Recent evidences support a role of menthol, a TRPM8 agonist, in enhanced energy expenditure, thermogenesis and BAT-like activity in classical WAT depots in TRPM8 dependent and independent manner. The present study was designed to analyze whether oral and topical administration of menthol is bioavailable at subcutaneous adipose tissue and is sufficient to induce desired energy expenditure effects directly. GC-FID was performed to study menthol bioavailability in serum and subcutaneous white adipose tissue following oral and topical administration. Further, 3T3L1 adipocytes were treated with bioavailable menthol doses and different parameters (lipid accumulation, “browning/brite” and energy expenditure gene expression, metal analysis, mitochondrial complex’s gene expression) were studied. No difference was observed in serum levels but significant difference was seen in the menthol concentration on subcutaneous adipose tissues after oral and topical application. Menthol administration at bioavailable doses significantly increased “browning/brite” and energy expenditure phenotype, enhanced mitochondrial activity related gene expression, increased metal concentration but didn’t alter the lipid accumulation. Further, we used pharmacological antagonism based approach to study the TRPM8 involvement in menthol effect. In conclusion, the present study provides an evidence that bioavailable menthol after single oral and topical administration is sufficient to induce “brite” phenotype in subcutaneous adipose tissue.

Enhanced electrical activity in detrusor smooth muscle (DSM) cells is a key factor in detrusor overactivity which causes overactive bladder pathological disorders. Transient receptor potential melastatin-4 (TRPM4) channels, calcium-activated cation channels, play a role in regulating DSM electrical activities. These channels likely contribute to depolarizing the DSM cell membrane, leading to bladder overactivity. Our research focuses on understanding TRPM4 channel function in mouse DSM cells using computational modeling. We aimed to create a detailed computational model of the TRPM4 channel based on existing electrophysiological data. We employed a modified Hodgkin-Huxley model with an incorporated TRP-like current to simulate action potential firing in response to current and synaptic stimulus inputs. Validation against experimental data showed close agreement with our simulations. Our model is the first to analyze the TRPM4 channel's role in DSM electrical activity, potentially revealing insights into bladder overactivity. In conclusion, TRPM4 channels are pivotal in regulating human DSM function and TRPM4 channel inhibitors could be promising targets for treating overactive bladder.

Migraine is a neurovascular disorder that affects approximately 12% of the global population. While its exact causes are still being studied, researchers believe that nociceptors in the trigeminal ganglia play a key role in the pain signals of migraine. These nociceptors innervate the intracranial meninges and convey pain signals from the meninges to the thalamus. Targeting these nociceptors is considered promising due to their accessibility and distinct molecular profile, which includes the expression of several transient receptor potential (TRP) channels. These channels have been linked to various pain conditions, including migraine. This review discusses the role and mechanisms of nociceptors in migraine, the challenges of current antimigraine drugs, and the evidence for well-studied and emerging TRP channels, particularly TRPC4, as novel targets for migraine prevention and treatment.

Transient receptor potential melastatin-8 (TRPM8) is a cation channel that is activated by cold and “cooling agents” such as menthol and icilin, which induce a cold sensation. Stimulation of TRPM8 activates an intracellular signaling cascade that ultimately leads to a change in the gene expression pattern of the cells. Here, we investigated the TRPM8-induced signaling pathway that links TRPM8 channel activation to gene transcription. Using a pharmacological approach, we show that inhibition of phosphatidylinositol 4-phosphate 5 kinase alpha (PIP5K), an enzyme essential for the biosynthesis of phosphatidylinositol 4,5-bisphosphate, attenuated TRPM8-induced gene transcription. Analyzing the link between TRPM8 and Gq proteins, we show that pharmacological inhibition of the beta gamma subunits impairs TRPM8 signaling. In addition, genetic studies showed that TRPM8 requires an activated Galpha subunit for signaling. In the nucleus, the TRPM8-induced signaling cascade triggers an activation of the transcription factor AP-1, a complex consisting of a dimer of basic region leucine zipper (bZIP) transcription factors. Here, we identified the bZIP protein c-Jun as an essential component of AP-1 within the TRPM8-induced signling cscade. In summary, with PIP5K, Gq subunits and c-Jun we have identified key molecules in the TRPM8-induced signaling from the plasma membrane to the nucleus.

Pain is unpleasant sensory and emotional experience accompanied by tissue injury. Often an indi-vidual experience, it can be influenced by different physiological, psychological, and social factors. Fibromyalgia, one of the most difficult-to-treat types of pain, is characterized by general muscle pain accompanied by obesity, fatigue, sleep, and memory and psychological concerns. Fibromyal-gia has increased nociceptive sensations via central sensitization in the brain and spinal cord level. We used intermittent cold stress to create a mouse fibromyalgia pain model (Day 0: 3.69  0.14 g; Day 5: 2.13  0.12 g). Mechanical pain could be reversed by eicosapentaenoic acid (EPA) admin-istration (Day 0: 3.72  0.14 g; Day 5: 3.69  0.13 g). A similar trend could be also observed for thermal hyperalgesia. The levels of elements in the transient receptor potential V1 (TRPV1) sig-naling pathway were increased in the ascending pain pathway, including the thalamus, medial prefrontal cortex, somatosensory cortex, anterior cingulate cortex, and cerebellum. EPA intake significantly attenuated this overexpression. Novel chemogenetics method was used to indeed in-hibit SSC to ACC activity presented an analgesic effect through TRPV1 downstream pathway. The present results provide insights as to the role of TRPV1 signaling pathway as in fibromyalgia and its potential as a clinical target.

Motivated by diffraction experiments on the $\left(2\sqrt{3}\times \sqrt{3}\right)\mathrm{R}{30}^{\circ }$ reconstructed Si(111) due to deposition of rare earth elements (Dy, Tb) and silicide formation we analyse the splitting and non-splitting of superstructure spots. For this purpose, we model diffraction patterns for one dimensional structures generated by the binary surface technique and use supercell models to keep the analysis simple. Diffraction pattern are calculated in the framework of the kinematical diffraction theory and they are analyzed as a function of the domains and domain boundaries. Basic properties of the diffraction pattern are analyzed for model systems of a two-fold and a three-fold periodicity. The rules derived from these calculations are applied to the "real-world" system of Si(111)-($\left(2\sqrt{3}\times \sqrt{3}\right)\mathrm{R}{30}^{\circ }$)-RESi$2_{}$ (RE = Dy or Tb). Depending on the combination of domains and domain boundaries of different types a plethora of different features are observed in the diffraction patterns. These are analyzed to determine the sizes of both domain boundaries and domains from experimentally observed splitting of specific superstructure spots.

The transient vanilloid receptor potential type 1 (TRPV1) regulates neuronal and vascular functions mediated by nitric oxide (NO) and by the calcitonin gene-related peptide (CGRP). Here we study the participation of TRPV1 in the regulation of myocardial injury caused by ischemia-reperfusion and in the regulation of NO, tetrahydrobiopterin (BH4), the cGMP pathway, CGRP, total antioxidant capacity (TAC), malondialdehyde (MDA) and phosphodiesterase-3 (PDE-3). Isolated hearts of Wistar rats were used (according to Langendorff) to study the effects of capsaicin (CS), capsazepine (CZ) and CZ+CS treatments. The hearts were divided into three subgroups; 1) perfusion, 2) ischemia and 3) ischemia-reperfusion. In all groups we studied cardiac work and levels of NO, cGMP, BH4, CGRP, TAC, MDA and PDE-3 in ventricular tissue. Western blots were used to determine the expressions of eNOS, iNOS and phosphorylated NOS (pNOS). Structural changes were determined by histological evaluation. CS prevented damage caused by ischemia-reperfusion by improving cardiac work and the levels of NO, cGMP, BH4, TAC and CGRP. TRPV1 and iNOS expression were increased under ischemic conditions, while eNOS and pNOS were not modified. We conclude that the activation of TRPV1 constitutes a therapeutic possibility to counteract the damage caused by ischemia and reperfusion by regulating the NO pathway through CGRP.

Our knowledge on the plastic functions of the serotonin (5-HT) receptor subtype 7 (5-HT7R) in the brain physiology and pathology considerably advanced in the last few years. A wealth of data show that the 5-HT7R is a key player in the establishment and remodeling of neuronal cytoarchitecture during development and in the mature brain, and its dysfunction is linked to neuropsychiatric and neurodevelopmental diseases. The involvement of this receptor in synaptic plasticity is further demonstrated by data showing that its activation allows to rescue long term potentiation (LTP) and long term depression (LTD) deficits in various animal models of neurodevelopmental diseases. In addition, it is becoming clear that the 5-HT7R is involved in inflammatory intestinal diseases, possibly playing a role in the gut-brain axis, and modulates the function of immune cells. In this review, we will mainly focus on recent findings on this receptor’s role in the structural and synaptic plasticity of the mammalian brain, although we will also illustrate novel aspects highlighted in gut and immune system.

Carboplatin, an anticancer drug, often causes chemotherapy-induced peripheral neuropathy (PN). Transient receptor potential ankyrin 1 (TRPA1), a non-selective cation channel, is a polymodal nociceptor expressed in sensory neurons. TRPA1 is involved not only in pain transmission but also in allodynia or hyperalgesia development. However, the effects of TRPA1 on carboplatin-induced PN is unclear. We revealed that carboplatin induced mechanical allodynia and cold hyperalgesia, and the pains observed in carboplatin-induced PN models were significantly suppressed by the TRPA1 antagonist HC-030031 without a change in the level of TRPA1 protein. In cells expressing human TRPA, carboplatin had no effects on changes in intracellular Ca2+ concentration ([Ca2+]i); however, carboplatin pretreatment enhanced the increase in [Ca2+]i induced by the TRPA1 agonist, allyl isothiocyanate (AITC). These effects were suppressed by an inhibitor of protein kinase A (PKA). The PKA activator forskolin enhanced AITC-induced increase in [Ca2+]i and carboplatin itself increased intracellular cyclic adenosine monophosphate (cAMP) levels. Moreover, inhibition of A-kinase anchoring protein (AKAP) significantly decreased carboplatin-induced enhancement of [Ca2+]i induced by AITC and improved carboplatin-induced mechanical allodynia and cold hyperalgesia. These results suggested that carboplatin induced mechanical allodynia and cold hyperalgesia by increasing sensitivity to TRPA1 via the cAMP-PKA-AKAP pathway.

REDD+ (Reducing Emissions from Deforestation and Forest Degradation) aims to achieve its purpose by working across multiple sectors and involving multi-level actors in reducing deforestation and forest degradation in tropical countries. By contrast, the European Union (EU) Action Plan on Forest Law Enforcement, Governance and Trade (FLEGT) and its Voluntary Partnership Agreements (VPAs) focus on forestry and functions at bilateral state level. The FLEGT Action Plan specifically aims to tackle illegal logging, legalise timber production and trade improve forest governance in countries exporting tropical timber to the EU. Since illegal logging is just one driver of deforestation and forest degeneration, and legalisation of logging does not necessarily reduce deforestation and forest degradation, the two instruments differ in scale and scope. However, by addressing the causes of deforestation and forest degradation and their underlying governance issues, the EU FLEGT and REDD+ share many functional linkages at higher levels of forest policy and forest governance. The contribution and participation of civil society organisations (CSOs) and other actors is imperative to both processes. Our study is based on a survey of key actors (national and international) in REDD+ and FLEGT VPA processes in the Lao People’s Democratic Republic. Our analysis was guided by the theoretical perspectives of the policy arrangement approach and examination of two specific dimensions of this approach, namely resources and rules of the game. This paper argues that participation of CSOs in both processes is crucial as it facilitates and nurtures the very much needed cooperation between other national and international actors. The paper also argues that participation of CSOs feeds valuable information and knowledge into REDD+ and FLEGT VPA processes, thus contributing to increased legitimacy, justice and transparency.

Materials based on platinum metals with very good catalytic activity were tested in the reduction of p–nitrophenol (pNP) to p–aminophenol (pAP). The majority of presented catalytic materials are based on the adsorption of p–nitrophenol on the surface of the catalyst simultaneously with molecular hydrogen, coming from sodium borohydride in an aqueous medium, which reduces it. In the present paper, a catalytic material based on osmium dispersed in n–decanol or n–dodecanol is presented, which also works as an emulsion membrane, for the absorption of p–nitrophenol and molecular hydrogen at the n–alcohol aqueous solution interface. The hydrogenation of p–nitrophenol is carried out in a reaction and separation column in which the acid receiving phase emulsion is dispersed in the osmium nanodispersion, in n–alcohols. This emulsion circulates from the base of the column to its upper part in co-current or counter-current with the source phase consisting of p–nitrophenol and sodium borohydride. Experiments show that the circulation of counter-current phases is superior to that in co-current, and the emulsion based on n–decanol is more efficient than the one based on n–dodecanol. The increase in the pH difference between the source and receiving phases leads to the increase in the conversion of p–nitrophenol to p–aminophenol. The efficiency of separation of the reaction product in the receiving phase is lower than the conversion at the same operating time. The apparent catalytic rate constant (kapp) of the new catalytic material based on the emulsion membrane with nanodispersion of osmium nanoparticles (0.1×10−3 for n–dodecanol and 0.9×10−3 for n-decanol) is lower by an order of magnitude compared to those based on adsorption on catalysts from platinum metal group. The advantage of the tested membrane catalytic material is that it extracts p–aminophenol in the acid receiving phase. The paper proposes a mechanism of the studied reduction system.

Codium fragile, a green algae, exhibit biological properties. In this study, we examined the effect of Codium fragile extract (CFE) on dextran sulfate sodium (DSS)-induced colitis. As the administration of CFE increased, the proliferation of Akkermansia muciniphila, which is key player in metabolic and gastrointestinal disorders, increased. After CFE administration for 10 weeks, acetic acid was revealed as the major metabolite in mouse cecum and β-glucuronidase activity in mouse feces is decreased. Further, CFE significantly alleviates the acute intestinal injury induced by DSS administration, including DAI scores and colon length. MPO activity in the colon was significantly reduced in the CFE-fed group, which indicated that CFE could inhibit neutrophils infiltration and inflammation in mice. In conclusion, a protective effect of CFE against DSS colitis suggests its clinical use for IBD patients.

The research presented in this article is based on a strategic approach to a rural area in the mountainous region of Romania and is underwritten by specialists in the economy of mountainous regions in order to elaborate relevant solutions to complex problems relating to sustainable development. In essence, the research underlines and promotes the particularities of performing research for the identification and valuation of endogenous resources, that is, creating relevant strategic options for the durable development of the mountainous region, centered on the renewal of economic activities related to the existent endogenous resources, by using methods, work techniques, and instruments of strategic analysis. These factors are subordinate to the process of harmonization to the requirements of community development and environmental protection according to the new strategy for the development of the European Union 2020 (European Green Pact). This pact also emphasizes the necessity of involving the different factor categories of local accountability, promotion, activation, and the development of specific economic activities of different local contexts of sustainability. The research methodology used involves a case study whose complexity necessitated the use of quality and quantity research methods in order to underline specific elements of the rural area in the Romanian mountainous region. Specifically, we used a strategic diagnosis of the Romanian mountainous region using the PESTEL and SWOT models. In order to have relevant strategic options available, the continuity of research was achieved through the use of SOR analysis, creating a problem tree and an objectives tree.

Objectives: To assess the short-term impact of a single global stretching session on plantar pressures and lumbar range of motion (RoM) over one week in sedentary university students. Design: A randomised controlled trial with two parallel groups. Participants: Sixty-four university students were randomly assigned to a stretching group or control group. The stretching group received a single session of global stretching and the control group remained seated for the same length of time as the stretching session. Main outcome measures: Lumbar RoM and plantar pressures were assessed before, immediately after, 48 hours after, and 7 days after intervention. Results: Group-by-time interaction was significant for lumbar lateral flexion (p = 0.044), right maximal pressure (p = 0.003), left maximal pressure (p = 0.008), right mean pressure (p = 0.025), left mean pressure (p = 0.002), and maximal pressure minus mean pressure in right foot (p = 0.007). The model with plantar pressures showed a significant difference for group-by-time interaction (p = 0.010).Conclusion: Global stretching seems to counteract the ill-effects of prolonged sitting up to seven days with respect to plantar pressure in standing without improving lumbar ROM

Background: Previous neuroimaging studies have identified brain regions related to respiratory motor control and perception. However, little is known about the resting-state functional connectivity (FC) associated with respiratory impairment. We aimed to determine the FC involved in mild respiratory impairment without changing the saturation of percutaneous oxygen. Methods: We obtained resting-state functional magnetic resonance imaging data from 36 healthy volunteers during normal respiration and mild respiratory impairment induced by resistive load (effort breathing). ROI-to-ROI and seed-to-voxel analyses were performed using Statistical Parametric Mapping 12 and the CONN toolbox. Results: Compared to normal respiration, effort breathing activated FCs within and between the sensory perceptive area of respiration (the postcentral gyrus, anterior insular cortex (AInsula), and anterior cingulate cortex) and visual cortex (the visual occipital, occipital pole (OP), and occipital fusiform gyrus). Graph theoretical analysis showed strong centrality in the visual cortex. A significant positive correlation was observed between the dyspnoea score (modified Borg scale) and FC between the left AInsula and right OP. Conclusions: These results suggested that the FCs within the respiratory sensory area via the network hub may be neural mechanisms underlying effort breathing and modified Borg scale scores.

Polyhydroxyalcanoates (PHAs) are biodegradable polymers synthesized in cytoplasmic granules in bacteria, such as Cupriavidus necator (Ralstonia eutropha), Alcaligenes latus, Pseudomonas spp., Comamonas spp. and other species. PHAs accumulation occurs in response to stress conditions, i.e. under high carbon and low nitrogen (24:1 ratio). PHA can be synthesized using recombinant microorganisms (provided with the operon phbA/phbB/phbC), escaping the constrains of nutrient request, except addition of high amount of sugar (glucose, lactose, fructose). In this study; E. coli was genetically modified for PHB production in biofermentors. The production of PHA at industrial scale requires a continuous supplementation of fermentable sugars to support the availability of nutrients and to assess the level of the exponential growth phase; since sugars are required either for bacterial growth either for PHA synthesis and energy storage. The biofermentors need to be run in automated system. Sensors are used at many points in fermentators; in the evaluation of parameters: consumption of sugars; cell density; quantification of PHB synthesis. The need of operational control during the fermentation has prompted us to application of three measurements; one unit linked to a Nanodrop to evaluate OD; one linked to a reaction chamber to measure sugars consumed by enzyme based fluorescence detection; and one for bacteria Nile Blue staining and fluorescence intensity reads. The growth of bacteria on three different plant by-products was monitored and PHB production in four days using a banana by-product feed was optimised. These detectors will make possible to exploit the full potential of bioreactors optimizing the time of use and maximizing the number of bacteria synthesizing PHA.

Glutamate NMDA receptor (NMDAR) hypofunction has been proposed to underlie schizophrenia symptoms because administration of NMDAR antagonists reproduces behavioral and molecular schizophrenia-like phenotypes in healthy humans and animal models. However, the role of specific NMDAR subunits in these schizophrenia-relevant characteristics is largely unknown. Mounting evidence implicates the GluN2D subunit of NMDAR in some of these symptoms and pathology. Firstly, genetic and post-mortem studies show changes in the GluN2D subunit in people with schizophrenia. Secondly, the psychosis-inducing effects of NMDAR antagonists are blunted in GluN2D-knockout mice, suggesting that the GluN2D subunit mediates NMDAR antagonist-induced psychotomimetic effects. Thirdly, in the mature brain, the GluN2D subunit is relatively enriched in parvalbumin (PV)-containing interneurons, a cell type hypothesized to underlie the cognitive symptoms of schizophrenia. Lastly, the GluN2D subunit is widely and abundantly expressed early in development which could be of importance considering schizophrenia is a disorder that has its origins in early neurodevelopment. The limitations of currently available therapies warrant further research into novel therapeutic targets such as the GluN2D subunit which may help us better understand underlying disease mechanisms and develop novel and more effective treatment options.

Single-phase-to-ground fault in non-effectively grounded systems poses serious public safety concern. Along with increasing deployment of low-voltage (LV) sensors, new opportunities and ways are created for solving this traditional problem in distribution systems. A new approach, identifying primary single-phase-to-ground line fault and locating it through measurement data from smart sensors deployed in the secondary side of distribution transformers, is proposed in this paper. When a fault occurs in primary distribution feeder, the transient aerial mode voltage (AMV) of each LV smart sensor is calculated. The fault line can be identified by an abrupt change value of AMV at LV side. Next, by finding the position of the maximum value of this AMV from LV sensors on the fault line, the fault location can be pinpointed to two neighboring distribution transformers. The proposed method has been proven to be efficient and reliable by simulation studies.

The speed-density or flow-density relationship is a fundamental aspect of traffic flow theory. Single-regime models often face challenges in consistently fitting empirical data under diverse traffic conditions. This paper addresses the inaccuracies of single-regime models, attributing them not only to their functional forms but also to data dispersion and sample selection bias. To mitigate these issues, the data is segmented into day and night periods, leading to the creation of separate models for each. Calibration results, conducted on data from two freeways, Tehran-Karaj and Tehran-Qom, reveal distinct challenges, with the former exhibiting high dispersion and the latter showing low dispersion. Surprisingly, single-regime models demonstrate notable effectiveness when applied to distinct day and night data. Further analysis, categorizing data into day and night, results in reduced errors (20-60% improvement in R-Square), emphasizing the potential for enhanced accuracy by considering distinct regimes. Overall, the study underscores the significance of regime-specific considerations for accurate traffic flow modeling. Upon thorough evaluation, the study highlights the superiority of the neural network Multi-layer Perceptron (MLP) over traditional models. The research discusses the implications of incorporating day and night parameters into the models, emphasizing their potential for accuracy enhancement.

A techno-economic model was developed to investigate the influence of components on the system costs of redox flow batteries. Sensitivity analyses were carried out based on a example of a 10 kW/120 kWh vanadium redox flow battery system and the costs of the individual components were analyzed. Particular consideration was given to the influence of material costs and resistances of bipolar plates and energy storage media as well as voltages and electric currents. Based on the developed model it was possible to formulate statements about the targeted optimization of existing battery systems and general aspects for future developments of redox flow batteries.

The Circular Bioeconomy (CBE) combines the concepts of bioeconomy and circular economy. As an alternative concept to the current fossil-based, linear economy, it de-scribes an economy based on the efficient valorization of biomass. It is regional in nature and aims to improve sustainability. An analysis of the transition process, by identifying its success criteria and assessing its impacts through the modelling of technology-specific scenarios is necessary to ensure that CBE concepts are sustainable. However, a compre-hensive consideration of regional influences on both is lacking. Based on extensive literature research and an expert survey, we (i) present a compre-hensive catalog of CBE success criteria and discuss their region-specific character and (ii) develop a methodology based on evaluation matrices that enable to match CBE technolo-gies with regions. The matrices support the evaluation of technological and regional characteristics influencing the successful CBE implementation. The results show that the success criteria "biomass resources", "technological", and "social" are perceived as highly important, and that most of the success criteria are both region- and technology-specific, highlighting the relevance of developing matrices to match them. We describe such matrices indicatively for the two broadest and most im-portant success criteria clusters “social acceptance” and “biomass supply chain”. With this, we substantiate the regional nature of CBE and raise the awareness on the importance of considering regional conditions in CBE transition processes. Furthermore, we provide practical guidance on how regional conditions can be reflected in the selection of technologies, e.g. in regional CBE technology scenarios.

Zika Virus (ZIKV) is a pathogenic member of the flavivirus family, with several unique charac-teristics. Unlike any other arbovirus, ZIKV can be transmitted sexually and maternally, and thus produce congenital syndromes (CZS) due to its neurotropism. This challenges the search for safe active molecules that can protect pregnant women and their fetuses. In this context, and in the ab-sence of any existing treatment, it seemed worthwhile to test whether the known cytoprotective properties of adiponectin and its pharmacological analog, AdipoRon, could influence the outcome of ZIKV infection. We showed that both AdipoRon and adiponectin could significantly reduce in vitro infection of A549 epithelial cells, a well-known cell model for flaviviruses infection studies. This effect was particularly observed when a pre-treatment was carried out. Conversely, ZIKV revealed an ability to down-regulate adiponectin receptor expression and thereby limit adi-ponectin signaling.

SARS-CoV2 (corona virus) has spread globally at an unprecedented rate; so far, increasing SARS-CoV2-infected individuals have been identified. Although the situation in China is improving and is currently under control, the outbreak in other countries and its pandemic management is only beginning to develop. Based on 154 SARS-CoV2 genome sequence analyses, we used receptor–ligand docking to identify one potential point mutation (V354F) on the spike structure which enhances spike binding to ACE2 receptors underlying potential super infection. Importantly, the V354F site on spike S1 had been identified in 5/10 infected French patients living in Paris, who sharing 100% identical SARS-CoV2 genomes. With Covid-19 cases increasing rapidly in France that could lead to a new explosion, we suggest that the French government should identify all potential super spreaders and treat them accordingly. In summary, our study provides on of the measures to avoid the potential second worldwide explosion of SARS-CoV2.

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.

Strawberry root rot caused by Neopestalotiopsis clavispora is one of the main diseases of strawberry and significantly impacts the yield and quality of strawberry fruit. There are now no effective control techniques available except for fungicide sprays, which may directly impact consumers. Biological control is becoming an alternative method for the control of plant diseases to replace or decrease the application of traditional synthetic chemical fungicides. Trichoderma is widely used as a biological agent for controlling strawberry root rot. In order to provide resources for screening the highly effective biocontrol fungus for controlling strawberry root rot caused by Neopestalotiopsis clavispora, the biocontrol mechanism,the control effects of Trichoderma asperellum CMT10 against strawberry root rot and growth-promoting effects on strawberry seedlings were investigated by plate culture, microscopy observation and root drenching methods.The results showed that CMT10 had obvious competitive, antibiotic and hyperparasitism effects on Neopestalotiopsis clavispora CMGF3. The CMT10 could quickly occupy nutritional space, and the inhibition rates of CMT10 against CMGF3 in confrontation culture on 7 d was 65.49%. The inhibition rates of volatile metabolite and fermentation metabolite produced by CMT10 against CMGF3 were 79.67% and 69.84%, respectively. The mycelium of strain CMT10 can act as hyperparasites by making contacting, winding and penetrating hyphae of CMGF3. Pot experiment showed that the biocontrol efficacy of CMT10 on strawberry root rot caused by Neopestalotiopsis clavispora was 63.00%. CMT10 had obvious promotion effect on strawberry growth, the plant height, root length, total fresh weight, root fresh weight, stem fresh weight and root dry weight, with the promotion rates were 20.09%, 22.39%, 87.11%, 101.58%, 79.82% and 72.33%, respectively. Overall, this study showed the ability of Trichoderma asperellum CMT10 to control strawberry root rot and their potential to develop as novel biocontrol agents to replace chemical fungicides for eco-friendly, sustainable agriculture.

Spinocerebellar ataxia type 3 is a neurodegenerative disease caused by an abnormal expansion of CAG repeats in the disease gene ATXN3, leading to prolonged polyglutamine (polyQ) tracts in the respective protein ataxin-3. The polyQ-expanded protein forms polyQ-containing aggregates in several brain regions which leads to neuronal cell loss. Autophagy is thought to play a significant role in clearing these polyQ-containing protein aggregates. Therefore, the autophagy mechanism was investigated in SCA3 with focus on the autophagic protein p62/sequestosome-1. Human and mouse RNA sequencing data were analyzed to determine RNA expression level of autophagic genes. Additionally, autophagy was studied in the SCA3 304Q knock-in mouse model and through several cell culture experiments using HEK-293T cells transfected with ATXN3 of differ-ent polyQ lengths. For cell culture experiments, autophagy was induced with rapamycin treat-ment, proteasomal degradation was blocked with MG132 and degradation of autophagic pro-teins was investigated using cycloheximide treatment. Here, we report an increased autophagy impairment with SCA3 disease progression seen in HEK-293T cells transfected with ATXN3 plasmid with expanded polyQ tracts, higher aged 304Q-knock-in mice, or human post-mortem brain material. Furthermore, co-localized aggregation of the autophagic protein p62 and the dis-ease protein ATXN3 was observed in the course of SCA3 disease. Therefore, we suggest a signifi-cant role for p62 in aggregate formation seen in the neurodegenerative disease SCA3.

Respiratory transmission is the primary route of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Angiotensin I converting enzyme 2 (ACE2) is the known receptor of SARS-CoV-2 surface spike glycoprotein for entry into human cells. A recent study reported absent to low expression of ACE2 in a variety of human lung epithelial cell samples. Three bioprojects (PRJEB4337, PRJNA270632 and PRJNA280600) invariably found abundant expression of ACE1 (a homolog of ACE2 and also known as ACE) in human lungs compared to very low expression of ACE2. In fact, ACE1 has a wider and more abundant tissue distribution compared to ACE2. Although it is not obvious from the primary sequence alignment of ACE1 and ACE2, comparison of X-ray crystallographic structures show striking similarities in the regions of the peptidase domains (PD) of these proteins, which is known (for ACE2) to interact with the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Critical amino acids in ACE2 that mediate interaction with the viral spike protein are present and organized in the same order in the PD of ACE1. In silico analysis predicts comparable interaction of SARS-CoV-2 spike protein with ACE1 and ACE2. In addition, this study predicts from a list of 1263 already approved drugs that may interact with ACE2 and/or ACE1, potentially interfere with the entry of SARS-CoV-2 inside the host cells and alleviate the symptoms of Coronavirus disease (COVID-19).

There is compelling evidence that the nuclear receptor TRβ, a member of the thyroid hormone receptor (TR) family, is a tumor suppressor in thyroid, breast and other solid tumors. Cell-based and animal studies reveal that the liganded TRβ induces apoptosis, reduces an aggressive phenotype, decreases stem cell populations, and slows tumor growth through modulation of a complex interplay of transcriptional networks. TRβ-driven tumor suppressive transcriptomic signatures include repression of known drivers of proliferation such as PI3K/Akt pathway and activation of novel signaling (JAK1/STAT1) and metabolic reprogramming in both thyroid and breast cancers. The presence of TRβ is also correlated with a positive prognosis and response to therapeutics in BRCA+ and triple-negative breast cancers respectively. Ligand activation of TRβ enhances sensitivity to chemotherapeutics. TRβ co-regulators and bromodomain-containing chromatin remodeling proteins are emergent therapeutic targets. This review considers TRβ as a potential biomolecular diagnostic and therapeutic target.

In recent years, there have been frequent reports on the adverse effects of synthetic cannabinoid (SC) abuse. SCs cause psychoactive effects, similar to those caused by marijuana, by binding and activating cannabinoid receptor 1 (CB1R) in the central nervous system. The aim of this study was to establish a reliable quantitative structure-activity relationship (QSAR) model to correlate the structures and physicochemical properties of various SCs with their CB1R-binding affinities. We prepared 15 SCs and their derivatives (tetrahydrocannabinol [THC], naphthoylindoles, and cyclohexylphenols) and determined their binding affinity to CB1R, which is known as a dependence-related target. We calculated the molecular descriptors for dataset compounds using an R/CDK (R package integrated with CDK, version 3.5.0) toolkit to build QSAR regression models. These models were established and statistical evaluations were performed using the mlr and plsr packages in R software. The most reliable QSAR model was obtained from the partial least squares regression method via external validation. This model can be applied in vivo to predict the addictive properties of illicit new SCs. Using a limited number of dataset compounds and our own experimental activity data, we built a QSAR model for SCs with good predictability. This QSAR modeling approach provides a novel strategy for establishing an efficient tool to predict the abuse potential of various SCs and to control their illicit use.

A bacterium known as Akkermansia muciniphila (AkkermansiaA. muciniphila) was detected in human feces in 2004. It is defined as a gram-negative, anaerobic, and mucin-degrading microbe belonging to the Verrucomicrobia species. Although the majority of A. muciniphila is found in the human intestinal tract playing a role in the gut microbiome, there are also smaller levels detected in breast milk and oral cavities as well as in the pancreas and appendix.Evidence suggests that having A. muciniphila present in the gut microbiome has positive effects on human health. As a result, A. muciniphila has been shown to have health benefits when taken as a dietary supplementation where it is considered a promising next-generation probiotic. However, the large-scale production of A. muciniphila remains a challenge due to its need for a stable environment. While culturing A. muciniphila in a mucin-based medium is one option, other strategies that use plate-based mediums have also been explored. Currently, both live and pasteurized forms of A. muciniphila are available on the market and shown to have promising outcomes in animal models. Additionally, researchers are investigating various prebiotics to increase the abundance of A. muciniphila in the human gut. This article presents a detailed summary of the phenotypic characteristics of A. muciniphila and its associations with various human health condition illnesses. Finally, the paper explores A. muciniphila's potential as an effective next-generation probiotic.

Daridorexant, as the first Dual Orexin Receptor Antagonist (DORA) marketed in Europe, offers a novel therapeutic approach to insomnia. However, data regarding its real-world safety are scarce. Thus, the aim of this study was to assess its safety profile using a large-scale pharma-covigilance database. Daridorexant-related Adverse Drug Reaction (ADR) reports from the FDA Adverse Event Reporting System were scrutinized, and ADRs were selected using reporting odds ratio (ROR) as a measure of disproportionality. Frequencies of events related to daridorexant were compared to all other drugs (reference group, RG1) and only to other DORAs (RG2). Only significant disproportionalities to both RGs were evaluated in-depth. A total of 845 dari-dorexant-related reports were selected; nightmares (n = 146; Dari vs. RG1: ROR = 113.74; 95%CI[95.13, 136]; Dari vs. RG2: ROR = 2.35; 95CI%[1.93, 2.85]), depression (n = 22; Dari vs. RG1: 2.13; [1.39, 3.25]; Dari vs. RG2: ROR = 2.31; 95CI%[1.45, 3.67]), and hangover (n = 20; Dari vs. RG1: ROR = 127.92; 95CI%[81.98, 199.62]; Dari vs. RG2: 3.38; [2.04, 5.61]) were considered as safety signals. These data provide valuable insights into the real-world safety profile of dari-dorexant, supporting the existence of safety signals related to nightmares, depression, and hang-over.

Silybin is a natural compound extensively studied for its hepatoprotective, neuroprotective and anti-cancer properties. Envisioning the enhancement of silybin potential by suitable modifications in its chemical structure, here, a series of new 7-O alkyl silybins derivatives were synthesized by Mitsunobu reaction starting from the silybins and tyrosol-based phenols, such as tyrosol (TYR, 3), 3-methoxytyrosol (MTYR, 4) and 3-hydroxytyrosol (HTYR, 5). This research sought to explore the antioxidant and anticancer properties of new eighteen derivatives and their mechanisms. In particular, the antioxidant properties of new derivatives outlined by DPPH assay, showed a very pronounced activity depending on the tyrosyl moiety (HTYR>MTYR>>TYR). A significant contribution of the HTYR moiety was observed for silybins and 2,3-dehydro-silybin based derivatives. According to the very potent antioxidant activity, 2,3-dehydro-silybin derivatives 15ab, 15a and 15b exerted the most potent anticancer activity in human prostate cancer PC-3 cells. Furthermore, flow cytometric analysis for cell cycle and apoptosis revealed that 15ab, 15a and 15b induce strong G1 phase arrest and increase late apoptotic population in PC-3 cells. Additionally, western blotting for apoptotic marker cleaved caspase-3 confirmed apoptosis induction by these silybin derivatives in PC-3 cells. These findings hold significant importance in the investigation of anticancer properties of silybin derivatives and strongly encourage swift investigation in pre-clinical models and clinical trials.

(1) Background: To investigate the effect of phosphohistone H3 (PHH3) and vitamin D receptor (VDR) in the risk assessment of endometriosis, in two cohorts of women with this pathology, those receiving hormonal treatment, and those without treatment; (2) Methods: In 60 cases of women with endometriosis, the paraffin-embedded endometriosis tissue samples, retrieved after surgery, were immunohistochemically (IHC) analyzed aiming to determine the expression status of PHH3 and VDR; (3) Results: The IHC positive index of PHH3 and VDR of these two groups were compared. PHH3 levels were positively correlated with vitamin D levels, both being increased in patients without treatment. Within the group without treatment, PHH3 and VDR expressions were positively associated; (4) Conclusions: IHC analysis of PHH3 and VDR can be used as an additional tool for risk stratification and prognostic assessment in patients with endometriosis.

Bulk composition, mineralogy and microchemistry of various fractions of the filling of the Crater No. 4 at Emmerting were investigated. Here we present mainly the fine fractions, which, in contrast to pebbles larger than ca. 4 cm, are relatively poor in material affected by melting. A 0.1 mm long meteorite fragment without ablation features was found, and remelted fragments of the same body have been identified. The projectile was dominated by enstatite, also containing forsterite, basic plagioclase, Ni-rich pyrrhotite and troilite, kamacite, silica, and probably merrillite. The molten fragments contain porous Mg-rich glass (indicating temperature > 1500 °C), minor Fe oxides, and occasionally uncommon Ni-rich minerals. The bulk composition and electron microprobe show that the amount of meteoritic material is low (<< 1 %), and it is not unequivocally manifested even in platinum-group elements abundances and osmium isotope ratios (the latter, however, were only measured in two samples). This can be explained by dilution of the filling by particles brought after the crater formation, and by probably achondritic composition of the projectile. Relatively large hollow spheroid Fe oxide particles were observed in thin sections from the magnetic fraction. A Mn oxide hollow spherule has also been found. In magnetically separated filling from the nearby Crater No. 5, bulk chemical composition points to contamination with several metals and metalloids probably due to influence of recent alluvial sediments. Therefore, the extent of meteoritic contamination in this crater may be even smaller.

More than 90 different modified nucleosides have been identified in tRNA. Among the tRNA modifications, the 7-methylguanosine (m⁷G) modification is found widely in eubacteria, eukaryotes, and a few archaea. In most cases, the m⁷G modification occurs at position 46 in the variable region and is a product of tRNA (m⁷G46) methyltransferase. The m⁷G46 modification forms a tertiary base pair with C13-G22, and stabilizes the tRNA structure. Recently, we have proposed a reaction mechanism for eubacterial tRNA m⁷G methyltransferase (TrmB) based on the results of biochemical studies and previous biochemical, bioinformatic, and structural studies by others. However, an experimentally determined mechanism of methyl-transfer remains to be ascertained. The physiological functions of m⁷G46 in tRNA have started to be determined over the past decade. To be able to better respond to diseases and infections in which the m⁷G modification is considered to be involved, it is still necessary to further understand the catalytic mechanism of AdoMet and/or the tRNA bound form of m⁷G methyltransferases. In this review, information of tRNA m⁷G modifications and tRNA m⁷G methyltransferases are summarized and the differences in reaction mechanism between tRNA m⁷G methyltransferase and rRNA or mRNA m⁷G methylation enzyme are discussed.

We describe the genomes of two Echovirus isolates from Nigeria as reference enterovirus species B genomes for the region. These Echovirus 7 and 19 genomes have 7,411nt and 7,426nt, and were recovered from sewage contaminated water (in 2010) and an acute flaccid paralysis case (in 2014), respectively.

Since the creation of the first parallel electrical power systems around the world, the rotor angle stability of synchronously operating generators has been one of the most crucial and challenging problems. In modern electricity networks, involving Kazakhstani, where the renewable energy technologies are rapidly penetrating, and the issue of stability takes on even greater importance due to the technical shortcomings of inverter-based generation. In this framework, an analysis of rotor angle transient stability was carried out when replacing existing synchronous generators with doubly fed induction generators under a certain pre-emergency mode. A critical proportion of active power generation by DFIG units was identified at which transient stability can still be maintained due to the sufficient stored kinetic energy of the synchronous machines remaining in operation. In addition, 2 simple solutions were investigated to improve transient stability, such as an increased time of the automatic reclosure operation and the use of special load shedding automation. For the analysis, a real power system of Mangystau region in Kazakhstan was considered, and the PowerWorld software was used.

Protein tyrosine phosphatase receptor type E (PTPRE) is a member of the “classical” protein tyrosine phosphatase subfamily and regulates a variety of cellular processes in a tissue-specific manner by antagonizing the function of protein tyrosine kinases. PTPRE plays a tumorigenic role in different human cancer cells, but its role in retinoblastoma (RB), the most common malignant eye cancer in children, remains to be elucidated. Etoposide resistant RB cell lines and RB patients display significant higher PTPRE expression levels compared to chemosensitive counterparts and the healthy human retina, respectively. PTPRE promotor methylation analyses revealed that PTPRE expression in RB is not regulated via this mechanism. Lentiviral PTPRE knockdown (KD) induced a significant decrease in growth kinetics, cell viability, and anchorage independent growth of etoposide resistant Y79 and WERI RB cells. Caspase-dependent apoptosis rates were significantly increased and a re-sensitization for etoposide could be observed after PTPRE depletion. In vivo chicken chorioallantoic membrane (CAM) assays revealed decreased tumor formation capacity as well as reduced tumor size and weight following PTPRE KD. Expression levels of miR631 were significantly downregulated in etoposide resistant RB cells and patients. Transient miR631 overexpression resulted in significantly decreased PTPRE levels and concomitantly decreased proliferation and increased apoptosis levels in etoposide resistant RB cells, impacts mirroring PTPRE KD effects and indicating PTPRE regulation via this miR. Additionally, PTPRE KD led to altered phosphorylation of protein kinase SGK3 and - dependent on the cell line - also AKT and ERK1/2, suggesting potential PTPRE downstream signaling pathways. In summary, these results indicate an oncogenic role of PTPRE in chemoresistant retinoblastoma.

Mannosylerythritol lipids (MELs), one of the most promising biosurfactants (BS), are glycolipids produced by yeasts or fungi, with great environmental performance and a high compatibility with the human body. MELs besides working as typical surfactants, can form diverse structures when in the critical aggregation concentration (CAC), reducing the surface tension of water and other solutions, and being stable over a wide range of conditions. Among others, MELs present anti-microbial, antitumor, antioxidant and anti-inflammatory activity, skin and hair repair capacity, which opens possibilities for their use in applications from cosmetics and pharmaceutics to bio-remediation and agriculture. However, their market share is still low when compared to other glycolipids, due to their less developed production process and higher production cost. This re-view gathers information on the potential applications of MELs mentioned on the literature since 1993. Furthermore, it is also explored the current strategies being developed to enhance the market presence of MELs, in parallel with the ones developed for rhamnolipids and sophorolipids.

The growing demand for nutritious foods has spurred investigations into alternative sources of nutrition beyond traditional options. For this reason, the present study approaches the amaranth, which is a plant with high potential, highlighting the morphological growth, grain biomass pro-duction, and quantitative traits of seven varieties of amaranth cultivated in the pedoclimatic con-ditions of Somes meadow in Transylvania. A bifactorial trial was implemented with factors ama-ranth species and amaranth varieties. Two amaranth species and seven varieties were studied. Differences are reported between morpho-productive and quantitative traits of the seven amaranth varieties studied in this research. The interrelationships between amaranth morphological traits quantified by using Pearson simple correlations show that morphological traits moderately con-tribute to grain fresh biomass yield, while morphological traits and fresh biomass strongly con-tributed to grains dry biomass yield. Our study shows that morpho-productive, and nutritional characteristics of the seven amaranth varieties comprised by our study recommend the plans to be used in various nutritional aims, being a valuable replacer of traditional raw materials in specific food and feed industry sectors.

The bioactive marine sulfated polysaccharides ulvan and carrageenan, formulated in gels at 1.5, 5.0 and 10% w/w concentrations, were evaluated for their wound healing potential on second-degree burn wounds. The polysaccharide-based gels were administered on the burn-inflamed skin of hairless female SKH-hr2 mice, and the therapeutic effect of the various treatments was assessed based on histopathological analysis, the clinical condition of mice, photo-documentation, evaluation of biophysical skin parameters, and FT-IR spectroscopy.Clinical and histopathological assessment, as well as the reduction rate of the burn wound area, indicated that the 10% w/w carrageenan gel significantly enhanced wound healing, especially at the early stages of the healing process, recovering both the α-helix of collagen and the glycosaminoglycans configuration as evidenced by the FT-IR absorption bandsof skin in vivo and ex vivo. At later stages, the healing effect of the 5% w/w ulvan gel was also notably significant, indicating that carrageenan and ulvan wound dressing gels could potentially contribute to the efficient wound healing of burn wounds.

The development of a highly specific drug delivery system (DDS) for anti-cancer therapeutics is an area of intense research focus. Chemical engineering of a “smart” DDS to specifically target tumor cells has gained interest, designed for safer, more efficient, and effective use of chemotherapeutics for the treatment of cancer. However, the selective targeting and choosing the critical cancer surface biomarker are essential for targeted treatments to work. The folic acid receptor alpha (FRalpha) has gained popularity as a potential target in triple-negative breast cancer (TNBC). We have previously reported on a functionalized folic acid (FA)-conjugated amphiphilic alternating copolymer poly(styrene-alt-maleic anhydride) (FA-DABA-SMA) via a biodegradable linker 2,4-diaminobutyric acid (DABA) that has the essential features for efficient “smart” DDS. This biocompatible DDS self-assembles in a pH-dependent manner, providing stimuli-responsive, active targeting, extended-release of hydrophobic chemotherapeutic agents, and can effectively penetrate the inner core of 3-dimensional cancer spheroid models. The empty FA-DABA-SMA decreased spheroid volume, revealing a previously unknown mechanism of action. Upon further investigation, a size- and shape-dependent interaction FA-DABA-SMA with FR reduced the expression of p53, the product of the highly mutated TP53 gene, and additional oncogenic c-Myc and STAT3 proteins. Here, we investigated how this copolymer influences FR behavior and disrupting the receptor’s functions. Results indicate that FA-DABA-SMA increases FR expression levels in breast MDA MB-231 cancer cells and disrupting FR signaling by the reduction in HES1 and NOTCH1 protein expression levels. Also, FA-DABA-SMA induces apoptosis and further causes a change in the morphology of the MDA MB-231 cells, as well as significantly reduces their ability to migrate in a Scratch wound assay. Collectively, these findings provide a novel insight into the functionalized FA-DABA-SMA copolymer. The 350 kDa and 20 kDa copolymers actively target FRα to initialize internationalization. However, only the large size and sheet-shaped 350 kDa copolymers disrupt FRα signaling. The significance of these novel findings reveals the intracellular activity of the copolymer that is critically dependent on the size and structural shape. This report offers novel therapeutic insight into a dual mechanism of FA-DABA-SMA copolymer for its therapeutic potential for the treatment of cancer.

Structurally related 7-acetyl-2-aryl-5-bromoindoles 2a–d and the 7-acetamido-2-aryl-5-bromoindoles 4a–d as well as their corresponding 3-trifluoroacetyl–substituted derivatives 5a–d and 5e–h were evaluated for potential antigrowth effect in vitro against the human lung cancer (A549) and cervical cancer (HeLa) cells. All of the 3-trifluoroacetyl–substituted 7-acetamido-2-aryl-5-bromoindoles 5e–h were found to be more active against both cell lines when compared to the chemotherapeutic drug, Melphalan. The most active compound 5g induced apoptosis in a caspase dependent manner for both cell lines. Compounds 5e–h were found to significantly inhibit tubulin polymerization. Molecular docking of 5g into the colchicine-binding site suggests that the compounds bind to tubulin by different type of interactions including pi-alkyl, amide-pi stacked and alkyl interactions as well as hydrogen bonding with the protein residues to elicit anticancer activity.

Proposed fundamental laws of biology and a model of health and disease underscore the importance of the lymphatic system. The lymphatics are responsible for two of the laws of biology and the fulcrum of health and disease balancing proliferation with regeneration through the immune system. It is responsible for protection from the environment and repair of senile and damaged tissue. Life is constantly bombarded by forces that increase entropy. Lymphatics provide negative entropy to maintain health. Lymphatics help maintain cellular homeostasis removing products of metabolism. Using these principles, the role of lymphatics is investigated in salt sensitivity hypertension, cardiorenal system, the new pillar of heart failure and kidney disease - Sodium-Glucose Transport Protein 2 (SGLT2) Inhibitors, and brain diseases. The realization of organ lymphatics in maintenance of health and disease opens the avenue to new therapeutics. This is the unrealized potential of lymphatic study.

We developed an ovarian cancer-targeted drug delivery system based on a follicle-stimulating hormone receptor (FSHR) peptide. The lipophilic chemotherapeutic drug SN38 and the photosensitizer IR820 were loaded into the phospholipid bilayer of liposomes. Near-infrared laser irradiation stimulated the generation of reactive oxygen species, causing short-term reactive molecular species and spatial-temporal restricted photodamage to the biological targets. The reactive molecular species and spatial-temporal restricted photodamage enhanced the release and uptake of chemotherapy drugs and increased the sensitivity to chemotherapy drugs in ovarian cancer cells. FSH liposomes loaded with SN38 and IR820 (SN38/IR820-Lipo@FSH) were prepared using thin-film hydration-sonication. FSH peptide binding was analyzed using 1H NMR spectrum and Maldi-Tof. The average size and zeta potential of SN38/IR820-Lipo@FSH were 105.1 ± 1.15 nm (PDI: 0.204 ± 0.03) and −27.8 ± 0.42 mV, respectively. SN38/IR820-Lipo@FSH exhibited good drug-loading properties and the in vitro release was slow. FSH significantly increased the uptake of liposomes, inhibited cell proliferation, and induced apoptosis in A2780 cells. Moreover, SN38/IR820-Lipo@FSH exhibited good tumor-targeting ability and anti-ovarian cancer activity in vivo. The SN38/IR820-Lipo@FSH exhibited specific targeting to A2780 ovarian cancer cells. The combination of chemotherapy and photodynamic treatment based on an FSH peptide-targeted delivery system may be an effective approach to treating ovarian cancer.

COX II containing a dual core CuA active site is one of the three core subunits of mitochondrial Cco, which plays a significant role in the physiological process. In this report, the full-length cDNA of COXⅡ gene was cloned from Sitophilus zeamais, which had an ORF of 684 bp encoding 227 amino acids residues. The predicted COXⅡ protein had a molecular mass of 26.2 kDa with pI value of 6.37, and multiple sequence alignment and phylogenetic analysis indicated that Sitophilus zeamais COXⅡ had high sequence identity 78.51% with the COXⅡ of other insect species, especially similarity to sitophilus oryzae. This gene was subcloned into the prokaryotic expression vector pET-32a, and induced by IPTG in E.coli Transetta (DE3) expression system. Finally the COXⅡ with 6-His tag was purified using affinity chromatography with Ni²⁺-NTA agarose. WB showed the recombinant COXⅡ was about 44 kD, and the concentration of fusion protein was 50μg/mL. UV-spectrophotometer and infrared spectrometer analysis showed that recombinant COXⅡ could catalyze the oxidation of substrate Cytc, and influenced by AITC. It was found that AITC could form a hydrophobic region with COXⅡ protein via molecular docking, besides, a sulfur atom of AITC structure could form a length of 2.9 Å hydrogen bond with Leu-31. These results will provide valuable information for elucidating the role of COXⅡ in Sitophilus zeamais responses to AITC, meanwhile, it will helpful to carry out a point mutation in AITC binding sites for the future research.

The purpose of this study was to determine the maximum tolerated dose (MTD) for stereotactic body radiation therapy (SBRT) in the treatment of non-metastatic prostate cancer. This study was a phase 1 dose escalation trial conducted in Japan. Patients with histologically proven prostate cancer without lymph node or distant metastasis were enrolled. The prescribed doses were 42.5, 45, or 47.5 Gy in five fractions. Dose-limiting toxicity (DLT) was defined as grade (G) 3+ gastrointestinal or genitourinary toxicity within 180 days after SBRT completion and a 6 plus 6 design was used as the method of dose escalation. A total of 16 patients were enrolled, with 6 in the 42.5 Gy group and 10 in the 45 Gy group. No DLT was observed in the 42.5 Gy group. In the 45 Gy group, one patient experienced G3 rectal hemorrhage, and another had G4 rectal perforation, leading to the determination of 42.5 Gy as the MTD. None of the patients experienced biochemical recurrence or death during the follow-up period. We concluded that SBRT for non-metastatic prostate cancer at 42.5 Gy in 5 fractions could be safely performed, but a total dose of 45 Gy increased severe toxicity.

Technological advancements in the Internet of Things (IoT), unmanned aerial vehicles (UAVs), and novel technological tools have transformed disaster management practices from localized approaches to a global framework. These innovations necessitate a unified understanding and application of diverse methodologies at an international level, ensuring they are accessible and operational across different sectors. This integration is crucial not only for technical personnel but also for medical teams, who play a pivotal role in disaster response and management. By fostering a comprehensive grasp of these methods, we can enhance coordination, efficiency, and effectiveness in addressing disasters on a global scale. The authors aimed to provide a comprehensive overview of emerging techniques that are driving shifts in strategic approaches and treatment technologies. Recognized as a domain of continuous research and development, this overview, by necessity, remains an incomplete snapshot of an evolving field. It highlights the dynamic nature of technological and strategic advancements, underscoring the importance of ongoing investigation and innovation to stay abreast of current trends and future directions. The article also highlights the importance of international collaboration beyond societal and national boundaries A single paragraph of about 200 words maximum. For research articles, abstracts should give a pertinent overview of the work. We strongly encourage authors to use the following style of structured abstracts, but without headings: (1) Background: Place the question addressed in a broad context and highlight the purpose of the study; (2) Methods: briefly describe the main methods or treatments applied; (3) Results: summarize the article’s main findings; (4) Conclusions: indicate the main conclusions or interpretations. The abstract should be an objective representation of the article and it must not contain results that are not presented and substantiated in the main text and should not exaggerate the main conclusions.

Soft Rot Pectobacteriaceae (SRP) bacteria as Pectobacterium and Dickeya are phytopathogenic agents responsible of blackleg disease on several crop as potato, affecting the yield and depressing the seed production quality. However, neither conventional nor biocontrol product are available on the market to control this disease. In this study Pseudomonas PA14H7, a bacteria isolated from potato rhizosphere, was selected as a potential antagonist agent against Dickeya. In order to understand the mechanism involved in this antagonism we managed to identify the main active(s) molecule(s) produced by PA14H7. In that way, cell-free supernatant (CFS) of PA14H7 cultures were extracted and analyzed by LC-MS, GC-MS and NMR. We have correlated biological activity in extracted CFS-PA14H7 to the presence of 7-hydroxytropolone (7-HT) complexed with iron. Even if this molecule is produced by other Pseudomonas and mostly known for its antibacterial and antifungal activities, it is the first description of its involvement as an effective molecule against pectinolytic bacteria. We have synthesized 7-HT in order to determine the real amount produced by PA14H7 and to compare its activity at the same concentration with that of CFS-PA14H7. This study aims to understand the origin of the antagonist activity of PA14H7 as a potential biocontrol agent against potato blackleg.

German noise action plans aim to reduce negative health outcomes from noise exposure and identify quiet areas free of noise pollution. Quiet area identification in German noise action plans is based primarily on noise mapping and spatial analysis and not empirical or qualitative data about acoustic environments, thus leaving a gap in the understanding of the quality of formally recognized quiet areas in noise action plans. This work presents a comparative empirical case study in Dortmund, Germany, with the aim to describe the diurnal dB(A) and biophonic properties of quiet areas versus noise 'hot spots'. Sound observations were collected (n=282,764) in five different natural or recreational land use patch types larger than four acres within 33 proposed quiet areas in Dortmund (n=70) and 23 noise hot spots between April 27^th, 2022 and March 2^nd, 2023. We find that quiet areas are on average more than 20 dB(A) quieter than noise hot spots almost every hour of the day. Forests, managed tree stands, cemeteries, and agriculture diel patterns are dominated by dawn dusk chorus in spring and summer, whereas sport and recreation as well as noise hot spots are dominated by traffic and human noise. A novel composite biophony mapping procedure is presented that finds distinct temporal distribution of biophony in forested and agriculture peri-urban locations positively associated with patch size, distance away from LDEN > 55, proximity to water, and the number of vegetation layers in the plant community. Anthrophony distribution dominates urban land uses in all hours of the day, but expands during day and evening and contracts at night and in dusk hours. The procedures presented here illustrate how qualitative information regarding quiet areas can be integrated into German noise action planning.

Stimulation of the alpha 7 nicotinic acetylcholine receptor (α7nAChR) has shown beneficial effects in several acute inflammatory disease models. This study aims to examine whether treatment with the selective α7nAChR agonist PHA 568487 can dampen inflammation and thereby improve cardiac function after myocardial infarction in mice. The possible anti-inflammatory properties of α7nAChR agonist PHA 568487 were tested in vivo using the air pouch model and in a permanent occlusion model of acute myocardial infarction in mice. Hematology parameters and cytokine levels were determined. Infarct size and cardiac function were assessed via echocardiography 24 h and one week after the infarction. Treatment with α7nAChR agonist PHA 568487 decreased 12 (CCL27, CXCL5, IL6, CXCL10, CXCL11, CXCL1, CCL2, MIP1a, MIP2, CXCL16, CXCL12 and CCL25) out of 33 cytokines in the air pouch model of acute inflammation. However, α7nAChR agonist PHA 568487 did not alter infarct size, ejection fraction, cardiac output or stroke volume at 24 h nor at 7 days after the myocardial infarction compared with control mice. In conclusion, despite promising immunomodulatory effects in the acute inflammatory air pouch model, α7nAChR agonist PHA 568487 did not affect infarct size or cardiac function after a permanent occlusion model of acute myocardial infarction in mice. Consequently, this study does not strengthen the hypothesis that stimulation of the α7nAChR is a future treatment strategy for acute myocardial infarction when reperfusion is lacking. However, whether other agonists of the α7nAChR can have different effects remains to be investigated.

Objective: to retrospectively evaluate the incidence rate (IR) of echocardiographic signs suspected for pulmonary hypertension (PH) in Systemic sclerosis (SSc) patients after the introduction of a combination therapy with bosentan and sildenafil for treatment or prevention of digital ulcers. Methods: patients attending the Scleroderma Unit of the Universital Hospital of Careggi from July 2010 to July 2023 were enrolled. Patients older than 18 years old, with an history of digital ulcers, treated with bosentan and sildenafil in combination for at least 12 months were included. Patients with a diagnosis of PH preceding the introduction of the therapy were excluded. Demographical data, disease duration, laboratoristic and instrumental data (pulmonary function tests, echocardiographic estimation of pulmonary artery pressure (PAPs) and ultrasonographic value of renal resistive index) were collected. The IR of echocardiographic signs suspected for pulmonary hypertension and their 95% confidence interval were calculated in events/1000 patients-years.Results: forty-seven patients were enrolled; mean disease duration was 12,14 years (SD 5,87). Mean duration of the combination treatment was 78.33 (SD 41.37) months and total at-risk time was 3525 months. Two patients (4,2%) presented echocardiographic signs of PH (sPAP 50 mmHg and 40 mmHg); the IR was calculated to be 6.8/1000 patients-years (95% CI 6,02-7,7). In one of the 2 patients RHC excluded PAH, while the other patient refused to undergo to RHC and PAH could not be confirmed/excluded. A stability of PFTs and echocardiografic PAPs was observed during the observation time. Conclusions: the results of this retrospective study suggest that combination therapy with endothelin receptor antagonist and Phosphodiesterase-5 (PDE5) inhibitors could help in preventing PAH in SSc; prospective case-control studies on larger population are needed to improve knowledge in this field.

High hopes were associated with the new anti-angiogenic medicament, bevacizumab, which due to the possibility of binding to isoform A of vascular endothelial growth factor (VEGF), inhibited the creation of new blood vessels. However, not only blood vessels are responsible for the tumor cells' spread. During the process of tumor growth, lymphangiogenesis is mediated by other isoforms of the VEGF family, specifically VEGF-C and VEGF-D, which are independent of the bevacizumab action. Therefore, based on the mechanism of bevacizumab action and the processes of angio- and lymphangiogenesis, we formed three hypotheses: 1) if the lymph nodes in the primary ovarian cancers are metastatic, the outcome of bevacizumab treatment is worsened; 2) concerning the second-line treatment, bevacizumab will act in a weakened manner if the recurrence occurs in lymph nodes compared to local recurrences; 3) patients treated by bevacizumab are more likely to have recurrences in lymph nodes. These hypotheses raise the issue of the existing gap of knowledge, which concerns the effect of bevacizumab on the metastatic lymph nodes.

The vomeronasal system serves as a pivotal element in mammalian sensory biology, allowing the perception of chemical signals essential for social communication via the activation of two main receptor families, V1R and V2R. The expression of V1Rs and V2Rs is linked with that of the G-protein alpha-subunits, Gαi2 and Gαo, respectively. The exploration of the evolutionary pathways of V1Rs and V2Rs across all mammalian species remains a main challenge, juxtaposing available genomic data against emerging immunohistochemical evidence. However, recent investigations, in contrast to what is predicted by the currently annotated genomic sequences, have revealed the expression of Gαo in the vomeronasal neuroepithelium of wild canids, including wolves and foxes. In the present study, the employment of a specific antibody raised against the mouse V2R2, member of the C-family of vomeronasal receptors, V2Rs, has confirmed the expression of this receptor in the fox and wolf, but it has revealed the lack of expression in the dog. This may reflect the impact of domestication on the regression of the VNS in this species, in contrast to their wild counterparts, and underscores the effects of artificial selection on sensory functions. Thus, these findings suggest a more refined chemical detection capability in wild species.

The importance of frailty in older people is getting constant recognition as an important aspect both in terms of public health, as well in personal level for the appropriate management of an older person health condition. This is reflected by the continuously increasing number of research studies carried out in several settings across different countries. Sometimes this is very solid, but in other cases there is a considerable gap in terms of accurate and well grounded documentation of frailty status. This is the case in Greece, where we are missing clinically validated tools to approach frailty. We are missing frailty screening tools, such as for instance PRISMA 7, the gold standard tool of Fried criteria is somehow problematic since the question referring to physical activity originates from a questionnaire that has not been translated and validated, while Clinical Frailty Scale has been validated for the translation but not for the capacity to detect frailty. Aim of this study is to validate these tools for their accuracy to detect frailty by using a measurable index of frailty, previously proposed for use in clinical studies: the Short Physical Performance Battery (SPPB). 74 male and female participants have been evaluated for their frailty status using different tools. We observed that PRISMA 7 translation detects frailty only when one question is removed at a cut-off of ≥ 2 and indicated a sensitivity of 88.1%, and specificity of 99.9% with a good correlation with SPPB measurements (r = 0.858; p < 0.001). When CFS was validated using SPPB it demonstrated a very good correlation (r = -0.838; p < 0.001 respectively) as it was the case for the modified Fried Criteria (r = -0.725; p < 0.001). All items demonstrated a good correlation between them. We can here propose that we can accurately assess frailty status in the community setting by using a modified version of Fried criteria, Clinical Frailty Scale translation in Greek and we can screen for frailty by using the Greek translation of PRISMA 7 only after removing the item 6 of the questionnaire.

Li-ion cell designs, component integrity and manufacturing processes all have critical influence on the safety of Li-ion batteries. Any internal defective features that induce a short circuit, can trigger a thermal runaway: a cascade of reactions, leading to a device fire. As consumer device manufacturers push aggressively for increased battery energy, instances of field failure are increasingly reported. Notably Samsung made a press release in 2017 following a total product recall of their Galaxy Note 7 mobile phone, confirming speculation that the events were attributable to the battery and its mode of manufacture. Recent incidences of battery swelling on the new iPhone 8 have been reported in the media, and the techniques and lessons reported herein may have future relevance. Here we look deeper into the key components of one of these cells and confirm evidence of cracking of electrode material in tightly folded areas, combined with a delamination of surface coating on the separator, which itself is an unusually thin monolayer. We report microstructural information about the electrodes, battery welding attributes and thermal mapping of the battery whilst operational. The findings point to the most likely combination of events and highlights the impact of design features, whilst providing structural considerations most likely to have led to the reported incidences relating to this phone.

Thermal fluctuations in two-dimensional (2D) isotropy systems at non zero finite temperatures can destroy the long-range (LR) magnetic order due to Mermin-Wanger theory. Interestingly, the magnetic anisotropy related to spin-orbit coupling (SOC) could stabilize magnetic order in 2D systems. Recently, 2D FexGeTe2 (3≤x≤7) with high curie temperature (TC), as a typical 2D van der Waals metallic ferromagnet, has not only made significant progress in synthetic methods and controlling ferromagnetism (FM), but also actively explored many device applications. In this Review, we introduce six experimental methods, ten ferromagnetic modulation strategies, and three spintronic devices of 2D FexGeTe2 materials. Overall, we have outlined the challenges and potential research directions in this field.

An imbalance between production and excretion of amyloid β peptide (Aβ) in the brain tissues of Alzheimer’s disease (AD) patients leads to Aβ accumulation and formation of noxious Aβ oligomers/plaques. A promising approach to AD prevention is reduction of free Aβ level by directed enhancement of Aβ binding to its natural depot, human serum albumin (HSA). We previously demonstrated the ability of specific low-molecular-weight ligands (LMWLs) of HSA to improve its affinity for Aβ. Here we develop this approach by bioinformatic search for the clinically approved AD-related LMWLs of HSA, followed by classification of the candidates according to the predicted location of their binding sites on HSA surface, ranking of the candidates, and selective experimental validation of their impact on HSA affinity for Aβ. The top 100 candidate LMWLs were classified into the five clusters. The specific representatives of the different clusters exhibit dramatically different behavior, with 3- to 13-fold changes in equilibrium dissociation constants for the HSA-Aβ40 interaction: prednisone favors HSA-Aβ interaction, mefenamic acid shows the opposite effect, while levothyroxine exhibits the bidirectional effects. Overall, the LMWLs of HSA chosen here provide a basis for drug repurposing for AD prevention, and for search for the medications promoting AD progression.

The human landscape transforming activity contributes to the global change of vegetation in different forms. Hunting is one of the most ancient human landscape-shaping activities. Feeders for hunting are particularly disruptive to vegetation. In the present study, we conducted a vegetation survey in these highly disturbed places. We are investigating the vegetation dynamics over several years in in the turkey oak–sessile oak zone, in two areas with different moisture and shade conditions (forest and clearing). One important background factor is changes in precipitation and temperature. The novelty of our present study lies in the fact that the observation takes place with continuous disturbance, where the human influence is very large. Our results confirm that the weed infestation be detectable at bait sites over a long period, and the interannual changes were typical in every year, according to the fact that in August, more weed species are usually present with a greater cover at the bait sites. The main meteorological factors played a role in the degree of weed infestation in each year. There was a higher proportion of vegetation regeneration in wetter years, while dry periods do not favor successional processes. With the drying of the climate, the disturbed areas are constantly losing their natural value, but wetter weather is not an automatic solution either. A more precise understanding of vulnerable systems and careful planning of treatment interventions is necessary.

Cancer treatment is a significant focus in medicine owing to the increasing global incidence. Patients with advanced cancers that do not respond to conventional therapies have limited options and an unfavorable prognosis. Consequently, researchers are investigating complementary approaches to conventional treatments. One such approach is alkalization therapy, which aims to neutralize the acidic tumor microenvironment (TME) by increasing its pH level. The acidic TME promotes inflammation, tumor progression, and drug resistance. Alkalization therapy has been demonstrated to be effective for various cancers. In addition, natural products, such as triterpenoids, parthenolides, fulvic acid, Taxus yunnanensis, and apple pectin have the potential to alleviate symptoms, maintain physical fitness, and improve treatment outcomes of cancer patients through their anti-inflammatory, antioxidant, and anticancer properties. In this review, we focus on the effects of alkalization therapy and natural products on cancer. Furthermore, we present a case series of advanced cancer patients who received alkalization therapy and natural products alongside standard treatments, resulting in long-term survival. We posit that alkalization therapy together with the supplementation of natural products may confer benefits to cancer patients by mitigating the side effects of chemotherapy and complementing standard treatments. However, further research is warranted to validate these clinical findings.

Complaint of transient impairment or loss of memory as an attendant feature in some migraine attacks has long been recognised. In some cases, migraine may be a trigger or precipitating factor for the syndrome of transient global amnesia (TGA). However, the exact frequency of this concurrence is unknown, perhaps related to the absence from the International Classification of Headache Disorders (ICHD3) of amnesia or memory loss symptoms in association with migraine, unlike the situation with epileptic seizure (migralepsy) or stroke (migrainous infarction). Similarly, headache has generally been regarded as an incidental feature of TGA, reported in about 10% of cases. We present further examples of TGA in the context of migraine headache; consider possible reasons why this concurrence might be under-recognised, such as the retrograde amnesia characteristic of TGA; review possible shared pathogenetic mechanisms; and suggest a new terminology, “migramnesia”, which may encourage clinicians to address the possible significance of migraine in the context of an episode of TGA.

Two heating surfaces with longitudinal fins are located within the closed channel inside the housing made of thermal insulation material. The air flow inside the channel was carried out by an axial fan. The heating of the fins is established by using two positive temperature coefficient heating elements (PTC). Air flows circularly from one finned surface to another, and after reaching the required temperature, it leaves the housing. In the heating system conceived in this way, a methodology based on transient thermal irreversibility of heating sources and circular air flow has been established. Volumetric air flow and circulation time within the channel were varied. The total entropy generated does not include hydraulic irreversibility, but transient thermal irreversibility of the air and heat sources. For conducting analytical modeling, the temperature of the PTC heater was considered constant at 423K and 473K. Volumetric air flow varied in the interval from 0.00001m3s-1 to 0.00006m3s-1. The experimental determination of the transient thermal entropy was performed at a much higher air flow rate of 0.005m3s-1 inside the closed channel. Due to the continuous increase in air temperature, the temperatures of both PTC heaters increased within the examined time interval of 300s. According to experimental testing, the total transient thermal entropy of the described heating system has a minimum after 175s from the start of the circular heating of the air. The minimum of transient entropy also implies the optimal time of channel opening and exit of heated air.

The current paper provides a cutting-edge information data length- theoretic approach to the transient M/M/Infinity queueing system. This is a first time ever investigation that unifies information data length and queueing theories. The significant impact of both time and the number of states for the transient M/M/ Infinity queue on both the upper and lower bounds of the obtained information data length is observed and noted. The paper concludes with some challenging open problems, combined with concluding remarks and future research pathways.

In recent years, intelligent identification and prediction of ore deposits based on deep learning algorithm and image processing technology has gradually become one of the research frontiers in the field of geological and metallogenic prediction. However, this method also has many problems that need to be solved. For example, (1) very few trainable image samples containing mineral point labels; (2) The geological image features are small and irregular, and the image similarity is high; (3) It is difficult to calculate the influence of different geological prospecting factors on ore mineralization. Based on this, this paper constructs a deep learning network model Multiscale Feature Attention Framework (MFAF) based on geo-image data. The results show that MFCA-Net module in MFAF model can solve the problem of scarce mine label images to a certain extent. In addition, the channel attention mechanism SE-Net module can quantify the difference of influence of different source factors on mineralization. The prediction map is obtained by applying the MFAF model in the study of deposit identification and prediction in the research area of the southern section of Qin-hang metallogenic Belt. In the forecast map, many regions have high metallogenic potential. Through observation, it is found that the above predicted area covers 100% of the known ore deposits at present, which has a good prediction effect. Later, we can find out the specific reasons through field verification. The multi-scale feature fusion and attention mechanism MFA Framework in this paper can provide a new way of thinking for geologists in mineral exploration. The research of this paper also provides resource guarantee and technical support for the sustainable exploitation of mineral resources and the sustainable growth of society and economy.

Abstract: Kiwifruit, a perennial horticultural crop known for its nutritional value, faces significant challenges due to biotic and abiotic stresses, affecting its yield and quality. Leucine-rich repeat receptor-like proteins (LRR-RLPs), a major group of receptor-like proteins in plants, have diverse functions in plant physiology, including growth, development, signal transduction, and stress responses. Despite their importance, the specific roles of kiwifruit LRR-RLPs in response to biotic and abiotic stresses remain poorly understood. In this study, we investigated the expression patterns of kiwifruit LRR-RLPs under various stress conditions, including pathogen stress, heat stress, waterlogging stress, and copper stress. Through genome and transcriptome analyses, we identified a total of 101, 164, and 105 LRR-RLPs in Actinidia Chinensis 'Hongyang', Actinidia eriantha 'Huate', and Actinidia chinensis 'Red5' kiwifruit, respectively, classified into 9 subgroups based on phylogenetic relationships. Synteny analysis revealed that the expansion of kiwifruit LRR-RLPs was primarily attributed to segmental duplication events. Using RNA-seq data from pathogen-infected kiwifruits, we identified specific LRR-RLP genes potentially involved in different stages of pathogen infection. Additionally, we observed the potential involvement of kiwifruit LRR-RLPs in abiotic stress responses, with upstream transcription factors possibly regulating their expression. Furthermore, protein interaction network analysis unveiled the participation of kiwifruit LRR-RLP genes in the regulatory network of abiotic stress responses. These findings highlight the crucial roles of LRR-RLPs in mediating both biotic and abiotic stress responses in kiwifruit, offering valuable insights for the breeding of stress-resistant kiwifruit varieties.

What does the way autistics bypass, learn, and eventually master language tell us about human linguistic ability? Here, we argue that non-social acquisition of language, in addition to representing a strong argument for nativist models of human language, may be encompassed within the human-specific orientation and mastery of complex embedded structures, of which language represents one realization. Non-social language learning could thus represent the extension of available linguistic, and non-linguistic material processed by human genetic constraints, allowing language acquisition. This deviation from typical developmental language acquisition may ultimately allow access to language, sometimes in its most elaborate forms, and also explains the possibility of the absence of its development when applied to primarily non-linguistic structured material. However, such enlargement of material-specificity does not cast doubts about its human nature. Regardless of the adaptive success or failure of non-social language learning, it is up to science, legal policies, and ethical principles to strive to maintain autism as a human potentiality to further foster our vision of a plural society.

Menaquinone-7 is a member of the vitamin K family whose interest has considerably increased over the last decade due to its beneficial role in human health mainly in respect to bone and cardiovascular health leading to a growing use in different nutritional supplement. Menaquinone-7 can be produced by synthesis or fermentation and its purity profile can differ depending on methodologies and extraction procedures. Finished formulation show a large heterogeneity of purity profiles as well as frequent discrepancies in the nominal content compared to the actual title. In the present study we compared purity profiles of different raw material and we related them to stability assay in normal (12months/25°C/60%RH) and accelerated conditions (6 months/40°C/75% RH) in order to test their performance in presence of different common excipients. Results show that higher purity profile correlates with enhanced stability and this could explain title discrepancies found in finished products found on the market worldwide.

Abstract: : 2,3-dihydro-5,6,7,8-tetranitro-1,4-benzodioxine (TNBD), molecular formula =C8H4N4O10 is a completely nitrated in aromatic ring 1,4-benzodioxane derivative. The con-venient method of TNBD synthesis was developed (yield=81 %). The detailed structure of this compound has been investigated by X-ray crystallography. The results of differential thermal analysis (DTA) obtained with twice re-crystallized material showed onset at 247 and isoterm at 288 0C, with further total degradation at 300 0C. The experimental density 1,85 g/cm3 of TNBD was determined by X-ray crystallography. The spectral properties of TNBD (NMR, FT-IR, Ra-man) were explored. The detonation properties of TNBD calculated by EXPLO 5 code was slightly superior in comparison to standard high energy material - tetryl (detonation velocity of TNBD - 7727 m/s; detonation pressure - 278 kbar; tetryl – 7570 m/s and 226.4 kbar at 1.614 g/cm3, or 260 kbar at higher density - 1.71 g/cm3. The obtained preliminary results might suggest TNBD can be a potential thermostable high energy and density material (HEDM).

Spodoptera frugiperda (J.E. Smith) is a global agricultural pest that poses a threat to crop production, characterized by its refractory polyphagous nature that makes it difficult to control and may lead to damage to woody plants. However, research on its adaptability to woody plants remains limited. This study compares the feeding adaptations (survival rate, pupation time, pupation rate, weight, length, and feeding volume), protective enzyme activities, and feeding preferences of S. frugiperda on leaves of six economically significant tree species (Areca catechu, Aquilaria sinensis, Cocos nucifera, Camellia oleifera, Dalbergia odorifera and Hevea brasiliensis) and maize as a control treatment. The results indicate that A. sinensis as the most vulnerable trees in high risk, H. brasiliensis and C. nucifera presented varying degrees of susceptibility, A. catechu, C. oleifera, and D. odorifera were unsuitability for S. frugiperda. In conclusion, this report extensively explores the feeding effects of S. frugiperda on six economically important tree species, and provides insights into the feeding preferences on these plants, thereby informing the potential threat posed by S. frugiperda to economically vital trees.

There are four subtypes of adenosine receptors (ARs), named A1, A2A, A2B and A3, all of which are G protein-coupled receptors. The A2BAR, coupled to both Gαi and Gαq G proteins, is one of the several G-protein-coupled receptors that are expressed in a significantly higher level in some cancer tissues in comparison to adjacent normal tissues. There is growing evidence that the A2BAR plays an important role in tumor cell proliferation, angiogenesis, metastasis, and immune suppression. Thus, A2BAR antagonists are potentially novel attractive anticancer agents. Several antagonists targeting at the A2BAR are currently in clinical trials for various types of cancers. In this review, we first describe the signaling, agonists, and antagonists of the A2BAR. We further discuss the role of the A2BAR in the progression of various types cancers, and the rationale of using A2BAR antagonists in cancer therapy

Keywords: retinoblastoma, RB, gastric inhibitory polypeptide receptor, GIPR, trefoil factor family peptide, TFF1, CAM, tumorigenesis, MK0893, miR5-542-5p

The pathogenesis of transient global amnesia (TGA), a dramatic but self-limiting episode of anterograde amnesia with a variable duration of retrograde amnesia, remains unknown. Although most episodes are single, TGA has a finite recurrence rate. Studies of case series and large patient cohorts have typically been used to investigate possible precipitating and predisposing factors for TGA. Study of recurrent TGA episodes in single cases might provide another way to address pathogenetic factors. A patient with recurrent TGA is presented to illustrate such considerations with respect to possible chronobiological factors in TGA pathogenesis.

Transient global amnesia (TGA) is an uncommon clinical syndrome characterized by a loss of short-term memory and disorientation that resolves in twenty-four hours. The etiology is unknown and the diagnosis is made by exclusion of other possible etiologies that may cause similar patterns and the reversibility of the condition in less than 24 hours. Here we report a 60-year-old male presented with sudden onset of disorientation and short-term memory loss early in the morning while at home and started to ask his whereabouts and what happened. He had no history of significant medical or psychiatric disease. There was no history of previous similar episodes. He had no recent history of sleep problems, head trauma, substance abuse, or loss of consciousness. He had no history of seizure disorder, or migraine. A neurologic examination revealed a normal wakefulness state with mild disorientation, and short-term memory impairment. He had score of 18/30 on mini-mental state examination (which later returned to normal baseline in 24 hours). Extensive lab investigations did not show any abnormal findings. Brain MRI did not show any acute cerebral pathology. The EEG was negative for any abnormal cerebral activity. His memory improved and returned to normal baseline over the course of a 20-hour from the onset. After exclusion of potential causes and the patient returned to normal state of memory, the diagnosis of transient global amnesia was made. At the follow-up visit, the patient was in a state of normal function without a recurrence of memory impairment. Here we presented this interesting case of transient global amnesia. TGA is diagnosis of exclusion and important to keep in mind when evaluating a patient with acute onset of short-term memory impairment, especially when etiological investigation revealed no potential cause.

In this paper, we analyzed the live fish trajectory recorded from an experiment in an experimental vertical slot fishway. Combined with a numerical simulation, we demonstrated that randomness shown in fish trajectory might not merely be attributed to fish's random choices in its swimming, also could be an adaption consequence to the bulk unsteady turbulent flow structure. Simple superposing the fish trajectory on the time-averaged flow field obtained either by interpolating on discrete point measurements or numerical simulation is not an ideal method for fish movement description in fishway engineering. How to model the fish paths in transient flow and the necessity of simultaneous recording of the flow field and the fish locomotion are challenging topics. The suggested spectrum analysis of the flow field may provide a new general method to reproduce the fish trajectory in a complex turbulent flow.

Despite the recognized potential of nanoparticles, only a few formulations have progressed to clinical trials, and an even smaller number have been approved by the regulatory authorities and marketed. Virus-like particles (VLPs) have emerged as promising alternatives to most explored nanoparticles because of the absence of viral genetic material, their incapacity to replicate, mimicry of viral structure, and tropism conservation. Furthermore, VLPs can be surface functionalized with small molecules to improve circulation half-life and target specificity. Through the functionalization and coating of VLPs, it is possible to optimize the response properties to a given stimulus, such as heat, pH, an alternating magnetic field, or even enzymes. Surface functionalization can also modulate other properties, such as biocompatibility, stability, and specificity, deeming VLPs as potential vaccine candidates or delivery systems. In this review, we address the different types of functionalization of VLPs, their importance, and their consequent biomedical applications.

Reducing GHG emissions is a crucial challenge in urban areas, characterized by high energy consumption and reduced exposure to nature. In this context, the urban green system could play a pivotal role. In the literature, scholars analyzed both the ability of species-specific and layout-specific green infrastructures to increase carbon sequestration and the best location sites of new green infrastructures, to increase the provision of overall ecosystem services. There is a lack of studies helping green urban planners and designers choose where and which green infrastructure to implement, based on vegetation species-specific performance and local carbon emissions of city components. This paper uses tree inventory data from a medium-sized city in central Italy (Perugia) to develop a spatial analysis of the urban parks' performance in carbon sequestration. Then, the method evaluates the carbon emission of a public city building to generate a spatialized balance between buildings’ demand and trees’ supply, to support local decisions about the best locations for new green infrastructures and the choice between species. The paper contributes to GIS-based tools that vary the recommended location sites and species for new green infrastructures based on the demanded ecosystem service.

Research on titanium oxo complexes (TOCs) are usually focused on their structure and photocatalytic properties. Findings from these investigations spurred our interest in exploring also their potential biological activities. In this study, we focused on the synthesis and structure of a compound with the general formula [Ti8O2(OiPr)20(man)4] (1), which was isolated from the reaction mixture of titanium(IV) isopropoxide with mandelic acid (Hman) in a molar ratio of 4:1. The structure (1) was determined using single-crystal X-ray diffraction, while spectroscopic studies provided insights into its physicochemical properties. To assess the potential practical applications of (1), its microcrystals were incorporated into a polymethyl methacrylate (PMMA) matrix, yielding composite materials of the type PMMA + (1) (2 wt.%, 5 wt.%, 10 wt.%, and 20 wt.%). The next stage of our research involved the antimicrobial activity evaluation of the obtained materials. Investigations carried out demonstrated antimicrobial activity of pure (1) and its composites (PMMA + (1)) against both Gram-positive and Gram-negative strains. Furthermore, MTT tests conducted on the L929 murine fibroblast cell line confirmed the lack of cytotoxicity of these composites. Our study identified (1) as a promising antimicrobial agent, also for producing composite coatings.

Indole is a versatile pharmacophore widely distributed in bioactive natural products. This privileged scaffold has been found in a variety of molecules isolated from marine organisms such as algae and sponges. Among these, indole alkaloids represent one of the biggest, most promising family of compounds, having shown a wide range of pharmacological properties, including anti-inflammatory, antiviral and anticancer activities. The aim of this review is to show the current scenario of marine indole alkaloid derivatives, covering not only the most common chemical structures, but also new synthetic routes developed during the last years as well as promising therapeutic applications.

Cell-culture meat is a novel concept to replace traditional meat produced from animals, and to satisfy rising food demands due to the world population growth. It is still a young field and requires to solve technical issues including cell sources and types, efficient culture for large scale production, taste and texture for customer satisfaction. The current review summarized traditional beef meat production and evaluation methods for customer satisfaction. In particular, serum biomarkers for beef meat evaluation are discussed, which can be applicated for cell-culture meat production.

This study aimed to investigate the appearance and frequencies of the booroola polymorphism of the bone morphogenetic protein receptor 1b (BMPR1B) gene (FecB) and the embrapa polymorphism of the growth differentiation factor 9 (GDF9) gene (FecGE) in sheep in Thailand. A total of 454 cross-bred sheep blood samples were collected from four provinces in Thailand during August 2022 to July 2023. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to identify the FecB and FecGE genotype. The history of ewe birth types was collected from the owners to analyze the association between Fecundity (Fec) genotypes and the history of birth types. The genotypic frequencies of FecB for homozygous genotype (B/B), heterozygous genotype (+/B) and wild-type (+/+) were 0.22%, 1.54%, and 98.24%, respectively. Meanwhile, the genotypic frequencies of FecGE for homozygous genotype (E/E), heterozygous genotype (+/E), and wildtype (+/+) were 0.00%, 2.42%, and 97.58%, respectively. Furthermore, three ewes exhibited both FecB and FecGE genotypes. Fisher’s exact test revealed that the possessor of FecB genotype was associated with multiple births (p<0.01). Both FecB and FecGE mutations were identified in crossbred sheep in Thailand. Sheep containing FecB allele is a better candidate to be selected to improve the prolificacy of crossbred sheep in Thailand.

The article focuses on mining of non-energy mineral resources with minimum environmental impacts. It issues from research results of a project Competence Centre for Effective and Ecological Mining of Mineral Resources implemented at the Faculty of Mining and Geology at VŠB-Technical University of Ostrava, Czech Geological Survey, a company Watrad ltd., a state enterprise Diamo, a company RPS Ostrava plc and a company Sedlecký kaolin plc. The paper starts with a partial analysis of the existing legal norms related to mining and processing of mineral resources. Next, it analyses mineral resource mining options free of negative environmental impacts. The fundamental tool to assess potential environmental impacts of mining is the implementation of Environmental Impact Assessment (EIA) process for a given mineral resource. In the Czech Republic environmental impact assessment is carried out by course of Act 100/2001 Coll. Its important amendment is Act 39/2015 Coll. claiming, inter alia, that the environmental impact assessment is rigidly connected with other permits and procedures, such as the zoning process and building construction permits. The article describes the environmental impacts of mining of non-energy mineral resources, including the following factors: appropriation of land, impacts on surface water, ground water and soil, noise, influence on the landscape character, and air pollution. The paper also includes a case study summarizing information on the environmental factors that may play a role in potential underground mining of graphite in the deposit Český Krumlov - Městský Vrch and the deposit Lazec - Křenov.

Fifty years on from the classical fluid-mosaic model of Singer and Nicolson, current views of the plasma membrane portray a much more complex view of this interface region. Compartmentalization, together with transbilayer and lateral asymmetries, provide the structural foundation for functional specializations at the cell surface, including the active role of the lipid microenvironment in the modulation of membrane-bound proteins. The chemical synapse, the site where neurotransmitter-coded signals are decoded by neurotransmitter receptors, adds another layer of complexity to the plasma membrane architectural intricacy, mainly due to the need to accommodate a sizeable number of molecules in a minute subcellular compartment with dimensions barely reaching the micrometer. In this review, we discuss how Nature has developed suitable adjustments to accommodate different types of membrane-bound receptors and scaffolding proteins via membrane microdomains, and how this “efford-sharing” mechanism has evolved to optimize crosstalk or separation or coupling where/when appropriate. To this end, we use a fast ligand-gated neurotransmitter receptor, the nicotinic acetylcholine receptor, and a second-messenger G-protein coupled receptor, the cannabinoid receptor, as paradigmatic example.

The Diophantine equation for which p is prime 2^n = p^2 + 7 and n is integers with p > 0, is examined in this work. It is demonstrated by examining the characteristics of the equation that the only solutions meeting these requirements are p = 3 with n = 5 and p = 5 with n = 7. In order to analyze the above equation, it is necessary to look at the properties of primes and how they relate to powers of two. These results advance our knowledge of prime numbers and how they behave in certain mathematical problems.

The purpose of our study was to discuss Rab 7 effects in chronic kidney disease (CKD). Methods: Using WT and Rab 7-/- mice as target animal, and HK-2 and HMEC-1 cell co-cultured to make cell model. Measuring kidney tissues were evaluated by Sirius red staining, immunohistochemistry staining to CD 34 protein, Transmission electron microscope (TEM) and gelatin zymography to MMP-2 activities. The cell proliferation were measured by CCK-8 and Ki67 protein expression. Measuring cell invasion and total length were evaluated by transwell and in vitro angiogenesis assay. MMP-2 activities were evaluated by gelatin zymography in cell groups. The relative proteins expression were evaluated by Western blot in kidney tissues and cell groups. Results: Hypoxia promoted the expression of Rab7 in HMEC-1, and the activity of MMP-2 related with regulatory molecules such as reversion-inducing-cysteine-rich protein with kazal motifs (RECK), negative correlation with membrane-type 1 MMP (MT1-MMP or MMP-14) on the membrane of TECs. In addition, the up-regulation of the expression of Rab7 inhibited the activity of MMP-2 and proliferation and cyclization of endothelial cells, and the inhibitor of MMP-2 partially blocked the effects of Rab7 on angiogenesis. Furthermore, the similar data were also obtained in the fibrosis kidney tissues of mice. Conclusion: Rab 7 might be an important role in hypoxic TECs regulated angiogenesis, Rab 7 knockdown could improve hypoxic TECs regulated angiogenesis, the relative mechanisms might be correlation with RECK pathway and MMP-2 activities in vivo and vitro study.

Extensive evidence indicates that activation of P2X7 receptor (P2X7R), an ATP-gated ion channel highly expressed in immune and brain cells, is strictly associated with the release of extracellular vesicles. Through this process, P2X7R-expressing cells regulate non-classical protein secretion and transfer bioactive components to other cells, including misfolded proteins, participating in inflammatory and neurodegenerative diseases. In this review, we summarize and discuss the studies addressing the impact of P2X7R activation on extracellular vesicle release and their activities.

We introduce a series of twisted donor-acceptor (D-A) carbazole-benzophenone based electroactive bipolar derivatives that were synthesized through the reaction of 4-fluorobenzophenone with various partially alkylated 3,3’-bicarbazoles. The comprehensive structural characterization of these compounds is provided. These amorphous materials exhibit suitable glass transition temperatures ranging from 57 to 102 °C and demonstrate high thermal stability, with decomposition temperatures reaching 400 °C. Moreover, the developed materials exhibit elevated photoluminescence quantum yields (PLQY) of up to 75.5% and favorable HOMO-LUMO levels, along with suitable triplet-singlet state energy values. Due to their good solubility and suitable film-forming properties, all the compounds were evaluated as blue emitters dispersed in 4,4’-bis(N-carbazolyl)-1,10-biphenyl (CBP) host for the fabrication of organic light-emitting diodes (OLEDs) in concentration dependent experiments. Among these experiments, the device containing 15 wt% of the guest 4-(9’-{2-ethylhexyl}-[3,3’]-bicarbazol-9-yl)benzophenone demonstrated the best characteristics, achieving maximum brightness of 3581 cd/m2, current efficiency of 5.7 cd/A, power efficiency of 4.1 lm/W and external quantum efficiency of 2.7%.

The review explores the therapeutic potential of mangrove plants as sources of bioactive compounds, particularly focusing on their anti-inflammatory properties. Mangroves, found in tropical and sub-tropical tidal coasts, exhibit unique ecological and biological activities. The review compiles and examines 136 research findings published between 1982 and 2018, with 41 studies specifically addressing the anti-inflammatory properties of mangroves in Indian coastal regions, including the Andaman and Nicobar Islands. It summarizes the chemical structures, molecular weights, formulas, solvents, and biological activities of these mangroves, as reported by various researchers over time. The data underscore the significant potential of tropical Indian mangroves in anti-inflammatory applications. However, a notable research gap exists regarding the extraction of bioactive compounds from mangrove species in the Andaman and Nicobar Islands compared to other regions such as Gujarat, Maharashtra, Goa, Karnataka, Kerala, Tamil Nadu, Andhra Pradesh, Odisha, West Bengal, and Puducherry. Overall, the compilation provides valuable insights into mangrove-based studies for drug discovery research, emphasizing the need for further exploration and exploitation of these natural resources.

Global warming may increase the potential evapotranspiration (Etp), thereby affecting the amount of clean water resources available in a region. In this study, the systematic biases in temperature outputs of 24 global climate models (GCMs) under 3 emission scenarios are corrected by using 8 bias correction methods. The trend of Etp in Yangzi River Delta in the 21st century is projected by using 4 Etp calculation formulas. The uncertainty of the projections is estimated and decomposed by using multi-way analysis of variance. The influence of uncertainty on the projected change signal is quantified by using the signal-to-noise ratio. The results show that, relative to the reference period (1971~2000), the annual mean daily Etp in Yangzi River Delta will increase by 0.14~0.17mm/d during the period 2021~2050 and by 0.21~0.41mm/d during the period 2061~2090, respectively. During 2021~2050, the uncertainty of Etp increase projections is dominantly contributed by the main effects of GCM (63%) and Etp calculation formula (24%). During 2061~2090, it is mainly contributed by the main effect of GCM (36%), followed by the main effects of emission scenario (34%) and Etp calculation formula (18%). The increase projections of Etp are generally reliable and robust during the two projection periods.

Transient analysis of gas flow in pipeline was studied. Finite Element Method based on ANSYS FLOTRAN was used to account for changes in pressure, temperature and flow rate. Compressibility factor function of temperature and pressure was considered. For non-isothermal transient results, the pressure and the flowrate gave wave propagation as a result of slow transients created by demand condition at the outlet end of custody transfer. Results obtained were in agreement with the demand restrictions at the outlet end of custody transfer indicating that the predictions are accurate and reliable. The results demonstrated that the Finite Element Method gave accurate prediction of pressure, temperature and flowrate in transient gas studies. For steady state non-isothermal model, results showed that the magnitude of the average pressure drop was higher when pressure was predicted with constant compressibility factor, but the same average pressure drop was reduced when the pressure was predicted with variable compressibility factor, z. Since compressibility factor is a function of temperature and pressure, the above findings signifies that in the case when gas temperature does not stabilize, the prediction of pressure with isothermal model and constant compressibility factor will lead to significant errors.

Introduction: Previous studies have suggested that the tyrosine kinase receptor RET plays a sig-nificant role in the hematopoietic potential in mice and could also be used to expand cord-blood derived hematopoietic stem cells (HSCs). The role of RET in the human iPSC-derived hematopoi-esis has not been tested so far. Methods: To test the implication of RET on the hematopoietic potential of iPSCs, we activated its pathway with the lentiviral overexpression of RETWT or RETC634Y mutation in normal iPSCs. An iPSC derived from a patient harboring the RETC634Y mutation (iRETC634Y) and its CRISPR-corrected isogenic control iPSC (iRETCTRL) were also used. Hematopoietic potential was tested using 2D cul-tures and evaluated regarding the phenotype and the clonogenic potential of generated cells. Results: Hematopoietic differentiation from iPSCs with RET overexpression (WT or C634Y) led to a significant reduction in the number and in the clonogenic potential of HSCs (CD34+/CD38-/CD49f+) as compared to control iPSCs. Similarly, the hematopoietic potential of iRETC634Y was reduced as compared to iRETCTRL. Transcriptomic analyses revealed a specific ac-tivated expression profile for iRETC634Y compared to its control with evidence of overexpression of genes which are part of the MAPK network with negative hematopoietic regulator activities. Conclusion: RET activation in iPSCs is associated with an inhibitory activity in iPSC-derived hematopoiesis, potentially related with MAPK activation.

Aiming at the limitations of single-functionality, limited applicability, and complex designs prevalent in current metasurfaces, we propose a terahertz multifunctional and multiband tunable metasurface utilizing a VO2-metal hybrid structure. This metasurface structure comprises a top VO2-metal resonance layer, a middle polyimide dielectric layer, and a gold film reflective layer at the bottom. This metasurface exhibits multifunctionality, operating independently of polarization and incident angle. The varying conductivity states of the VO2 layers, enable the metasurface to achieve various terahertz functionalities, including single-band absorption, broadband THz absorption, and multiband perfect polarization conversion for linear (LP) and circularly polarized (CP) incident waves. Finally, we believe that the functional adaptability of the proposed metasurface expands the repertoire of options available for future terahertz device designs.

Modern organic synthesis is majorly focused on developing environmentally benign synthetic protocols by employing green chemistry principles. Accordingly, in our recent research work, we herein report the use of modified supramolecular host cyclodextrin as an effective solid based green catalyst for accessing structurally diverse and medicinally relevant pyrimidone architectures. The catalyst and the synthesized compounds 4 (a-r) were characterized using FT-IR, NMR and GC-Mass spectroscopy. Major highlights of the reported work include: atom economical process, extremely milder reaction conditions, operational simplicity, high isolated yields, and excellent catalyst turnover number. The molecular docking studies suggest that the compound 4n has the hydrogen bonding, hydrophobic and π-pair interactions with the active site of active sites of CXT M 15 receptor.

Non-normal mode stability analysis has long been employed to study linear transient characteristics of wall bounded shear flows. However, the application of this approach to investigate shear flows with stratified thermal conditions (STCF) has received limited attention. This paper examines thermal effects on Taylor-Couette flow. The results in this study indicate the possibility of a subcritical bifurcation in stratified Taylor-Couette flow.

We discuss a central concept of nanothermdynamics; the subdivision potential. We explain how it can be measured or calculated for some typical ensembles, as this has been disputed in the literature. We proceed to discuss its meaning for particular systems, and predict scaling laws for three ensembles. The laws depend on the small system geometry in a predictable way for an ideal gas model with surface adsorption. We provide new equations which relate the subdivision potential to experimental investigations, and give expressions for grand canonical ensembles of spheres, cylinders, slit pores and fluids confined in porous media. The subdivision potential is not compatible with the popular Hadwiger theorem in geometry, and can therefore not be described by a Minkowski set of variables. It is equivalent to Gibbs descriptions when shape- and size variables are defined.

A Pogorelov polytope is a combinatorial simple 3-polytope realizable in the Lobachevsky (hyperbolic) space as a bounded right-angled polytope. It has no 3- and 4-gons and may have any prescribed numbers of k-gons, k ≥ 7. Any polytope with only 5-, 6- and at most one 7-gon is Pogorelov. For any other prescribed numbers of k-gons, k ≥ 7, we give an explicit construction of a Pogorelov and a non-Pogorelov polytopes. Any Pogorelov polytope different from Löbel polytopes can be constructed from the 5- or the 6-barrel by cuttings off pairs of adjacent edges and connected sums with the 5-barrel along a 5-gon with the intermediate polytopes being Pogorelov. For fullerenes there is a stronger result. Any fullerene different from the 5-barrel and the (5, 0)-nanotubes can be constructed by only cuttings off adjacent edges from the 6-barrel with all the intermediate polytopes having 5-, 6- and at most one additional 7-gon adjacent to a 5-gon. This result can not be literally extended to the latter class of polytopes. We prove that it becomes valid if we additionally allow connected sums with the 5-barrel and 3 new operations, which are compositions of cuttings off adjacent edges. We generalize this result to the case when the 7-gon may be isolated from 5-gons.

During the last years there has been a high interest in the development of new purely-organic single-component conductors. Very recently, we have reported a new neutral radical conductor based on the perchlorotriphenylmethyl (PTM) radical moiety linked to a monopyrrolo-tetrathiafulvalene (MPTTF) unit by a -conjugated bridge (1). Interestingly, this system behaves as a semiconductor with high conductivity and small energy gap under high pressure. With the aim of developing a new material with improved conducting properties, we have designed and synthesized the radical dyad 2 which was functionalized with an ethylenedithio (EDT) group in order to improve the intermolecular interactions of the TTF subunits. The physical properties of the new radical dyad 2 were studied in detail in solution to further analyze its electronic structure as well as its potential use as radical conductor in the solid state.

SARS-CoV-2 resembles the ancient mythical creature Hydra. Just like with the Hydra, when one head is cut, it is followed by appearance of two more heads, suppression of one SARS-CoV-2 variant causes appearance of newer variants. Unlike Hydra that grows identical heads, newer SARS-CoV-2 variants are usually more infective, which can be observed as time evolution of the virus at hand, which occurs through acquisition of mutations during time. The appearance of new variants is followed by appearance of new COVID-19 pandemic waves. With the appearance of new pandemic waves and determining of sequences, in the scientific community and general public the question is always raised of whether the new variant will be more virulent and more pathogenic. The two variants characterized in this paper, BA.5.2 and BF.7, have caused a pandemic wave during the late 2022. This paper gives full chemical and thermodynamic characterization of the BA.5.2 and BF.7 variants of SARS-CoV-2. Having in mind that Gibbs energy of binding and biosynthesis represent the driving forces for the viral life cycle, based on the calculated thermodynamic properties we can conclude that the newer variants are more infective than earlier ones, but that their pathogenicity has not changed.

The pharmacological effects of the fruiting body of Ophiocordyceps sinensis (Os) exerted antioxidant, anti-virus, and immunomodulatory, whereas the anti-inflammatory effects and active components of Os mycelial submerged culture (OMSC) are not known. This study aimed to investigate the active compounds in the fermented liquid (FLOS), hot water (WEOS), and 50-95% (EEOS-50, EEOS-95) ethanol extracts of OMSC and their anti-inflammatory effects and potential mechanisms in LPS-stimulated microglial BV2 cells. The results demonstrated that all of the OMSC extracts could inhibit NO production in BV2 cells. EEOS-95 exhibited the strongest inhibitory effects (41 % inhibitory ability at 500 µg/mL), and its ergosterol, GABA, total phenolic, and total flavonoid contents were significantly higher than those of the other extracts (18.60, 18.60, 2.28, and 2.14 mg/g, p < 0.05, respectively). EEOS-95 also has a strong inhibitory ability against IL-6, IL-1β and TNF-α with IC50 of 617, 277 and 507 µg/mL, respectively, which is higher than that of 1 mM melatonin. The anti-inflammatory mechanism of EEOS-95 seems to be associated with up-regulation of PPAR-γ/Nrf-2/HO-1 antioxidant-related expression and down-regulation of NF-κB/COX-2/iNOS pro-inflammatory expression signaling. Therefore, we hypothesized that EEOS-95 can prevent neurodegenerative diseases, but the effect on the application in vivo should be further investigated.

The synthesis of new collagen, chitosan and chitosan-collagen coated magnetic nanoparticles have been done. Two types of cross-linkers for polymer shell stabilization were used: glutaraldehyde (Gla) as a standard cross-linker and new one – squaric acid (SqA). Structure and morphology of prepared nanoparticles were characterized by ATR-FT IR, XRD and TEM analysis. The immobilization of lipase from Candida rugosa was performed on the nanoparticles surface. The amount of immobilized enzyme was quantified by the Bradford method. All of lipase-biopolymers coated nanoparticles were characterized with good activity recovery. A little hyperactivation of lipase immobilized on nanoparticles with SqA was observed. All of prepared lipase-immobilized nanoparticles were characterized with very good reusability.

Pancreatic cancer (PC) has a poor prognosis and displays resistance to immunotherapy. A better understanding of tumor-derived extracellular vesicles (EVs) effects on immune responses might contribute to improved immunotherapy. EVs derived from Capan-2 and BxPC-3 PC cells isolated by ultracentrifugation were characterized by atomic force microscopy, western blot (WB), nanoparticle tracking analysis and label-free proteomics. Fresh PBMCs from healthy donors were treated with PC- or control-derived heterologous EVs followed by flow cytometry analysis of CD8+ and CD4+ lymphocytes. Proteomics of lymphocytes sorted from EV-treated, or -untreated PBMCs was performed and IFN-γ concentration was measured by ELISA. Notably, most of the proteins identified in Capan-2 and BxPC-3 EVs by proteomic analysis were connected in a single functional network (p=1x10-16) and were involved in “Immune System” (FDR: 1.10x10-24 and 3.69x10-19, respectively). Interestingly, treatment of healthy donor-derived PBMCs with Capan-2 EVs, but not with BxPC-3 EVs or heterologous control EVs induced early activation of CD8+ and CD4+ lymphocytes. Proteomics of lymphocytes sorted from EV-treated PBMCs was consistent with their activation by Capan-2 EVs, indicating IFN-γ among major upstream regulators, as confirmed by ELISA. Proteomic and functional analyses indicate that PC-EVs have pleiotropic effects, and some may activate early immune response, which might be relevant for the development of highly needed immunotherapeutic strategies in this immune-cold tumor.