneous) striae; Marfan syndrome, MS. These are inherited connective tissue diseases, provoked by a mutation of the encoding gene for a protein(fibrillin 1, FBN1) which has major importance in the formation of elastic fibers.The study had the following main objectives: the correlation between disc displacement, DD( a major sign for temporomandibular joint dysfunction, TMD) on magnetic resonance imaging, MRI, and aortic Z score(a major sign for aortic root dilation) on echocardiography; the predictive value of DD towards aortic Z score. DD had 2 types of severity: DD with reduction(the mild type, DDwR) , and DD without reduction( the severe type, DDwoR). Materials and Methods: The type of fibrillinopathy was precised by clinical exam( systemic score), ophthalmic exam(for ectopia lentis), and echocardiography(aortic Z score, MVP). Medical treatment consisted in betablockers, BB(for patients with tachycardia), or angiotensin II receptor blockers, ARB. Surgical treatment was addressed to aortic root aneurysm, and severe MR. DD benefited by dental conservatory treatment, or surgical restoration.Results: DD- Z score had a powerful correlation in MASS(Rho= 0.787, p&lt; 0.01), and in MS patients(Rho=0.819, p&lt; 0.01). For the entire sample, both DDwR- Z score, and DDwoR- Z score had a moderate correlation(Rho= 0.469, and respectively 0.669). Muchmore, DD was an important predictor for Z score. DDwoR had a double power of prediction for Z score, comparative with DDwR(B coefficient= 1.661 for DDwR, and 3.281 for DDwoR). Conclusions: TMD had a powerful correlation with aortic root dilation, in MASS, and MS patients from the sample. Likewise, TMD was a major predictor for aortic root dilation, in the entire sample. We can utilize in clinical practice, an extracardiac finding, TMD, obtained by a non-invasive technique, MRI, for cardiac severity stratification of fibrillinopathies.

Almost contact complex Riemannian manifolds, known also as almost contact B-metric manifolds, are equipped with a pair of pseudo-Riemannian metrics that are mutually associated with each other using the tensor structure. Here we consider a special class of these manifolds, those of the Sasaki-like type. They have an interesting geometric interpretation: the complex cone of such a manifold is a holomorphic complex Riemannian manifold (also called a Kähler–Norden manifold). The basic metric on the considered manifold is specialized here as a soliton, i.e. has an additional curvature property such that the metric is a self-similar solution of an intrinsic geometric flow. Almost solitons are more general objects than solitons because they use functions rather than constants as coefficients in the defining condition. A β -Ricci-Bourguignon-like almost soliton ( β is a real constant) is defined using the pair of metrics. The introduced soliton is a generalization of some well-known (almost) solitons (such as those of Ricci, Schouten, Einstein), which in principle arise from a single metric rather than a pair of metrics. The soliton potential is chosen to be pointwise collinear to the Reeb vector field, or the Lie derivative of any B-metric along the potential to be the same metric multiplied by a function. The resulting manifolds equipped with the introduced almost solitons are characterized geometrically. Appropriate examples for two types of almost solitons are constructed and the properties obtained in the theoretical part are confirmed.

Co-delivery of antigens and adjuvants to the same antigen presenting cells (APCs) can significantly improve the efficacy and safety profiles of vaccines. Here, we report amine-grafted silica nanoparticles (A-SNPs) as a tunable vaccine co-delivery platform for TLR7/8 agonists along with the recombinant influenza antigen hemagglutinin H7 (H7) to APCs. A-SNPs of two different sizes (50 and 200 nm) were prepared and coated with INI-4001 at different coating densities, followed by co-adsorption of H7. Both INI-4001 and H7 showed &gt; 90% adsorption to the tested A-SNP formulations. TNF-α and IFN-α cytokine release by human peripheral blood mononuclear cells as well as TNF-α, IL-6, and IL-12 release by mouse bone marrow-derived dendritic cells revealed that the potency of the INI-4001-adsorbed A-SNPs (INI-4001/A-SNP) formulations can be improved relative to aqueous formulation control. This improved potency was dependent on particle size and ligand coating density. In addition, slow-release profiles of INI-4001 were measured from INI-4001/A-SNP formulations in plasma with 30-50% INI-4001 released after 7 days. In vivo murine immunization studies demonstrated significantly improved H7-specific humoral and Th1/Th17-polarized T cell immune responses with no observed adverse reactions. Low-density 50 nm INI-4001/A-SNP elicited significantly higher IFN-γ and IL-17 induction over that of the H7 antigen only group and INI-4001 aqueous formulation controls. In summary, this work introduces an effective and biocompatible SNP-based co-delivery platform that enhances the immunogenicity of TLR7/8 agonist-adjuvanted subunit influenza vaccines.

The paper covers the development of formulations and technology for low energy building materials based on the alkaline alumino-silicate binder and appropriate for special purposes. The microstructure of the binder was investigated using scanning electron microscopy and atomic force microscopy. The identification of the phase compositions was done by means of X-ray diffraction. By leach rate measurement and chemical analysis of pore liquid, the linkage of the alkali metal ions in water-insoluble composites was researched. The dependence of structure formation on mix design and curing conditions was investigated. Specific examples of manufacture and application of binder-based glues and adhesives have been considered, incl. ones for low-temperature insulating composite materials, heat insulation perlite-based materials, heat insulation of industrial boilers, and the fire resistant heat insulating system. The advantages of the binder-based temperature insulating composites compared to traditionally used ones are shown.

Manipulating cloth-like deformable objects (CDOs) is a long-standing problem in the robotics community. CDOs are flexible (non-rigid) objects that do not show a detectable level of com- pression strength while two points on the article are pushed towards each otherand include objects such as ropes (1D), fabrics (2D) and bags (3D). In general, CDOs’ many degrees of freedom (DoF) introduce severe self-occlusion and complex state-action dynamics as significant obstacles for perception and manipulation systems. These challenges exacerbate existing issues of modern robotic control methods such as imitation learning (IL) and reinforcement learning (RL). This review focuses on the application details of data-driven control methods on four major task families in this domain: cloth-shaping, rope manipulation, dressing and bag manip- ulation. Furthermore, we identify specific inductive biases in these four domains that present challenges for more general IL and RL algorithms, and summarise the future direction for the development of the field.

A key in controlling the SARS-CoV-2 pandemic is the assessment of the immune status of the population. We explored the utility of SARS-CoV-2 virus-like particles (VLPs) as antigens to detect specific humoral immune reactions in an enzyme-linked immunosorbent assay (ELISA). For this purpose, SARS-CoV-2 VLPs were produced from an engineered cell line and characterized by western blot, ELISA and nanoparticle tracking analysis. Subsequently, we collected 42 serum samples from before the pandemic (2014), 89 samples from healthy-, and 38 samples from vaccinated subjects. Seventeen samples were collected less than three weeks after infection, and 44 samples more than three weeks after infection. All serum samples were characterized for their reactivity with VLPs and the SARS-CoV-2 N- and S-protein. Finally, we compared the performance of the VLP-based ELISA with a certified in vitro diagnostic device (IVD). In the applied set of samples, we determined a sensitivity of 95.5 % and a specificity of 100 % for the certified IVD. There were 7 samples with an uncertain outcome. Our VLP-ELISA showed superior performance with a sensitivity of 97.5 %, a specificity of 100 %, and only 3 uncertain outcomes. This result warrants further research to develop a certified IVD based on SARS-CoV-2 VLPs as an antigen.

Jumping side volley has created breathtaking moments and cherished memories for us. Regrettably, a scientific study on the skill has not been found in literature. Relying on talent of athletes to improvise on the fly can hardly be considered a viable learning strategy. This study targets to fill the gap by quantifying factors contributing to develop its coaching method. Using 3D motion capture (12-cameras, 200Hz) and full-body biomechanical modeling, our study aimed to identify elements that govern entrainment of the skill by examining jumping, kicking and falling phases of its execution. Given the rarity of players who have acquired this skill, we found five subjects for the study. Twenty-three trials were captured and quantified. The results unveil the following key elements: 1) the control of trunk rotation during the jumping, 2) the angle between thighs upon take-off, 3) the whip-like control of the kicking leg during airborne, 4) timing between ball motion and limbs’ coordination, and 5) damping mechanism during falling. An accurate kick can only be achieved through repetitive training. This underlines the need for athletes to master a safe landing technique that minimizes risk of injury during practice. Therefore, training should begin with learning a safe falling technique.

We profiled the transcriptomes of primary mouse cortical astrocytes cultured alone or co-cultured with immortalized precursor oligodendrocytes. The experimental set-up (insert systems) prevented formation of gap junction channels but allowed free exchange of the two culture media. The study complements our previously published reports that the genomic fabrics of major functional pathways in oligodendrocytes are substantially remodeled by the proximity of non-touching astrocytes. Here, we present new analysis indicating that the transcriptomic landscape of astrocytes likewise changes significantly in the proximity of non-touching oligodendrocytes. The research was stimulated by the reported transcriptomic similarity between the brains of Cx43KO and Cx32KO mice, both substantially different from that of the Cx36KO mice. Since the three connexins are expressed in different cell types (Cx43 in astrocytes, Cx32 in oligodendrocytes and Cx36 in neurons), altogether these findings support the idea of a “panglial transcriptomic syncytium” in the mouse brain. Going further, our results suggest that integration in a heterocellular tissue modulates not only the expression profile but also the expression control and networking of the genes in each cell phenotype.

We discuss the role of water bridging the DNA-enzyme interaction by resorting to recent 1 results showing that London dispersion forces between delocalized electrons of base pairs of DNA 2 are responsible for the formation of dipole modes that can be recognized by Taq polymerase. 3 We describe the dynamical origin of the high efficiency and precise targeting of Taq activity in 4 PCR. The spatiotemporal distribution of interaction couplings, frequencies, amplitudes, and phase 5 modulations comprise a pattern of fields instantiating the electromagnetic image of DNA in its 6 water environment, which is what the polymerase enzyme actually recognizes at long range. The 7 experimental realization of PCR amplification, achieved through replacement of the DNA template 8 by the treatment of pure water with electromagnetic signals recorded from viral and bacterial DNA 9 solutions, is found consistent with the gauge theory paradigm of quantum fields.

The mineralocorticoid hormone aldosterone regulates sodium and potassium homeostasis but also adversely modulates the maladaptive process of cardiac adverse remodeling post-myocardial infarction. Through activation of its mineralocorticoid receptor (MR), a classic steroid hormone receptor/transcription factor, aldosterone promotes inflammation and fibrosis of the heart, the vasculature, and the kidneys. This is why MR antagonists reduce morbidity and mortality of heart disease patients and are part of the mainstay pharmacotherapy of advanced human heart failure. A plethora of animal studies using cell type–specific targeting of the MR gene have established the importance of MR signaling and function in cardiac myocytes, vascular endothelial and smooth muscle cells, renal cells, and macrophages. In terms of its signaling properties, the MR is distinct from nuclear receptors in that it has, in reality, two physiological hormonal agonists: not only aldosterone but also cortisol. In fact, in several tissues, including in the myocardium, cortisol is the primary hormone activating the MR. There is a considerable amount of evidence indicating that the effects of the MR in each tissue expressing it depend on tissue- and ligand-specific engagement of molecular co-regulators that either activate or suppress its transcriptional activity. Identification of these co-regulators for every ligand that interacts with the MR in the heart (and in other tissues) is of utmost importance therapeutically, since it can not only help elucidate fully the pathophysiological ramifications of the cardiac MR`s actions but also help design and develop novel better MR antagonist drugs for heart disease therapy. Among the various proteins the MR interacts with are molecules involved in cardiac G protein-coupled receptor (GPCR) signaling. This results in a significant amount of crosstalk between GPCRs and the MR, which can affect the latter`s activity dramatically in the heart and in other cardiovascular tissues. This review summarizes the current experimental evidence for this GPCR-MR crosstalk in the heart and discusses its pathophysiological implications for cardiac adverse remodeling as well as for heart disease therapy. Novel findings revealing non-conventional roles of GPCR signaling molecules, specifically of GPCR-kinase (GRK)-5, in cardiac MR regulation are also highlighted.

: The present paper tackles the important issue of tensile ultimate strength of ceramic matrix composites, using a multiscale approach. The ultimate strength is investigated at the successive increasing length scales inherent to 2D woven SiC/SiC composites, i.e. single filaments, fiber tow, minicomposites reinforced with a single tow, and 2D woven composite. First experimental results on tensile behavior under strain-controlled conditions are summarized for tows, minicomposites and composites. Then, models of tow ultimate failure under controlled force and strain are presented. A criterion of tow failure is developed for filament fracture initiation and then propagation based on applied stress and on filament strength gradient. The model of ultimate failure of minicomposite under strain-controlled condition is based on the strength of filaments in the presence of matrix cracks and the overstress induced by interactions of broken filaments and the matrix. The variability of ultimate strengths of filaments, minicomposites and composites at various gauge lengths is described by linear p-quantile diagrams which indicates that the data follow normal distribution function. The contribution of structural effects to variability of composite and minicomposite strength under strain-controlled loading is analyzed. Their dependence on specimen size is related to reproducibility of critical flaw population and structural effects.

Experimental studies and numerical analyses were conducted to estimate the laminar flame speeds of butyl ether, n-octane, iso-octane, and 1-octene at temperatures of 373 and 443 K and pressures ranging from 0.03 to 0.3 MPa in a constant-volume combustion chamber. Iso-octane had the slowest laminar flame speed whereas butyl ether had the highest. The LLNL model for large hydrocarbons and the Cai model for butyl ether were combined to describe the chemical kinetic mechanism for the test fuels. The simulation data calculated with the constructed model agree with the experimental data. The discrepancies in the laminar flame speeds of the four fuels were clarified from the perspectives of thermodynamics, diffusion, and chemical kinetics. The results reveal that the thermodynamics and chemical kinetics were dominant. Butyl ether had the highest laminar flame speed. This was attributed to it having the highest adiabatic flame temperature and a higher concentration of H and OH radicals, which have a high reactivity in a flame. Iso-octane produces the highest concentration of CH3, which inhibits flame propagation, so that it had the slowest laminar flame speed.

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

Damage to peripheral arteries by the atherosclerotic process accounts for about 3% of the world's population, which puts this problem in the category of major social problems. Modified lipoproteins and cholesterol crystals are known to accumulate in the arterial intima and cause the formation of proatherogenic macrophages, foam cells, and inflammation. Defective efferocytosis of apoptotic foam cells leads to the formation of a necrotic core, a sign of failure to resolve inflammation. Resolution of inflammation is mediated by specialized pro-resorption lipid mediators, proteins and signaling gases. Improving the balance between pro-inflammatory and anti-inflammatory factors contributes to the reverse development of local atherogenesis. Active direct intervention in the reconstruction of the adventitial layer of the arterial wall using cholesterol-affinity polysaccharide hydrogels containing a cocktail of growth factors creates conditions for the formation of additional extracellular matrix and reversal of cholesterol mass from the subintimal zone. Creating concentration and electrostatic gradients in the adventitia zone using a hydrogel may be one of the effective ways to degrade early soft atherogenic plaques and locally restore the damaged structure of the vessel wall. Growing scientific interest in the previously insufficiently studied adventitia indicates its important role in angionesis and atherogenesis.

Excessive oxidative stress and exercise-induced fatigue reduce physical performance and can lead to dysfunction in antioxidant systems within muscular and hepatic tissues. Integrating natural substances with exercise may mitigate fatigue via anti-oxidant effects. This study aims to compare and evaluate the effects of exercise and supplementation with Sundarbans honey vs energy drinks on the strength, anxiety physiological profiles, and hepatic antioxidant capacity in mice undergoing extraneous exercise and fatigue. Forty-eight four-week-old Swiss albino mice were randomly assigned to one of eight groups: (1) Control, (2) Speed™ (Sp), (3) Royal Tiger™ (RT), (4) Sundarbans Honey (SH), (5) Exercise (Ex), (6) Exercise + Sundarbans Honey (Ex+SH), (7) Exercise + Speed™ (Ex+Sp), and (8) Exercise + Royal Tiger™ (Ex+RT). Supplements were administered via oral gavage: Sp (2.5 ml/kg BW), RT (2.5 ml/kg BW), and SH (1 g/kg BW), four times a week for 60 days. Mice in the Ex, Ex+SH, Ex+Sp, and Ex+RT groups underwent daily swimming and running. The strength, fatigue, anxiety levels, lipid profiles, and antioxidant biomarkers were evaluated post-treatment. The SH, Ex, and Ex+SH groups exhibited significantly enhanced physical performance (p<0.05). Plasma lipid profiles, including LDL, triglycerides, total cholesterol, and fatigue-related biomarkers (ALP, AST, ALT, LDH, CK, LA, BUN, and glucose) were markedly increased in the Sp and RT groups but decreased in the SH, Ex, and Ex+SH groups compared to control (p<0.05). Exercise-induced fatigue elevated the Nrf2/HO-1 antioxidant defense system in liver tissue. IL-6 levels were reduced in the SH, Ex, and Ex+SH groups (p<0.05). These findings indicate that regular exercise combined with SH supplementation increases strength and improves lipid profiles, reducing exercise-induced oxidative stress and fatigue via modulation of the Nrf2/HO-1 pathway in liver tissue. These results highlight SH supplementation’s potential as a complementary strategy to enhance exercise outcomes and mitigate exercise-induced stress.

Background Olfactory perception is an important physiological function for the human well-being and health. Loss of olfaction, or anosmia, caused by viral infections such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) received a considerable attention especially in the persistent cases that take long time to recover. Objectives This review discusses the integration of different components of the olfactory epithelium to serve as a structural and functional unit, and explores how they are affected during viral infections, leading to the development of olfactory dysfunction. Methods The review mainly focused on the role of receptors mediating the disruption of olfactory signal transduction pathways such as ACE2, TMPRSS2 protease, neuropilin 1 (NRP1), basigin (CD147), olfactory, TRPV1, purinergic, and interferon gamma receptors. Furthermore, the compromised function of the epithelial sodium channel (ENaC) induced by SARS-CoV-2 infection and its contribution in olfactory dysfunction is also discussed. Results Collectively, this review provides fundamental information about the many types of receptors that may modulate olfaction and participate in olfactory dysfunction. It will help to understand the underlying pathophysiology of virus-induced anosmia which may help in finding and designing effective therapies targeting molecules involved in viral invasion and in olfaction. Conclusion This wide and complex spectrum of receptors that mediates the pathophysiology of olfactory dysfunction reflects the many ways by which anosmia can be therapeutically managed.

Observations of the X-ray binary system Her X-1 by the AstroSat Soft X-ray Telescope 1 (SXT) were carried out in 2020 through 2023 with the goals of measuring X-ray spectrum changes with the 35-day disk rotation phase and measuring eclipses at different 35-day phases. The four multi-day long observations were scheduled during: turn-on to Main High (MH) and MH rise; MH state; Short High (SH) state; and Low State (LS). 35-day phase was determined using monitoring observations with the Swift Burst Alert Telescope (BAT). Nine eclipses were observed at a range of 35-day phases, with at least one eclipse during each observation. Data with dips were separated from data without dips. The variation of X-ray spectral parameters vs. 35-day phase shows the following: eclipse parameters are nearly constant, showing that the scattering corona does not change with 35-day phase; dips show an increase in covering fraction but not column density compared to non-dip data; the 1 keV line normalization indicates an origin in a small region near the continuum emission region, likely the magnetospheric accretion flow from the inner disk onto the neutron star; and the change in blackbody normalization (area) shows that the emission region is much larger than the 1 keV emission region, and consistent with the inner edge of the accretion disk.

Long-range HNCO NMR spectra for proteins show crosspeaks due to 1JNC, 2JNC, 3JNCg and h3JNC couplings. The h3JNC couplings are transmitted through hydrogen bonds and are correlated to hydrogen bond lengths. We collected long-range HNCO data at a series of temperatures for four protein states. P22i and CUS-3i are six-stranded beta-barrel I-domains from phages P22 and CUS-3 that share less than 40% sequence identity. The cis and trans states of the C-terminal domain from pore-forming toxin hemolysin ΙΙ (HlyIIC) arise from isomerization of a single G404-P405 peptide bond. For P22i and CUS-3i the hydrogen bonds detected by NMR agree with those observed in the corresponding domains from cryoEM structures of the two phages. Hydrogen bond lengths derived from the h3JNC couplings, however, are poorly conserved between the distantly related CUS-3i and P22i domains and show differences even between the cis and trans states of HlyIIC. This is consistent with hydrogen bond lengths being determined by local differences in structure rather than the overall folding topology. With increasing temperature hydrogen bonds typically show an apparent increase in length, which has been attributed to protein thermal expansion. Some hydrogen bonds are invariant with temperature, however, while others show apparent decreases in length suggesting they become stabilized with increasing temperature. Considering the data for the three proteins in this study and previously published data for ubiquitin and GB3, lowered protein folding stability and cooperativity correlates with a larger range of temperature responses for hydrogen bonds. This suggests a partial uncoupling of hydrogen bond energetics from global unfolding cooperativity as protein stability decreases.

Populational aging is marked by chronic non-communicable diseases, such as metabolic syndrome (MetS). IL-10 and IL-1β are pleiotropic cytokines with multiple biological effects linked to metabolic disorders. This cross-sectional study assessed 193 participants' IL-10 and IL-1β serum levels regarding their role in developing MetS, clinical characteristics, and their IL1B rs1143627 and IL10 rs1800890 variants' genotype frequencies in a population over 60. IL-10 levels correlated weakly with HDL levels and fat mass and inversely with triglycerides, glucose, glycated hemoglobin, and estimated average blood glucose levels. IL-10 levels were also indirectly influenced by the patient's T2DM duration, lean mass amount, and bone mineral content. Participants with altered HDL, elevated serum glucose, raised HbA1c levels, or those over 80 had reduced serum IL-10 levels compared to those with normal levels or other age groups, respectively. Women also had higher serum IL-10 levels than men. Dissimilarity, IL-1β levels correlated directly only with the number of total leukocytes and segmented neutrophils, showing only significant variations with self-reported alcohol consumption. Our study also found that those with the IL10 AA genotype (lower IL-10 levels) had a significantly higher risk of developing MetS. These findings may help direct future research and more targeted therapeutic approaches in older adults.

Neuronal cells are believed to rely on autophagy to maintain cellular homeostasis. Nevertheless, autophagy may be a therapeutic target for neurodegenerative diseases because of the role it plays in neuronal cell death. Despite Beclin 1 association with autophagy and apoptosis, the molecular mechanisms that underlie Tau-induced vesicular pathology and Tau protein aggregates in humans remain poorly understood. Here, we set out to examine the role of three genes-ATG14L, Beclin 1 and VPS34- in autophagy nucleation failure-associated Tau disorders in fruit fly models. We found that either reduced ATG14L levels improve neuronal outcomes, or transgenic expression of ATG6/Beclin 1 greatly reduced age-dependent neurodegeneration and Tau pathology; whereas, the loss of Beclin 1 exacerbated these effects. Prior to p-Tau accumulation, the neuronal Beclin 1 network is critical for reducing p-Tau accumulation, indicating that the loss of Beclin 1 causes Tau pathology and neurodegeneration. As neurodegeneration progressed, glial cells showed an upregulation of vesicular Beclin 1 immunoreactivities. The reduced VPS34 also resulted in p-Tau accumulation, suggesting that neurons require both Beclin 1 and VPS34 to reduce p-Tau accumulation. Our results provide mechanistic insight into the molecular pathways that cause age-dependent Tau pathology and neurodegeneration due to an excess of autophagy nucleation processes and autophagy activity, and we derive novel inferences on the therapeutic possibilities of rebalanced Beclin 1 network by reducing autophagic specific nucleation component of ATG14L.

The aim of this study was to determine the microbial stability, challenge to L. monocytogenes, and some physicochemical properties of turkey breast meat by alginate-based coating enriched with postbiotics (8% concentration, CFS) of Bifidobacterium bifidum DSM 20456 and Bifidobacterium bifidum BB12 strains. For this purpose, firstly, some antimicrobial and total phenolic matter, flavonoid, and DPPH activity values of postbiotics were determined. In addition, FTIR analysis was performed to see the intermolecular interactions of the biological coating agent. As a result of the study, alginate solution with postbiotic showed significant differences in pH, a*, b*, yeast-mold values of turkey meat during storage (7 days), while L* value, total aerobic mesophilic bacteria count (TMAP), psychrotrophic bacteria (PAB), lactic acid bacteria (LAB) and Listeria monocytogenes count were not effective (p&gt;0.05).

(1) Background: The aim of study was to investigate the salt consumption by children and adolescents from the Silesian Province (Poland), taking into account the region’s dietary traditions and number of years of school education. (2) Methods : 300 students aged 10–18 from different types of schools, were enrolled in the study and divided into groups in terms of: school, sex, the state of nutrition. The survey questionnaire about dietary habits, including the frequency and serving size with respect to 12 salty products was used. On the basis of the frequency and the amount of consumed products, as well as the data on salt content, the amount of total daily intake of salt was estimated.; (3) Results: The mean daily intake of salt by children and adolescents was 1.083 g ( 0.433 g of sodium); children aged 10–12 consumed the highest amount of salt (1.296 g/day) compared to pupils aged 13–15 (1.131 g of sodium) and adolescents aged 16–18 (0.863 g/day); (4) Conclusions: With age, as a result of various factors, the consumption of salt declines. The parents impact and the familial socio-environmental factors begin to wane, and other factors start to have influence, e.g. school education of healthy lifestyle, health behavior of peers.

Keywords: Spine surgery 1; Metastatic spinal cord compression 2; Spinal metastasis 3; Cancer treatment.

Results showed that mulberry leaves could significantly reduce backfat thickness (P&lt;0.05) and increase intramuscular fat (IMF) content (P&lt;0.05). Lipidomics analysis showed that mulberry leaves improved lipid profile composition and increased the proportion of triglycerides (TG). Interestingly, IMF content was positively correlated with acyl C18:2 and negatively correlated with C18:1 of differential TGs. In addition, cecal microbiological analysis showed that mulberry leaves could increase the abundance of bacteria such as UCG−005, Muribaculaceae_norank, Prevotellaceae_NK3B31_group, Limosilactobacillus, and so on. At the same time improve the L-tyrosine-baton rouge ester, Oleic acid methyl ester, 21-deoxycortisol, N-acetyldihydrosphingosine, Mulberrin relative abundance. In this study, we found that mulberry leaves could extremely significantly increasing the mRNA relative expression of lipoprotein lipase (LPL), fatty acid-binding protein 4 (FABP4) and peroxisome proliferators-activated receptor γ (PPARγ) in muscle (P＜0.01), significantly increasing mRNA relative expression of diacylglycerol acyltransferase 1 (DGAT1) (P＜0.05) and significantly decreasing the mRNA relative expression of acetyl CoA carboxylase (ACC) (P＜0.05), and aignificantly upregulated hormone-sensitive triglyceride lipase (HSL), peroxisome proliferators-activated receptor α (PPARα) mRNA relative expression (P＜0.05) in backfat. In addition mulberry leaves could increased serum leptin and adiponectin (P＜0.01). Ultimately lead to up-regulation of IMF and down-regulation of backfat.

The objective of the present report is the dissemination of information acquired during the application of ISO 6579-1:2017 for the isolation of Salmonella spp. from swine samples. ISO 6579-1:2017 is the officially recommended by the EU protocol for the isolation of Salmonella spp., aiming in the harmonization of effective successful control of Salmonella infection in food producing animals. Successful control of animal salmonellosis is highly dependent on the sensitivity of the biochemical methods reliably detecting the presence of the pathogen in various stages of food production. Application of ISO 6579-1:2017 resulted in the isolation of twelve Salmonella spp. and eighteen other members of the family of Enterobacteriaceae biochemically and antigenically resembling salmonellae. The findings necessitated in the depth evaluation of the culture media xylose-lysine-desoxycholate agar (XLD), Salmonella-Shigella Agar (SS), Brilliant Green Agar (BGA), Salmonella Chromogenic Agar (SCA), Triple Sugar Iron (TSI) and modified semi-solid Rappaport–Vassiliadis (MSRV) agar. The evaluation showed that these culture selective media differed significantly in their performance regarding the isolation of Salmonella from swine samples. It was concluded that the presence of atypical Salmonella strains negatively affects the prevalence of Salmonella, thus the identification of carrier pigs, eventually affecting the efficiency of control programs. Thus, doubtful results require additional biochemical testing for confirming the accuracy of such universally recommended isolation methods.

Background: PD1 and its ligand PD-L1 are related to the prognosis in many solid tumors, whether its role in oral squamous cell carcinoma (OSCC) remains unclear. Methods: Retrospective monocentric study including all patients with OSCC diagnosed and treated between 01/2020 and 05/2022. PD-L1 expression was assessed by combined positive score (CPS), considering CPS > or equal to 1 as positive (1-20 “low expression”, and ≥20 “high”). Descriptive analysis of patient cohort and tumors was performed, including tumor size, stage, lymph node involvement, recur-rence and survival. Results: 65 patients (65 tumors) were analyzed. 66.15% of tumors were ad-vanced stages (III-IV), of them, 97.67% PD-L1+ versus 71.42% within early stages (I-II). T4 tumors expressed PD-L1 in 100% of cases, compared with 54’54% in T1 tumors. 50.79 % of tumors showed lymph node involvement (pN+), 100% of them showing PD-L1+. Prevalence of pN+ was 59.38% for PD-L1 high expression versus 40.63% for low expression. Patients' follow-up ranged from 2 to 34.5 months. No significant difference was seen between overall survival (OS) and PD-L1 +/- (CPS ≥1 vs CPS <1) neither PD-L1 high (CPS ≥20) vs low CPS <20) (p 0.97 and 0.64, re-spectively). Conclusions: The method used to measure (laboratory test with Dako 22C3 an-ti-PD-L1 primary antibody) PD-L1 was reliable and accurate, with a correlation coefficient be-tween the PD-L1 expression in the biopsy and surgical piece of 0.83 (p 0.0001). CPS≥1 was ob-served in large tumors (p<0.001), and was correlated with of lymph node metastases (p<0.004). Further analysis of PD-L1 expression and its relevance in tumor biology and prognosis is needed.

Herpesvirus is a prevalent pathogen that primarily infects human epithelial cells and has the ability to reside in neurons. In the field of otolaryngology, herpesvirus infection primarily leads to hearing loss and vestibular neuritis, and is considered the primary hypothesis regarding the pathogenesis of vestibular neuritis. In this review, we provide a summary of the effects of herpes virus on cellular processes in both host cells and immune cells, with a focus on HSV-1 as illus-trative examples.

Storing apples for up to a year is a well-established practice aimed at providing a continuous, locally-produced fruit supply to consumers and adapting to market trends for optimized profits. Temperature control is the cornerstone of postharvest conservation and apples are typically kept at temperatures from 0 to 3 °C. However, the energy-intensive process of the initial cool down and subsequent temperature maintenance poses significant financial challenges and contributes to the carbon footprint. Higher storage temperatures could reduce cooling-related energy usage but also pose the risk of enhanced ripening and quality loss. This work explores different storage technologies aiming to reduce energy consumption such as 1-methylcyclopropene, ultra-low oxygen and dynamic controlled atmosphere together with raised temperatures. The integration of advanced monitoring and control systems, coupled with data analytics and energy management in apple storage is also discussed. These sustainable strategies can be implemented without cost-intensive construction measures in standard storage facilities. Furthermore, beneficial side effects of higher storage temperatures in terms of a reduced occurrence of storage disorder symptoms and higher maintenance of quality attributes are also discussed for this special issue on sustainable horticultural production systems and supply chains.

Tocilizumab against interleukin-6 receptor (IL-6R) has been demonstrated to inhibit the progression of diverse cancers in vitro and in vivo. Nonetheless, evidence regarding the anti-tumor effects of Tocilizumab on human colorectal carcinoma (CRC) corresponding to IL-6R expression levels re-mains scarce. To investigate the influence of IL-6R expression, SW480 and HT-29 cells inoculated subcutaneously into NU/NU mice were used as our human CRC xenograft models with anti-IL-6R antibody (Tocilizumab) therapy. IL-6R expression levels, the histology of CRC growth/ invasiveness and tumor growth-related signaling pathway were estimated by H&E and immunohistochemical staining. SW480 tumor cells with higher IL-6R expression levels exerted better responsiveness in Tocilizumab therapy than the treated HT-29 group. Likewise, therapeutic effects of Tocilizumab on the proliferative ability with mitotic index and Ki-67 expressions, the invasiveness with MMP-9 proteinase expressions, ERK 1/2 and STAT3 signaling transduction in SW480 treatment group were superior to HT-29 treatment group. In light of our results, IL-6R is the key indicator for the efficacy of Tocilizumab treatment in CRC xenografts. From the perspective of precision medicine, tumor response to anti-IL-6R antibody therapy could be predicted on the basis of IL-6R expression levels. In this manner, Tocilizumab may serve as a targeted and promising anti-CRC therapy.

With an estimated 10 million people infected, the deltaretrovirus human T-cell lymphotropic virus type 1 (HTLV-1) is the second most prevalent pathogenic retrovirus in humans after HIV-1. Like HIV-1, HTLV-1 overwhelmingly persists in a host via a reservoir of latently infected CD4+ T cells. Although most patients are asymptomatic, HTLV-1-associated pathologies are often debilitating and include childhood infective dermatitis and adult T-cell leukaemia/lymphoma (ATLL), which presents in mature adulthood and is associated with poor prognosis with short overall survival despite treatment. Curiously, the strongest indicator for the development of ATLL is the acquisition of HTLV-1 through breastfeeding. There are no therapeutic or preventative regimens for HTLV-1. However, antiretrovirals (ARVs), which target the essential retrovirus enzymes, have been developed for and transformed HIV therapy. Since the architectures of retroviral enzyme active sites are highly conserved, some HIV-specific compounds may be active against HTLV-1. Here, we expand on our work showing that integrase strand transfer inhibitors (INSTIs) and some nucleoside reverse transcriptase inhibitors (NRTIs) block HTLV-1 transmission in cell culture. Specifically, we find that dolutegravir, the INSTI currently recommended as the basis of all new combination antiretroviral therapy prescriptions, and the latest prodrug formulation of the NRTI tenofovir, tenofovir alafenamide, also potently inhibit HTLV-1 infection in cell culture. Our results, if replicated in a clinical setting, could see transmission rates of HTLV-1 and future caseloads of HTLV-1-associated pathologies like ATLL dramatically cut via the simple redistribution of already widely available HIV pills to HTLV-1 endemic areas. Considering our findings with the old medical saying ‘it’s better to prevent than cure’, we highly recommend the inclusion of INSTIs and tenofovir prodrugs in upcoming HTLV-1 clinical trials as potential prophylactics.

The inaugural AIDS Program in Brazil was established in São Paulo in 1983, with the Instituto Adolfo Lutz appointed for laboratory assistance. Subsequently, research on HIV infections and HIV/HTLV (HIV/HTLV-1 and HIV/HTLV-2) co-infections were conducted. This narrative review focuses on studies from the Immunology Department (1983–2017) that significantly influenced AIDS diagnosis or provided epidemiological data such as prevalence rates, sex, age, and risk factors. Ten studies, encompassing over 8,000 individuals, are discussed. During 1983–1985, nearly all AIDS cases were attributed to homosexual/bisexual men aged 31 years old. Subsequently, heterosexual men and women emerged as risk groups owing to intravenous drug use (IDU) and/or unprotected sexual intercourse with AIDS patients or multiple partners per year. From 1985 onwards, vertical transmission led to child infections. HIV/HTLV co-infection rates decreased over time, initially associated with male IDU, and in the 2010s, with females, IDU, and individuals aged &gt;40 years. Trends in HIV and HIV/HTLV co-infections among younger men and women (&lt;30 years of age) were observed from 2015–2017. The changing characteristics and risk groups for HIV and HIV/HTLV co-infections over the years underscore the necessity for ongoing public policies to prevent retrovirus transmission, particularly among adolescents and young adults.

The vascular endothelium is key target for immune, and thrombotic responses that has to be controlled in successful xenotransplantation. Several genes were identified that if induced or overexpressed help to regulate the inflammatory response and preserve the transplanted organ function and metabolism. However, few studies addressed combined expression of such genes. The aim of this work was to evaluate in vivo the effects of the simultaneous expression of a three human genes in a mouse generated using the multi-cistronic F2A technology. Male 3-month-old mice that express human heme oxygenase 1 (hHO-1), ecto-5’-nucleotidase (hE5NT), and ecto-nucleoside triphosphate diphosphohydrolase 1 (hENTPD1) (Transgenic) were compared to wild-type FVB mice (Control). Background analysis include extracellular nucleotide catabolism enzymes profile on the aortic surface, blood nucleotide concentration and serum L-arginine metabolites. Furthermore, inflammatory stress induced by LPS in transgenic and control mice was used to characterize interleukin 6 (IL-6) and adhesion molecules endothelium permeabil-ity responses. Transgenic mice had significantly higher rates of extracellular adenosine triphosphate and adenosine monophosphate hydrolysis on the aortic surface in comparison to control. Increased levels of blood AMP and adenosine were also noticed in transgenics. Moreover, transgenic ani-mals demonstrated the decrease in serum monomethyl-L-arginine level and a higher L-arginine/ monomethyl-L-arginine ratio. Importantly, significantly decreased serum IL-6, and adhesion mol-ecule levels were observed in transgenic mice in comparison to control after LPS treatment. Fur-thermore, reduced endothelial permeability in the LPS-treated transgenic mice was noted as com-pared to LPS-treated control. The human enzymes (hHO-1, hE5NT, hENTPD1) simultaneously encoded in transgenic mice demonstrated benefits in sev-eral biochemical and functional aspects of endothelium. This is consistent in use of this approach in the context of xenotransplantation.

Soil moisture plays a crucial role in various hydrological processes and energy partitioning of the global surface. The Soil Moisture Active Passive-Sentinel (SMAP-Sentinel) remote sensing technology has demonstrated a great potential in monitoring soil moisture at a scale greater than 1 km. This capability can be applied to improve weather forecast accuracy, enhance water management for agriculture, and climate-related disasters. Despite the techniques increasing used worldwide, its accuracy still requires field validation in specific regions like Thailand. In this paper, we report on extensive in-situ monitoring of soil moisture (from surface up to 1 m depth) at 10 stations across Thailand spanning the years 2021 to 2023. The aim was to validate SMAP surface soil moisture (SSM) Level 2 product over a period of two years. Using one month averaging approach, the study revealed linear relationships between the two measurement types, with the coefficient of determination (R-squared) varying from 0.13 to 0.58. Notably, areas with more uniform land use and topography such as croplands tended to have a better coefficient of determination. We also conducted detailed soil core characterization, including soil-water retention curves, permeability, porosity, and other physics properties. These soil properties were then used for estimating the correlation constants between SMAP and in-situ soil moistures using multiple linear regression. The results demonstrated R-squared values between 0.933 and 0.847. An upscaling approach of SMAP was proposed which showed a promising results when using 3-month average of all measurements in cropland together. The finding also suggest that the SMAP-Sentinel remote sensing technology exhibits significant potential for accurate soil moisture monitoring in diverse applications. Further validation efforts and research, particularly in terms of root zone depths and area-based assessments, especially in the agricultural sector, can greatly improve the technology’s effectiveness and usefulness in the region.

Abstract: The spectral and dynamic properties of 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO)

Biological pretreatment of lignocellulosic residues has the potential to serve as a sustainable, less energy-intensive alternative to harsh chemical treatments for enhancing cellulose accessibility, despite the requirement of a lengthy incubation period. The study characterized the simultaneous delignification of corn stover by the white-rot fungus Pyrenophora phaeocomes S-1, as well as the co-production of a ligno-hemicellulolytic enzyme cocktail consisting of laccase, xylanase, and mannanase. The maximum yields of all three components of the cocktail were achieved after just 4 days of incubation under solid-state conditions. Following a 40-day fermentation period, we achieved a cellulose recovery of 44.25 ± 1.72%, attributed to the activities of 133.88 U/gds of laccase, 14.93 U/gds of xylanase, and 1.34 U/gds of mannanase co-produced by the fungus in the medium. Subsequently, through the extraction of biologically treated biomass with 0.5N NaOH after 40 days, the cellulose recovery increased to 66.4 ± 1.39%. Enzymatic hydrolysis of the same, employing only 5 FPU/gds of in-house produced cellulases, resulted in the liberation of 397.84 mg/gds of total reducing sugars after 144h. The findings of this study encourage further optimization of biological pretreatment of lignocellulosic residues and enzymatic hydrolysis to enhance the yields of total reducing sugars for their valorization.

Personalized recommendation is an important part of ecommerce platform. In the recommendation system, the neural network is used to enhance collaborative filtering to accurately capture user preferences, so as to obtain better recommendation performance. Traditional recommendation methods focused on the results of a single user behavior, ignoring the modeling of multiple interactive behaviors of users, such as click, add to cart and purchase. Although many studies had also focused on Multi-Behavior modeling, two important challenges remained. 1)Since multiple behavioral context information was ignored, it was still a challenge to identify the multimodal relationships of behaviors. 2) Surveillance signals were still sparse. In order to solve this problem, this paper proposes Two-path Multi-behavior Sequence Modeling(TP_MB). First, a two-path learning strategy is introduced to maximize the multiple interaction information of user items learned by the two paths, which effectively enhances the robustness of the model. Second, a multi-behavior dependent encoder is designed. Contextual information is obtained through behavior dependencies in the interaction of different user. In addition, three contrastive learning methods are designed, which not only obtain additional auxiliary supervision signals, but also alleviate the problem of sparse supervision signals. Extensive experiments on two real datasets demonstrate that our method outperforms state-of-the-art multi-behavior recommendation methods.

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

Cancer is a complex disease, considered a major public health problem worldwide. Among the types of cancer, melanoma, and leukemias present high mortality rates in Brazil and worldwide. Currently, conventional cytotoxic treatments cause severe side effects by the non-selectivity between normal cells and cancer cells. Therefore, molecules of natural origin with more efficient anticancer properties and that present fewer adverse effects are of extreme importance for cancer therapy and improvement in patients’ quality of life. This study isolated, identified, and characterized the chemical structure of a new anthraquinone present in the extract of the roots of Senna velutina. In addition, we sought to evaluate the anticancer potential of this molecule against melanoma and leukemic cell lines and identify the pathways of cell death involved. To this end, a novel anthraquinone was isolated from the barks of the roots of S. velutina, analyzed by HPLC-DAD, and its molecular structure was determined by NMR. Subsequently, their cytotoxic activity was evaluated by the MTT method against non-cancerous, melanoma, and leukemic cells. The migration of melanoma cells was evaluated by the scratch assay. By flow cytometry technique, the apoptosis process, caspase-3 activation, analysis of mitochondrial membrane potential, and measurement of ROS were evaluated. In addition, the pharmacological cell death inhibitors NEC-1, RIP-1, BAPTA, Z-VAD, and Z-DEVD were used to confirm the related cell death mechanisms. With the results, it was possible to elucidate the novel compound characterized as 2'-OH-Torosaol I. In normal cells, the compound showed no cytotoxicity in PBMC but reduced the cell viability of all melanoma and leukemic cell lines evaluated. 2'-OH-Torosaol I inhibited chemotaxis of B16F10-Nex2, SK-Mel-19, SK-Mel28 and SK-Mel-103. The cytotoxicity of the compound was induced by apoptosis via the intrinsic pathway with reduced mitochondrial membrane potential, increased levels of reactive oxygen species, and activation of caspase-3. In addition, the inhibitors demonstrated the involvement of necroptosis and CA+ in the death process and confirmed caspase-dependent apoptosis death as one of the main programmed-cell death pathways induced by 2'-OH-Torosaol I. Taken together, the data characterize the novel anthraquinone 2'-OH-Torosaol I, demonstrating its anticancer activity and potential application in cancer therapy.

Inflammation is the response of the innate immune system to any type of injury. Although acute inflammation is critical for survival, dysregulation of innate immune response leads to chronic in-flammation. Many synthetic anti-inflammatory drugs have side effects, and thus, natural an-ti-inflammatory compounds are still needed. Cannabis sativa L. may provide a good source of in-flammation-reducing molecules. Here, we tested the anti-inflammatory properties of cannabis ex-tracts and pure cannabinoids in lipopolysaccharide (LPS)-induced inflammation in human THP-1 macrophages. We found that pre-treatment with cannabidiol (CBD), delta-9-tetrahydrocannabinol (THC), or extracts containing high levels of CBD or THC reduce the level of induction of various cytokines. The CBD was more efficient than THC, and the extracts were more efficient than pure cannabinoids. Finally, IL-6, IL-10 and monocyte chemoattractant protein-1 (MCP-1) were most sensitive to pre-treatments with CBD and THC, while IL-1β, IL-8 and TNF-α were less responsive. Thus, our work demonstrates the potential of use of cannabinoids or/and cannabis extracts for the reduction of inflammation and establishes IL-6 and MCP-1 as the sensitive markers for the analysis of the effect of cannabinoids on inflammation in macrophages.

Foxtail millet (Setaria italica (L.) P. Beauv) is an important food and forage crop that is well adapted to nutrient-poor soils. However, little is known about how foxtail millet adapts to low nitrogen (LN) at the physiological and molecular levels. In the present study, two foxtail millet varieties with contrasting low nitrogen (LN) tolerance properties were investigated through integrative analyses of physiological featureparameters and transcriptomics. The physiological results showed that JG20 (high tolerance to LN) had higher biomass accumulation, nitrogen content and nitrogen use efficiency compared with JG22 (low tolerancesensitive to LN) under LN. JG20 had higher soluble sugar and soluble protein concentration in shoots compared with JG22 under LN, while contcentrations of soluble sugar and soluble protein contents were higher in the roots of JG22. Higher levels of CTK contentzeatin concentration were found in the shoots of JG20 com-pared with JG22, and a higher ABA contcentration was found in both the shoots and roots of JG22 compared with JG20 under LN. In the transcriptomics results, JG20 had more differentially ex-pressed genes (DEGs) than JG22 both in shoots and roots in response to LN. These LN-responsive genes were enriched in glycolysis, starch and sucrose metabolism, photosynthesis, biosynthesis of amino acids, hormone metabolism and nitrogen metabolism. Furthermore, the high-affinity nitrate transporter gene, SiNRT2.1, and glutamine synthetase gene, SiGS5, chlorophyll apoprotein of photosystem II gene, SiPsbQ, ATP synthase subunit gene, b, auxin-responsive protein gene, SiIAA25, and aldose 1-epimerase gene, SiAEP, in shoots, and high-affinity nitrate transporter gene, SiNRT2.3, SiNRT2.4, and glutamate synthase gene, SiGOGAT2, auxin-responsive protein gene, SiIAA4, fructose-bisphosphate aldolase gene, SiAEP5, in root, were important genes in-volved in the LN tolerance of foxtail millet. These results provide a detailed description of the physiological and transcriptome response of foxtail millet under LN condition.

Diabetes is a group of diseases characterized by loss of β cell mass and/or -function, resulting in hyperglycemia. Approx. 537 million people worldwide suffer from diabetes – a number which is expected to increase. Diabetes is primarily treated by exogenous insulin, which comes with the challenges of maintaining glycemic control to prevent ketoacidosis and severe complications. The need for a curative treatment has initiated the research in β cell regeneration. Several studies in mice have identified essential genes for β cell fate, which can be manipulated in other cells to induce generation of new β cells. Zebrafish, a regeneration-positive animal model, has shown several different sources of new β cells, including regeneration by self-replication, neogenesis by duct-associated progenitor cells, and transdifferentiation of other endocrine islet cells. The animal models used in this research area are either limited by their low regenerative ability (mice), or their small size and remoteness from humans (zebrafish). There is a need for new animal models of diabetes, in which the molecular pathways of endogenous regeneration can be studied. This study proposes the axolotl salamander (Ambystoma mexicanum) as a model for studying the regeneration of β cells. The axolotl has shown great regenerative capability, as they have proven capable of regenerating amputated limbs, and hearts with myocardial infarction, among other organs. This study aims to establish a diabetic axolotl model, investigate their regenerative ability in the pancreas, and examine the potential systemic effects of the induced disease. In a pilot study, five different protocols using STZ (streptozotocin) were tested, and the most optimal protocol was found. Furthermore, the glucose tolerance test was optimized to characterize the glycemic state of the animals. The effect of the treatment on blood glucose levels was measured to characterize the development and decline of the disease. The histological changes in the pancreas were examined. Moreover, the systemic effects of the STZ treatment were investigated in blood and urine. The study indicated that it is possible to induce diabetes in the axolotl, but variations between the animals should be minimized, or the sample size should be increased to conduct a satisfying experiment, as it was not possible to induce diabetes in all animals. Regeneration was not observed histologically, but a restoration of blood glucose levels was seen over the span of the experiment. Lastly, edema formation was observed in some of the STZ-treated animals, but the cause of edema remains undetermined.

Cerebrospinal fluid (CSF) viral escape has been poorly described among people with HIV-associated cryptococcal meningitis. We determined the prevalence of CSF viral escape and HIV-1 viral load (VL) trajectories in individuals treated for HIV-associated cryptococcal meningitis. A retrospective longitudinal study was performed using paired CSF and plasma collected prior to and during the antifungal treatment of 83 participants recruited at the Botswana site of the phase-3 AMBITION-cm trial (2018-2021). HIV-1 RNA levels were quantified then CSF viral escape (CSF HIV-1 RNA ≥ 0.5 log10 higher than plasma) and HIV-1 VL trajectories were assessed. CSF viral escape occurred in 20/62 (32.3%; 95% confidence interval [CI]: 21.9%-44.6%), 13/52 (25.0%; 95% CI: 15.2%-38.2%) and 1/33 (3.0%; 95% CI: 0.16%-15.3%) participants at days 1, 7 and 14 respectively. CSF viral escape was significantly lower on day 14 compared to days 1 and 7, p=0.003 and p=0.02, respectively. HIV-1 VL de-creased significantly from day 1 to day 14 post antifungal therapy in the CSF but not in the plasma (OR, 0.56; 95% CI: 0.41-0.77; p<0.001). CSF viral escape is high among individuals presenting with HIV-associated cryptococcal meningitis; however, antifungal therapy may reverse this, highlighting the importance of rapid initiation of antifungal therapy in these patients.

In Korea, rice is a major staple grain and is mainly cultivated using various agricultural machinery. Air pollutants emitted from agricultural machinery have their origins mainly from the exhaustion of internal combustion engines. In this study, emission characteristics of five main air pollutants by European Environment Agency's Tier 1 method for rice cultivation was analyzed. Diesel is a main fuel for agricultural machinery and gasoline is generally used only for rice transplanters as a fuel in Korea. Tractors consume 46% of total fuel consumption and 56% of diesel fuel consumption. Gasoline used for rice transplanters accounts for 17% of total fuel consumption each year. Tractors and rice transplanters are emitting 82% of all total pollutants. From 2011 to 2019, the total amount of air pollutant emissions was decrease by 15%. That accounted for the reduction of rice cultivation fields in those periods. Rice transplanting operation was in charge of 42% of total emissions. Then, harrowing, harvesting, tilling, leveling, and pest control operations generated 10%, 10%, 8%, 8% and 7% of total emissions, respectively. The contribution of each air pollutant held 54% of CO, 39% of NOx, 5% of NMVOC, and 2% of TSP from the total emission inventory. The three major regions emitting air pollutants from mechanized agricultural practices were Jeollanam-do, Chungcheongnam-do, and Jeollabuk-do, which consume 55% of total fuel usage in rice farming. The total amount of air pollutant emissions from rice cultivation practices in 2019 was calculated as 8,448 Mg in Korea.

Dominance hierarchies are ubiquitous in invertebrates and vertebrates, but little is known on how genes influence dominance rank. Our gaps in knowledge are specifically significant concerning female hierarchies and in insects. To start filling these gaps we studied the social bumble bee Bombus terrestris, in which social hierarchies among females are common and functionally significant. Dominance rank in this bee is influenced by multiple factors, including juvenile hormone (JH) that is a major gonadotropin in this species. We tested the hypothesis that the JH responsive transcription factor Krüppel homologue 1 (Kr-h1) mediates hormonal influence on dominance behavior in the bumble bee. We first developed and validated a perfluorocarbon nanoparticles-based RNA interference protocol for knocking down Kr-h1 expression. We then used this procedure to show that Kr-h1 mediates the influence of JH not only on oogenesis and wax production, but also on aggression and dominance rank. To the best of our knowledge, this is the first study causally linking a gene to dominance rank in social insects, and one of only a few such studies in insects or in female hierarchies. These findings are important for determining whether there are general molecular principles governing dominance rank across gender and taxa.

SARS-CoV-2 infection produces a response of the innate immune system causing oxidative stress and a strong inflammatory reaction termed ‘cytokine storm’ that is one of the leading causes of death. Paraoxonase-1 (PON1) protects against oxidative stress by hydrolyzing lipoperoxides. Alterations in PON1 activity have been associated with pro-inflammatory mediators such as the chemokine (C-C motif) ligand 2 (CCL2) and the glycoprotein galectin-3. We aimed to investigate the alterations in the circulating levels of PON1, CCL2 and galectin-3 in 126 patients with COVID-19 and their interactions with clinical variables and analytical parameters. A machine learning approach was used to identify predictive markers of the disease. For comparisons, we recruited 45 COVID-19 negative patients and 50 healthy individuals. Our approach identified a synergy between oxidative stress, inflammation and fibrogenesis in positive patients that is not observed in negative patients. PON1 activity was the parameter with the greatest power to discriminate between patients who were either positive or negative for COVID-19, while their levels of CCL2 and galectin-3 were similar. We suggest that the measurement of serum PON1 activity may be a useful marker for the diagnosis of COVID-19.

At present, the world is at the peak of production of traditional fossil fuels. Much of the resources that humanity has been consuming (oil, coal and natural gas) are coming to an end. The human being faces a future that must necessarily go through a paradigm shift, which includes a progressive movement towards increasingly less polluting and energetically viable resources. In this sense, nanotechnology has a transcendental role in this change. For decades, new materials capable of being used in energy processes have been synthesized that undoubtedly will be the cornerstone of the future development of the planet. In this review, we report on the current progress in the synthesis and use of one-dimensional (1D) nanostructured materials (specifically nanowires, nanofibers, nanotubes and nanorods), with compositions based on oxides, nitrides, or metals, for applications related to energy. Due to its extraordinary surface-volume relationship, tunable thermal and transport properties, and its high surface area, these 1D nanostructures have become fundamental elements for the development of energy processes. The most relevant 1D nanomaterials, their different synthesis procedures, and useful methods for assembling 1D nanostructures in functional devices will be presented. Applications in relevant topics such as optoelectronic and photochemical devices, hydrogen production or energy storage, among others, will be discussed. The present review concludes with a forecast on the directions towards which future research could be directed on this class of nanostructured materials.

Sentinel-1A/B radar remote sensing data were applied for the first time to determine the sixth nuclear test, its underground explosion h-bomb location and affected zone in North Korea, on September 3, 2017. Location of epicenters nuclear test were found according to line-of-sight displacement images via its maximum value. Line-of-sight displacement images were obtained by processing in the GMTSAR package in the VirtualBox virtual machine of the Linux Ubuntu 16.04 operation system. In this research, three scenes Sentinel-B data with descending orbits were considered, one after and two before the event (the nuclear test date) scene were used.

Systemic lupus erythematosus (SLE) is a heterogenous autoimmune disease. While its etiology remains elusive, current understanding suggests a multifactorial process with contributions by genetic, immunologic, hormonal, and environmental factors. A hypothesis that combines several of these factors proposes that genomic elements, the L1 retrotransposons, are instrumental in SLE pathogenesis. L1 retroelements are transcriptionally activated in SLE and produce two proteins, ORF1p and ORF2p, which are immunogenic and can drive type I interferon (IFN) production by producing DNA species that activate cytosolic DNA sensors. In addition, these two proteins reside in RNA-rich macromolecular assemblies that also contain well-known SLE autoantigens like Ro60. We surmise that cells expressing L1 will exhibit all the hallmarks of cells infected by a virus, resulting in a cellular and humoral immune response similar to those in chronic viral infections. However, unlike exogenous viruses, L1 retroelements cannot be eliminated from the host genome. Hence, dysregulated L1 will cause a chronic, but perhaps episodic, challenge for the immune system. The clinical and immunological features of SLE can be largely explained by this model. Here we review the support for, and the gaps in, this hypothesis of SLE and its potential for new diagnostic, prognostic, and therapeutic options in SLE.

Only two percent of Glioblastoma multiforme (GBM) patients respond to standard care and survive beyond 36 months (long-term survivors, LTS) while the majority survive less than 12 months (short-term survivors, STS). To understand the mechanism leading to poor survival, we analyzed publicly available datasets of 113 STS and 58 LTS. This analysis revealed 198 differentially expressed genes (DEGs) that characterize aggressive tumor growth and may be responsible for the poor prognosis. These genes belong largely to the GO-categories “epithelial to mesenchymal transition” and “response to hypoxia”. In this paper we applied upstream analysis approach which involves state-of-art promoter analysis and network analysis of the dysregulated genes potentially responsible for short survival in GBM. Binding sites for transcription factors associated with GBM pathology like NANOG, NF-κB, REST, FRA-1, PPARG and seven others were found enriched in the promoters of the dysregulated genes. We reconstructed the gene regulatory network with several positive feedback loops controlled by five master regulators – IGFBP2, VEGFA, VEGF165, PDGFA, AEBP1 and OSMR which can be proposed as biomarkers and as therapeutic targets for enhancing GBM prognosis. Critical analysis of this gene regulatory network gives insights on mechanism of gene regulation by IGFBP2 via several transcription factors including the key molecule of GBM tumor invasiveness and progression, FRA-1. All the observations are validated in independent cohorts and their impact on overall survival is studied.

We scrutinize the reliability of multilooked interferograms for deformation analysis. Designing a simple approach in the evaluation of the accuracy of the estimated deformation signals, we reveal a prominent bias in the deformation velocity maps. The bias is the result of propagation of small phase error of multilooked interferograms through the time series and can sum up to 6.5 mm/yr in case of using the error prone short temporal baseline interferograms. We further discuss the role of the phase estimation algorithms in reduction of the bias and put recommend a unified intermediate InSAR product for achieving high-precision deformation monitoring.

T cells follow a triphasic distinct pathway of activation, proliferation and differentiation before becoming functionally and phenotypically ‘exhausted’ in settings of chronic infection, autoimmunity and in cancer. Exhausted T cells progressively lose canonical effector functions, exhibit altered transcriptional networks and epigenetic signatures and gain constitutive expression of a broad coinhibitory receptor suite. This review outlines recent advances in our understanding of exhausted T cell biology and examines cellular and molecular mechanisms by which a state of dysfunction or exhaustion is established, and mechanisms by which exhausted T cells may still contribute to pathogen or tumour control. Further, this review describes our understanding of exhausted T cell heterogeneity and outlines the mechanisms by which checkpoint blockade differentially engages exhausted T cell subsets to overcome exhaustion and recover T cell function.

Neurokinin-1 receptor (NK-1R) antagonists exert an antitumor action, are safe and do not cause serious side-effects. These antagonists (via the NK-1R) exerted multiple actions against cancer: antiproliferative and anti-Warburg effects, apoptosis, anti-angiogenic and antimetastatic. These multiple effects have been shown in a broad-spectrum of cancers. The drug aprepitant (an NK-1R antagonist) is currently used in clinical practice as antiemetic. In in vivo and in vitro studies, aprepitant also showed the aforementioned multiple antitumor actions against many types of cancer. A successful combination therapy (aprepitant and radiotherapy) has recently been reported in a patient suffering from lung carcinoma: the tumor mass disappeared and side-effects were not observed. Aprepitant could be considered as an intelligent bullet against cancer. The administration of aprepitant in cancer patients to prevent recurrence and metastasis after surgical procedures, thrombosis and thromboembolism is discussed as well as the possible link, through the SP/NK-1R system, between cancer and depression. Our main aim is to review the multiple antitumor actions exerted by aprepitant and the use of this drug is suggested in cancer patients. Altogether, the data support the reprofiling of aprepitant for a new therapeutic use as an antitumor agent.

In this research work, we present a mathematical model for novel coronavirus -19 (NCOVID-19) which is consisted on three different compartments susceptible, infected and recovered classes abbreviated as under convex incident rate involving and emigration rate. We first derive the formulation of the model. Also, we give some qualitative aspects for the model including existence of equilibriums and its stability results by using various tools of nonlinear analysis. Then by mean of nonstandard finite difference scheme (NSFD), we simulate the results against the data of Wuhan city for the sixty days. By means of simulation, we show how protection, exposure, emigration, death and cure rates affect the susceptible, infected and recovered population with the passage of time involving emigration. On the basis of simulation, we observe the dynamical behavior due to emigration of susceptible and infected classes or one of these two.

This study investigates the spatial signatures of seasonal snow in Synthetic Aperture Radar (SAR) observations at different spatial scales and for different physiographic regions. Sentinel-1 C-band (SAR) backscattering coefficients (BSC) were analyzed in the Swiss Alps (SA), in high elevation forest and grasslands in Grand Mesa (GM), Colorado, and in North Dakota (ND) croplands. GM BSC exhibit 10dB sensitivity to wetness at small scales (~100 m) over homogeneous grassland. Sensitivity decreases to 5 dB in the presence of trees, and it is demonstrated that VH BSC sensitivity enables wet snow mapping below the tree-line. Area-variance scaling relationships show minima at ~100 m and 150-250 m respectively in barren and grasslands in SA and GM, increasing up to 1 km and longer in GM forests and ND agricultural fields. The spatial organization of BSC (as described by 1D-directional BSC wavelength spectra) exhibits multi-scaling behavior in the 100 -1,000 m range with a break at (180-360 m) that is also present in UAVSAR L-band measurements in GM. Spectral slopes in GM forested areas steepen during accumulation and flatten in the melting season with mirror behavior for grasslands reflecting changes in scattering mechanisms with snow depth and wetness, and vegetation mass and structure. Overall, this study reveals persistent patterns of SAR scattering variability spatially organized by land-cover, topography and regional winds with large inter-annual variability tied to precipitation. This dynamic scaling behavior emerges as an integral physical expression of snowpack variability that can be used to model sub-km scales and for downscaling applications.

HIV treatment strategies against viral enzymes are continuously hampered by viral drug resistance. Recent findings show that viral substrate Gag contributes to HIV-1 Protease Inhibitor (PI) resistance, leading to demands for new strategies in HIV treatment where Gag is recognized as a drug target. To successfully target Gag, there is a need of in-depth understanding of the Gag polyprotein and the effects of Gag mutations. Here, we propose new strategies in designing novel Gag inhibitors against existing and novel emerging Gag mutations via a structural understanding of the Gag-Protease relationship in PI resistance. In this review, we discuss the role of both novel and previously reported mutations, revealing insights to how they aid in PI resistance, and how new Gag inhibitors can be designed.

A double-stranded RNA (dsRNA) virus was isolated and characterized from a strain EW220 of the phytopathogenic fungus Botryosphaeria dothidea. The full-length cDNAs of dsRNAs were 6,434 bp and 5,986 bp in size, respectively. The largest dsRNA of BdBRV1 encodes a cap-pol fusion protein that contains part coat protein gene and a RNA-dependent RNA polymerase (RdRp) domain, and the second dsRNA encodes a hypothetical protein. The dsRNA virus was named Botryosphaeria dothidea botybirnavirus 1 (BdBRV1). BdBRV1 contains spherical virions that are 37 nm in diameter consisting of two segments. The structural proteins of BdBRV1 virus particles were 110 kDa, 90 kDa, and 80 kDa, which encoded by dsRNA1 and 2-ORFs. The analysis of genome sequences revealed that the sequences of BdBRV1 shared 99% identity with Bipolaris maydis botybirnavirus 1(BmBRV1). Phylogenetic reconstruction indicated that BdBRV1 and BmBRV1 are phylogenetically related to the genus Botybirnavirus. Importantly, BdBRV1 influences the growth of B. dothidea and confers hypovirulence to the fungal host. BdBRV1 and BmBRV1 were two strains of the same virus. To our knowledge, this is the first report of a botybirnavirus in B. dothidea and our result might be the first funding in the different fungi infected by the same virus.

The present study is the second step (concerning the normal-diet restoration) of the our previous one (concerning the calcium-free diet) to determine whether the normal-diet restoration, with/without concomitant PTH(1-34) administration, can influence amounts and deposition sites of the total bone mass. Histomorphometric evaluations and immunohistochemical analysis for Sclerostin expression were conducted on the vertebral bodies and femurs in rat model. The final goals are: i) to define timing and manners of bone mass changes when calcium is restored in the diet; ii) to analyze the different involvement of the two bony architectures having different metabolism (i.e. trabecular versus cortical bone); iii) to verify the eventual role of PTH(1-34) administration. Results evidenced the greater involvement of the trabecular bone with respect to the cortical one, in answering to different calcium diet content, and the effect of PTH mostly in the recovery of trabecular bony architecture. The main findings emerged from the present study are: i) the importance of the interplay between mineral homeostasis and skeletal homeostasis in modulating and guiding bone answers to dietary/metabolic alterations and ii) the evidence that the more involved bony architecture is the trabecular one, the most susceptible to the dynamical balance of the two homeostases.

Two X chromosomes of female mammals randomly inactivate one of paternal or maternal X chromosome in early embryonic development and all the daughter cells produced from these cells retain the same feature of X chromosome inactivation, which is called X chromosome inactivation (XCI). Studying the mechanisms of XCI is important for understanding epigenetic that plays an important role in age-associated diseases. The previous studies have demonstrated that binding of RNAs and DNAs may play a role in activating gene expression. In this paper, our study aims to explore whether the mechanisms of XCI involve the RNA binding strength to X chromosome DNAs. The bioinformatics analyses based on big data were used to analyze the simulated binding strength of RNAs (RNA binding strength) to 23 chromosomes (including X chromosome and 22 human autosomes) and the characteristics of repetitive sequences in the X-inactivation centre. The results revealed that RNA binding strength of the long arm of the X chromosome that is almost entirely inactivated in XCI was significantly lower than that of all autosomes and the short arm of X chromosome, meanwhile the RNA binding strengths of inactivation regions in X chromosome were significantly lower than that of regions escaping from XCI. Different repetitive sequence clusters within the center of XCI presented a cross distribution characteristic. To further prove whether the repetitive sequences in human X chromosome involve in XCI, we cloned long interspersed element (LINE-1, L1) and short interspersed element (Alu) from human Xq13, the center of XCI, and constructed expression vectors carrying sense-antisense combination repetitive sequences (L1s or Alus). Effects of combined L1 or combined Alu sequences on expression of EGFP reporter gene were examined in stably transfected HeLa cells, which simulates the effects of repetitive sequences located on chromosomes. The results of experiments revealed transcribed L1 repetitive sequences activated EGFP reporter gene expression, so did the Alus. The experiment results suggested repetitive sequences activated genes by interaction of transcribed RNAs and DNAs. Since the binding of RNAs and DNAs can activate gene, so the low RNA binding strength of human X chromosome may be one of reasons of XCI. The cross distribution characteristics of different repetitive sequence clusters leading to a cascade of gene activation or gene inactivation may be the reason of transcriptional silencing one of the X chromosomes in female mammals.

The rapid urbanization that takes place in developing regions such as Sub-Saharan Africa is associated with a large range of environmental and social issues. In this context, remote sensing is essential to provide accurate and up-to-date spatial information to support risk assessment and decision making. However, mapping urban areas remains a challenge because of their heterogeneity, especially in developing regions where the highest rates of misclassification are observed. Nevertheless, urban areas located in arid climates --- which are among the most vulnerables to anthropogenic impacts, suffer from the spectral confusion occurring between built-up and bare soil areas when using optical imagery. Today, the increasing availability of satellite imagery from multiple sensors allow to tackle the aforementioned issues by combining optical data with Synthetic Aperture Radar (SAR). In this paper, we assess the complementarity of the Landsat 8 and Sentinel-1 sensors to map built-up areas in twelve Sub-Saharan African urban areas, using a pixel-level supervised classification based on the Random Forest classifier. We make use of textural information extracted from SAR backscattering data in order to reduce the speckle noise and to introduce contextual information at the pixel level. Results suggest that combining both optical and SAR features consistently improves classification performances, mainly by enhancing the differentiation between built-up and bare lands. However, the fusion was less beneficial in mountainous case studies, suggesting that including features derived from a Digital Elevation Model (DEM) could improve the reliability of the proposed approach. As suggested by previous studies, combining features computed from both VV and VH polarizations consistently led to better classification performances. On the contrary, introducing textures computed from different spatial scales did not improve the classification performances.

Here we present an overview of speleothem δ18O records from South America, which mostly are available in the Speleothem Isotopes Synthesis and Analysis (SISAL_v1) database. South American tropical and subtropical δ18O time series are primarily interpreted as being driven by the amount effect and, consequently show the past history of the convection intensity of convergence zones such as the Intertropical Convergence Zone and the South America Monsoon System. We investigate past hydroclimate scenarios in South America related to the South American Monsoon System in three different time scales: Late Pleistocene, Holocene and the last two millennia. The precession driven insolation is the main driver of convective variability over the continent during the last 250 kyrs, including the Holocene period. However a dipole is observed between the west and east portions of the continent. Records located in the central region of Brazil appear to be weakly affected by insolation driven variability and more susceptible to the South Atlantic Convergence Zone. Cold episodic events in Northern Hemisphere increase the activity of the South American Monsoon System on all time scales, in turn increasing rainfall amounts in South America, as was documented during Heinrich events in the late Pleistocene and Bond events in the Holocene, as well as during the Little Ice Age.

DR2B and DR2C extracts, from peel of commercially and physiologically ripe eggplants, were studied for the antioxidative cytoprotective properties and anti-HSV-1 activity, in line with the evidence that several antioxidants can impair viral replication by maintaining reducing conditions into the host cells. The antioxidative cytoprotective effects against tBOOH-induced damage was assessed in Caco2 cells, while the antiviral activity was studied in Vero cells; phenolic and anthocyanin fingerprint was characterized by integrated phytochemical methods. Results highlighted different compositions of the extracts, with chlorogenic acid and delphinidin-3-rutinoside as the major constituents; other peculiar phytochemicals were also identified. DR2C resulted able to partly counteract the tBOOH-induced cytotoxicity, with a remarkable lowering of lactate metabolism under both normoxia and hypoxia. DR2B and DR2C reduced ROS production, possessed scavenging and chelating properties. Interestingly, DR2C increased intracellular GSH levels. Furthermore, DR2C inhibited the HSV-1 replication when added for 24 h after viral adsorption, as also confirmed by the reduction of many viral proteins expression. Since DR2C was able to reduce NOX4 expression during HSV-1 infection, its antiviral activity may be correlated to its antioxidant properties. Although further studies are needed to better characterize DR2C activity, the results suggest this extract as a promising new anti-HSV-1 agent.

We construct families of ground state representations of the U(1)-current net and of the Virasoro nets Vir_c with central charge c ≥ 1. We show that these representations are not covariant with respect to the original dilations, and those on the U(1)-current net are not solitonic. Furthermore, by going to the dual net of with respect to the ground state representations of Vir_c, one obtains possibly new family of Möbius covariant nets on S¹.

Wetlands benefits can be summarized but are not limited to their ability to store floodwaters and improve water quality, providing habitats for wildlife and supporting biodiversity, as well as aesthetic values. Over the past few decades, remote sensing and geographical information technologies has proven to be a useful and frequent applications in monitoring and mapping wetlands. Combining both optical and microwave satellite data can give significant information about the biophysical characteristics of wetlands and wetlands` vegetation. Also, fusing data from different sensors, such as radar and optical remote sensing data, can increase the wetland classification accuracy. In this paper we investigate the ability of fusion two fine spatial resolution satellite data, Sentinel-2 and the Synthetic Aperture Radar Satellite, Sentinel-1, for mapping wetlands. As a study area in this paper, Balikdami wetland located in the Anatolian part of Turkey has been selected. Both Sentinel-1 and Sentinel-2 images require pre-processing before their use. After the pre-processing, several vegetation indices calculated from the Sentinel-2 bands were included in the data set. Furthermore, an object-based classification was performed. For the accuracy assessment of the obtained results, number of random points were added over the study area. In addition, the results were compared with data from Unmanned Aerial Vehicle collected on the same data of the overpass of the Sentinel-2, and three days before the overpass of Sentinel-1 satellite. The accuracy assessment showed that the results significant and satisfying in the wetland classification using both multispectral and microwave data. The statistical results of the fusion of the optical and radar data showed high wetland mapping accuracy, with an overall classification accuracy of approximately 90% in the object-based classification. Compared with the high resolution UAV data, the classification results give promising results for mapping and monitoring not just wetlands, but also the sub-classes of the study area. For future research, multi-temporal image use and terrain data collection are recommended.

Several studies suggests that ghrelin (GHRL) has neurobiological effects that extend beyond control of food intake. Our previous results confirmed that GHRL modulates the secretory activity of the pineal gland (PG) through nocturnal melatonin (MEL) secretion in sheep, the seasonally reproductive animals. Here we investigated the effects of GHRL (10 ng/ml) on the expression of enzymes limiting synthesis of MEL, including tryptophan 5-hydroxylase 1 (TPH1), serotonin N-acetyltransferase (AA-NAT) and its phosphorylated form p31T-AA-NAT in sheep PG explants (n = 72) during the 4-hour incubation in a gas-liquid interface, at a short (SD) and long (LD) photoperiods. After each hour of incubation selected explants were frozen in liquid nitrogen and stored at -80°C for subsequent analysis (real-time PCR, western-blotting, ELISA). Results show that GHRL regulates nightly MEL secretion in a TPH1-independent manner. The factor modulating GHRL activity was photoperiod. During SD photoperiod GHRL significantly reduced the expression of p31T-AA-NAT, AA-NAT and inhibited MEL secretion from PG explants. Whereas, during LD photoperiod no effect of GHRL on MEL secretion and expression of examined enzymes was noted. Studies indicate that GHRL directly affects PG under in vitro conditions and causes MEL secretion in animals which exhibit seasonality in reproductive and metabolic processes.

Neural membranes are composed of phospholipids, sphingolipids, cholesterol and proteins. In re-sponse to cell stimulation or injury, metabolism of lipids generates various lipid mediators, which perform many cellular functions. Thus, phospholipids release arachidonic acid or docosahex-aenoic acid from the sn-2 position of glycerol moiety by the action of phospholipases A2. Ara-chidonic acid is a precursor for prostaglandins, leukotrienes, thromboxane, and lipoxins. Among these mediators, prostaglandins, leukotrienes, and thromboxane produce neuroinflammation. In contrast, lipoxins produce anti-inflammatory and pro-resolving effects. Prostaglandins, leukotri-enes, and thromboxane are also involved in cell proliferation, differentiation, and blood clotting, and blood vessel permeability. In contrast, DHA-derived lipid mediators are called as specialized pro-resolving lipid metabolites (SPMs). They include resolvins, protectins, and maresins. These mediators regulate immune function by producing anti-inflammatory, pro-resolving, and cell pro-tective effects. Sphingolipid derived-metabolites are ceramide, ceramide1-phosphate, sphingosine, and sphingosine 1 phosphate. They regulate many cellular processes including enzyme activities, cell migration and adhesion, inflammation, and immunity. Cholesterol is metabolized into hy-droxycholesterols and 7-ketocholesterol, which not only disrupts membrane fluidity, but also promotes inflammation, oxidative stress, and apoptosis. These processes lead to cellular damage.

The distribution of tiny sensors over a specific area was first proposed in the late 1990s as a concept known as Smart Dust. Several efforts focused primarily on computing and networking capabilities but quickly ran into problems related to power supply, cost, data transmission, and environmental pollution. To overcome these limitations, we propose using paper-based (confetti-like) chemosensors that exploit the inherent selectivity of chemical reagents, such as colorimetric indicators. In this work, cheap and biodegradable passive sensors made from cellulose could successfully indicate the presence of hazardous chemicals, e.g., strong acids, by a significant color change. A conventional color digital camera attached to a drone could easily detect this from a safe distance. The collected data was processed to define the hazardous area. Our work presents a combination of the smart dust concept, chemosensing, paper-based sensor technology, and low-cost drones for flexible, sensitive, economical, and rapid detection of hazardous chemicals in high-risk scenarios.

Rasagiline (Azilect®) is a selective monoamine oxidase B (MAO-B) inhibitor that provides symp-tomatic benefit in Parkinson’s disease (PD) treatment and found to exert preclinical neuroprotec-tive effects. Here, we investigated the neuroprotective signaling pathways of rasagiline in the PC12 neuronal cultures exposed to an ischemic-like insult. Exposure of neurons to oxy-gen-glucose deprivation for 4 h followed by 18 h of reoxygenation caused 40% aponecrotic cell death. Rasagiline induced dose-dependent neuroprotection by decreasing cell death and produc-tion of the neurotoxic reactive oxygen species, and reducing the nuclear translocation of glycer-aldehyde-3-phosphate dehydrogenase (GAPDH). Rasagiline increased protein kinase B (Akt) phosphorylation and decreased protein expression of the ischemia-induced α-synuclein protein, in correlation to the neuroprotective effect. Treatment with rasagiline induced nuclear shuttling of transcription factor Nrf2 and increased the mRNA levels of the antioxidant enzymes heme oxy-genase-1, (NAD (P) H- quinone dehydrogenase, and catalase. These results indicate that rasagiline provides neuroprotection in the ischemic neuronal cultures with inhibition of α-synuclein and GAPDH-mediated aponecrotic cell death, and via mitochondrial protection, as by increasing mi-tochondria-specific antioxidant enzymes by a mechanism involving the Akt/Nrf2 redox-signaling pathway. These findings may be exploited for neuroprotective drug development in PD and stroke therapy.

We introduce a new generalized inverse which is a natural generalization of (pseudo) right core inverse in a Banach *-algebra. We characterize this generalized inverse by using right core and quasi-nilpotent decomposition. We then present its polar-like characterization and investigate related algebraic properties. Finally, the right core-EP inverse is characterized by certain new ways.

Diamond-like carbon (DLC) layers are known for their high corrosion and wear resistance, low friction, and high biocompatibility. However, it is often necessary to dope DLC layers with additional chemical elements to strengthen their adhesion to the substrate. Ti-DLC layers (doped with 0.4, 2.1, 3.7, 6.6, 12.8 at.% of Ti) were prepared by dual pulsed laser deposition, and pure DLC, glass, and polystyrene (PS) were used as controls. In vitro cell-material interactions were investigated with an emphasis on cell adhesion, proliferation, and osteogenic differentiation. We observed slightly increasing roughness and contact angle and decreasing surface free energy on Ti-DLC layers with increasing Ti content. Three-week biological experiments were performed using adipose tissue-derived stem cells (ADSCs) and bone marrow mesenchymal stem cells (bmM-SCs) in vitro. The cell proliferation activity was similar or slightly higher on the Ti-doped materials than on glass and PS. Osteogenic cell differentiation on all materials was proved by collagen and osteocalcin production, ALP activity, and Ca deposition. The bmMSCs exhibited greater initial proliferation potential and an earlier onset of osteogenic differentiation than the ADSCs. The ADSCs showed a slightly higher formation of focal adhesions, higher metabolic activity, and Ca deposition with increasing Ti content.

The classification of tumors in subtypes, characterized by phenotypes determined by specific differentiation pathways, aids diagnosis and directs therapy towards targeted approaches. However, with the advent and explosion of next-generation sequencing, cancer phenotypes are turning out to be far more heterogenous than initially thought, and the classification is continually being updated to include more subtypes. Tumors are indeed highly dynamic and they can evolve and undergo various changes in their characteristics during disease progression. The picture becomes even more complex when tumor responds to a therapy. In all these cases, cancer cells acquire the ability to trans-differentiate, changing subtype, and adapt to changing microenvironments. These modifications affect the tumor's growth rate, invasiveness, response to treatment, and overall clinical behavior. Studying tumor subtype transitions is crucial for understanding tumor evolution, predicting disease outcomes, and developing personalized treatment strategies. We discuss this emerging hallmark of cancer and the molecular mechanisms involved at the crossroads between tumor cells and their microenvironment, focusing on four different human cancers in which tissue plasticity causes a subtype switch: breast cancer, prostate cancer, glioblastoma and pancreatic adenocarcinoma.

Shiga toxins (Stxs), and more specifically the Stx2a subtype, are the major virulence factors involved in enterohemorrhagic Escherichia coli (EHEC)-associated hemolytic uremic syndrome (eHUS); a life-threatening disease causing acute kidney injury, especially in children. Cleavage of Stxs A subunit, when followed by reduction, boosts the enzymatic activity causing damage to targeted cells. This cleavage was assumed to be mostly mediated by furin during Stx intracellular trafficking. Cleavage of A subunit, without reduction, changes the binding properties of Stxs for blood components during HUS pathogenesis. To investigate whether the cleavage could occur in the intestine, even prior entering target cells, Stx2a structure was characterized after its exposure to specific host factors present in human stool. The structure of Stx2a A subunit was determined by immunoblotting after electrophoretic separation under reducing conditions. Trypsin and chymotrypsin-like elastase 3B (CELA3B), two serine proteases, were identified as potential candidates that may trigger the extracellular cleavage of Stx2a A subunit directly after its secretion by EHEC in the gut. Whether this observation indeed translates to natural infections and plays a role in eHUS pathogenesis has yet to be determined as well as whether host's protease profile could affect disease development by changing the toxin’s biological features.

RNA interference (RNAi) is one of the main mechanisms for disease resistance and small RNA production in plants. The main proteins involved in RNAi include Dicer-like (DCL), RNA-dependent RNA polymerase (RDR), double-stranded RNA-binding (DRB), and Argonaute (AGO). Juglandaceae contains a variety of important woody plants, and walnuts are one of the four major woody plant groups and one of the four major dried fruits in the world. To clarify the evolution and functional differentiation of RNAi-related proteins in the walnut (Juglans regia) genome, this study integrated various web resources from gene family acquisition to structural analysis and transcriptome data to correlate walnuts and their congeners. The walnut genome has 5 DCL, 13 RDR, 15 DRB and 15 AGO genes, similar genes encoding conserved protein structural domains and conserved motifs with similar subcellular localization. Walnut AGO proteins are classified into three classes and seven subclasses. The DCL is divided into four categories, while RDR is mainly divided into four categories, and DRB can be divided into six categories. The exception is that the copy number of walnut RDR1 is 9, in which seven RDR1 are distributed in clusters on chromosome 16. Purifying selection drove the formation of walnut genes, but protein classes were subjected to varying degrees of purifying selection. Additionally, these results showed some similarity in other plants of the walnut family. Moreover, different RNAi-related genes of walnut produced abundant selective expression in response to different tissues and stresses. In this study, DCL, RDR, DRB and AGO gene families were identified and analysed in the genome of the walnut family for the first time and preliminarily examined the evolution, structure and expression characteristics of these families to provide a preliminary basis for the evolution of the walnut RNAi pathway and breeding research.

In this paper, we study the deflection angle for wormhole-like static aether solution by using Gibbons and Werner technique in non-plasma, plasma and dark matter mediums. For this purpose, we use optical spacetime geometry to calculate the Gaussian optical curvature, then implement the Gauss-Bonnet theorem in weak field limits. Moreover, we compute the deflection angle by using a technique known as Keeton and Petters technique. Furthermore, we analyze the graphical behaviour of the bending angle ψ with respect to the impact parameter b, mass m as integration constant and parameter q in non-plasma and plasma mediums. We examine that deflection angle is exponentially increasing as direct with charge. Also, we observe that for small values of b, ψ increases and for large values of b the angle deceases. We also considered an analysis to the shadow cast of the wormhole relative to an observer at various locations. Comparing it the the Schwarzschild shadow, shadow cast is possible for wormhole as r<2m. At r>2m, the Schwarzschild is larger. As r → ∞, we have seen that the behavior of the shadow, as well as the weak deflection angle, approaches that of the Schwarzschild black hole. Overall, the effect of plasma tends to decrease the value of the observables due to the wormhole geometry.

The Particle-In-Cell (PIC) method has been developed in order to investigate microscopic phenomena, and with the advances of computing power, newly developed codes have been used for several fields such as astrophysical, magnetospheric, and solar plasmas. PIC applications have grown extensively with large computing powers available on supercomputers such as Pleiades and Blue Waters in the US. For astrophysical plasma research PIC methods have been utilized for several topics such as reconnection, pulsar dynamics, non-relativistic shocks, relativistic shocks, relativistic jets, etc. PIC simulations of relativistic jets have been reviewed with the emphasis on the physics involved in the simulations. This review summarizes PIC simulations, starting with the Weibel instability in slab models of jets, and then focuses on global jet evolution in helical magnetic field geometry. In particular we address kinetic Kelvin-Helmholtz instabilities and mushroom instabilities.

The correlation of periodic seasonal vertical ground movement (SVGM) with climatic data from earth observation was investigated in this work. The European Ground Motion Service (EGMS) vertical ground movement measurements, provided from 2018 to 2022, were compared with temperature and precipitation data from MODIS and CHIRP datasets respectively. Measurement Points (MP) from EGMS over Italy provided a value of ground vertical movement approximately every 6 days. Precipitation and temperature datasets were processed to provide Drought Code (DC) maps calculated ad hoc for this study at 1 km spatial resolution and daily temporal resolution. Seasonal patterns were analysed to assess correlation with Spearman’s rank correlation coefficient (ρ) between this measure and DC from Copernicus CEMS (DCCEMS) and from MODIS+CHIRP (DC1km) and from temperature. Results over the considered area (Italy) showed that 0.46% of all MPs (32 826 MPs out of 7 193 676 MPs) have a ρ greater than 0.7: 12 142 of those have positive correlation, and 20 684 have negative correlation. DC1km was the climatic factor that provided the higher number of correlated MPs, roughly giving +59% more correlated MPs than DCCEMS and +300% than temperature data. If ρ greater than 0.8 was considered, the number of MPs drops by a factor of 10; from 12 142 to 1 275 for positive correlation and from 20 684 to 2 594 for negative correlation between DC1km values and SVGM measurements. Correlations lagged in time resulted in most of the correlated MPs being inside a window of +/- 6 days (a single satellite overpass time). Because DC and temperature are strongly co-linear, further analysis to assess which is better at explaining the seasonality of MPs was carried out, resulting in DC1km significantly explaining more variance of the SVGM than temperature for the inversely correlated points more than the directly correlated points. Spatial distribution of correlated MPs shows that they are unevenly distributed in clusters the Italian territory. This work will lead to further investigation both at local scale and at a pan-European scale. An interactive WebGIS application open to the public is available for data consultation. Data are shared in a public repository for replication of the method.

This paper presents an advanced methodology for processing radar imagery stacks using Persistent Scatterer and Distributed Scatterer Interferometry (PSDS) to enhance spatial coherence and improve displacement detection accuracy. The workflow leverages Level 2 Coregistered Single Look Complex (L2-CSLC) images generated by the open-source COMPASS (COregistered Multi-temPorAl Sar SLC) framework in combination with the Combined eigenvalue maximum likelihood Phase Linking (CPL) approach as implemented in MiaplPy. Starting the analysis directly from Level 2 products offers a significant advantage to end-users, as they simplify processing by being pre-geocoded and ready for immediate analysis. Additionally, the open-source nature of the workflow and the use of L2-CSLC products simplify the processing pipeline, making it easier to distribute directly to users for practical applications in monitoring infrastructure stability in dynamic environments. The ISCE3-MiaplPy workflow is compared against ISCE2-MiaplPy and the European Ground Motion Service (EGMS) to assess its performance in detecting infrastructure deformation in dynamic environments, such as the Algeciras port. Results indicate that ISCE3-MiaplPy delivers significantly denser measurements, albeit with increased noise, compared to its counterparts. This higher resolution enables a more detailed understanding of infrastructure stability and surface dynamics, which is critical for environments with ongoing human activity or natural forces.

Diabetic cardiac autonomic neuropathy (DCAN) is a severe complication of type 1 diabetes mellitus (T1DM) characterized by autonomic nerve fiber dysfunction in the heart and blood vessels. This study aimed to elucidate the histopathological mechanisms underlying DCAN and evaluate the therapeutic potential of MCC950, an NLRP3 inflammasome inhibitor, in a Wistar rat model. Male Wistar rats were divided into control and T1DM groups, with diabetes induced by streptozotocin (STZ) injection. Following confirmation of DCAN through elevated serum noradrenaline levels, diabetic rats were subdivided into positive control (insulin-treated), treatment (MCC950), and untreated groups. The stellate ganglia, thoracic aorta, and left ventricle were dissected for histological examination using Haematoxylin and Eosin (H&E) and Masson Trichrome staining. STZ-induced hyperglycemia was evident by Week 2 and sustained throughout the study. Serum noradrenaline levels significantly increased by Week 14 in diabetic rats, indicating DCAN onset. Histological analysis revealed atrophy in stellate ganglia, endothelial damage in the thoracic aorta, and myocardial fibrosis in untreated diabetic rats. MCC950 treatment preserved ganglionic structure, mitigated vascular damage, and reduced myocardial fibrosis, demonstrating its potential in attenuating DCAN progression. These findings highlight MCC950 as a promising therapeutic agent for DCAN by targeting inflammation and preserving autonomic and cardiovascular function. Further investigations are warranted to validate MCC950’s efficacy in human trials, with the potential to improve clinical outcomes for T1DM patients at risk of DCAN.

The chronic high fat dysbiosis diet (HFD) instigates cardiac remodeling, dysfunction and chronic heart failure (CHF). The therapeutic approaches focusing oxidative stress, inflammation and hyperlipidemia have not yielded significant positive clinical outcomes. Recent studies report that although mitochondrial ATP citrate lyase (ACLY) supports cardiac function, however, decreases more in human HFpEF than HFrEF. Interestingly, the ACLY synthesizes lipids and creates hyperlipidemia. Epigenetically, ACLY acetylates histone. The mechanism(s) are unknown. One hypothesis is that the HFD induces epigenetic folate 1-carbon metabolism (FOCM), heperhomocysteinemia (HHcy, a cause of abrogation of sleep-time dipping in blood pressure and hypertension) and heart failure. Interestingly, the probiotics utilizes the fat/lipids post-biotically, and increases the mitochondrial bioenergetics and attenuates the HFD induced heart failure. We suggest a novel and paradigm-shift epigenetic mitochondrial sulfur transsulfuration pathways that selectively target HFD-induced CHF. The HFD via transport and metabolomic pathways instigates cardiac remodeling and dyfunction. Previous studies from our laboratory, using a single cell analysis, revealed increase in transporter (SLC25A) of s-adenosine-methionine (SAM) during elevated levels of homocysteine (Hcy, i.e., hyperhomocysteinemia, HHcy), a consequence of impaired epigenetic recycling of Hcy back to methionine by increase in FOCM methylation of H3K4, K9, H4K20 and gene writer (DNMT) and decrease in eraser (TET/FTO). The Hcy transported to mitochondria by SLC7A for clearance via sulfur metabolomic transsulfuration by 3-mercaptopyruvate sulfur transferase (3MST). Interestingly, the HHcy decreases ATP, OCR, H₂S, PGC1α, TFAM, and increase in fission/fusion ratio, causing mitochondria dysfunction. We suggest that gut dysbiosis by HFD disrupts rhythmic epigenetic memory via FOCM and increase in DNMT1 and creates HHcy, leading to decrease mitochondrial transsulfuration and bioenergetics. The treatment with a probiotic, lactobacillus will eat the fat/lipids post-biotically and bi-directionally will produce folic acid and lactone-ketone body that will mitigate the HFD-induced mitochondrial remodeling and heart failure.

This study explores the integration of genome sequencing and polymerase chain reaction (PCR) based methods for tracking the diversity of Covid-19 variants in wastewater. The research focuses on monitoring various Omicron subvariants during a period of significant viral evolution. Genome sequencing, particularly using Oxford Nanopore Technology (ONT), provides a detailed view of emerging variants, surpassing the limitations of PCR-based detection kits that rely on known sequences. This study highlights the effectiveness of combining these methodologies to enhance early detection and inform public health strategies, especially in regions with limited clinical sequencing capabilities.

UVA1 phototherapy has been reported to mediate some of its effects via FICZ/AHR/MAPK signaling. A proof-of-concept study was performed to assess whether a topical solution of L tryptophan formulated to favor the generation 6-formylindolo[3,2-b] carbazole (FICZ) demonstrated activity at the aryl hydrocarbon receptor (AHR) as assessed by the intensity of cytochrome P450 1A2 staining. Ten participants applied a trial agent consisting of L- tryptophan, lecithin, polyvinyl alcohol and ethanol followed by 36 sessions of graduated sun exposure increasing to a total of 20 Joules per square centimetre. At the end of the trial, biopsies were taken from a treated site with photo-protected buttock skin used as a control. Assessment was via intensity of cytochrome P450 1A2 staining. An average baseline value of 53488923 units was obtained at the control site and 972214294 at the treatment site supporting the concept that this preparation displays activity at the AHR. As the components of this preparation are known to have UV absorbing properties and are potentially permissive of UVA-1 transmission, UV absorbance was assessed for natural sunlight and at 365 and 395nm confirming strong absorption in the UVB and UVA-2 spectra with partial transmission in the UVA-1 spectrum.

Hydroperoxides (ROOH) are known as damaging agents capable of mediating mutation, while a role as signaling agents through oxidation of protein sulfhydryls that can alter cancer-related pathways has gained traction. Glutathione peroxidase 2 (GPX2) is an antioxidant enzyme that reduces ROOH at the expense of glutathione (GSH). GPX2 is noted for a tendency of large in-creases or decreases in expression levels during tumorigenesis that leads to investigators focusing on its role in cancer. However, GPX2 is only one component of multiple enzyme families that metabolize ROOH and GPX2 levels are often very low in the context of these other ROOH reducing activities. Colorectal cancer (CRC) was selected as a case study for examining GPX2 function as colorectal tissues and cancers are sites where GPX2 is highly expressed. A case can be made for a significant impact of changes in expression levels. There is also a link between GPX2 and NADPH oxidase 1 (NOX1) from earlier studies that is seldom addressed and is discussed, presenting data on a unique association in colon and CRC. Tumor-derived cell lines are quite commonly used for pre-clinical studies involving the role of GPX2 in CRC. Generally, selection for this type of work is limited to identifying cell lines based on high and low GPX2 expression with the standard re-search scheme of overexpression in low expressing lines and suppression in high expressing lines to identify impacted pathways. This overlooks CRC subtypes among cell lines involving a wide range of gene expression profiles and a variety of driver mutation differences along with a large difference in GPX2 expression levels. A trend for low and high GPX2 expressing cell lines to segregate into different CRC subclasses, indicated in this report, suggests that choices based solely on GPX2 levels may provide misleading and conflicting results by disregarding other properties of cell lines and failing to factor in differences in potential protein targets of ROOH. CRC and cell line classification schemes are presented here that were intended to assist workers in performing pre-clinical studies but are largely unnoted in work on GPX2 and CRC. Studies are often initiated on the premise that the transition from normal to CRC is associated with up-regulation of GPX2. This is probably correct. However, the source normal cells for CRC could be almost any colon cell type, some with very high GPX2 levels. These factors are addressed in this study.

A multi-environment evaluation of sorghum genotypes was conducted across six environments in the 2021 main growing season in a randomized complete block design with three replications. The objectives of the study were to estimate the magnitude of genotypes by environment interaction (GEI) and grain yield stability of drought-tolerant sorghum genotypes across different environments. Data were subjected to analysis of variance, Additive Main Effects and Multiplicative Interaction (AMMI), and GGE biplot analysis. Combined analysis of variance revealed significant variations among genotypes, environments, and GEI for yield and yield-related traits, indicating that these factors significantly affected grain yield. The maximum mean grain yield value of genotypes due to the mean effect of the environment was obtained from G1 (5119.93kg ha-1), followed by G14 (4834.57 kg ha-1), and G18 (4801.20 ha-1), while the least mean grain yield was obtained from G3 (3314.50 kg ha-1). The multiplicative variance of the treatment sum of squares due to GEI was partitioned into four principal component axes (PCA). Sum squares of the first and second interaction principal component axis (IPCA) explained 71.07% and 17.50% of the GEI variation, respectively. The IPCA1&2 mean squares were highly significant (P≤0.01), indicating the adequacy of the AMMI model with the first two IPCAs for cross-validation of grain yield variation. The magnitude of the GEI sum squares was 3.9 times that of the genotype sum squares for grain yield, indicating the presence of substantial differences in genotypic responses across environments. The results of cultivar superiority measure (Pi), yield stability index (YSI), AMMI stability value (ASV), regression coefficient (bi), and deviation from regression (S2di) depicted that genotypes G18, G22, G31, and 32 were the most stable genotypes for grain yield and biomass yield, respectively. AMMI2 biplot showed Jinka, Alduba, and Kako were the most discriminating environments as indicated by the long distance from the origin; whereas testing locations Meioso and Gato with short vector length indicated that these locations had less discriminating power on the genotypes' performance. The study has provided precious information on the yield stability status of the sorghum genotypes and the best environments for future improvement programs in Ethiopia.

The goal of the study is to assess the potential correlation between maternal Sars-cov-2 infection , detected three months before the second trimester anomaly scan, and fetal iperecogenicity in order to determine whether or not this could be considered a predictive factor for maternal-fetal complications . The study included 48 pregnant women who did not have any clear maternal or fetal problems. These individuals had an anomaly scan in the second trimester, as well as amniocentesis and fetal cariotyping, and then RT-PCR testing on their placental tissue after birth to rule out transplacental transmission. There have been no reports of fetal abnormalities via amniocentesis or fetal cariotyping. The patients experienced a high rate of spontaneous births (83%). Fetal development problems (2%) and premature delivery (4%) were uncommon, although placental swabs revealed a possibility of viral transmission across the placenta itself. To the best of our knowledge, this is the first observational study to show that detecting isolated intestinal hyperechogenicity during an abnormality scan in fetuses of women infected with Sars-Cov-2 in the previous three months does not appear to be a predictor of poor maternal-fetal outcomes, but may be linked to transplacental virus transmission.