Imbalance in the oxidative status in neurons, along with mitochondrial damage, are common characteristics in some neurodegenerative diseases. The maintenance in energy production is crucial to face and recover from the oxidative damage and the coexistence of different sources of energy production, such as mitochondrial and glycolytic ATP, allows faster adaptative mechanisms to situations of high energy demand and may help in the maintenance of neuronal function in stress situations. Fingolimod phosphate is a drug with neuroprotective and antioxidant actions, used in the treatment of Multiple Sclerosis. This work has been performed in a model of oxidative damage on neuronal cell cultures exposed to menadione, in presence or absence of fingolimod phosphate. We have studied the mitochondrial function and several pathways related with glucose metabolism, including oxidative, glycolytic and pentose phosphate in neuronal cells cultures. Our results showed a beneficial effect on neuronal survival probably based in the recovery of all, oxidative balance, glycolysis and pentose phosphate, promoted by fingolimod phosphate. These effects are mediated, at least in part by the interaction with its specific receptor. These actions would make this drug a potential tool to the treatment of neurodegenerative processes, either to slow progression or alleviate symptoms.

Salinity is considered as one of the most important abiotic challenges that affect crop productivity. Plant hormones, including salicylic acid (SA), are key factors in the defence signalling output triggered during plant responses against environmental stresses. We have previously reported in peach a new SA biosynthetic pathway from mandelonitrile (MD), the molecule at the hub of the cyanogenic glucoside turnover in Prunus sp. In this work, we have studied whether this new SA biosynthetic pathway is also present in plum and the possible role this pathway plays in plant plasticity under salinity, focusing on the transgenic plum line J8-1, which displays stress tolerance via an enhanced antioxidant capacity. The SA biosynthesis from MD in non-transgenic and J8-1 micropropagated plum shoots was studied by metabolomics. Then the response of J8-1 to salt stress in presence of MD or Phe (MD precursor) was assayed by measuring: chlorophyll content and fluorescence parameters, stress related hormones, levels of non-enzymatic antioxidants, the expression of two genes coding redox-related proteins, and the content of soluble nutrients. The results from in vitro assays suggest that the SA synthesis from the MD pathway demonstrated in peach is not clearly present in plum, at least under in vitro conditions. Nevertheless, in J8-1 NaCl-stressed seedlings, an increase in SA was recorded as a result of the MD treatment, suggesting that MD could be involved in the SA biosynthesis under NaCl stress conditions in plum plants. We have also shown that the plum line J8-1 was tolerant to NaCl under greenhouse conditions, and this response was somewhat different in MD-treated plants. In that regards, the MD treatment produced an increase in SA, jasmonic acid (JA) and reduced ascorbate (ASC) contents as well as in the coefficient of non-photochemical quenching (qN) and the gene expression of Non-Expressor of Pathogenesis-Related 1 (NPR1) and thioredoxin H (TrxH) under salinity conditions, suggesting a crosstalk between different signalling pathways (NPR1/Trx and SA/JA) leading to salinity tolerance in the transgenic plum line J8-1.

Antipsychotic drug (APD) medication can lead to metabolic dysfunctions and weight gain, which together increase morbidity and mortality. Metabolically active visceral adipose tissue (VAT) in particular plays a crucial role in the etiopathology of these metabolic dysregulations. Here we studied the effect of 12 weeks drug medication by daily oral feeding of clozapine and haloperidol on the perirenal fat tissue as part of VAT of male and female Sprague Dawley rats in the context of complex former investigations on brain, liver, and blood. Adipocyte area values were determined as well as triglycerides, non-esterified fatty acids (NEFAs), glucose, glycogen, lactate, malondialdehyde equivalents, ferric iron and protein levels of Perilipin-A, hormone-sensitive-lipase (HSL), hepcidin, glucose transporter-4 (Glut-4) and insulin receptor-ß (IR-ß). We found increased adipocyte mass in males with slightly higher adipocyte area values in both males and females under clozapine medication. Triglycerides, NEFAs, glucose and oxidative stress in the medicated groups were unchanged or slightly decreased. In contrast to controls and haloperidol medicated rats, perirenal adipocyte mass and serum leptin levels were not correlated under clozapine. Protein expressions of perilipin-A, Glut-4 and HSL were decreased under clozapine medication. IR-ß expression changed sex-specifically in the clozapine medicated groups associated with higher hepcidin levels in the perirenal adipose tissue of clozapine-medicated females. Taken together, clozapine and haloperidol have a smaller effect than expected on perirenal adipose tissue. The perirenal adipose tissue shows only weak changes in lipid and glucose metabolism. The main changes can be seen in the proteins examined and probably in their effect on liver metabolism.

Keywords: Agrobacterium 1; Xenorhabdus 2; NR-AMP 3 T-DNA keyword 4; TI-plasmid 5; Intact/Cured/T-DNA Deleted 6 Sensitive/Resistant 7; EMA_PF2 8; HPLC 9

In the current context of worldwide honey bee colony losses, among which the varroa mite plays a major role, hope to improve honey bee health lies in part in the breeding of varroa resistant colonies. To do so, methods used to evaluate varroa resistance need better understanding. Repeatability and correlations between traits such as Mite Non-Reproduction (MNR), Varroa Sensitive Hygiene (VSH) and hygienic behaviour are poorly known, due to practical limitations and to their underlying complexity. We investigate (i) the variability, (ii) repeatability of the MNR score and (iii) its correlation with other resistance traits. To reduce the inherent variability of MNR scores, we propose to apply an Empirical Bayes correction. On the short-term (ten days) MNR had a modest repeatability of 0.4 whereas on the long- term (a month) it had a low repeatability of 0.2, similar to other resistance traits. Within our dataset there was no correlation between MNR and VSH. Although MNR is amongst the most popular varroa resistance estimates in field studies, its underlying complex mechanism is not fully understood. Its lack of correlation with better described resistance traits and low repeatability suggest that MNR need to be interpreted cautiously, especially when used for selection.

A novel concept of ion separation Anisotropic Diffusion Mobility Analyser (ADMA) with Individual Ion Counter (IIC) was shown by numerical modelling to be able to separate ions with high resolution and ultra-high sensitivity. An ADMA-IIC device has been developed and tested at sheath flow rates below 40 l/min with a number of chemicals relevant to airport security and military applications. The resolving power of the ADMA was observed to be in the range of 40 to 80. These data were close to the resolution obtained in numerical modelling predictions. It is greater than or comparable with the RP of currently available on-the-market devices for airport security and other applications. It was also confirmed that the ADMA technology enables very fast detection of analytes, at least 100 times faster than ion mobility spectrometers. It was shown that Brownian diffusion can be controlled and even overpowered by generating highly anisotropic diffusion in the ADMA device. The ultimate sensitivity of single-ion detection below the ppq range has been demonstrated.

The purpose of this study is to examine the relationship between the institutional investors which can affect financial performance for corporate sustainability on the income smoothing. Therefore, this study focus on the connection between the nature of stock rights and income smoothing in China. For this study, hypotheses were established on the relationship each state-controlled companies, income smoothing, and information equilibrium of individual investors, and empirical analysis was conducted through related variables. The analysis results are summarized in three categories as follows. First, this research finds that state-controlled firms (CONTs) prefer income smoothing activities compared to non-state-controlled firms for the long-term sustainable development of firms using data from 2011 to 2019. Second, this study found out that Institutional investors support the behavior of CONTs to smooth their earnings because this behavior is seen as an attempt by CONTs to convey valuable private information to other investors. Third, we was able to discover that institutional investors' monitoring effect is predominantly driven by pressure-resistant institutional investors. This research complements the lack of empirical research on income smoothing and enable to give a guideline that the type of stock rights is a critical key determinant of participation in income smoothing activities for stable growth and sustainability in the future.

On the thirty-fifth anniversary of the first description of O2-sensitive K+ channels in the carotid body chemoreceptors [1], O2 sensing remains a salient issue in the literature. Whereas much has been learned about this subject, important questions such as the identity of the specific K+ channel subtype(s) responsible for O2 sensing by chemoreceptors and the mechanism(s) by which their activities are altered by hypoxia have not yet been definitively answered. O2 sensing is a fundamental biological process necessary for the acute and chronic responses to varying environmental O2 levels which allow organisms to adapt to hypoxia. Whereas chronic responses depend on the modulation of hypoxia-inducible transcription factors which determine the expression of numerous genes encoding enzymes, transporters and growth factors, acute responses rely mainly on the dynamic modulation of ion channels by hypoxia, causing adaptive changes in cell excitability, contractility, and secretory activity in specialized tissues. The most widely studied oxygen-sensitive ion channels are potassium channels but oxygen sensing by members of both the calcium and sodium channel families has also been demonstrated. Given the explosion of information on this topic, in this review we will focus on the mechanisms of physiological oxygen chemotransduction by PO2-dependent K+ channels, with particular emphasis on their function in carotid body chemoreceptor cells (CBCC) and pulmonary artery smooth muscle cells (PASMC), highlighting areas of consensus and controversy within the field. We will first describe the most well-established concepts, those reproduced in multiple laboratories, and then discuss selected observations or questions that remain unresolved, and that limit our progress in this field.

In light of the current situation where no testing equipment is available for measuring thermal deformation of objects, this paper proposes a novel method for accurate and precise measurement. The method overcomes the limitations of previous approaches that relied on pitch angle. By utilizing the principle of biplane multiple reflections, a bivariate laser spot displacement analysis algorithm is devised to attain highly precise measurements of bivariate angles. Additionally, a temperature gradient comparison algorithm is introduced to calculate the indicator test results under specific temperature conditions. To validate the effectiveness and reliability of this method, a testing system is constructed and utilized. The results demonstrate that the thermal deformation angle change test achieves an impressive accuracy of 0.015″ and a rate of thermal deformation angle change of 0.3247″/°C. These values are in close agreement with the previously simulated analysis result of 0.359″/°C, with only a relative error of 9.55%. Therefore, the test results confirm the efficacy and reliability of this testing method along with the feasibility of the algorithm processing.

The aim of the current study was to develop and evaluate the therapeutic potential of apocynin (APO) loaded pH-sensitive nanoparticles (NPs) based transdermal hydrogel for management of rheumatoid arthritis (RA). Slightly modified nanoprecipitation technique was used for preparation of polymeric nanoparticles. Optimization was done through design expert software. Optimized APO-NPs were loaded into carbopol-934 based hydrogel as final dosage form and further studied for physicochemical properties. Optimized APO-NPs formulation had a minimum particle size 63.44 nm, polydisperibility index 0.161, and zeta potential -15mV with a maximum encapsulation efficiency of 89%. In-vitro and ex-vivo studies of APO-NPs based hydrogel was performed at pH 5.5 (pH of normal skin) and 6.8 (pH of inflammed joint) showed a pH-responsive sustained drug release and increased penetration in comparison to free APO based hydrogel. The stability studies of APO-NPs based hydrogel were done to strengthen the potential use of the prepared formulation through transdermal route. Assessment and therapeutic efficacy of the prepared pH-sensitive nanocarriers system was evaluated in chronic inflammatory RA mice model. Parameters associated with chronic inflammation were investigated including behavioral changes and histopathological, and radiological x-rays images of joints of mice paws. In-vivo study depicts improvement in behavioral parameter, decline in synovial hyperplasia and bone structure restoration. In conclusion, APO loaded pH-sensitive NPs based transdermal is a promising carrier system that can effectively manage RA.

This study evaluated the effectiveness of an electronic system for managing drug-sensitive pulmonary tuberculosis patients in the Kyrgyz Republic. This was a cohort study using programmatic data. The study included patients registered on the paper-based system in 2019 and the electronic system between June 2021 and May 2022. Data was taken from 302 individuals from the electronic system for completeness and concordance in comparison with the paper-based system. The study showed that for most variables the completeness and concordance was 85.3%-93.0% and was lowest for non-mandatory fields such as medication side effects (26.8% vs 13.6%). No significant difference was observed in time taken from symptom onset to diagnosis and treatment initiation between the two systems. However, the electronic system had a significantly higher percentage of patients who initiated treatment on the same day of diagnosis (80.3% vs. 57.1%). The proportion with successful outcomes was similar in both groups, but the electronic system had a significantly lower proportion of patients with outcomes that were not evaluated or recorded (4.8% vs. 14.3%, p < 0.001). The study highlights the potential advantages of implementing an electronic TB register system for improving records. We advocate for similar studies in other regions in Kyrgyz Republic.

The world is moving to the next phase of the energy transition with high penetrations of renewable energy. Flexible and scalable redox flow battery (RFB) technology is expected to play an important role in ensuring electricity network security and reliability. Continuous performance improvements will further enhance their value by reducing parasitic losses and maximizing available energy conversion over broader operating conditions. Concentration overpotentials from poor internal reactant distribution at high and low states of charge (SOC) limit power densities and are thus an important area of investigation. However, efforts to address these coupled electrochemical phenomena can compromise mechanical performance. Modelling and simulation of cell design innovations have shown it is possible to reduce losses from pump energy while increasing the availability of active species where required. The combination of wedge-shaped cells with static mixers investigated in this paper can reduce pressure drop and improve energy efficiency. Toroidal vanadium redox flow battery (VRB/VRFB) designs incorporating this innovation are presented for further development to improve community engagement with the technology.

Maintenance of integrity and function of the gastric mucosa (GM) requires a high regeneration rate of epithelial cells during the whole life span. The health of the gastric epithelium highly depends on redox homeostasis, antioxidant defense and activity of detoxifying systems within the cells as well as robustness of blood supply. Bioactive products of lipid peroxidation, in particular second messengers of free radicals, the bellwether of which is 4-hydroxynonenal (HNE), are important mediators in physiological adaptive reactions and signaling but they are also thought to be implicated in the pathogenesis of numerous gastric diseases. Molecular mechanisms and consequences of increased production of HNE and its protein adducts in response to stressors during acute and chronic gastric injury are well studied. However, several important issues related to the role of HNE in gastric carcinogenesis, tumor growth and progression, the condition of GM after eradication of Helicobacter pylori, or the relevance of antioxidants for HNE-related redox homeostasis in GM still need more studies and new comprehensive approaches. In this regard, preclinical studies and clinical intervention trials are required, which should also include the use of state-of-the-art analytical techniques such as HNE determination by immunohistochemistry and ELISA as well as modern mass-spectroscopy methods.

For a linear ordinary differential equation (ODE in short) of the third order, results are presented that supplement the theory of conjugate points and extremal solutions by W. Leighton, Z. Nehari, M. Hanan. It is especially noted the sensitivity of solutions to the initial data, which makes their numerical study difficult. Similar results were obtained for the third-order nonlinear equations of the Emden-Fowler type.

As the increase threat of flood risk and environmental safety due to the urbanization, Sponge city research has been attracting extensive attention both in practical and theoretical research field. To date, there are only scattered studies about Sponge city. Moreover, vary names of Sponge city prevalent in different countries, which leads to disconnection of literature in the same field of Sponge city. In this paper, a thorough systematic literature mining of Sponge city is presented. A literature analysis system is created, which includes literature export from Web of Sciences and systematic analysis via NoteExpress and CiteSpace. Some literature statistical results are derived. Challenges and opportunities for future research are anticipated. Our goals are to promote this promising thought, summarize past research, and identify issues for future research to create impacts on the practice of Sponge city.

De novo metastatic hormone-sensitive PC (mHSPC) accounts for 5-10% of all prostate cancer (PC) diagnoses but it is responsible for nearly 50% of PC-related deaths. Since 2015, the prognosis of mHSPC has slightly improved thanks to the introduction of new hormonal agents and chemotherapy combined with androgen deprivation therapy from the first-line setting. This review describes the current therapeutic opportunities in de novo mHSPC, focusing on potential molecular biomarkers identified in the main clinical trials that have changed the standard of care, the genomic features of de novo mHSPC, and the principal ongoing trials that are investigating new therapeutic approaches and the efficacy of a biomarker-guided treatment in this setting. The road towards a personalized treatment for de novo mHSPC is still long considering that the randomized clinical trials, which have furnished the basis of the current therapeutic options, stratified patients according to clinical criteria that not necessarily reflect the biological rationale of the chosen therapy. The role of transcriptomic profiling of mHSPC as predictive biomarker requires further validation, as well as it remains to ascertain how the genomic alterations detected in mHSPC, that are considered predictive in the castration-resistant disease, can be exploited in the mHSPC setting.

Carbon dioxide capture and storage (CCS) is a necessary requirement for high-emitting CO2 industries to significantly reduce volumes of greenhouse gases released to the atmosphere and mitigate the climate change. Geological CO2 storage into depleted oil and gas fields is the fastest and most accessible option for CCS deployment allowing for re-purposing of existing infrastructure and utilizing the significant knowledge about the subsurface acquired during the field production operations. Location of such depleted fields in neighbourhood of high-emitting CO2 industries is additional advantage available for matured on-shore Europe fields. Considering these advantages, the oil and gas operators are now evaluating different possibilities for CO2 sequestration projects for the fields approaching end of production. This article describes an integrated approach to reservoir simulations focused on evaluating CO2 injection pilot at one of such matured fields operated by MND and located in the Czech Republic. The potential CO2 injection site in focus is a naturally fractured carbonate reservoir. This oil-bearing formation has a gas cap at the top and a limited aquifer at the bottom of the reservoir and was produced mainly by pressure depletion with quite limited pressure support from water injection. The article summarizes results of efforts taken by the multi-disciplinary team to develop and apply an integrated approach to reservoir simulation started from geological modelling of the naturally fractured reservoir and integrating results of laboratory studies and their interpretation (geomechanical and geochemistry laboratory experiments) and dynamic field data analysis (pressure transient analysis including time-lapse) into the history matching of the reservoir model and simulations of pilot CO2 injection. Attention is given to evaluating and modelling stress-sensitive fracture properties and safe injection envelope preventing induced fracturing as well as impact of potential salt precipitation in the near wellbore area. These effects are considered in the context of pilot CO2 injection and addressed in reservoir simulations of the injection scenarios. Single porosity and permeability reservoir simulations with dominating fracture flow and black-oil formulation with CO2 simulated as a solvent were used in this study and arguments for such choice of the simulation approach for the site in focus are shortly discussed. The reservoir simulations have indicated larger site injection capacity than required for the pilot injection and allowed to evaluate CO2 migration pathway within the reservoir. The application of the approach to the site in focus has also revealed large uncertainties, related to fracture description and geomechanical evaluations, resulted in an uncertain safe injection envelope. These uncertainties should be addressed in further studies in preparation to the pilot. The article concludes with an overview of the outcomes of the integrated approach and its application to the field in focus including discussion of issues and uncertainties revealed.

One of the earliest hallmarks of plant immune response is production of reactive oxygen spe-cies (ROS) in different subcellular compartments, which regulate plant immunity. A suitable equilibrium, which is crucial to prevent ROS over-accumulation leading to oxidative stress, is maintained by salicylic acid (SA), a chief regulator of ROS. However, ROS are not only acting downstream of SA signaling, but were also proposed to be a central component of a self-amplifying loop that regulates SA signaling as well as the interaction balance between dif-ferent phytohormones. The exact role of this crosstalk, the position where SA interferes with ROS signaling and ROS interferes with SA signaling and the outcome of this regulation depend on the origin of ROS but also on the pathosystem. The precise spatiotemporal regulation of or-ganelle specific ROS and SA levels determine the effectiveness of pathogen arrest and is there-fore crucial for a successful immune response. However, the regulatory interplay behind still remain poorly understood, as up till now, the role of organelle specific ROS and SA in HR-conferred resistance has mostly been studied by altering the level of a single component. In order to address these aspects, a sophisticated combination of research methods for monitoring the spatiotemporal dynamics of key players and transcriptional activity in plants is needed, and will most probably consist of biosensors and precision transcriptomics.