It is estimated that pancreatic cancer will be the 2^nd leading cause of cancer-related deaths globally by 2030, highlighting the ongoing lack of effective treatment options in this devastating condition. There is a lack of reliable prognostic or predictive markers in pancreatic cancer to guide management decisions, whether for systemic chemotherapy, molecularly targeted therapies, or immunotherapies. To date, the results for targeted agents and immunotherapies in unselected populations of chemo-refractory pancreatic cancer have not met expectations. The reasons for this lack of efficacy of immunotherapy in pancreatic cancer are incompletely understood. The challenges in pancreatic cancer include the physical barrier created by the dense desmoplastic stroma surrounding the tumor, chemokine-mediated exclusion of T cells, poor antigenicity, paucity of infiltrating T cells within the tumor, ultimately leading to an immunosuppressive microenvironment. A better understanding of the role of inflammation in pancreatic cancer, its tumor microenvironment and individualized patient-related features, be they molecular, clinical or histopathological would enable a more effective tailored approach to the management of pancreatic cancer. In this review, the role of inflammation, the immune tumor microenvironment and potential immune biomarkers in pancreatic cancer are explored.

Reservoir computers (RCs) are a biology inspired computational framework for signal processing typically implemented using recurrent neural networks. Recent work has shown that Boolean networks (BN) can also be used as reservoirs. We analyze the performance of BN RCs, measuring their flexibility and identifying factors that determine effective approximation of Boolean functions that are applied in a sliding-window fashion over a binary signal, either non-recursively or recursively. We train and test BN RCs of different sizes, signal connectivity, and in-degree to approximate 3-bit, 5-bit and 3-bit recursive binary functions. We analyze how BN RC parameters and function average sensitivity, a measure of function smoothness, affect approximation accuracy as well as the spread of accuracies for a single reservoir. We found that approximation accuracy and reservoir flexibility are highly dependent on RC parameters. Overall, our results indicate that not all reservoirs are equally flexible and RC instantiation and training can be more efficient if this is taken into account. The optimum range of RC parameters opens up an angle of exploration for understanding how biological systems might be tuned to balance system restraints with processing capacity.

Inflorescence architecture underpins sexual reproduction in wild Musa species and productivity in edible banana cultivars. In a functional analysis we identified the apical inflorescence and lateral ‘cushion’ meristems and the change in flower type as the three primary components of inflorescence architecture. Five genotypes of two clone-sets of edible plantains (Musa AAB), were grown for four generations along an elevation gradient (1100 m to 2200 m, 16°C to 24°C) straddling the equator in the humid highlands of East Africa. The data consisted of peduncle length at harvest, fruit per hand (Fh) and hands per bunch (Hb). The activity of the apical inflorescence meristem drives peduncle length and lateral ‘cushion’ meristems determine fruit per hand. However, Hb is determined by a change in flower type – from fruit-forming to non-fruit forming. Site temperature affected Hb more than Fh, while development of the genet (rhizome) changed the allocation of resources between Hb and Fh, independently of the effect of site temperature. Clone-sets differed in their response to genet development. Cooler temperatures reduced the number of fruit-forming flowers in an inflorescence and changed the balance away from female towards male flowers. In banana breeding schemes, manipulating inflorescence components independently raises options for producing genotypes better suited to markets, environments, and cultural practices.

Thermodynamics of protein-ligand interactions seems to be associated to a narrow range of Gibbs Free Energy. As a consequence, a linear enthalpy-entropy relationship showing an apparent Enthalpy-Entropy compensation (EEC) is frequently observed associated to the study of protein-ligand interactions. This EEC affects negatively the design and discovery of new and more efficient drugs capable of binding protein-targets with a higher affinity. Originally attributed to experimental errors, compensation between H and TS values is a real observable fact, although its molecular origin has remained obscure and controversial. Herein we show the results of a data search of G values of 2558 protein-ligand interactions and 3025 “in vivo” ligand concentrations from the Protein Data Bank bind Database and the Metabolome Data Base (2020). These results, together with the mechano-statistical interpretation of the thermodynamic properties leads to the conclusion that the EEC has no basis in statistical thermodynamics. It can be plausibly explained as a consequence of the narrow range of G associated to protein-ligand interactions. The Gaussian distribution of the G values matches very well with that of ligands. These results suggest the hypothesis that the set of G values for the protein-ligand interactions is the result of the evolution of proteins. The conformation versatility of present proteins and the exchange of thousands (even millions) of minute amounts of energy with the environment may have functioned as a homeostatic mechanism to make G of proteins adaptive to changes in availability of ligands, and therefore achieve the maximum regulatory capacity of the protein function. Finally, a plausible strategy to avoid the EEC is suggested.

In this work, the problem is considered for eliminating a non-uniform rectilinear smearing of an image by mathematical and computer-based way, for example, a picture of several cars taken with a fixed camera and moving with different speeds. The problem is described by a set of 1-dimensional Fredholm integral equations (IEs) of the first kind of convolution type with a 1-dimensional point spread function (PSF) at uniform smearing and by a set of new 1-dimensional IEs of a general type (not convolution type) with a 2-dimensional PSF at non-uniform smearing. The problem is also described by one 2-dimensional IE of convolution type with a 2-dimensional PSF at uniform smearing and by a new 2-dimensional IE of a general type with a 4-dimensional PSF at non-uniform smearing. The problem for solving Fredholm IE of the first kind is ill-posed (unstable). Therefore, IEs of convolution type are solved by the Fourier transform (FT) method and Tikhonov's regularization (TR), and IEs of general type are solved by the quadrature/cubature and TR methods. Moreover, the magnitude of the image smear Δ is determined by the original “spectral method”, which increases the accuracy of image restoration. It is shown that the use of a set of 1-dimensional IEs is preferable to one 2-dimensional IE in the case of non-uniform smearing. In the inverse problem (image restoration), the Gibbs effect (the effect of false waves) in the image may occur. It can be edge or inner. The edge effect is well suppressed by the proposed technique “diffusing the edges". In the case of an inner effect, it is eliminated with difficulty, but the image smearing itself plays the role of diffusing and suppresses the inner Gibbs effect to a large extent. It is shown (in the presence of impulse noise in an image) that the well-known Tukey median filter can distort the image itself, and the Gonzalez adaptive filter also distorts the image (but to a lesser extent). We propose a modified adaptive filter. A software package was developed in MatLab and illustrative calculations are performed.

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.

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.

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.

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.

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.

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.

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.

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.

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

The SARS-CoV-2 Hydra with many heads (variants) has been causing the COVID-19 pandemic for 3 years. The appearance of every new head (SARS-CoV-2 variant) causes a new pandemic wave. The last in the series is the XBB.1.5 “Kraken” variant. In the general public (social media) and in the scientific community (scientific journals), during the last several weeks since the variant has appeared, the question was raised of whether the infectivity of the new variant will be greater. This article attempts to provide the answer. Analysis of thermodynamic driving forces of binding and biosynthesis leads to the conclusion that infectivity of the XBB.1.5 variant could be increased to a certain extent. The pathogenicity of the XBB.1.5 variant seems to be unchanged compared to the other Omicron variants.

Viroids represent the simplest, but are also among the most interesting life-like forms. They represent a great problem in agriculture. Moreover, pathogens similar to viroids, such as the hepatitis Delta virus represent a risk for human health. Viroids encode no proteins, but are still able to hijack their host cells’ metabolism to perform multiplication. This paper attempts to reply three questions about viroids. First, how can viroids hijack their host cells’ metabolism, even though they encode no proteins to achieve this? Second, what advantages do viroids have from their simplicity? Third, what can viroids, as the simplest life-like forms, tell us about life as a natural phenomenon? These questions are discussed from the perspective of biothermodynamics. In order to do this, elemental composition, biosynthesis reactions and standard thermodynamic properties of viroids have been determined and analyzed.

HIV-1, like other viruses, represents an open thermodynamic system. This is why it is important to know its thermodynamic properties. Virus-host interactions are performed at the membrane as antigen-receptor binding. Antigen-receptor binding represents a chemical reaction, similar to protein-ligand interactions. The driving force for antigen-receptor binding is Gibbs energy of binding. Knowing Gibbs energy of binding, it is possible to estimate the rate of virus binding and entry into host cells. In this paper, binding equilibrium constants and standard Gibbs energies of binding between the HIV-1 gp120 antigen and the CD4 receptor have been reported at 4°C, 22°C and 37°C.

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.

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.

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.

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.

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.

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.

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.

The novel coronavirus disease (COVID-19) pandemic has resulted in over 720 million confirmed cases and 7 million deaths worldwide, with insufficient treatment options. Innumerable efforts are being made around the world for faster identification of therapeutic agents to treat the deadly disease. Postacute sequelae of SARS-CoV-2 infection or COVID-19 (PASC), also called Long COVID, is still being understood and lacks treatment options as well. A growing list of drugs are being suggested by various in silico, in vitro and ex vivo models, however currently only two treatment options are widely used: the RNA-dependent RNA polymerase (RdRp) inhibitor remdesivir, and the main protease inhibitor nirmatrelvir in combination with ritonavir. Computational drug development tools and in silico studies involving molecular docking, molecular dynamics, entropy calculations and pharmacokinetics can be useful to identify new targets to treat COVID-19 and PASC, as shown in this work and our recent paper that identified alendronate as a promising candidate. We have now investigated all bisphosphonates which can bind competitively to nidovirus RdRp-associated nucleotidyl (NiRAN) transferase domain, and systematically down selected seven candidates (CHEMBL608526, CHEMBL196676, CHEMBL164344, CHEMBL4291724, CHEMBL4569308, CHEMBL387132, CHEMBL98211), two of which closely resemble the approved drugs minodronate and zoledronate. This work and our recent paper together provide an in silico mechanistic explanation for alendronate and zoledronate users having dramatically reduced odds of SARS-CoV-2 testing, COVID-19 diagnosis, and COVID-19-related hospitalizations, and indicate that similar observational studies with minodronate could be valuable.

A burgeoning body of scholarship identifies and discusses botanic gardens as increasingly important centres of biodiversity conservation and sustainability. Notwithstanding the high quality and richness of this literature, it encompasses relatively autonomous fields of expertise that are neither designed nor expected to promote cross-disciplinary, integrative, accounts of botanic gardens as institutions of conservation and sustainability. Bridging key aspects of the botanic garden literature, this article brings into conversation historical accounts with contemporary scholarship on the matter. In so doing, it unveils dilemmas and challenges faced by botanic gardens as they grapple with their historic legacies, but also renew their relevance in nurturing sustainable socio-environmental futures. The article proceeds by covering three focal points. First, it summarizes the scholarly literature on the history of botanic gardens. Second, it presents accounts of current scientific and biodiversity conservation endeavours as reflexive engagements with their historical legacies. Third, it addresses the recent emergence of socio-cultural missions at botanic gardens as a significant step beyond their historical focus on plants and plant ecosystems.

Intracellular aggregates of the alpha-synuclein protein result in cell loss and dysfunction in Parkinson’s disease and atypical parkinsonism, such as multiple system atrophy and dementia with Lewy bodies. Each of these neurodegenerative conditions, known collectively as alpha-synucleinopathies, may be characterized by a different suite of molecular triggers that initiate pathogenesis. The mechanisms whereby alpha-synuclein aggregates in turn mediate cytotoxicity also remain to be fully elucidated. However, recent studies have implicated the cell-to-cell spread of alpha-synuclein as the major mode of disease propagation between brain regions during disease progression. Here, we review the current evidence for different modes of alpha-synuclein cellular release, movement and uptake, including exocytosis, exosomes, tunnelling nanotubes, glymphatic flow and endocytosis. A more detailed understanding of the major modes by which alpha-synuclein pathology spreads throughout the brain may provide new targets for therapies that halt the progression of disease.

(1) Background: Globally, about 600 million people are afflicted with diabetes, and one of its most prevalent complications is neuropathy, a debilitating condition. At present, the exploration of novel therapies for alleviating diabetic neuropathy-associated pain is genuinely captivating, considering that current therapeutic options are characterized by poor efficacy and significant risk of side effects. In the current research, we evaluated the antihyperalgesic effect of sildenafil (phosphodiesterase-5 inhibitor) – metformin (antihyperglycemic agent) combination and its impact on biochemical markers in alloxan-induced diabetic neuropathy in rats; (2) Methods: The study comprised a cohort of 70 diabetic rats and 10 non-diabetic rats which were submitted to hot, cold, and tactile stimulus tests. Morover, we investigated the influence of this combination on TNF-α, IL-6 nitrites and thiols levels in brain and liver tissues; (3) Results: The results demonstrated that all sildenafil-metformin combinations decreased the pain sensitivity in von Frey test, Hot-plate test and Cold-plate test. Furthermore, alterations in nitrites and thiols concentrations and pro-inflammatory cytokines (specifically TNF-α and IL-6) were noted following a 15-day regimen of various sildenafil-metformin combinations. (4) Conclusions: The combination of sildenafil and metformin has a synergistic effect in alleviating pain in alloxan-induced diabetic neuropathy rats. Additionally, the combination effectively decreased inflammation, inhibited the rise in NOS activity, and provided protection against glutathione depletion.

To assess the community health workers’ (CHWs) knowledge, attitude, and practices (KAP) in type-2 diabetes (T2D) and hypertension (HTN) management. We thus also sought to assess the potential health system barriers for incorporating CHWs in T2D and HTN management. Mixed-method study comprised (1) a survey among 153 active CHWs to assess their KAP of T2D and HTN, and (2) semi-structured interviews with key informants to understand challenges of the health system and proposed solutions in incorporating CHWs in T2D and HTN management. The majority of CHWs correctly answered general knowledge questions on NCDs, risk factors, and prevention; however, only one-quarter correctly answered questions on smoking, family history, or tobacco use as risk factors. Most respondents appeared to have positive attitudes and have been practicing some activities related to T2D and HTN. Both financial and non-financial resource constraints were cited as challenges of the health system; therefore, re-structuring the role definition of CHWs and task of responsibilities, and assessment the need and workload have been proposed as ways forwards to effectively incorporate CHWs in T2D and HTN care. CHWs in Cambodia have shown their potential in T2D and HTN management; however, a well-designed strategy including technical training, clearly defined roles and responsibilities, and strong supporting structure are important to maximize their potential in the health system.

Here we will model the curvature and contraction of space-time using as a basis the equation of state of an ideal gas and the Hawking´s equation for the temperature of a black hole. We will use this mathematical model to hypothesize that the Boltzmann´s constant depends on the state of matter, that is, there is a known Boltzmann´s constant for flat space-time and an effective Boltzmann´s constant for curved space-time. This model will allow us to quantify the structure of space-time and will serve as a basis to determine the origin of gravity and the origin of elementary particles. Using the Shannon-Boltzmann-Gibbs entropy relation, we will demonstrate that information is not lost and depends on the state of matter, the information is encoded and depends on the effective Boltzmann´s constant.

Similarly to a phoenix, SARS-CoV-2 has appeared periodically in waves. The new variants that appeared through mutations have during the 4 years of the pandemic suppressed earlier variants, causing new waves of the pandemic. The Omicron BA.2.86 Pirola variant is the latest in the sequence of SARS-CoV-2 variants, which appeared in 2023. The BA.2.86 variant has started to spread rapidly and we are witnesses of a new epidemic wave. In this short period, an increased infectivity was noticed, which results in rapid spreading and decreased pathogenicity, which results in a lower number of severe cases. However, in the public there is a fear of further development of the epidemic. This analysis was made with the goal to assess the risks in the period of late 2023. Mutations that were developed by the BA.2.86 variant have led to a change in empirical formula and thermodynamic properties. It seems that there is no ground for fear of an extensive spreading of severe forms, but there are reasons for caution and monitoring of the spreading of the epidemic and potential appearance of new mutations.

Obesity poses significant challenges in rural communities worldwide due to limited resources and healthcare access. Practical, innovative, and culturally sensitive approaches are essential. Time-Restricted Eating (TRE), aligning food intake with circadian rhythms, emerges as a promising strategy. By restricting eating to specific time windows, TRE synchronizes with the body's internal clock, offering potential metabolic health benefits. This review examines TRE's potential in rural obesity management, highlighting its simplicity and scalability. While TRE may address rural health disparities, cultural considerations and challenges such as undernutrition must be acknowledged for effective implementation. Overall, TRE shows promise in improving metabolic health and well-being in rural populations.

Concrete contributes 8% of all global carbon emissions making the need to find substitute critical for environmental sustainability. Research has indicated the potential for recycled plastics to be used as concrete substitutes. This study extends existing research by investigating the use of polycarbonate (PC) in plastic sand bricks as a mechanical equivalent to concrete. PC has high compressive strength, durability, impact strength, thermal resistivity, clarity, fatigue resistance, and UV resistance. This work provides a method and mold to produce a matrix of sand-plastic sample compositions with dimensions adhering to ASTM D695 standard for compressive properties of rigid-plastic. Compositions of 0% (control), 20%, 30%, 40%, and 50% sand by weight were tested. Samples were tested for compressive strength until yield and stress-strain behaviors plotted. The results for 100% PC demonstrated an average and maximum compressive strength of 71 MPa and 72 MPa, respectively. The 50% PC and 50% sand composition yielded an average and maximum compressive strength of 71 MPa and 73 MPa respectively with an increase in compressive stiffness, and transition to shear failure resembling cement. With a composite density of 1.86 g/cm3 against concrete’s average 2.4 g/cm3, and a compressive strength exceeding commercial concrete demands of 23.3 MPa to 30.2 MPa, this lightweight alternative meets the strength demands of concrete, reduces the need for new construction materials, and provides an additional recycling opportunity for nonbiodegradable waste plastic.

Plant leaf area index (LAI) is a key characteristic affecting field canopy microclimate. In addition to traditional professional measuring instruments, smartphone camera sensors have been used to measure plant LAI. However, when smartphone methods were used to measure conifer forest LAI, very different performances were obtained depending on whether the smartphone was held at the zenith angle or at a 57.5° angle. To validate further the potential of smartphone sensors for measuring conifer LAI and to find the limits of this method, this paper reports the results of a comparison of two smartphone methods with an LAI-2000 instrument. It is shown that both methods can be used to reveal the conifer leaf-growing trajectory. However, the method with the phone oriented vertically upwards always produced better consistency in magnitude with LAI-2000. The bias of the LAI between the smartphone method and the LAI-2000 instrument was explained with regard to four aspects that can affect LAI: gap fraction, leaf projection ratio, sensor field of view (FOV), and viewing zenith angle (VZA). It was concluded that large FOV and large VZA cause the 57.5° method to overestimate the gap fraction and hence underestimate conifer LAI, especially when tree height is greater than 2.0 m. For the vertically upward method, the bias caused by the overestimated gap fraction is compensated for by an underestimated leaf projection ratio.

Responding to changing value creation processes in the sheet metal working sec-tor, where the complexity and interchangeability of products challenge traditional dif-ferentiation strategies, this empirical analysis explores integrating service-oriented and data-driven business models as new paths to ensure competitiveness, especially for small and medium-sized enterprises (SMEs). This study aims to capture the current state and challenges associated with the implementation of these business models in this sector. The research was conducted through semi-structured interviews with SMEs in the industry. The findings indicate that service-oriented and data-driven business models are not yet widely adopted and that manufacturing companies re-quire support in their implementation. Fields of action were identified for the industry. These are "Creating awareness and understanding", "Recognizing added value", "In-creasing company maturity" and "Understanding the change process". Cooperation between science and industry is essential in tackling these fields of action to ensure the successful integration of such business models in manufacturing companies. This pa-per identifies challenges in the fields of action that companies must address through a structured approach promoting awareness, recognizing value, improving organiza-tional maturity, and understanding the change process to successfully implement ser-vice-oriented and data-driven business models.

Lumpy skin disease (LSD), caused by a virus within the Poxviridae family and Capripoxvirus genus, induces nodular skin lesions in cattle, spreading through direct contact and insect vectors, significantly affecting global cattle farming. Despite available vaccines, their effectiveness is limited by poor bioavailability and adverse effects. Our study aimed to identify potential inhibitors targeting LSD-associated DNA polymerase protein, selecting LSDV039 for further investigation through comprehensive analysis and computational methods. Virtual screening revealed rhein and taxifolin as potent binders among 380 phytocompounds, with respective affinities of -8.965 and -7.195 kcal/mol. Canagliflozin and tepotinib exhibited strong affinities (-9.858 and -8.856 kcal/mol) among 718 FDA-approved antiviral drugs. Molecular dynamics simulations of canagliflozin, tepotinib, rhein, and taxifolin highlighted taxifolin's superior stability and binding energy. Rhein displayed compactness in RMSD and RMSF but fluctuations in Rg and SASA, while canagliflozin demonstrated stability compared to tepotinib. The study highlights the promising potential of repurposed drugs and phytocompounds as LSD therapeutics. However, extensive validation through in-vitro, in-vivo, and clinical trials is crucial for their practical application.

Much research has been conducted to determine how hair regeneration is regulated, as this could provide therapeutic, cosmetic, and even psychological interventions for hair loss. The current study focused on the hair growth effect and effective utilization of fatty oil obtained from Bryde's whales through high-throughput DNA microarray approach in conjunction with immunohistochemical observations. The research also examined the mechanisms and factors involved in hair growth. In an experiment using female C57BL/6J mice, the vehicle control group (VC: propylene glycol: ethanol: water), the positive control group (MXD: 3% minoxidil), and the experimental group (WO: 20% Whale Oil) were topically applied to the back of the mouse. The results showed that 3% MXD and 20% WO were more effective than VC in promoting hair growth, especially 20% WO. Furthermore, in hematoxylin and eosin-stained skin tissue, an increase in the number of hair follicles and subcutaneous tissue thickness was observed with 20% WO. Whole-genome transcriptomic analysis also showed that 20% WO may have lower stress- and inflammation-related responses than 3% MXD. Therefore, whale oil can be expected to be used as a safe hair growth agent.

Leishmaniasis are neglected diseases that affect regions such as South Asia, South Africa and Latin America, less developed regions. Current treatment, for cutaneous, mucocutaneous and visceral leishmaniosis, which are the main forms of the disease, is based on the administration of pentavalent antimonial and amphotericin B. However, these drugs have low efficacy and high toxicity. For this reason, the search for new treatments for this disease is necessary, based on studies of new molecules and their conformations. The research proposed the conformational study of brominated guanidine compounds with potential antileishmanial activity using Nuclear Magnetic Resonance (NMR) and X-ray diffraction (XRD) techniques. The present study involves the bro-minated molecules, LQOF-G2, LQOF-G30, LQOF-G35 and LQOF-G35-Br. The later was synthesized by the reaction of LQOF-G35 with NBS under IR irradiation at 120 Watts of potency and dichloro-methane as solvent by 12-h of exposition. The obtained results demonstrated the efficiency of the bromination method, since two bromines atoms entered the molecule. Furthermore, NMR analysis showed the occurrence of a conformational change from Z to E when compound LQOF-G35 was brominated to LQOF-G35-Br. This feature was well confirmed by comparative DRX study of the LQOF-G35 and LQOF-G35-Br compounds. The antileishmanial activity of LQOF-G2 e LQOF-G35 motivated the synthesis of new brominated compounds LQOF-G30 e LQOF-G35-Br.

Postprandial glucose levels between 4 and 7.9 hours (PPG4–7.9h) correlate with mortality from various diseases including hypertension, diabetes, cardiovascular disease, and cancer. This study aimed to assess if predicted PPG4–7.9h could diagnose diabetes. Two groups of participants were involved: Group 1 (4420 participants) had actual PPG4–7.9h, while Group 2 (8422 participants) lacked this measure but had all the diabetes diagnostic measures. Group 1 underwent multiple linear regression to predict PPG4–7.9h using 30 predictors, achieving accuracy within 11.1 mg/dL in 80% of the participants. Group 2 had PPG4–7.9h predicted using this model. Receiver operating characteristic curve analysis showed that predicted PPG4–7.9h could diagnose diabetes with an accuracy of 87.3% in Group 2, with a sensitivity of 75.1% and specificity of 84.1% at the optimal cutoff of 102.5 mg/dL. Simulation on 10,000 random samples from Group 2 revealed that 175 participants may be needed to investigate PPG4–7.9h as a diabetes diagnostic marker with a power of at least 80%. In conclusion, predicted PPG4–7.9h appears to be a promising diagnostic indicator for diabetes. Future studies seeking to ascertain its definitive diagnostic value might require a minimum sample size of 175 participants.

Based on the Flashing Ratchet Potential (FRP) and Electro-Spectroscopy detection techniques, a new detection method was experimentally examined. This method allows the detection of sub-micro particles in the human exhaled air such as viral particles and other biological agents. The detection signal created by this method is carried out by electron current buildup forming an Electric Current-Spectrum (ECS) distinguishing the contents of the exhaled air samples. The detection method was developed based on FRP and a beam of free charges passing through the electrodes of the FRP. The ECS is characterized by low-energy free charges interacting with the medium through which they pass, where numerous free charges are scattered (delayed) as a result of these interactions. The resulting ECS is characterized by FRP's capacity to drift back the delayed free charges to their original starting positions. By comparing the ECS of two exhale air samples, this new technology can be utilized to identify the presence of viral and microorganisms’ particles. The time-escalating ECS difference quickly indicates the presence of such particles. Moreover, the FRP's optimal operating settings was experimentally defined, in addition to the experimental evaluation of its functionality to confirm the FRP's promising sensing capabilities, which were statistically examined several times to ensure the reproducibility of the results.

SARS-CoV-2 belongs to the group of RNA viruses with a pronounced tendency to mutate. Omicron BA.2.75 is a subvariant believed to be able to suppress the currently dominant BA.5. Omicron BA.2.75 is characterized by a greater infectivity compared to earlier Omicron variants. However, Gibbs energy of biosynthesis of virus particles is slightly less negative compared to those of other variants. Thus, the multiplication rate of Omicron BA.2.75 is lower than that of other variants. This leads to slower accumulation of newly formed virions and less damage to host cells, indicating evolution of SARS-CoV-2 towards decreasing pathogenicity.

Scientific studies on the impact of wood species on solid fuel production, performance, and sustainability are grossly inadequate. The knowledge of this is imperative as users of solid fuels are increasing rapidly, especially in Africa. On this note, it becomes necessary to explore measures that will improve its efficiency and sustainability as an energy source. This study investigates some properties of selected wood species used as an energy source in Nigeria and their pelleting potential. Nine (9) samples were characterized and assessed for suitability of pelleting following four wood pellet quality standards. The findings revealed Anogeissus leiocarpus as the species with the best rating score in terms of fuel properties while Vitellaria paradoxa as the lowest. However, in terms of conformity with the four wood pellets standards, Khaya senegalensis, Parkia biglobosa and Anogeissus leiocarpus having presented density, calorific value, sulfur, arsenic, cadmium, and lead within the limits of the wood pellet quality standards were considered the best wood species in terms of fuel suitability and pelleting potential. The findings therefore suggest that not all wood species are suitable as fuel. Thus, for species that do not meet the standard wood pellet requirements, alternatives such as the use of biomass blends, additives, or process adjustments can be employed to adapt the quality to the standards or by using the fuels in improved cookstoves.

Background: Learning arrangements in health care profession education are increasingly taking place in digital environments. VR in nursing education, as one of the digital elements, is the subject of controversial debate. On the one hand it supports the authenticity of case studies by adding realistic perspectives and information. On the other hand, the costs of developing and maintaining software and hardware hinder long-term implementation. Methods: In this paper, we describe our findings and insights from two different research projects focused on the incorporation of digital tools, particularly virtual reality (VR), into nursing education. Based on the German context, our aim is to promote the adoption of innovative digital methods in nursing education and to offer invaluable experiences from the field. Results: Starting with a brief recapitulation of the projects, we then elucidate the pedagogical strategies for embedding VR-driven scenarios in nursing education. Based on our experiences during the projects we identify various positive aspects, such as change of perspective and simulating acute situations. Key findings: Although potential drawbacks remain, we advocate long-term implementation and specific use of VR at the interface between theory and practice. Nevertheless it is crucial to establish regular evaluation observing the value of digitalisation, especially VR; for nursing education.

Sarcopenia is an age-related condition that involves a progressive decline in muscle mass and function, leading to increased risks of falls, frailty, and mortality. Although the exact mechanisms are not fully understood, aging-related processes like inflammation, oxidative stress, reduced mitochondrial capacity, and cell apoptosis contribute to this decline. Disruption of the circadian system with age may initiate these pathways in skeletal muscle, preceding the onset of sarcopenia. At present, there is no pharmacological treatment for sarcopenia, only resistance exercise and proper nutrition may delay its onset. Melatonin, derived from tryptophan, emerges as an exceptional candidate for treating sarcopenia due to its chronobiotic, antioxidant, and anti-inflammatory properties. Its impact on mitochondria, organelle where it is synthesized and crucial in aging skeletal muscle, further highlights its potential. In this review, we discuss the influence of clock genes in muscular aging, with special reference to peripheral clock genes in the skeletal muscle, as well as their relationship with melatonin, which is proposed as a potential therapy against sarcopenia.

Ewing sarcoma (EWS) is an aggressive pediatric malignancy of the bone and soft tissues in need of novel therapeutic options. To identify potential therapeutic targets, we focused on essential biological pathways that are upregulated by EWS-FLI1, the primary oncogenic driver of EWS, including mitotic proteins such as Aurora Kinase A (AURKA), Kinesin Family Member 15 (KIF15) and its binding partner, targeting protein for Xklp2 (TPX2). KIF15/TPX2 cooperates with KIF11, a key mitotic kinesin essential for mitotic spindle orientation. Given the lack of clinical grade KIF15/TPX2 inhibitors, we chose to target KIF11 (using SB-743921) in combination with AURKA (using VIC-1911), given phosphorylation of KIF15S1169 by Aurora A is required for its targeting to the spindle. In vitro, the drug combination demonstrated strong synergy (Bliss score ≥10) at nanomolar doses. Colony formation assay revealed significant reduction in plating efficiency (1-3%) and increased percent accumulation of cells in G2/M phase with the combination treatment (45-52%) upon cell-cycle analysis indicating mitotic arrest. In vivo studies in EWS xenograft mouse models showed significant tumor reduction and overall effectiveness: drug combination vs vehicle control (p≤0.01), SB-743921 (p≤0.01) and VIC-1911 (p≤0.05). Kaplan-Meier curves demonstrated superior overall survival with the combination compared to vehicle or monotherapy arms (p≤0.0001).

Clusterin (CLU) protein is involved in various pathophysiological processes including carcinogenesis and tumor progression. In recent years, the role of the secretory isoform has been demonstrated in tumor cells, where it inhibits apoptosis and favors the acquisition of resistance to conventional treatments used to treat cancer. To determine the possible therapeutic potential of inhibiting this protein, numerous studies have been carried out in this field. In this paper, we show the existing knowledge on the inhibition of this protein in different types of cancer and discuss the importance it could have in the development of new therapies directed against this pathology.

The model of T4 phage, Lambda phage and Escherichia coli is often used in research on virus-host interactions. This paper reports for the first time the thermodynamic driving force of biosynthesis, catabolism and metabolism for the three organisms, on the M9 medium. Moreover, the influence of activities of nutrients and metabolic products is analyzed. All three organisms were found to have very similar Gibbs energies of metabolism. Moreover, since they share the same catabolism, their Gibbs energies of catabolism are identical. However, Gibbs energies of biosynthesis differ. The calculated thermodynamic properties have been used to explain the coexistence of both bacteria and phages in a dynamic equilibrium in natural ecosystems.

The calculation of the vapour pressure of organic molecules at 298.15K is presented using a commonly applicable computer algorithm based on the group-additivity method. The basic principle of this method rests on the complete breakdown of the molecules into their constituting atoms, further characterized by their immediate neighbour atoms. The group contributions are calculated by means of a fast Gauss-Seidel fitting algorithm using the experimental data of 2036 molecules from literature. A ten-fold cross-validation procedure has been carried out to test the applicability of this method, which confirmed excellent quality for the prediction of the vapour pressure, expressed in log(pa), with a cross-validated correlation coefficient Q2 of 0.9938 and a standard deviation  of 0.26. Based on these data, the molecules' standard Gibbs free energy G°vap has been calculated. Furthermore, using their enthalpies of vaporization, predicted by an analogous group-additivity approach published earlier, the standard entropy of vaporization S°vap has been determined and compared with experimental data of 1129 molecules, exhibiting excellent conformance with a correlation coefficient R2 of 0.9598, a standard error  of 8.14 J/mol/K and a medium absolute deviation of 4.68%.

Lung cancer remains the main cause of global cancer-related deaths. Currently low-dose computed tomography (LD-CT) shows a 20% reduction of mortality. However, its clinical suitability is hindered by cost, radiation, and some false positives. Thus, the discovery non-invasive and less-expensive biomarker is urgent needed. In this scenario, proteins released in biological fluids could be considered interesting biomarkers for their role in cancer development. We conducted a pioneering case-control pilot study aimed at assessing the usefulness of Raf Kinase Inhibitory Protein (RKIP) and its phosphorylated form (pRKIP) as potential early-stage lung cancer biomarkers. Urine and Blood samples of two consecutive and independent cohorts of lung cancer patients and healthy controls were screened by means of a novel experimental ELISA assay designed to evaluate both forms of the biomarker. Although urinary levels of RKIP were not statistically different between the lung cancer group and high-risk healthy group, serum ones instead increased significantly in early stage LC patients and permitted to discriminate LC patients from both low-risk (HS) and high-risk healthy subjects (HR-HS) with an overall 93% accuracy (AUC 0.93) when LC was compared to HS and 74% (AUC 0.73) when it was compared to high-risk group. Of note, the analysis of RKIP/pRKIP ratio also showed a high accuracy (90% - AUC 0.95) in discriminating LC patients from HS and more importantly, it allowed to identify LC patients compared to HR-HS, with a higher accuracy (79% - AUC 0.79) than RKIP alone. We hypothesize that serum RKIP levels may be correlated to the activation of the immune systems against the tumor during the first phases of its development. Our study identified a preliminary, non-invasive, RKIP and pRKIP profile able to discriminate with high specificity and sensitivity the early-stage lung cancer patients from high-risk Healthy Subjects. These results, although preliminary, suggest the utility of measuring RKIP/pRKIP as potential new screening test for lung cancer and provide the basis for future validation studies.

Exosome-based therapy has emerged as a promising strategy for addressing diverse disorders, indicating the need for further exploration of the potential therapeutic effects of the exosome cargos. This study introduces "enhanced exosomes," a novel type of exosomes developed through a novel cell culture system. These specific exosomes may become potent therapeutic agents for treating ovarian disorders. In this study, we conducted a comparative analysis of the protein and miRNA cargo compositions of enhanced exosomes and naïve exosomes. Our findings revealed distinct cargo compositions in enhanced exosomes, featuring upregulated proteins such as EFEMP1, HTRA1, PAM, RSU1, and SDF4, suggesting their potential for treating ovarian disorders. MicroRNA profiling revealed that miR-1-3p, miR-103a-3p, miR-122-5p, miR-1271-5p, miR-133a-3p, miR-184, miR-203a-3p, and miR-206 are key players in regulating ovarian cancer and chemosensitivity by affecting cell cycle progression, cell proliferation, and cell development. We examined polycystic ovary syndrome and premature ovarian insufficiency and identified altered expression of various miRNAs, such as miR-106a-5p, miR-130b-5p, and miR-130b-3p, for diagnostic insights. This study highlights the potential of enhanced exosomes as new therapeutic agents for women's reproductive health, offering a detailed understanding of the impact of their cargo on ovarian disorders.

Pakistan relies mostly on fossil fuel for fulfilling its energy demand which is expensive as 11 well as not friendly for the environment. The need of the hour is to shift from fossil fuels to renew-12 able energy resources like geothermal, wind, solar etc. to cater for global warming issues. Pakistan 13 has a lot of potential geothermal sites because of several fault lines and hot springs. A sound 14 knowledge of ground temperature is essential to use geothermal energy, which is obtained by drill-15 ing boreholes and putting sensors making it an expensive procedure. Thus, to avoid huge cost for 16 drilling bore holes, particularly for ground temperature analysis, a numerical approach has been 17 considered for determining ground temperature. Furthermore, correlation charts between air and 18 ground temperatures have been developed as there were no proper studies on the ground temper-19 ature of Pakistan. Then, with the help of a boreholes drilled in National University of Sciences and 20 Technology Islamabad Pakistan, the actual ground and numerically calculated temperatures have 21 been compared which shows an error margin in the range between 0.27% for higher depths to 7.3% 22 near surface. Thus, it is shown that the proposed method is easy to implement and better than large 23 scale testing methods for the depths at which geothermal energy is extracted.

Herbal Coffee is getting more popular due to its unique flavor and higher concentration of bioactive compounds, mainly polyphenols. Rosemary is a unique herb with potent antioxidant properties. A green technique called ultrasound aids in releasing bioactive substances from the plant cell wall. In this context, ultrasound-assisted herbal coffee prepared and their anti-diabetic, anti-Alzheimer, and antioxidant activities were measured while the LC/MS was used to determine the bioactive components from the herbal coffee infusion. A total of 95 secondary metabolites were putatively reported, including alkaloids, phenolic acids, and flavonoids, which we identified in the herbal coffee infusion. The total phenolic content (61.5 ± 5.1 mg GAE/g), total flavonoid content (19.3 ± 0.9 mg QE/g), and total condensed tannin (7.6 ± 0.7 mg CE/g) of herbal coffee infusion were observed to be highest of the two remaining samples. The herbal coffee extracts were used to determine all samples' antioxidant, anti-diabetic, and anti-Alzheimer activities. Using LC-MS/MS, we semi-quantified 19 phenolic metabolites. The results show numerous bioactive components in herbal coffee infusion with more potent antioxidant, antidiabetic, and anti-Alzheimer potential. Moreover, more studies must be conducted to confirm how the metabolomic profile of herbal coffee affects its flavor profile.

Tuberculosis (TB) remains a global health threat, necessitating innovative strategies for control and prevention. This comprehensive review explores the Mycobacterium tuberculosis Lysine Exporter (LysE) gene, unveiling its multifaceted roles and potential uses in controlling and preventing tuberculosis (TB). As a pivotal player in eliminating excess L-lysine and L-arginine, LysE contributes to the survival and virulence of M. tuberculosis. This review synthesizes findings from different electronic databases and includes 13 studies focused on the LysE of M. tuberculosis. The research unveils that LysE can be a potential drug target, a diagnostic marker for TB, and a promising candidate for vaccine development. The absence of LysE in the widely used BCG vaccine underscores its uniqueness and positions it as a novel area for TB prevention. In conclusion, this review underscores the significance of LysE in TB pathogenesis and its potential as a drug target, diagnostic marker, and vaccine candidate. The multifaceted nature of LysE positions it at the forefront of innovative approaches to combat TB, calling for sustained research efforts to harness its full potential in the global fight against this infectious disease.

Cranberries are rich in bioactive constituents reported to influence a variety of health benefits, ranging from improved immune function and decreased infections to reduced cardiovascular disease and more recently cancer inhibition. A review of cranberry research targeting cancer revealed positive effects of cranberries or cranberry derived constituents against 17 different cancers utilizing a variety of in vitro techniques; whereas, in vivo studies supported the inhibitory action of cranberries toward cancers of the esophagus, stomach, colon, bladder, prostate, glioblastoma and lymphoma. Mechanisms of cranberry-linked cancer inhibition include cellular death induction via apoptosis, necrosis and autophagy; reduction of cellular proliferation; alterations in reactive oxygen species; and modification of cytokine and signal transduction pathways. Given the emerging positive preclinical effects of cranberries, future clinical directions targeting cancer or premalignancy will be considered

Wilms tumor (WT), the most prevalent type of renal cancer in children, exhibits overall survival rates exceeding 90%. However, chemotherapy resistance, which occurs in approximately 10% of WT cases, is a major challenge for the treatment of WT, particularly for advanced-stage patients. In this study, we aimed to discover potential mutation markers and drug targets associated with chemotherapy resistance in advanced stage WT. We performed exome sequencing to detect somatic mutations and molecular targets in 43 WT samples, comprising 26 advanced stage WTs, of which 7 cases are chemotherapy-resistant. Our analysis revealed four genes (ALPK2, C16orf96, PRKDC, and SVIL) that correlated with chemotherapy resistance and reduced disease-free survival in ad-vanced-stage WT. Additionally, we identified driver mutations in 55 genes within the chemo-therapy-resistant group, including 14 druggable cancer driver genes. Based on the mutation profile of the resistant WT samples, we propose potential therapeutic strategies involving platinum-based agents, PARP inhibitors, and antibiotic/antineoplastic agents. Our findings provide insights into the genetic landscape of WT and offer potential avenues for targeted treatment, particularly for patients with chemotherapy resistance.

Several recent studies have indicated that miR-30a plays critical roles in various biological processes and diseases. However, the mechanism of miR-30a participation in the regulation of idiopathic pulmonary fibrosis (IPF) is ambiguous. Our previous study demonstrated that miR-30a may function as a novel therapeutic target for lung fibrosis by blocking mitochondrial fission, which is dependent on dynamin-related protein-1 (Drp-1). However, the regulatory mechanism between miR-30a and Drp-1 has yet to be investigated. In addition, whether miR-30a can act as a potential therapeutic has not been verified in vivo. In this study, the miR-30a expression in IPF patients was evaluated. Computational analysis and a dual luciferase reporter system assay were used to identify the target gene of miR-30a, and cell transfection was used to confirm this relationship. Ten-eleven translocation 1 (TET1) was validated as a direct target of miR-30a, and the transfection of miR-30a mimic/inhibitor significantly reduced/increased the expression of TET1 protein. Further experiment verified that the interference on TET1(siRNA) could inhibit the hydroxymethlation of the Drp-1 promoter. Finally, miR-30a agomir was designed and applied to identify and validate the therapeutic effect of miR-30a in vivo. Our study demonstrated that miR-30a could inhibit the TET1 expression by base pairing with complementary sites in the 3′ untranslated region to regulate the hydroxymethlation of the Drp-1 promoter. Furthermore, miR-30a could act as a potential therapeutic target for IPF.

Extracts of Cordyceps militaris which possess the bioactive capacity such as antimicrobial activity and DPPH-free radical scavenging capacity, are applied to the serum product. This finished serum product has been evaluated the in vitro bioactivity and the stability with expect to find out a good extract with a suitable percentage used for serum product as natural materials on preservatives and antioxidation.

Cercospora beticola Sacc. is an ascomycete pathogen that causes Cercospora leaf spot in sugar beets (Beta vulgaris L.) and other related crops. The disease symptoms are characterized by circular lesions with an ash-gray centre and dark brown to purple margins on the leaves. It can lead to significant yield losses if not effectively managed. This study aims to characterize and assess the impact of bacterial biological control agents against C. beticola. Following a dual-culture screening, 18 bacteria exhibiting over 50% inhibition were selected, with six of them demonstrating more than 80% control. Identification of the bacteria was carried out through sequencing of the16S rDNA, revealing potentially 12 species belonging to six genera including Bacillus which was represented by four species. Additionally, the bacteria underwent in-depth characterization of biochemical and molecular properties, as well as plant-growth promotion. PCR detection of genes responsible for producing antifungal metabolites revealed that 83%, 78%, 89%, and 56% of the selected bacteria possessed the bacillomycin, iturin, fengycin, and surfactin encoding genes, respectively. Infrared spectroscopy analysis confirmed the presence of lipopeptide structure in the bacteria supernatant filtrate. Subsequently, the bacteria were assessed for their effect on sugar beet plants in controlled conditions. The bacteria exhibited notable capabilities, promoting growth in both roots and shoots, resulting in significant increases in root length, weight, and shoot length. The field experiment with four bacterial candidates demonstrated good performance against C. beticola compared to difenoconazole fungicide. These bacteria played a significant role in disease control, achieving a maximum efficacy of 77.42%, slightly below the 88.51% efficacy attained by difenoconazole. Additional field trials are necessary to verify the protective and growth-promoting effects of these candidates, whether applied individually, combined in consortia, or integrated with chemical inputs in sugar beet crop production.

: Microplastics and nanoplastics (MNPs) are becoming an increasingly severe global problem due to their widespread distribution and complex impact on living organisms. Apart from their environmental impact, the effects of MNPs on living organisms have also continued to attract attention. The harmful impact of MNPs has been extensively documented in marine invertebrates and larger marine vertebrates like fish. However, the research on the toxicity of these particles on mammals is still limited, and their possible effects on humans are poorly understood. Considering that MNPs are commonly found in food or food packaging, humans are primarily exposed to them through ingestion. It would be valuable to investigate the potential harmful effects of these particles on gut health. This review focuses on recent research exploring the toxicological impacts of micro- and nanoplastics on the gut, as observed in human cell lines and mammalian models. Available data from various studies indicate that the accumulation of MNPs in mammalian models and human cells may result in adverse consequences, in terms of epithelial toxicity, immune toxicity, and disruption of gut microbiota. The paper also discusses the current research limitations and prospects in this field, aiming to provide a scientific basis and reference for further studies on the toxic mechanisms of micro- and nanoplastics.

The influenza virus has been the primary cause of the pandemic, posing a constant threat to human society. Due to its genetic evolution and continuous outbreak, antiviral research currently focuses on exploring a novel lead agent. A comprehensive antiviral screening discovered a marine bacterium whose extract exerted excellent efficacy against influenza viruses. Parerythrobacter sp. M20A3S10, a novel strain under the family Erythrobacteraceae, could produce carotenoids exhibiting antiviral and anticancer activity by enhancing the cellular immune system. Post-treatment of M20A3S10 extract showed outstanding therapeutic indexes: against influenza virus A/PR8 (H1N1) [selectivity index (SI) = 24.0], A/Wisconsin/15/2009 (H3N2) (SI = 30.1) and B/Florida/78/2015 (SI = 38.2). Comparably, the effectiveness was demonstrated against Zika virus (ZIKV) and dengue virus type 2 (DENV2) with an SI of 22.5 and 24.1, respectively, namely broad-spectrum activity. Of note, the antiviral responses resulted from the common replication mechanism between IAV, ZIKV, and DENV2. The stimulation of apoptosis-mediated cellular immunity prevented the viral release and protected the host, suggesting that switching from necroptosis to apoptosis is a novel antiviral target. Although the specific compound affecting the antiviral activity was not identified, its promising efficacy with broad activity will contribute to developing a strategy for preventing future pandemics.

Hypertensive diseases of pregnancy (HDP) represent a global clinical challenge, affecting 5-10% of women and leading to complications for both maternal well-being and fetal development. At the heart of these complications is endothelial dysfunction, with oxidative stress emerging as a pivotal causative factor. The reduction in nitric oxide (NO) bioavailability is a vital indicator of this dysfunction, culminating in blood pressure dysregulation. In the therapeutic context, although antihypertensive medications are commonly used, they come with inherent concerns related to maternal-fetal safety, and a percentage of women do not respond to these therapies. Therefore, alternative strategies that directly address the pathophysiology of HDP are required. This article focuses on the potential of the nitrate-nitrite-NO pathway, abundantly present in dark leafy greens and beetroot, as an alternative approach to treating HDP. The objective of this review is to discuss the prospective antioxidant role of nitrate. We hope our discussion paves the way for using nitrate to improve endothelial dysfunction and control oxidative stress, offering a potential therapy for managing HDP.

Worldwide, approximately 15 million people per year suffer from stroke. With about 5 million deaths, stroke is the second most common cause of death and a major cause of long-term disability. It is estimated that about 25% of people older than 85 years will develop stroke. Cannabis sativa and derived cannabinoids are used for recreational and medical purposes for many centuries. However, due to past legal status, research faced restrictions and cannabis use was stigmatized for potential negative impacts on health. With the legalization of cannabis in many countries of the world, cannabis and cannabis-derived substances such as cannabinoids and terpenes have gained more interest in medical research. Several medical effects of cannabis have been scientifically proven and potential risks were identified. In the context of stroke, the role of cannabis is controversial. Negative impact of cannabis use on stroke has been reported through anecdotal case reports and some population-based studies. However, potential beneficial effects of specific cannabinoids are described in animal studies under certain conditions. In this review, the existing body of evidence regarding the negative and positive impacts of cannabis use prior to stroke will be critically appraised.

Cutaneous mycoses are common infections whose treatment has become more complex due to increasing antifungal resistance and the need for prolonged therapies, hindering patient adher-ence and increasing the incidence of adverse effects. Consequently, the use of physical therapies, especially photodynamic therapy (PDT), has increased for the treatment of onychomycosis due to its antimicrobial capacity mediated by the production of reactive oxygen species. This study investigates the in vitro effect of the combination of blue light (448 nm) and red light (645 nm) with terbinafine on the cell viability of human keratinocytes and the production of reactive ox-ygen species. The combination of terbinafine and blue light exhibits a synergistic effect on the production of reactive oxygen species and a significant increase in the expression of superoxide dismutase (SOD), an enzyme involved in the reduction of superoxide ions (O2-) and the genera-tion of hydrogen peroxide (H2O2). Such effect could be useful in clinical practice to improve the response of cutaneous mycoses to pharmacological treatment, reduce their toxicity, and shorten their duration.

Hypertensive disorders of pregnancy (HDP), including preeclampsia (PE) and gestational hypertension (GH), are major causes of maternal and fetal morbidity and mortality. This review elucidates the role of regulatory T cells (Tregs) in the immunological aspects of HDP and explores their therapeutic potential. Tregs, known for maintaining immune tolerance, are crucial in pregnancy to prevent immune-mediated rejection of the fetus. In HDP, Treg numbers and function imbalance are observed, correlating with disease severity. The review highlights that Tregs contribute to immunological adaptation in normal pregnancy, ensuring fetal acceptance and placental development. In contrast, HDP is associated with Treg dysfunction, marked by decreased numbers and impaired regulatory capacity, leading to inadequate immune tolerance and abnormal placental development. This dysfunction is particularly evident in PE, where Tregs fail to adequately modulate the maternal immune response against fetal antigens, contributing to the pathophysiology of the disorder. Therapeutic interventions aiming to modulate Treg activity represent a promising avenue for HDP management. Studies in animal models and limited clinical trials suggest that enhancing Treg functionality could mitigate HDP symptoms and improve pregnancy outcomes. However, the review acknowledges the complexity of translating these findings into effective clinical therapies, given the multifactorial nature of HDP and the intricate regulatory mechanisms of Tregs. In conclusion, while the precise role of Tregs in HDP is still being unravelled, their central role in immune regulation during pregnancy is indisputable. Further research is needed to fully understand the mechanisms by which Tregs contribute to HDP and to develop targeted therapies that can safely and effectively harness their regulatory potential for treating hypertensive diseases of pregnancy.

The main sources of intrinsic noise in excitable cells at the microcircuit and network levels are the stochastic characteristics of ion channel gating and activation of the synaptic conductance. Studies using in vivo, in vitro, and in silico methods to examine the effects of synaptic background activity were not adequately investigated in non-neuronal excitatory cells, where neurotransmitter-based innervation also occurs. We created a mathematical model to replicate the background synaptic noise dynamics in a non-neuronal cell. We utilized the stochastic Ornstein-Uhlenbeck process to represent excitatory synaptic conductance, which was incorporated into a whole-cell model to produce spontaneous and evoked cellular electrical activities. The single-cell model includes many biophysically detailed ion channels represented by a set of ordinary differential equations in Hodgkin-Huxley and Markov formalisms. This paradigm effectively induced irregular spontaneous depolarizations (SDs) and spontaneous action potential (sAP) resembling in vitro-like electrical activity in the cells. The input resistance decreased by multiple factors, and the spontaneous action potential firing rate elevated. The potential to reach the action potential threshold is altered. Background synaptic activity can alter the input/output characteristics of non-neuronal excitatory cells. Suppressing these baseline activities would facilitate the discovery of new pharmaceutical targets for different clinical diseases.

We have developed a family of N-alkyl-nitrobenzamides that exhibit promising antitubercular ac-tivities. These compounds are a simplification of the structure of known inhibitors of DprE1, an essential Mtb enzyme and an emergent anti-TB target. The compounds were obtained by a simple synthetic methodology and their antitubercular, cyto-toxicity and stability were studied. The most active compounds were the 3,5-dinitro and the 3-nitro-5-trifluoromethyl derivatives. Lipophilicity was shown to be a main parameter modulating activity within each family. The most active compound presented MIC of 16 ng/mL and had in-termediate lipophilicities. The activity was also studied in a macrophage model of infection. In this model the compounds with chain lengths of 6 and 12 carbon atoms presented the best results, ex-hibiting activity profiles comparable to isoniazid. Docking studies performed suggested that the fit of our highly active compounds to the DprE1 binding pocket was very similar to the literature compounds. Furthermore, the metrics used in the analysis were able to distinguish between the families of the highly and least active compounds. Assessment of susceptibility over multiple species and computational together with the structure of the compounds are complementary information that supports DprE1 as a likely target of action for this type of compounds.

Background: Nurses are essential members of the healthcare workforce and were among the first line carers for patients in community and hospital settings during the COVID-19 pandemic. As a result, they were at a heightened risk of contracting the disease, resulting in a significant number of reported deaths among them. Several preventive measures were adopted to contain the spread of this potentially lethal virus. This study aims to explore the knowledge, attitudes, and practices (KAP) of nurses regarding hand hygiene, mask wearing, and social distancing measures in healthcare settings in Barbados during the COVID-19 pandemic. Method: An online survey of nurses working in public hospitals and polyclinics (public primary care clinics) of Barbados from December 2020 to July 2021, was conducted. Participants completed a questionnaire capturing socio-demographic information and knowledge and practices related to hand hygiene, using face masks, and social distancing . Each correct response received one mark. Overall knowledge scores were categorized as poor (<60%), average (60-80%), or good (>80-100%). Results: Of 192 participants, the majority were female (82.8%) and had >5 years of experience (82%). Findings revealed that 45.8% had poor knowledge of hand hygiene, and the knowledge of 43.8% of respondents was average. Multivariable logistic regression showed that, after adjustment for age and gender, registered nurses had 2.1 times increased odds (95% CI 1.0, 4.2) of having good knowledge compared to other nursing categories. Regarding mask-wearing, 53.6% of nurses had average and 27.1% had good knowledge. Multivariable logistic regression showed that, after adjustment for age and gender, registered nurses had 3.3 times increased odds (95% CI 1.5, 7.4) of having good knowledge compared to nursing assistants. 68.6% of respondents followed the correct steps of handwashing every time, and 98.3% wore a mask in public places. More than half of the nurses (51.2%) kept a safe distance from others to avoid spreading SARS-CoV-2; one-third were in a crowded place(s) in the past three months, and 55.8% usually followed guidelines for social isolation as recommended by WHO. Conclusion: The study identified knowledge deficiencies related to hand hygiene and wearing masks among nurses. It is imperative to provide additional training on infection control measures.

The occurrence of potential spikes in a cell is a sign of life, and it is called action potential. There is a common notion that neuron signal conduction is the conduction of action potential. Hence, action potential is a typical and essential life activity. However, such potential spikes occur even in simple nonliving systems. According to the experimental observations by Pollack, structured water molecules can generate a negative potential environment. From this observation, the potential spike generation process for both living and nonliving systems caused by ion and water molecule adsorption-desorption process could be explained in this paper. So, taking into consideration the electrically neutral water molecules,the action potential generation mechanism could be explained. It is a fully inanimate model. Hence, the action potential may not be a life activity. Here, the role of water molecules in life is investigated further. It was found that the phase transition of the membrane is involved in the neuron signal conduction, but the membrane phase transition could be due to the change of state of the water molecules, which forms a large-scale structure in the cavities created by a number of lipids.

Omicron BA.2.75 may become the next globally dominant strain of COVID-19 in 2022. BA.2.75 sub-variant has acquired more mutations (9) in spike protein and other genes of SARS-CoV-2 than any other variant. Thus, its chemical composition and thermodynamic properties have changed comparing to earlier variants. In this paper Gibbs energy of binding and antigen-receptor binding rate is reported for the BA.2.75 variant. Gibbs energy of binding (driving force of binding) of Omicron BA.2.75 variant is more negative than that of the competing variants BA.2 and BA.5.

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

The pervasive presence of atmospheric pollution, particularly polycyclic aromatic hydrocarbons such as 7,12-dimethylbenz(a)anthracene, instigates aberrant cellular and tissue conditions, precipitating oxidative damage and inflammatory cascades conducive to the onset of cancer, notably mammary cancer. Given the hepatic metabolism of 7,12-dimethylbenz(a)anthracene, the imperative of employing natural antioxidants becomes apparent. In this study, we delve into the antioxidant and hepato-protective properties of Pistacia lentiscus against 7,12-dimethylbenz(a)anthracene-induced toxicity, alongside exploring its potential anticancer attributes. Our investigations unveil Pistacia lentiscus's anti-proliferative efficacy against human breast cancer cell lines. Notably, 7,12-dimethylbenz(a)anthracene-intoxication escalates body weight, disrupts lipid profiles, and incites serum oxidative damage. Concurrently, hepatic and renal oxidative stress ensue, accompanied by heightened antioxidant enzyme activity in the 7,12-dimethylbenz(a)anthracene-exposed-group compared to controls (p&lt;0.05). Nonetheless, Pistacia lentiscus co-administration rectifies biochemical imbalances, significantly attenuates oxidative stress aberrations, and augments antioxidant enzyme responses (p&lt;0.05). Importantly, histological analysis evinces Pistacia lentiscus's shielding effect against 7,12-dimethylbenz(a)anthracene induced hepatocyte injury and steatosis. Our findings underscore Pistacia lentiscus's robust anti-proliferative, antioxidant, and hepato-protective capacities, mitigating metabolic disturbances, oxidative stress propagation in liver and kidney functions, and potential histological alterations, thereby impeding 7,12-dimethylbenz(a)anthracene-induced mammary cancer initiation. We posit that Pistacia lentiscus may serve as a prophylactic agent against breast cancer instigated by this carcinogen.

.(1) Background: Groundwater resources management in dry lands, characterized by climate var-iability and population growth, is difficult. Exploration and exploitation of groundwater, due to inadequate surface water is very costly. The present study employed Analytic Hierarchy Process (AHP) and GIS to identify Ground-Water Potential (GWP) areas in a semi-arid region of Nigeria; (2) Methods: Land-use-land-cover, drainage density, slope, rainfall, static water level, soil media, vadose media and aquifer media were selected for GWP analysis. Parameters weights were de-termined using AHP and ranked based on their contribution to GWP by experts. The parameters were then integrated using weighted overlay tool in ArcGIS 10.5 to produce GWP map of the study area. Boreholes yield data from 245 wells were collected to determine the model accuracy and model validation; (3) Results: Results classified the study area into very high GWP (1.9%), high GWP (8.8%), moderate GWP (62%), low GWP (20.70%) and very low GWP (6.6%). Validation of the AHP model with boreholes yield data shows a correlation coefficient of 71.3% giving a good prediction; (4) Conclusions: AHP and GIS can be used to successfully map GWP areas which could serve as an exploration guide for sustainable management of groundwater resources in semi-arid areas.

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.

There have been beaching events of the marine alga pelagic sargassum in coastal regions of the Caribbean Sea, West African countries, and the north-northeast region of Brazil since 2011. Its presence has caused environmental and socioeconomic impacts while several studies were conducted in order to understand the causes of this phenomenon, as well as alternatives to mitigate its impacts. The objective of this research was to evaluate pelagic sargassum biomass as a raw material for the manufacture of medium-density multilayer particleboards. These are composed of 30% sargassum particles in their inner layer and 70% sugarcane bagasse particles on their outer layers which are bonded with castor oil-based polyurethane resin. A physical and chemical characterization was carried out in order to evaluate sargassum particles while physical and mechanical tests were carried out in order to evaluate the panels. Results were subsequently compared with indications from NBR 14810-2:2018 and ISO 16893:2016 standards. A life cycle assessment based on ISO 14040:2006 and 14044:2006 was carried out as to complement the feasibility study of these panels and to compare their different manufacturing processes. The multilayer panels met the minimum requirements for physical and mechanical properties established by regulations, indicating that the Sargassum spp. biomass can be used as filling. The life cycle assessment study indicates that sargassum panels produced in the Belém-PA-Brazil region present lower environmental impacts in four of seven evaluated categories when compared to conventional panels. As such, they constitute an alternative way to mitigate environmental impacts generated by beaching events.

A two-year field experiment (2022–2023) was carried out to investigate the impact of different sowing periods (spring and winter) and nitrogen levels (0, 30, 60 kg/ha) on the phytoextraction potential of flax. The study site is characterized by high concentrations of heavy metals (Cd, Ni, Cu, Pb, Zn) and belongs to the Mediterranean climate type. Flax (var. Calista) was sown in the spring of 2022 and in the winter of 2023, following a split plot experimental design with three rep-lications, and applying low-input practices. Results showed that spring-sown flax produced short-er but thicker plants with significantly higher biomass (5.27 tn ha-1) when treated with 30 kg ha-1 N compared to winter-sown (2.30 tn ha-1) when treated with 60 kg ha-1 N. The concentration of contaminants in the aerial biomass varied according to metal type and sowing period. The higher biomass production in spring resulted in a higher quantity of heavy metals being removed from the soil, making flax a promising crop for phytoextraction purposes, especially in soils contami-nated with multiple heavy metals.

The microbial contamination in food packaging have been a major concern that paved the way for the search for natural based new anti-microbial agents, such as modified α-mangostin. In the present work, twelve synthetic analogs were obtained via semi-synthetic modification of α-mangostin by Ritter reaction, reduction by palladium-carbon (Pd-C), alkylation, and acetylation. The evaluation of the anti-microbial potential of the synthetic analogs showed higher therapeutic value than the parent molecule. The anti-microbial studies proved that I E showed higher antibacterial activity whereas I I showed most significant antifungal activity. Due to their microbial properties, modified α-mangostin can be utilized as active anti-microbial agents in food packaging.

Binary mixtures of surfactants build a binary mixed micelle in which the ratio of surfactants usually differs from the initial ratio of surfactants in their binary mixture. The thermodynamic stabilization of the binary mixed micellar pseudophase about the hypothetical ideal state (intermolecular interactions between the different particles and the conformational states of the particles are identical to those of monocomponent states) is described by the molar excess Gibbs free energy (gE). The dependence of gE on the molar fraction of surfactant i (xi) from the binary mixed micelle can be described by a symmetric function (symmetry is described to the line parallel to the y-axis and passes through xi = 0.5) or by an asymmetric function. Theoretical analysis (canonical partition function, conformational analysis) examines how the presence of different polar functional groups, some of which are sterically shielded from the steroid skeleton of bile salt (surfactant), affect the symmetry of the function gE of the binary mixed micelle of the cholic acid anion (bile salt) and classical cationic surfactant (hydrophobic tail and polar head). Suppose the steroid skeleton of the bile salt contains non-sterically shielded polar groups (or the temperature is relatively high). In that case, gE is a symmetric function. At the same time, if the steroid skeleton also contains sterically shielded polar groups, then the gE function is asymmetric.

The Chromogranin A (CgA)-derived peptide Catestatin (CST: hCgA352-372) is highly conserved (>90% in 90% species) in mammalian species. The highest-evolved primates show 58.8% similarity with the lowest-evolved monotremes. CST was initially identified as a physiological brake in catecholamine secretion by inhibiting nicotinic-cholinergic signaling. CST also inhibits desensitization of catecholamine secretion, indicating that CST can act both as a cholinergic antagonist (short-term) and as a cholinergic agonist (long-term). The long-term effect sustains catecholamine secretion during stressful situations. CST is now established as a pleiotropic hormone: it affects the cardiovascular system by lowering blood pressure and cardiac contractility, enhancing baroreflex sensitivity, increasing heart rate variability, and promoting angiogenesis; and it increases insulin sensitivity by reducing inflammation, inhibiting hepatic glucose production, attenuating endoplasmic reticulum stress, and inducing glycogen production. The present review will highlight the important direct and indirect effects of CST, CST1-15 (aka cateslytin), D-CST1-15 (where L-amino acids were changed to D-amino acids), and human variants of CST (Gly364Ser-CST and Pro370Leu-CST) on microbial growth inhibition and their potential as therapy for antibiotic-resistant pathogenic microbes.

Proprotein convertase subtilisin/Kexin type 9 (PCSK9) is a proteolytic enzyme that indirectly regulates serum LDL cholesterol by destroying LDL receptors. In clinical studies, the main role of the proprotein convertase subtilisin/Kexin type9 (PCSK9) inhibitor in cholesterol regulation was elucidated. It is produced in the liver but is also present in the kidney and intestine. It prevents HMGCo from synthesizing cholesterol. SREBP-2 is a reductase that is induced by statins. In a dose-dependent manner, increasing SREBP-2 levels enhanced LDL-R and PCSK9 gene expression. At the minimum, two procedures have been developed to overcome the plasma level of PCSK9. This is the LDLR test, polyclonal antibodies, and sentience oligonucleotide. Lower dosage statin treatment with a proprotein convertase subtilisin/Kexin type9 inhibitor will be most efficient in lowering LDL and avoiding statin adverse effects. In multiple long-term trials, statins have been found to reduce cardiovascular mortality by 30% and stroke incidence by 20%. In this way, we conclude the role of PCSK9 in hypercholesterolemia.

The creative potential of homo sapiens is the biological basis of his spirituality. To take into account factor of spirituality in analysis of global problems of demography and ecology used analogies of chemical kinetics. Stable in the historical time, population of people was modeled by open thermodynamic system, equilibrium state of which depends on climate and geophysics. The demography of creative potential was divided into two geographical zones - north and south. Process of society sapientation was formalized by introducing into logistic equation of Verhulst, in addition to a couple of parents, at least one more teacher from among educated people. Stationary solution of the modified kinetic equations determines optimal demography for sustainable development of population in accordance with its education index. The solution of the demographic, energy and environmental problems of mankind is determined by the level of world creative potential, the growth of which is currently limited by the consumption paradigm.

A drug repositioning effort supported the possible use of the anti-HIV drug etravirine as a treatment for Friedreich Ataxia (FRDA). Etravirine increases frataxin protein and corrects the biochemical defects in cells derived from FRDA patients. Because of these findings, and since etravirine displays a favorable safety profile, we conducted this pilot open-label phase 2 clinical trial assessing the safety and potential efficacy of etravirine in FRDA patients. Thirty-five patients were stratified into 3 severity groups and randomized to etravirine 200 mg/day or 400 mg/day. They were treated for 4 months. Efficacy endpoints were represented by changes in peak oxygen uptake and workload as measured by incremental exercise test, SARA score, cardiac measures, measures of QoL and disability. Data were collected 4 months before the start of the treatment (T-4), at the start (T0), at the end (T4) and 4 months after the termination of the treatment (T+4). Etravirine was well tolerated. Etravirine completely stopped the progression of the SARA score during the 4-months treatment period, compared to the 4 months pre and post treatment. It increased peak workload, while the improvement of peak oxygen uptake was not statistically significant. No changes in the cardiac measures were observed. Health and QoL measures showed a worsening at the suspension of the drug. In this open trial etravirine significantly improved neurological function and was generally safe and reasonably tolerated. This suggests that etravirine represents a potential therapeutic agent in FRDA deserving testing in a randomized placebo controlled clinical trial.

Cancer being a multi-factorial disease, a multi-target approach is needed to treat it with minimal side-effects. Therefore, combined use of a proven herbal formula with chemo-therapy could be the better therapeutic. It may maintain homeostasis by synergistically targeting multiple signaling pathways involved in tumorigenesis, thus circumventing recurrence, resistance, and immunosuppression. Here we aim to determine the effectiveness and safety of an FDA-approved herbal formula, SR033 in combination with 5-fluorouracil (5FU) and paclitaxel (PTX). We report chemo-sensitization and chemo-synergy in HeLa and MCF-7 cell lines, immunomodulation of COX-2, PD-L1, VEGF and TGFβ and overall survival in-vitro and in-vivo via oral and topical delivery of SR033. In-vitro, SR033/5FU significantly reverses 5FU and PTX-resistance, lower COX-2, and PD-L1, resulting in TGFβ/ VEGF axis modulation. Furthermore, the study suggests that due to anti-oxidative potential of SR033, oral administration exerts chemo-preventive activity and restores cellular compartment in solid tumor and ascites-bearing mice models. Furthermore, the topical application, SR033L with low-dose 5FU increases survival rate, reduces tumor growth, and completely restores local and peripheral neutrophil-lymphocyte ratio in solid tumor mice model. The study indicates that SR033 could be a strong candidate in combination with low-dose 5FU and PTX for a holistic approach to cancer management.

Urban environments face escalating challenges, e.g. due to uncontrolled urbanization, rapid population growth or climate changes, prompting the exploration of sustainable solutions for enhancing urban green spaces (UGS). For this reason, poplars (Populus L.), due to their rapid growth, wide range adaptability to environmental conditions and versatility of use, would have emerged as very promising. This comprehensive review synthesizes current knowledge regarding poplar's application in urban landscapes, emphasizing its multifaceted contributions and benefits. However, challenges arise from the variable lifespans of different poplar cultivars, necessitating strategic management approaches. Selecting cultivars based on growth rates, root system characteristics, and adaptability to urban conditions is pivotal. Adaptive replanting strategies, incorporating species with varying lifespans, offer solutions to maintain continual greenery in urban landscapes. Collaborative efforts between researchers, urban planners, and policymakers are essential for devising comprehensive strategies that maximize benefits while addressing challenges associated with their variable lifespans. In conclusion, harnessing poplar's potential in urban greenery initiatives requires a balanced approach that capitalizes on their benefits while mitigating challenges. Further research and adaptive strategies are crucial for sustained and effective utilization in creating resilient and vibrant urban landscapes.

Every year around 800 000 people commit suicide, this represents one death every 40 seconds. In the search for possible biological biomarkers associated with suicide and/or psychiatric disorders, serum cholesterol levels have been extensively explored. Several studies have indicated that cholesterol and associated proteins, especially apolipoproteins (Apos), may play an important role in the diagnosis, prognosis, and susceptibility of suicide. Here, we describe the current knowledge and findings in the relationship between apolipoproteins and suicide.

This paper evaluates the potential of solar concentration technologies—compound parabolic collector (CPC), linear Fresnel collector (LFC) and parabolic trough collector (PTC)—as an alternative to conventional sources of energy for industrial processes in Latin America, where high levels of solar radiation and isolated areas without energy supply exist. The analysis is addressed from energy, economic and environmental perspective. A specific application for Argentina in which fourteen locations are analyzed is considered. Results show that solar concentration technologies can be an economically and environmentally viable alternative. Levelized cost of energy (LCOE) ranges between 2.5 and 16.9 c€/kWh/m² and greenhouse gas (GHG) emissions avoided range between 33 and 348 kgCO₂/(m²·year). CPC technology stands out as the most recommendable technology when the working fluid temperature ranges from 373K to 423K. As the working fluid temperature increases the differences between the LCOE values of the CPC and LFC technologies decrease. When 523K is reached LFC technology is the one which presents the lowest LCOE values for all analyzed sites, while the LCOE values of PTC technology are close to CPC technology values. Results show that solar concentration technologies have reached economic and environmental competitiveness levels under certain scenarios, mainly linked to solar resource available, thermal level requirements and solar technology cost.

We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD), to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies for such investigations. PubMed was searched using specified search terms. One small prospective study on diet and anti-TNF treatment in 56 patients with CD found similar remission rates after 56 weeks among 32 patients with good compliance that received concomitant enteral nutrition and 24 with poor compliance that had no dietary restrictions (78% versus 67%, p = 0.51). A meta-analysis of 295 patients found higher odds of achieving clinical remission and remaining in clinical remission among patients on combination therapy with specialised enteral nutrition and Infliximab (IFX) compared with IFX monotherapy (OR 2.73; 95% CI: 1.73–4.31, p < 0.01, OR 2.93; 95% CI: 1.66–5.17, p < 0.01, respectively). In conclusion, evidence-based knowledge on impact of diet on anti-TNF treatment response for clinical use is scarce. Here we propose a mechanism by which Western style diet high in meat and low in fibre may promote colonic inflammation and potentially impact treatment response to anti-TNF drugs. Further studies using hypothesis-driven and data-driven strategies in observational, animal and interventional studies are warranted.

Cancer is a disease that encompasses multiple and different malignant conditions and is among the leading causes of death in the world. Therefore, the search for new pharmacotherapeutic options and potential candidates that can be used as treatments or adjuvants to control this disease is urgent. Natural products, especially those obtained from plants, have played an important role as a source of specialized metabolites with recognized pharmacological properties against cancer, therefore, they are an excellent alternative to be used. The objective of this research was to evaluate the action of the monoterpene isoespintanol (ISO) against the human tumor cell lines MDA-MB-231, A549, DU145, A2780, A2780-cis and the non-tumor line MRC-5. Experiments with MTT and fluorescence with propidium iodide (PI), DAPI and green plasma revealed the cytotoxicity of ISO against these cells; furthermore, morphological and chromogenic studies revealed the action of ISO on cell morphology and the inhibitory capacity on reproductive viability to form colonies in MDA-MB-231 cells. Likewise, 3D experiments validated the damage in these cells caused by this monoterpene. These results serve as a basis for progress in studies of the mechanisms of action of these compounds and the development of derivatives or synthetic analogues with a better antitumor profile.

To assess if SARS-CoV-2 infection induces changes in the urinary volatilomic fingerprint able to be used in the non-invasive COVID-19 diagnosis and management, urine samples of SARS-CoV-2 infected patients (62), recovered COVID-19 patients (30), and non-infected individuals (41) were analysed using solid-phase microextraction technique in headspace mode, combined with gas chromatography hyphenated with mass spectrometry (HS-SPME/GC-MS). In total, 101 volatile organic metabolites (VOMs) from 13 chemical families were identified, being terpenes, phenolic compounds, norisoprenoids, and ketones the most represented groups. Overall, a decrease in the levels of terpenes and phenolic compounds was observed in the control group, whereas norisoprenoids and ketones showed a significant increase. In turn, a remarkable increase was noticed in norisoprenoids and ketones and a milder increase in alcohols, furanic, and sulfur compounds in the recovery group than in the COVID-19 group. Multivariate statistical analysis identified sets of VOMs with the potential to constitute volatile signatures for COVID-19 development and progression. These signatures are composed of D-carvone, 3-methoxy-5-(trifluoromethyl)aniline (MTA), 1,1,6-trimethyl-dihydronaphthalene (TDN), 2-heptanone, and 2,5,5,8a-tetramethyl-1,2,3,5,6,7,8,8-octahydro-1-naphthalenyl ester acetate (TONEA) for COVID-19 infection and nonanoic acid, α-terpinene, β-damascenone, α-isophorone, and trans-furan linalool for patients recovering from the disease. This study provides evidence that changes in the urinary volatilomic profile triggered by SARS-CoV-2 infection constitute a promising and valuable screening and/or diagnostic and management tool for COVID-19 in clinical environment.

We argue that several potentials proposed recently for the analysis of the vibrational-rotational spectra of diatomic molecules and their thermodynamic properties exhibit a flaw. One can easily show that the parameters $D_e $ and $r_e$ in those potentials are not the dissociation energy and equilibrium bond length, respectively, as the proposers believe. We show how to overcome the mistake in a simple and quite general way.

Cordycepin has good antitumor activity, but its clinical application is limited due to the easy deamination of N6 in structure. In this study, a large lipopolysis group was introduced at the cordycepin N6 to improve the problem, Cordycepin derivatives(3a-4c) were synthesized, and biological evaluation of compounds were studied. In the study, the vitro antitumor activity of the compounds against MCF7 cells, HepG2 cells and SGC-7901 cells was evaluated by MTT assay. In the results, compound 4a showed the most obvious inhibitory effect on MCF7 cells with IC50 value of 27.566±0.52 μM, which was much lower than cordycepin. Compound 4a showed high selectivity between MCF7 and normal MCF-10A cells. Further biological evaluation showed that compound 4a promoted apoptosis and blocked the cell cycle in G0/G1 phase. Then, Western Blot was used to detect related apoptotic proteins. It was found that Compound 4a could down-regulate the expression of Bcl-2 protein and up-regulate the expression of p53, Bax, Caspase-3, and Caspase-9 proteins. The mitochondrial membrane potential decreased continuously and the positive expression rate decreased. It was speculated that compound 4a induced the apoptosis of MCF7 cells through the mitochondrial pathway.

Early disease detection in livestock allows for target treatment decreasing antibiotics use and allow advancements in precision veterinary medicine. MicroRNA (miRNA) -driven signaling cascades play a crucial role in the context of farm animal disease diagnostics and prediction, and their proper understanding remains a challenge. In livestock farm animals, only a small number of miRNAs have been fully validated with respect to disease conditions and physiological or behavioral traits. Low abundance of miRNAs in blood and bodily fluids, along with a small number of nucleotides, makes detection and discrimination tedious and challenging task in. miRNAs usually are homologous, owing to which detection specificity becomes next to impossible when screening for multiple miRNAs in the same analyte sample. Hence, a concurrent, multiplexing, approach becomes crucial for the development of on-farm point-of-care based detection systems. Comprehensive screening methods demand broad dynamic range and enhanced specificity. For on-farm handheld platform development, the ability to screen for multiple varieties of miRNA is essential. In this review paper, I provide an overview of the recent developments of miRNA sensing and the current bottlenecks in the realization of the sensors for detecting miRNAS as target analyte for various livestock disease detection applications. Due to the nascent stages of this research, the possibilities of exploiting miRNAs as a biomarker opens up ways to move from reactive to predictive possibilities in diseases detection in the modern digital livestock farming.

The concerning worldwide increase of obesity and chronic metabolic diseases such as T2D, dyslipidemia, and cardiovascular disease motivates further investigations into preventive and alternative therapeutic approaches. Over the past decade, there is growing evidence that the formation and activation of thermogenic adipocytes (brown and beige) may serve as therapy to treat obesity and its associated diseases owing to its capacity to increase energy expenditure and to modulate circulating lipids and glucose levels. Thus, understanding the molecular mechanism of brown and beige adipocytes formation and activation will facilitate the development of strategies to combat metabolic disorders. Here, we provide a comprehensive overview of pathways and players involved in the development of brown and beige fat as well as the role of thermogenic adipocytes in energy homeostasis and metabolism. Also, we discuss the alterations in brown and beige adipose tissue function during obesity and, explore the therapeutic potential of thermogenic activation to treat metabolic syndrome.

Cervical cancer (CC) is the most common cancer in women worldwide and is almost always associated with repeated infections by human papillomavirus (HPV). Screening by traditional tests combined with biomarker identification techniques for low- or high-grade injuries, are becoming increasingly important in diagnosis and prognosis, avoiding countless deaths. This article explores existing literature on the main serum biomarkers and the identification of biomarkers associated with the oncogenesis of HPV expression in the identification of pre-cancerous lesions and of CC for an effective treatment, with reduction of recurrence, as well as we explain strategies for the development of biomarkers based on DNA, proteins and other markers. We also describe how markers of chromosomal instability host DNA, promoting hypo- or hypermethylation of DNA, as well as polymorphisms and epigenetic events in the p53 gene. Finally, we discuss changes in gene expression using cDNA microarray techniques and changes in the expression of proteins and markers identified through mass spectrometry.

Pakistan is an important country located in South Asia and ranks the world's sixth most populous country. It has diverse landscapes with their own specific vegetation. The country specific vegetative diversity has a great ecological and economic impact on the conservation of local fauna. It has huge potential for sustainable beekeeping industry if properly exploited. Beekeeping in Pakistan is mainly focused in Khyber Pakhtunkhwa and central and north regions of Punjab provinces but nowadays it is growing rapidly across the country. Honey produced in Pakistan enjoys good repute in the Middle East due to its unique taste and quality. Pakistan exports around 4000 tons of the honey with the worth of about $ 23.00 million to Arab countries every year.

Aflatoxins are a known cause of primary liver cancer in Mozambique since pre-independence epidemiological studies. However, their impact goes beyond the public health, affecting the country’s economy and raising legal concerns. As a developing country endemic for Aspergillus, the nation has been struggling to keep pace with external trade quality demands, delicate policy making, still dealing with the farmers’ limitations to control the contamination. The contamination shows variations over time, space and the different commodities. Considering the recommendations of the Codex Alimentarius, the major crops will be highly implicated unless there is major intervention from the authorities to control the toxins.

Maintaining sufficient levels of plant nutrients in the soil and controlling certain heavy metals, which can be toxic to the environment, are critical to ensure sustainable agricultural production. The study aimed to assess the linkage of crop-specific agricultural practices established by farmers in the Kvemo Kartli region (Georgia) with metal accumulation in soils of agricultural lands being subject to influence from polluted irrigation water in the past. In particular, we tried to identify the primary sources of micronutrients, including iron (Fe), copper (Cu), manganese (Mn), nickel (Ni), and zinc (Zn), and toxic elements such as cadmium (Cd) and lead (Pb), and share of the contaminated irrigation water and other factors related to agricultural practices under different land uses, such as intensive and extensive arable farming, vineyards, orchards, and permanent pastures having the least disturbed soil. Based on principal component analysis, five primary sources were identified and categorized according to farmers' interviews and previous studies conducted in the region. The results showed that increased concertation of plant-available Cu, Zn, Cd and Pb were mainly associated with irrigation water and intensive use of fungicides; Fe, Mn, and Ni were closely linked to several factors, such as the mineralogical composition of soils, mineral and organic fertilizers inputs, and atmospheric deposition from diffuse sources, where exhausts from transport are probably the primary source. During our study, we attempted to differentiate irrigation water inputs from fungicides using simulation based on irrigation pattern and irrigation water quality on the one hand and fungicide application rate and their metal content on the other. The simulation revealed that the intensive application of fungicides, especially in vineyards, is more significant in enriching soils with Cu and Zn than irrigation water. Identification of factorial dependences was supported by statistical analysis and application of a number of contamination assessment methods: Contamination Factor (CF), Pollution Load Index (PLI), single-factor Pollution Index (PI), Nemerow’s comprehensive pollution index (PIN), Enrichment Factor (EF), and Geo-Accumulation Index (Igeo). Applied environmental indices indicate that the soils under the former and existing vineyards are the most enriched with Cu and Zn, highlighting the significance of agricultural practices on heavy metals accumulation in soils of agricultural lands.