Background: One of the main diseases of worldwide concern is non–insulin dependent Diabetes mellitus. 90-95% of patients with diabetes suffers from Type II diabetes, a metabolic diabetes whose prevalence is increasing in the world.Given the current prevalence of diabetes type II in society, research of natural compounds able to regulate glycaemia and insulin–resistance is nowadays covering importance, as alternative or co–adjuvant treatment to existing hypoglycaemic medicines. In pre–clinical steps of research, C. elegans is considered a promising in vivo model for the study of the molecular mechanism of glucose as part of anti–diabetic bioactivity.Most of the studies of insulin resistance with this in vivo model are carried out by using mutant strains such as daf-2 and the effects of the compounds are attributed a posteriori, after a physiological response of the worms rather than directly measuring preservation of activity inside the worm. Methods: The in vitro α-glucosidase inhibition of two oral formulations with Origanum vulgare extract before and after a simulated process of gastrointestinal digestion was evaluated. After confirming the in vitro activity, the α-glucosidase inhibition was tested in vivo through the new method proposed. Results: The crude extract showed an IC50 value similar to acarbose (positive control), before and after the gastrointestinal digestion. The encapsulated extract (111.86±1.25 µg/mL) did not present statistical differences with the positive control (110.10±1.15 µg/mL) after digestion. However, the powder formulation showed the highest hypoglycaemic activity (59.55±0.85 µg/mL).In vivo, the IC50 values showed similar profile than in vitro. Conclusion: A new simple and reliable method has been developed to determine pharmacological activities inside in vivo model C. elegans.The method has been evaluated with a hydroalcoholic extract of O. vulgare. The method is accurate and valid for the quantification of the inhibition of in vivo, allowing the direct attribution of this in vivo hypoglycaemic activity to the treatment. In addition, it opens the door to further research into in vitro pharmacological activities that require an in vivo counterpart.

Methane (CH4) has attracted attention as not only synthetic natural gas, but also one of the hy-drogen carriers in terms of energy density. On the other hand, there exist bacterial ecosystems in nature that can decompose organic compounds to produce CH4 and CO2. In this study, Clostridi-um cellulovorans was first cultivated with pig manure (PM) as an unused biomass. Regarding the measurement of organic acids by high-performance liquid chromatography (HPLC), acetate and butyrate were increased in the C. cellulovorans medium containing 0.5% PM, while formate and lactate were decreased in it. Next, in comparison with carbon sources such as glucose, cellobiose, and acetate, cocultivation of C. cellulovorans and Methanosarcina mazei or microbial flora of me-thane production (MFMP) was performed in the C. cellulovorans medium. These results revealed that 0.5% acetate as the sole carbon source produced CH4 only by cocultivating C. cellulovorans and MFMP. Furthermore, MFMP was only cultivated with 1% acetate or 1% methane as a carbon source after precultivated with 0.5% glucose medium for 12 h. As a result, methane productivity of MFMP with 1% methanol medium was approximately eight times higher than that with 1% acetate medium. Finally, next-generation sequencing (NGS) analysis of MFMP after cultivation with 1% acetate or 1% methane was carried out. Interestingly, Methanofollis (0.211%) belonging to H2/CO2 -using methanogens (CO2 reduction pathway) was dominant in the 1% acetate medium for 72 h cultivation, whereas Methanosarcina siciliae (1.178%), M. barkeri (0.571%), and Methano-follis (0.490%) were major species in 1% methanol medium for 72 h cultivation. Since Methano-sarcina spp. are belonging to acetoclasts (acetoclastic pathway), methanol could promote to grow Methanosarcina spp. rather than acetate. Therefore, it seemed Methanosarcina spp. may play a key methanogenesis in MFMP. Thus, these results will provide important information for low cost biomethane production.

Methane (CH4) has attracted attention as not only synthetic natural gas, but also one of the hy-drogen carriers in terms of energy density. On the other hand, there exist bacterial ecosystems in nature that can decompose organic compounds to produce CH4 and CO2. In this study, Clostridi-um cellulovorans was first cultivated with pig manure (PM) as an unused biomass. Regarding the measurement of organic acids by high-performance liquid chromatography (HPLC), acetate and butyrate were increased in the C. cellulovorans medium containing 0.5% PM, while formate and lactate were decreased in it. Next, in comparison with carbon sources such as glucose, cellobiose, and acetate, cocultivation of C. cellulovorans and Methanosarcina mazei or microbial flora of me-thane production (MFMP) was performed in the C. cellulovorans medium. These results revealed that 0.5% acetate as the sole carbon source produced CH4 only by cocultivating C. cellulovorans and MFMP. Furthermore, MFMP was only cultivated with 1% acetate or 1% methane as a carbon source after precultivated with 0.5% glucose medium for 12 h. As a result, methane productivity of MFMP with 1% methanol medium was approximately eight times higher than that with 1% acetate medium. Finally, next-generation sequencing (NGS) analysis of MFMP after cultivation with 1% acetate or 1% methane was carried out. Interestingly, Methanofollis (0.211%) belonging to H2/CO2 -using methanogens (CO2 reduction pathway) was dominant in the 1% acetate medium for 72 h cultivation, whereas Methanosarcina siciliae (1.178%), M. barkeri (0.571%), and Methano-follis (0.490%) were major species in 1% methanol medium for 72 h cultivation. Since Methano-sarcina spp. are belonging to acetoclasts (acetoclastic pathway), methanol could promote to grow Methanosarcina spp. rather than acetate. Therefore, it seemed Methanosarcina spp. may play a key methanogenesis in MFMP. Thus, these results will provide important information for low cost biomethane production.

Steel slag is a co-product of the steelmaking industry, this material is rarely used as a binder due to its low cementitious properties. Thus, it´s believed that the alkaline activation of steel slag can enable its use as a cementitious material. This work has the objective of making a systematic bibliographic review on the theme "slag melt as a precursor in activated alkali binders". To this end, the ProKnow-C method was used for the selection and analysis of relevant research on the topic. The portfolio resulted in 71 texts, mostly journals paper. Bibliometrics showed that the country with the most publications is China and the journal with the most publications is Construction and Building Materials. The critical analysis concluded that the XRD, XRF, and compressive strength tests are the most used for the characterization of the material. It is possible to establish that there are some knowledge gaps on the subject, such as better mechanical characterization and greater production of works with dosing by the one-part method.

A clear relationship between the tau assemblies and toxicity has still to be established. To correlate the tau conformation with its proteotoxic effect in vivo we developed an innovative cell-worm-based approach. HEK293 cells expressing tau P301L under a tetracycline-inducible system (HEK T-Rex) were employed to produce different tau assemblies whose proteotoxic potential was evaluated using C. elegans. Lysates from cells induced for five days, significantly reduced the worm’s locomotor activity. This toxic effect was not related to the total amount of tau produced by cells or to its phosphorylation state but was related to the formation of multimeric tau assemblies, particularly tetrameric ones. We investigated the applicability of this approach for testing compounds acting against oligomeric tau toxicity, using doxycycline (Doxy) as prototype drug. Doxy affected the tau solubility and promoted the disassembly of already formed toxic aggregates in lysates of cells induced for five days. These effects translated into a dose-dependent protective action in C. elegans. These findings confirm the validity of the combined HEK T-Rex cells and C. elegans-based approach as a platform for pharmacological screening.

Acute myeloid leukaemia (AML) is characterized by the accumulation of undifferentiated blast cells in the bone marrow and blood. In most AMLs, relapse frequently occurs due to resistance to chemotherapy. Compelling research results indicate that drug resistance in cancer cells is highly dependent on the intracellular levels of reactive oxygen species (ROS). Modulating ROS levels is therefore a valuable strategy to overcome the chemotherapy resistance of leukemic cells. In this study, we evaluated the efficiency of diphenyleneiodonium (DPI), a well-known inhibitor of ROS production, in targeting AML cells. Results showed that although inhibiting cytoplasmic ROS production, DPI triggered an increase in the mitochondrial ROS levels caused by the disruption of the mitochondrial respiratory chain. We also demonstrated that DPI blocks the mitochondrial oxidative respiration (OxPhos) in a dose-dependent manner and that AML cells with high OxPhos status were highly sensitive to treatment with DPI, which synergizes with the chemotherapeutic agent cytarabine (Ara-C). Thus, our results suggest that targeting mitochondrial function by DPI might be exploited to target AML cells with high OxPhos status.

In this work, a tool for estimating the contact angle from the molecular dynamics simulations is developed and presented. The tool (Achilles) can detect water droplet on hydrophobic and hydrophilic surfaces. The tool can reconstruct the droplets broken across the periodic boundaries. Further a neighbor density based accurate filter is used to find the droplet liquid vapor interface and a circle is fitted using it after removing the dense layers of water next to solid surface. This fitted circle is solved for contact angle and results are outputted in the form of graphical images and text. The entire content of the internal computations of the tool is broken down into 4 phases and users can monitor the outcomes at every phase through output images. The tool is tested using sample molecular dynamics results of water droplet on hydrophobic and hydrophilic surfaces. We believe this tool can be a good addition to the molecular dynamics simulation community who work on the interfacial physics, droplet evaporation, super hydrophobic surfaces, and wettability etc.

Background & Aims: The covid19 is a world changing challenge. Furthermore, this disease challenges our capacities to change our point of view in the domain of infectiology, immunology and global public health. Many trials try some drug such as antiviral (lopinavir, remdesivir) interferon, and the chloroquine. Unfortunately, all approach is not really convincing at this time. We are proposing another approach on this issue. In infectiology there are two protagonists : the host and its immune system versus pathogens and its virulence. Our approach focuses on an intervention on the host’s immune system and how stimulate and modulate its reactions. Methods: We searched on PubMed and Google Scholar databases for French and English-language studies, without a limit of date of publications, for randomized clinical trials, meta-analyses, reviews, systematic reviews, observational studies, case report. We performed a review on the field of immunology enhancements by nutrients use. Results: We identified groups of vitamins (D and C), oligo-elements (magnesium, zinc, selenium) and nutrition advice which enhance immune system response. Indeed, these supplements have some proved properties in modulating and stimulating the immune system. For example, a recent study demonstrates that vitamin D deficiency is linked with the severity of covid19. Majority of the population has a deficiency in these elements. According to this, we propose a therapeutic protocol using these elements to reach an efficient therapy against covid19 by enhancing host’s immune system. Conclusion: Due to this serious pandemic, any solutions must not be disregarded. The nutrition way is an entire part of the solution.

Background and Objective: Although whole body-electromyostimulation (WB-EMS) has been shown to favorably improve body composition in several research studies, it has not been confirmed how it affects adipose tissue-derived biomarkers and circumferences of the abdomen and thighs. Materials and Methods: Twenty participants of obese elderly women were randomly classified into an EMS group (EMSG; n = 10) or a non-EMS group (CON; n = 10). The WB-EMS suits used in this study enabled the simultaneous activation of 8 muscle groups with selectable intensities for each phase. Stimulation frequency was selected at 85 Hz, impulse-width at 350 μ seconds, and impulse-rise as a rectangular application. Impulse duration was 6 seconds with a 4-second break between impulses. The EMS sessions were combined with aerobic dancing 3 times a week for 12 weeks. Both groups received the same program; however, the CON did not receive electrical stimuli. Biomarkers and body composition including circumferences of the abdomen and thighs were measured on Week 0 and Week 12. Results: Compared with the CON, 1) a significant effect of the EMS-intervention concerning decreased body weight (p = 0.032) and increased basal metabolic rate (p = 0.029) were evident. The thigh subcutaneous fat and total fat of EMSG were not significantly changed, but those of CON were significantly increased after 12 weeks. 2) The biomarkers of CON either increased or showed no change, although the interleukin (IL)-6 was significantly (p = 0.028) decreased in EMSG. Specifically, C-reactive protein (CRP; p = 0.005) and alpha-fetoprotein (p = 0.050) of CON were significantly increased after 12 weeks. In addition, the IL-6 (p = 0.034), CRP (p = 0.001), carcinoembryonic antigen (p = 0.017), and low density lipoprotein (p = 0.005) of EMSG were lower than those of CON in the end of experiment. 3) Conclusions: The results indicate that EMS intervention improved body composition and reduced negative biomarkers, thus highlighting its effectiveness.

Prototype of a family of at least nine members, c-src tyrosine kinase is a therapeutically interesting target, because its inhibition might be of interest not only in a number of malignancies, but also in a diverse array of conditions, from neurodegenerative pathologies to certain viral infections. Computational methods in drug discovery are considerably cheaper than conventional methods and offer opportunities of screening very large numbers of compounds in conditions that would be simply impossible within the wet lab experimental settings. We have explored the use of global QSAR models and molecular ligand docking in the discovery of new c-src tyrosine kinase inhibitors. Using a data set of 1038 compounds from ChEMBL and 19 blocks of molecular descriptors, we have developed over 200 QSAR classification models, based on six machine learning algorithms and 17 feature selection methods. We have selected 49 with reasonably good performance (positive predictive value and balanced accuracy higher than 70% in nested cross validation) and the models were assembled by stacking with a simple majority vote and used for the virtual screening of over the “named” ZINC data set (over 100,000 compounds). 744 compounds were predicted by at least 50% of the QSAR models as active, 147 compounds were within the applicability domain and predicted by at least 75% of the models to be active. The latter 147 compounds were submitted to molecular ligand docking using Vina and Ledock, and a number of 90 were predicted to be active based on the binding energy. External data from CHEMBL and PUBCHEM confirmed that at least 7.83% (in the case of QSAR) or 6.67% (in the case of integrated QSAR and molecular docking) of the compounds are active on the c-src target.

During analysis of kiwifruit derived from hybrids between the high AsA species Actinidia eriantha and A. chinensis var chinensis, we observed bimodal segregation of fruit AsA concentration suggesting major gene segregation. To test this hypothesis we performed whole-genome sequencing on pools of high and low AsA fruit from tetraploid A. chinensis var. deliciosa x A. eriantha backcross families. Pool-GWAS revealed a single QTL spanning more than 5 Mbp on chromosome 26, which we denote as qAsA26.1. A co-dominant PCR marker was used to validate this association in four diploid (A. chinensis x A. eriantha) x A. chinensis backcross families, showing that the eriantha allele at this locus increases fruit AsA levels by 250 mg/100 g fresh weight. Inspection of genome composition and recombination in other A. chinensis genetic maps confirmed that the qAsA26.1 region bears hallmarks of suppressed recombination. The molecular fingerprint of this locus was examined in leaves of backcross validation families by RNASEQ. This confirmed strong allelic expression bias across this region as well as differential expression of transcripts on other chromosomes. This evidence suggests that the region harboring qAsA26.1 constitutes a supergene, which may condition multiple pleiotropic effects on metabolism.

Background: The myeloid-epithelial-reproductive tyrosine kinase (MERTK) is involved in hepatic steatosis, inflammation and liver fibrosis. Here we evaluated the association between the MERTK rs4374383 single nucleotide polymorphism (SNP) and liver fibrosis progression in hepatitis C virus (HCV)-infected patients. Methods: We performed a retrospective study (repeated measures design) in 208 patients who had liver stiffness measurement (LSM), which was assessed by transient elastography No patient had cirrhosis at baseline (LSM≥12.5 kPa). Results: At baseline, 53.8% were male, the median age was 47.1 years, 13.5% reported a high intake of alcohol, 10.1% were prior injection drug users, 85.3% were infected by HCV genotype 1, and 22.6% had previously failed antiviral therapy (pegylated-interferon-alpha/ribavirin). During a median follow-up of 46.6 months, 26 patients developed cirrhosis. The rs4374383 G carriers had a higher risk of increasing LSM (adjusted arithmetic mean ratio (aAMR)=1.14; p=0.006) and a higher likelihood of having an increase in LSM greater than 5 kPa (ΔLSM≥5 kPa) [adjusted odds ratio (aOR)=2.37; p=0.029], and greater than 7 kPa (ΔLSM≥7 kPa) [aOR=3.24; p=0.032], after controlling for confounding. The SNP’s association with cirrhosis progression was close to statistical significance (aOR=2.18; p=0.070). Conclusions: MERTK rs4374383 A carriers had a lower risk of liver fibrosis progression than G carriers, supporting the hypothesis that this SNP seems to have a critical role in the pathogenesis of liver disease in HCV-infected patients.

In Belgium, silages are often infected by Penicillium roqueforti sensu lato (s.l.). These toxigenic fungi are well adapted to silage conditions, and their prevention during feed-out is difficult. Bacillus velezensis strain NRRL B-23189 has been reported to inhibit P. roqueforti s.s. conidiospore germination in vitro by the production of lipopeptides. In the present study, the antagonistic effect of this B. velezensis strain towards P. roqueforti s.l. was evaluated in vitro and in vivo. In vitro, corn silage conditions were simulated, and the impact of B. velezensis culture supernatant or cell suspension on P. roqueforti s.l. growth, conidiospore germination and survival and roquefortine C production was evaluated. The antagonism was promising, but growth of B. velezensis in corn silage infusion was poor. An in vivo experiment with microsilos containing a mixture of perennial ryegrass and white clover artificially contaminated with P. roqueforti s.l. was carried out to determine if B. velezensis cell suspension could be used as an antagonistic silage inoculant. The B. velezensis cell suspension applied was unsuccessful in reducing P. roqueforti s.l. numbers at desiling after 56 days compared to no additive application. However, feed-out of the silage was not simulated, so it remains elusive whether or not B. velezensis exerts antagonistic activity during this phase.

Background: Reliable HPV testing and genotyping are essential for quality assurance in HPV-based primary screening, disease management and for monitoring the impact of HPV vaccination. The clinical validation of HPV molecular diagnostic assays has significantly contributed to these objectives, however little emphasis has been placed in assuring sample quality. This study aims to assess the accuracy of sample cellularity assessment using C-C Motif Chemokine Receptor 5 (CCR5) gene target as a marker of sample adequacy in molecular diagnostics. Methods: Jurkat cell line samples were counted both using Thoma cell-counting chamber and Fluorescent-Activated Cell Sorting (FACS). Jurkat cell line samples at three different concentrations were subsequently evaluated using the OncoPredict HPV Quality Control (QC) real-time PCR assay, employing CCR5 for molecular cellularity quantification. Results: Cellularity values obtained were comparable across the 3 different methods for all dilutions of the cell line tested. Conclusions: The results obtained from this study show that CCR5 represents a promising molecular marker for the accurate quantification of sample cellularity, confirming its use as a reliable sample adequacy control, thus reducing the risk of “false negative” results.

Powerful emitters of the ultraviolet C (UVC) light in the wavelength range of 230-280nm are necessary for the development of effective and safe optical disinfection technologies, high-sensitive optical spectroscopy and non-line-of-sight optical communication. This review considers such UVC-emitters with electron-beam pumping of heterostructures with quantum wells in the (Al,Ga)N material system. The important advantages of these emitters include the absence of the critical problem of p-type doping and the possibility of achieving record (up to several tens of watts for peak values) output optical power values in the UVC range. The review consistently considers about a decade of world experience in the implementation of various UV emitters with various types of thermionic, field-emission, and plasma-cathode electron guns (sources) used to excite various designs of active (light-emitting) regions in heterostructures with quantum wells AlxGa1-xN/AlyGa1-yN (x = 0 − 0.5, y = 0.6 − 1) fabricated either by metal-organic chemical vapor deposition or by plasma-activated molecular beam epitaxy. Special attention is paid to the production of heterostructures with multiple quantum wells/two-dimensional(2D) quantum disks GaN/AlN with a monolayer (1ML ~ 0.25nm) thickness, which ensures a high internal quantum efficiency of radiative recombination in the UVC range, low elastic stresses in heterostructures, and a high output UVC-optical powers.

Functional Near Infrared Spectroscopy (fNIRS) systems for e-health applications usually suffer of poor signal detection mainly due to a low end-to-end signal to noise ratio of the electronics chain. Lock-In Amplifiers (LIA) historically represent a powerful technique helping to improve performances in such circumstances. In this work it has been designed and implemented a digital LIA system, based on a Zynq® Field Programmable Gate Array (FPGA), trying to explore if this technique might improve fNIRS system performances. More broadly, FPGA based solution flexibility has been investigated, with particular emphasis applied to digital filter parameters, needed in the digital LIA, and it has been evaluated its impact on the final signal detection and noise rejection capability. The realized architecture was a mixed solution between VHDL hardware modules and software ones, running within a softcore microprocessor. Experimental results have shown the goodness of the proposed solutions and comparative details among different implementation will be detailed. Finally a key aspect taken into account throughout the design was its modularity, allowing an ease increase of the input channels while avoiding the growth of the design cost of the electronics system.

We compare the effect on amyloid fibril formation by two homologous proteins from the family of cystatins, human stefin B (stB) and cystatin C (cysC) in presence of 3 polyphenols: curcumin, resveratrol and quercetin and 2 non-phenolic anti-oxidants: vitamin C (VitC) and N-acetyl cystein (NAC). Some of the experimental data have already been presented, here we compare, further discuss and highlight the results. The amyloid fibril formation was followed by ThT fluorescence and transmission electron microscopy. Inhibitory effects on amyloid fibrillation reaction depended on anti-oxidant class and concentration. The fact that different effect of polyphenols was observed with the two cystatins; Cur acted inhibitory on stB but not on cysC fibril formation, could be explained if the 3 polyphenols would not bind to the same binding site in the fibrils core. Other differences are pointed out and discussed. Synergistic effects of VitC and chosen polyphenols on amyloid fibrilllation of human stB have been explored and are reported here for the first time.

Ellagitannins (ETs) are the group of tannins found in fruits, nuts and seeds; they undergo hydrolysis in the human digestive tract to form ellagic acid (EA). EA further converted into various forms of Urolithin derivatives (A, B, C, D, M-5, M-6 and M-7) by gut micro biota. Perhaps, the pharmacological properties of said Urolithins were extensively studied, while, little is known about the therapeutic role of synthetic Urolithin-C on oxidative stress induced eryptosis and tissue damage. Therefore, in the current study we investigated the ameliorative role of chemically syn-thesized Urolithin-C on sodium nitrite and Diclofenac (DFC) induced eryptosis and vital organ damage respectively. Urolithin-C was synthesized using chemical method and characterized by High-Performance Liquid Chromatography (HPLC), Nuclear Magnetic Resonance (NMR), Fourier Transform Infrared Spectroscopy (FTIR), and Liquid Chromatography Mass Spectroscopy (LC-MS). The synthesized Urolithin-C scavenged free radicals (DPPH, H2O2) and reduced ferric iron to ferrous iron, revealed its antioxidant activity. The observed antioxidant potential of Uro-lithin-C was investigated in sodium nitrite induced stress in RBC and Diclofenac induced tissue damage in rats. Interestingly, Urolithin-C normalized the sodium nitrate-induced oxidative stress in red blood cells by regulating stress markers, such as lipid peroxidation (LPO), total thiol (TT), and protein carbonyl content (PCC), and endogenous antioxidant enzymes superoxide dis-mutase (SOD) and catalase (CAT) in a dose dependent manner. Similar effect was also observed in the tissue homogenates of liver, kidney, heart and pancreas taken from the Diclofenac injected Sprague Dawley rats. The tissue sections (liver, kidney, heart and pancreas) obtained from the Diclofenac (DFC) received rats showed massive destruction of hepatocytes, nephrons, cardiocytes and pancreas. However, Urolithin-C received rats tissue sections showed normal histology compared to the positive (Silymarin) control treated groups. In addition, Urolithin-C regulated the key tissue specific biochemical markers in DFC injected Sprague Dawley rats serum strengthened its tissue protective role. In conclusion, chemically synthesized Urolithin-C regulated NaNO2 and diclofenac induced oxidative stress in RBC and vital organs through its antioxidant property.

Hydroponics, a soilless cultivation method, is increasingly being adopted for its ability to produce high-quality vegetables while reducing resource usage and minimizing the risks of soil-borne pathogens. However, the reuse of nutrient solutions in hydroponics can accelerate the spread of pathogenic microorganisms. This study aimed to evaluate the bacterial decontamination effects of UV-C light (254 nm) on a hydroponic nutrient solution. The solution was contaminated with Escherichia coli and irradiated with UV-C at energy doses of 20.37 and 489.02 mJ/cm². Experiments were conducted under both static and dynamic fluid conditions to assess bacterial inactivation and changes in electrical conductivity over time. Results showed no significant change in electrical conductivity after 144 hours of UV-C exposure. Under static conditions, bacterial inactivation was observed, with a reduction of 1.7 log CFU/mL at 20.37 mJ/cm², though no significant additional reduction was seen at the higher dose. However, dynamic conditions resulted in greater inactivation, with reductions of 4.2 and 5.2 log CFU/mL at 20.37 and 489.02 mJ/cm², respectively. These findings suggest that fluid agitation plays a crucial role in enhancing UV-C efficiency by preventing bacterial sedimentation, which occurs in static conditions. The use of UV-C as an eco-friendly disinfection method appears promising for hydroponic systems, as it does not alter the composition of the nutrient solution.

The present article outlines the Positive Carbon Building certification's pioneering approach, aiming to establish a clear and rigorous methodology for buildings that are not only neutral in their environmental impact but are net positive. This certification challenges the industry by setting a higher bar — achieving net positivity. The approach does not just mitigate harm but actively contributes to environmental regeneration, thereby pushing the construction and real estate sectors towards innovative practices and collaborations. It calls for a reevaluation of how buildings are designed, constructed, and operated, encouraging the incorporation of renewable energy sources, energy-efficient designs, and materials with lower embodied carbon. This ambition signifies a move towards structures that produce more energy than they consume annually, thereby offering a surplus to the energy grid and reducing their carbon footprint comprehensively. This certification intends to work in conjunction with existing green building certifications, emphasizing net-positive energy production and ensuring alignment with both European and national legislations concerning nearly Zero Energy Buildings (nZEB) [1]. Traditionally, the focus has been on minimizing the negative environmental impacts of buildings, but the methodology for Positive Building Certification will mark a significant shift in the conceptualization of green building standards.

Jararhagin-C (JarC) is a protein from the venom of Bothrops jararaca consisting of disintegrin-like and cysteine-rich domains. JarC shows a modulating effect on angiogenesis and remodeling of extracellular matrix constituents improving wound healing in mice experimental model. JarC is purified from crude venom and the yield is less than 1 %. The aim of this work was to obtain the recombinant form of JarC and to test its biological activity. For this purpose, the bicistronic vector pSUMOUlp1 was used. This vector allowed the expression of the recombinant toxin JarC (rJarC) in fusion with the small ubiquitin-related modifier (SUMO) as well as the SUMO protease Ulp1. After expression, this protease was able to efficiently remove SUMO from rJarC inside the bacteria. rJarC free from SUMO was purified at the expected molecular mass, and recognized by polyclonal anti-Jararhagin antibodies. In terms of biological activity, both the native and recombinant forms showed no toxicity to the HUVEC cell line CRL1730 and were effective in modulating cell migration activity in experimental in vitro model. These results demonstrate the successful production of rJarC and the preservation of its biological activity, which may facilitate further investigations into the therapeutic potential of this snake venom-derived protein.

A Co–doped porous carbon was successfully fabricated by a facile carbonizing procedure using coal hydrogasification semi-coke (SC) as the carbon and cobalt nitrate as the magnetic precursors, respectively. The microwave absorption (MA) performances were regulated by adjusting the mass ratio of the precursors. The dielectric loss from the carbon framework, the magnetic loss from nano–sized Co particles coupled with multiple scattering from the residual pores synergistically contribute to the favorable MA capabilities. When the initial mass ratio of cobalt nitrate and SC was 1:1, the Co/C composite showed the lowest reflection loss of -33.45 dB at the thickness of 4.0 mm. The effective absorbing bandwidth (EAB) could achieve 3.5 GHz at 2 mm in thickness. This work not only exploits a new avenue for the structural design and facile fabrication of dielectric and magnetic loss combinations, but also opens up another way for the high value–added utilization of SC.

The utilization of black mulberry fruit as a precursor for C-dot synthesis represents a novel ap-proach to biosynthesizing C-dots. Through the implementation of a hydrothermal autoclave, we successfully produced C-dots using the fruit extract. This environmentally conscious and sustain-able method of synthesis presents a promising avenue for C-dot production. Our findings demon-strate the remarkable photocatalytic activity of the C-dots, as evidenced by their effective degra-dation of pollutants under visible light irradiation. This discovery holds significant implications for addressing water contamination issues and promoting environmental remediation efforts. Fur-thermore, we conducted a thorough investigation to determine the optimal doping concentration of C-dots, ultimately identifying 0.2 M as the ideal concentration. At this specific concentration, the photo catalytic degradation of pollutants reached an impressive rate of 95.8%. The enhanced photocatalytic activity can be attributed to the increased electron trapping resulting from the presence of additional surface sites and the absorption of different wavelengths of light. In sum-mary, this research contributes to the sustainable synthesis of carbon dots using black mulberry fruits as a precursor, while also providing a comprehensive analysis of their optical and photo-catalytic properties.

Increasing efforts have been devoted to promoting sustainable demolition waste management (DWM) from a life cycle-thinking perspective. To this end, facilitating sustainability-oriented de-cision-making for DWM planning requires a sustainability assessment framework for assessing multifaceted criteria. This study develops a BIM-based DWM sustainability assessment ap-proach to facilitate the life cycle assessment (LCA) and decision-making by coupling the enriched IFC model with hybrid Multi-Criteria Decision-Aiding (MCDA) methods using Dynamo visual scripting. To streamline the data-intensive LCA process, this study enriched the BIM properties and accommodated them into the LCA data template to enhance data interoperability, thus achieving seamless data transfer. Moreover, hybrid MCDA methods are integrated into the deci-sion-making workflow for DWM scenario ranking. A pilot study is employed to verify the ap-plicability of the decision-aiding framework. The results unveil that the sustainability score ascended with the recycling rate. The optimal DWM alternative with the highest recycling rate yields the highest sustainability score at 91.63. Conversely, a DWM alternative reflecting the ‘status quo’ in China’s recycling industry has the lowest score at 8.37, significantly lower than the baseline scenario with a 50% recycling rate. It is worth noting that the ‘growth curve’ of the sustainability score continuously flattens as the target recycling rate escalates. The increment in recycling rate from the “Australian standard” scenario to the optimal scenario is 18.4%, while the sustainability score merely increases by 2.3%, signal-ling that the former scenario arrived at an optimum point for maximising the cost-efficiency of DWM under the predefined framework and contexts.

The combination of several therapeutic strategies is often seen as a good way to decrease the resistance rates, since bacteria overcome better single-drug treatments than multi-drug ones. This strategy is especially attractive when several targets and subpopulations are affected, as it is the case of Klebsiella pneumoniae persister cells, a subpopulation of bacteria able to transiently survive antibiotic exposures. This work aims to evaluate the potential of a repurposed anticancer drug, mitomycin C, combined with the K. pneumoniae lytic phage vB_KpnM-VAC13 in vitro and the safety in an in vivo murine model against two clinical isolates of this pathogen, one of them exhibiting an imipenem-persister phenotype. At the same time, we verified the absence of toxicity of mitomycin C at the concentration using the human chondrocyte cell line T/C28a2. The viability of these human cells was checked both by cytotoxicity assays and flow cytometry.

The effect of land use on sandy soils of southern Botswana was carried out by comparing the composition and properties of soil organic matter. Virgin and disturbed soils were sampled from savanna ecosystems (Central District and Kweneng District). The biodegradability of organic matter was evaluated by incubation in the laboratory. Humic fractions were quantified and humic acids were analyzed by visible and infrared spectroscopy. The results indicate that continued disturbance, whether due to grazing or subsistence farming, has resulted in small significant changes in the concentration of available nutrients and organic matter in the soil. Nevertheless, substantial changes could be established in soil C/N ratio, humic acid/fulvic acid ratio and in the biodegradability of soil organic matter and the structural characteristics of humic acids. The increased aromaticity of humic acid (visible and IR spectroscopies) following disturbance, suggests increased biogeochemical activity and/or the impact of abiotic processes (such as periodic fires) selectively removing aliphatic constituents. The overall results indicate a low potential soil fertility, the sustainable preservation of which depending more on features related to quality than to the total amount of the soil organic matter, which shows considerable aromatization parallel to its degree of association with the mineral fraction.

Boeing and Airbus developed a special testing procedure to investigate the compressive response of laminates that have been impacted (following standards ASTM D 7137 and DIN 65561). This study focuses on both experimental and numerical analysis of Kevlar plates subjected to compression after impact. To ensure high quality and appropriate mechanical properties, the composite plates were manufactured using autoclaving. The DIN 65561 protocol was followed for all three test systems. Initially, ultrasonic C-scanning was performed on all plates before testing to confirm they were free of any significant defects arising from the manufacturing process. Subsequently, low-energy impact testing was conducted at levels ranging from 0 to 8 Joules. Three specimens were tested at each energy level. After the impact, all specimens underwent ultrasonic C-scanning again to assess the internal delamination damage caused by the impactor. Finally, both pristine and impacted specimens were subjected to compressive testing using the special jig specified in DIN 65561. The compressive impact strength results obtained from these tests were plotted against the delamination area measured by C-scanning. This data was then compared to results obtained from specimens with artificial damage. Semi-empirical equations were used to fit both sets of curves. The same procedure (impact testing, C-scanning, and data analysis) was repeated to investigate the relationship between impact energy and total delamination area. Lastly, finite element modeling was employed to predict the buckling stresses that develop under compression in the impacted systems studied. These modelling approaches have demonstrated good accuracy in reproducing experimental results for CAI tests.

Abstract: To obtain bovine oocytes in high quality, effects of vitamin C (VC) on in vitro maturation (IVM) of bovine oocytes and early embryo development were investigated. The results showed that: 1) The IVM medium containing 50 µg/mL VC improved the oocyte maturation rate, while no effects on the development of parthenogenetic embryos; 2) The in vitro culture (IVC) medium containing 20 µg/mL VC increased the cleavage rate of the in vitro fertilized (IVF) embryos, enhanced the mRNA levels of pluripotency gene Oct4, Sox2, Cdx2 and Nanog in the blastocysts, but no effect on the blastocyst rate; 3) Combing supplemention of 50 µg/mL in IVM medium + 20 µg/ml VC in IVC medium (VC 50/20) increased the cleavage rate of IVF embryos and enhanced the mRNA levels of Oct4, Sox2, Cdx2 and Nanog in the blastocysts; 4) Combination of VC 0/20 and VC 50/20 enhanced the expression of anti-apoptotic gene Bcl-2 and VC 50/0 weakened the expression of pro-apoptotic gene Bax, while VC 0/40 and VC 0/60 increased Bax expression and decreased the Bcl-2/Bax ratio in blastocysts. Together, VC supplementation at tuned concentration as well its combination in IVM and IVC media improves the developmental rates of bovine oocytes and embryos.

Effects of the enzyme N-acetylgalactosamine-4-sulfatase (Arylsulfatase B, ARSB), which removes the 4-sulfate group at the non-reducing end of chondroitin 4-sulfate, on the expression of PD-L1 were determined and the underlying mechanism of PD-L1 expression elucidated. Initial experiments in human melanoma cells (A375) showed PD-L1 expression increased from 357 ± 31 to 796 ± 50 pg/mg protein (p

L-Theanine, a unique non-protein amino acid, is an important bioactive component of green tea. Previous studies have shown that L-theanine has many potent health benefits, such as anti-anxiety effect, regulation of immune response, relaxing neural tension, reducing oxidative damage. However, little is known concerning whether L-theanine can improve the clearance of mitochondrial DNA (mtDNA) damage in organisms. Here, we reported that L-theanine treatment increased ATP production and improved mitochondrial morphology to extend the lifespan of UVC-exposed nematodes. Mechanistic investigations showed that L-theanine treatment enhanced the removal of mtDNA damage and extended lifespan by activating autophagy, mitophagy, mitochondrial dynamics, and mitochondrial unfolded protein response (UPRmt) in UVC-exposed nematodes. In addition, L-theanine treatment also up-regulated the expression of genes related to mitochondrial energy metabolism in UVC-exposed nematodes. Our study provided a theoretical basis for the possibility that tea drinking may prevent mitochondrial related diseases.

In the last three decades the presence of phospholipids in the nucleus has been shown and thoroughly investigated. A great interest raised about nuclear inositol lipids mainly because of their role in signalling acting. Here we review the main issues of nuclear phospholipid localization and the role of nuclear inositol lipids and their related enzymes in cellular signaling both in physiological and pathological conditions.

Background: Effective identification and management in the early stages of sepsis are critical for achieving positive outcomes. In this context, neutrophil activation status (NEUT-RI) emerges as a promising and easily interpretable parameter. This study aimed to assess the predictive value of NEUT-RI in diagnosing sepsis and to evaluate its prognostic significance in distinguishing 28-day mortality outcomes. Materials: The study is a secondary retrospective observational analysis. Clinical data upon ICU admission were collected. A control group of critically ill patients without sepsis criteria was included. Patients were divided into subgroups based on renal function for biomarker evaluation, with 28-day outcomes reported for septic and non-septic patients. Results: 200 patients were included in the study. A significant difference between the "septic" and "non-septic" groups was detected in the NEUT-RI plasma concentration (53.80 [49.65–59.05] vs. 48.00 [46.00–49.90], p< 0.001, respectively). NEUT-RI and PCT distinguished between not complicated sepsis and septic shock (PCT 1.71 [0.42 - 12.09] vs 32.59 [8.83 - 100.00], < 0.001 and NEUT-RI 51.50 [47.80 - 56.30] vs 56.20 [52.30 - 61.92], p=0.005). NEUT-RI, PCT and CRP values were significantly different in patients with “renal failure”. NEUT-RI and PCT at admission in ICU in septic group were higher in patients who died (58.80 [53.85-73.10] vs 53.05 [48.90-57.22], p=0.005 and 39.56 [17.39-83.72] vs 3.22 [0.59-32.32], p=0.002, respectively). Both NEUT-RI and PCT showed high negative predictive value and low positive predictive value. Conclusions: The inflammatory biomarkers assessed in this study offer valuable support in the early diagnosis of sepsis. NEUT-RI elevation appears particularly promising for early sepsis detection and severity discrimination upon admission

PCSK9 is implicated in familial hypercholesterolemia via targeting the cell surface PCSK9-LDLR complex toward lysosomal degradation. The M2 repeat in the PCSK9's C-terminal domain is essential for its extracellular function, potentially through its interaction with an unidentified “protein X”. The M2 repeat was recently shown to bind an R-x-E motif in MHC-class-I proteins (implicated in the immune system), like HLA-C, and causing their lysosomal degradation. These findings suggested a new role of PCSK9 in the immune system and that HLA-like proteins could be “protein X” candidates. However, the participation of each member of the MHC-I protein family in this process and their regulation of PCSK9's function have yet to be determined. Herein, we compared the implication of MHC-I-like proteins such as HFE (involved in iron homeostasis) and HLA-C on the extracellular function of PCSK9. Our data revealed that the M2 domain regulates the intracellular sorting of the PCSK9-LDLR complex to lysosomes, and that HFE is a new target of PCSK9 that inhibits its activity on the LDLR, whereas HLA-C enhances its function. This work suggests the potential modulation of the PCSK9 functions through interactions of HFE and HLA-C.

Hepatitis B and C are major health issues in developing countries such as Pakistan and Afghan-istan. The aim of this study was to determine the prevalence and effectiveness of a screening program for hepatitis B and C in a region with no existing programs, and to estimate their prev-alence in the general population in Khyber Pakhtunkhwa Province, Pakistan, as well as in Afghan refugees or migrants. A prospective cohort study was done in the general population of Peshawar and its adjacent districts, as well as migrants from neighboring provinces of Afghani-stan, who presented to our tertiary-care health facility. A Microsoft Excel registry was created for data collection, which were analyzed using IBM SPSS via descriptive analysis, normal distribution curve histograms, and chi-squared tests. A total of 9563 individuals were screened for hepatitis (5894 males and 3669 females), including Afghan migrants in Peshawar and surrounding districts. 876 individuals tested positive for hepatitis, with 538 positive for hepatitis B (383 males and 155 females) and 330 positive for hepatitis C (198 males and 134 females). Eight individuals had a hepatitis B and C co-infection. Among the study population, the prevalence rates were 2.2% for hepatitis B and 2.3% for hepatitis C, of which the Afghan migrants accounted for 2.7% and 0.5%, respectively. According to the gender-based distribution, hepatitis B was more prevalent in males, whereas there was no significant gender-based difference for hepatitis C. Our results highlight the need for a comprehensive approach to control hepatitis B and C in Pakistan and Afghanistan. Increased awareness, improved healthcare, and preventive measures such as screening and elimination programs to prevent severe liver diseases and eradicate hepatitis are necessary.

Cassava mosaic disease (CMD) and cassava brown streak disease (CBSD) are endemic threats to cassava production. To fill the existing gaps in the understanding of the epidemiology of these diseases in Côte d’Ivoire, nationwide field surveys were conducted in 2016, 2017 and 2020. The leaf samples collected were analysed by PCR. CBSD was not detected in all fields visited. However, an increase of CMD incidence was observed from 45.95% in 2016 to 51.37% in 2020 while CMD severity remained moderate over the years with a mean value of 2.29. Low whiteflies number was observed in field and decreasing over the years. Molecular analysis allowed detection of East African cassava mosaic Cameroon virus (EACMCMV) in single as well as in mixed infection with African cassava mosaic virus (ACMV). Single EACMCMV infection, which was detected only in three agroecological zones of the eastern Côte d’Ivoire in 2016, spread throughout the country in 2017 and became more widespread in 2020 with a preponderance in the central and southern zones, whereas the ACMV+EACMCMV coinfection has spread to the entire zones studied. Knowing the dynamics of the evolution of these viruses across the country, better disease management strategies could be adopted to control the disease.

The current communication presents the application of a consolidated model combination strategy to analyze the medium-term carbon fluxes in two Mediterranean pine wood ecosystems. The modelling strategy is based on the use of a NDVI-driven parametric model, Modified C-Fix, and of a bio-geochemical model, BIOME-BGC, the outputs of which are combined taking into account the actual development phase of each ecosystem. The two pine ecosystems examined correspond to an old-growth forest and to a secondary succession after clearcuts, which differently respond to the same climatic condition during a ten-year period (2013-2022). Increasing dryness, in fact, exerts a fundamental role in controlling the gross primary and net ecosystem production of the mature stand, while the effect of forest regeneration is prevalent for the uprising of the same variables in the other stand. In particular, the simulated net carbon exchange fluctuates around 200 g C m-2 year-1 in the first stand and rises to over 600 g C m-2 year-1 in the second stand; correspondingly, the accumulation of new biomass is nearly undetectable in the former case while becomes notable in the latter. The study therefore supports the potential of the applied strategy for predicting the forest carbon balances consequent on diversified natural and human-induced factors.

Pericyte and their tunnelling nanotubes (P-TNTs) have been described as involved in the early phases of angiogenesis in the human normal developing brain and glioblastoma, being a common feature of combined endothelium/pericyte vessel sprouts. Based on the few data available so far about this ‘alternative’ pericyte-TNT-driven mode of angiogenesis, whose precise function in vessel growth through vascular cells communication, has still to be determined, this study aims to cast light on the regulative molecules involved in this process, governed by intimate pericyte-endothelial interactions. After considering the existence of the sprout guiding pericyte and P-TNT, as shown by pioneering ultrastructural studies as well as by more recent observations with NG2/CD146 pericyte markers and basal lamina molecules, a step-by-step profile of the process has been suggested and an investigation undertaken on ‘unconventional’, pro-angiogenic ligand/receptor systems, that may have a role aside from the canonical pathways. In this context, a possible candidate worthy of investigation is the c-KIT receptor, a member of the tyrosine kinase family of proteins, which also includes the well-known VEGFR and PDGFR. According to the obtained results showing a primary localization of c-KIT on endothelial cells and pointing out a differential distribution of the receptor on normal vs glioblastoma vessels, it seems conceivable to propose the stem cell factor/c-KIT signaling as a key factor in pericyte-TNT-driven angiogenesis, advancing this alternative mode of angiogenesis and the c- KIT pathway as possible targets for devising effective antiangiogenic therapeutic strategies.

Wheat is widely grown in the Mediterranean region, where plants frequently face water shortages. Recently, more attention to rationalizing irrigation water has been increased due to the adoption of sustainable agricultural systems. Therefore, two field trials were conducted at the Agriculture Research Station of Nubaria, Egypt, in two consecutive seasons (2017/2018 and 2018/2019) to examine three irrigation regimes' effects, i.e., 60, 80, and 100% of crop evapotranspiration (ETc) combined with foliar ascorbic acid (AsA) or vitamin B2 (VB2) on yield and water productivity of wheat in two separate experiments. A split-plot design was used with three replicates. Irrigation treatments occupied the main plots, while the subplot in the first experiment was placed by ascorbic acid (AsA) and vitamin B2 in the second experiment. Results indicated that 100% ETc produced higher wheat yield and its attributes and insignificantly surpassed 80% ETc. Compared to the unsprayed plots, the foliar application of 6 mM ascorbic acid or 2.0 mM vitamin B2 significantly increased grain yield, components, and water use efficiency. The interaction between irrigation regimes (100% ETc or 80% ETc) and foliar application of 6.0 mM ascorbic acid or 2.0 mM vitamin B2 resulted in the highest values with no significant difference. Foliar application of ascorbic acid or vitamin B2 saved 20% of irrigation water while yielding a reduction that did not exceed 10%. The biplot graph of treatments x traits (TT) was a useful statistical tool for examining the impact of treatments on yield and its characteristics and identifying the links between these factors. Results suggest that riboflavin or ascorbic acid may have a potential role as an effective antioxidant for enhancing the tolerance for drought stress in wheat.

Ready-to-eat fresh fruit have an increasing presence in international markets due to its convenience and health benefits. However, these produces are highly perishable and efficient technologies to increase their shelf life are needed. In the present research, different citrus fruit species and cultivars from organic farming were assayed to obtain enzymatically citrus segments. The best results in terms of segment quality were observed for ‘Hernandina’ clementine which was chosen to make a new ready-to-eat produce based on peeled citrus segments packaged in glass jars with slight syrup made on citrus juice and organic sugar cane. The most appreciated syrup was those containing 50-50 (v/v) of ‘Fino’ lemon juice and ‘Hernandina’ clementine based on the sensory scores given by the panellists. In addition, different pasteurization treatments were assayed to preserve the new produce safety and nutritional and sensory quality properties during storage at cold temperature. Results showed that pasteurization treatment at 50 °C for 45 min could be enough to avoid microbial contamination with mesophilic and psychrophilic aerobic bacteria or yeast and mould and to maintain sensory properties until five weeks of storage at 4 °C. In addition, only a 10 % reduction of vitamin C was observed from fresh segments or syrup until the end of storage period, showing that the new ready-to-eat produce would conserve high bioactive compound content and health benefits after pasteurization and prolonged cold storage.

FeZnNa@SiO2-C catalyst with graphitized carbon (GC) modified mesoporous SiO2 support metal nanoparticles was prepared by sol-gel method. The effect of adding metal Na and Zn promoters as a dispersion on the CO2 hydrogenation to low olefins was systematically studied. The results showed that Zn-Na, as a combination, promoted the absorption of CO2 and improved the conversion rate of CO2. Na as an alkaline substance can improve the absorption of more acidic CO2, improving the conversion rate of CO2 to 59.03%. Meanwhiles, addition of secondary metal Zn into Fe-based catalysts to form a surface alloy could alter the adsorption of CO2 and the activation of C-O bonds, inhibit the subsequent hydrogenation of olefins to paraffins, facilitate the reduction of Fe2O3 and the formation of active Fe5C2 species. From TEM and XRD, the formation of active Fe5C2 species was found, the selectivity of the target product was 41.07%. The deep hydrogenation of olefins is inhibited, by inhibiting their deep hydrogenations, the STY of C2=-C4= was raised again, up to 0.0436. However, the corresponding STY does not increase infinitely with the increase of Na content, and when the Na content to 6.4%, which can be shown higher CO2 hydrogenation catalytic performance. Compared with Fe@SiO2-C catalyst, Na and Zn promoted Fe-based catalysts prepared by modified sol-gel method, can be used directly for highly efficient CO2 hydrogenation to low olefins and thus will be more promising in the future.

Background: this study aimed to describe the distribution of the genotype and allele frequencies of GJB2 variants in the Chinese population of the Dongfeng Tongji cohort and to analyze the features of the hearing phenotype. Methods: we used data from 9910 participants in the Dongfeng Tongji cohort in 2013 and selected nine GJB2 variants. Pure-tone audiometry was employed to measure hearing. Differences in genotype and allele frequencies were analyzed by chi-squared test or Fisher's exact test. Results: of the 9910 participants, 5742 had hearing loss. The genotype frequency of the GJB2 variant p.V37I was statistically significantly distributed between the normal and impaired hearing groups, but not for the variant c.235delC. A higher frequency of the p.V37I homozygous genotype was found in the hearing loss group (0.5%) than in the normal hearing group (0.1%). Patients with p.V37I and c.235delC homozygous mutations exhibited varying degrees of hearing loss, mainly presenting sloping and flat audiogram shapes. Conclusions: a significant difference was found in the genotype frequency of the GJB2 variant p.V37I between the case and control groups, but not for the variant c.235delC. Different degrees of hearing loss and various audiogram shapes were observed in patients with p.V37I and c.235delC homozygous mutations.

The study aimed to manage and to analyse the results of the laboratory tests, routinallypractice for hepatitis C diagnosis, using blood tests. Statistical analysis of this study results, was performed using the laboratory informatic system. The results of the study are substantial and intricate reffering to comparision between two methods concretlly ELISA method (Enzyme-Linked Immunosorbent Assay) and chemiluminescence methods and their results. Good to know our opinion that RT-PCR technique, it is considered proper for the diagnosis of HCV ( Hepatitis C virus).

It is widely reported that the mitochondrial membrane potential, ∆Ψm, is reduced in aging animals. It was recently suggested that the lower ∆Ψm in aged animals modulate mitochondrial bioenergetics and that this effect is a major cause of aging since artificially increased ∆Ψm in C. elegans increased lifespan. Here I review, critically, studies that reported reduction of ∆Ψm in aged animals, including worms, and conclude that many of these observations are best interpreted as evidence that the fraction of depolarized mitochondria is increased in aged cells because of the enhanced activation of the mitochondrial Permeability Transition Pore, mPTP. Activation of the voltage-gated mPTP depolarizes the mitochondria, inhibits oxidative phosphorylation, releases large amounts of calcium and mROS, and depletes cellular NAD+, thus accelerating degenerative diseases and aging. Since the inhibition of mPTP was shown to restore ∆Ψm and retard aging, the reported lifespan extension by artificially generated ∆Ψm in C. elegans is best explained by inhibition of the voltage-gated mPTP. Similarly, the reported activation of the mitochondrial Unfolded Protein Response by reduction of ∆Ψm, and the reported preservation of ∆Ψm in dietary restriction treatment in C. elegans are best explained as a resulting from activation or inhibition of the voltage-gated mPTP, respectively.

Increasing the loading density of nanoparticles on carbon support is essential for making Pt-alloy/C catalysts practical in H2-air fuel cells. The challenge lies in increasing the load-ing while suppressing the sintering of Pt-alloy nanoparticles. This work presents a 40% Pt-weighted sub-3 nm PtCo/C alloy catalysts via a simple incipient wetness impregnation method. By carefully optimizing the synthetic conditions such as Pt/Co ratios, calcination temperature and time, the size of supported PtCo alloy nanoparticles is successfully con-trolled below 3 nm, and a high electrochemical surface area achieves of 94 m2/g is achieved, which is 2.8 times of commercial PtCo/C-TKK catalysts. Demonstrated by elec-trochemical oxygen reduction reaction, PtCo/C alloy catalysts present an enhanced mass activity of 0.45 A/mg at 0.9 V vs. RHE, which is 1.7 times that of PtCo/C-TKK catalyst. Therefore, the developed PtCo/C alloy catalyst can potentially be a highly practical cata-lyst for H2-air fuel cells.

The nematode Angiostrongylus cantonensis has been reported worldwide, however, some basic questions remain unanswered about the presence of A. cantonensis in Ecua-dor: 1) Was the invasion of A. cantonensis in Ecuador unique, or did it occur in different waves? 2) Was this invasion as recent as historical records suggest? 3) Did this inva-sion come from other regions of South America or elsewhere? To address these issues, we assessed the genetic diversity of MT-CO1 gene sequences from isolates obtained in eleven of Ecuador's 24 provinces. Our Bayesian inference phylogenetic tree recovered A. cantonensis as a well-supported monophyletic group. All eleven sequences from Ec-uador were identical and identified as AC17a. The haplotype AC17a, found in Ecuador and the USA, formed a cluster with AC17b (USA); AC13 (Thailand); and AC12a-b (Cambodia). It is notable that all the samples, obtained in different geographic and climatic regions of different Ecuadorian provinces, had no genetic difference between them. Despite the lack of genetic information on A. cantonensis in Latin America, ex-cept in Brazil, our finding differs from previous studies by its absence of genetic diver-sity in Ecuador. We concluded that the invasion of A. cantonensis in Ecuador may have occurred: 1) as a one-time event, 2) recently, and 3) from Asia via the USA. Further re-search should include samples from countries neighboring Ecuador to delve deeper in-to this.

The mechanistic target of rapamycin (mTOR) kinase is one of the top drug targets for promoting health and lifespan extension. Besides rapamycin, only a few other mTOR inhibitors have been developed and shown their ability to slow aging. We used machine learning to predict novel small molecules targeting mTOR. We selected one small molecule, TKA001, based on in-silico predictions of a high on-target probability, low toxicity, favorable physicochemical properties, and preferable ADMET profile. We confirmed TKA001 binding in silico by molecular docking. TKA001 potently inhibits both TOR complex 1 and 2 downstream signaling in vitro. Furthermore, TKA001 inhibits human cancer cell proliferation in vitro and extended the lifespan of C. elegans, suggesting that TKA001 can slow aging in vivo.

Since the discovery of mitochondrial-derived peptides (MDP), their participation in cellular metabolism is no longer considered as the sole function of the mitochondria, but importance was also attached to its role as a source of protective factors of metabolic stress. These peptides are encoded in the mitochondrial genome and translated into the mitochondria or cytoplasm, to signal within the cell or be released and bind to membrane receptors. The objective of this work was explored and compare the frequency of MT-RNR1 and MT-RNR2 variants in sequences obtained from T2D individuals and control population. 213 different mitochondrial polymorphisms previously reported in the literature associated with T2D and cardiovascular diseases were analyzed. We can found three variants in the MT-RNR1 not related with MOTS-c coding sequence: m.1189T>C (rs28358571), m.1420T>C (rs111033356), and m.1438A>G (rs2001030); and secondly, three polymorphisms associated to MT-RNR2 m.2667T>C (rs878870626) related to humanin, m.1811A>G (rs28358576) in SHPL3 and m.3027T>C (rs199838004) in SHPL6 associated with statistical differences between the T2D and control group. All these findings were previously related to cardiovascular complications in literature and, as far as we know, relating for the first time in diabetic patients.

Restrictive cardiomyopathy is a rare cardiac disease causing severe diastolic dysfunction, ventricular stiffness and dilated atria. In consequence, it induces heart failure often with preserved ejection fraction and is associated with a high mortality. Since a poor clinical prognosis, patients with restrictive cardiomyopathy require frequently heart transplantation. Genetic as well as non-genetic factors contribute to restrictive cardiomyopathy and a significant portion of cases remains of unknown etiology. However, the genetic forms of restrictive cardiomyopathy and the involved molecular pathomechanisms are only partially understood. In this review, we summarize the current knowledge about primary genetic restrictive cardiomyopathy and describe its genetic landscape, which might be of interest for geneticists as well as for cardiologists.

Nicotinamide adenine dinucleotide (NAD+) is an essential molecule involved in various metabolic reactions, acting as an electron donor in the electron transport chain and as a co-factor for NAD+-dependent enzymes. In the early 2000s, reports that NAD+ declines with aging introduced the notion that NAD+ metabolism is globally and progressively impaired with time. Since then, NAD+ became an attractive target for potential pharmacological therapies aiming to boost NAD+ levels to promote vitality and protect against age-related diseases. This review summarizes and discusses a collection of studies that report the levels of NAD+ with aging in different species (i.e., yeast, C. elegans, rat, mouse, monkey, and human) to determine whether the notion that overall NAD+ levels decrease with aging stands true. We find that despite systematic claims of overall changes in NAD+ levels with aging, the evidence to support it is very limited and often restricted to a single tissue or cell type. This is particularly true in humans, where the development of NAD+ levels during aging is still poorly characterized. There is a need for much larger, preferably longitudinal, studies aimed to assess how NAD+ levels develop with aging in various tissues. This will strengthen our conclusions on NAD+ during aging and should provide a foundation for better pharmacological targeting of relevant tissues.

SCARED-C instrument (the child version, 41 items) is used for screening anxiety in children between 8 to 18 years old and has been first introduced by Birmaher & collab. in 1995, with good psychometric data - internal consistency from α =.74 to .93 - and good discriminative validity indices in the original versions (1997, 1999). Since then, many countries have adopted the scale, for its utility in identifying five subsets of anxiety disorders (subscales): somatic/panic disorder, generalized anxiety, separation anxiety, social phobia, and school avoidance. The present study contains the first Romanian translated and adapted version of the SCARED-C instrument on a community sample of 477 children (8-18 years old) from Mureș county schools. The instrument showed moderate to good internal consistency (α Cronbach from to .63 to .91 for the total scale) and good test-retest reliability (.70) on a subset of 85 children sample. A confirmatory factorial analysis (CFA) was conducted to test the factor structure of the Romanian version of SCARED-C; results showed that SCARED-C has good psychometric properties to be used for screening anxiety in Romanian children and adolescents. The implications for using SCARED-C in dental practice are discussed. Future studies need to be conducted for exploring convergent and discriminative validity of the instrument and the sensitivity to current DSM-V criteria. Application on a dental pediatric sample is also required.

Feline calicivirus (FCV) causes upper respiratory tract disease (URTD) and sporadic outbreaks of virulent systemic disease (FCV-VSD). The basis for the increased pathogenicity of FCV-VSD viruses is incompletely understood, and antivirals for FCV have yet to be developed. We investigated the clinicoepidemiology and viral features of three FCV-VSD outbreaks in Australia and evaluated the in vitro efficacy of nitazoxanide (NTZ), 2’-C-methylcytidine (2CMC) and NITD-008 against FCV-VSD viruses. Overall mortality among 23 cases of FCV-VSD was 39%. Metagenomic sequencing identified five genetically distinct FCV lineages within the three outbreaks, all seemingly evolving in situ in Australia. Notably, no mutations that clearly distinguished FCV-URTD from FCV-VSD phenotypes were identified. One FCV-URTD strain likely originated from a recombination event. Analysis of seven amino acid residues from the hypervariable E region of the capsid in the cultured viruses provided no support for the contention that properties of these residues can reliably differentiate between the two pathotypes. On plaque reduction assays, dose-response inhibition of FCV-VSD was obtained with all antivirals at low micromolar concentrations; NTZ EC50, 0.4-0.6 µM, TI 21; 2CMC EC50, 2.7-5.3 µM, TI >18; NITD-008, 0.5 to 0.9 µM, TI >111. Investigation of these antivirals for treatment of FCV-VSD is warranted.

This prospective observational study aimed to describe voriconazole administrations and trough concentrations in patients with Child-pugh class C clinically, and to investigate the variability of trough concentration. A total of 144 voriconazole trough concentrations from 43 Child-pugh class C patients were analyzed. The majority of patients (62.8%) received adjustments. The repeated measured trough concentration was higher than the first and final ones generally (median, 4.33 vs. 2.99, 3.90 mg/L). Eight patients with ideal initial concentration later got supratherapeutic with no adjusted daily dose, implying accumulation. There was a significant difference in concentrations among the six groups by daily dose (P=0.006). The bivariate correlation analysis showed that sex, CYP2C19 genotyping, daily dose, prothrombin time activity, international normalized ratio, platelet, and Model for end-stage liver disease score were significant factors for concentration. Subsequently, the first four factors mentioned above entered into a stepwise multiple linear regression model (variance inflation factor &lt; 5), implying that CYP2C19 testing makes sense for precision medicine of Child-pugh class C cirrhosis patients. The equation fits well and explains the 34.8% variety of concentrations (R^2 = 0.348). In conclusion, it needs more cautious administration clinically due to no recommendation for Child-pugh class C patients in the medication label. The adjustment of the administration regimen should be mainly based on the results of repeated therapeutic drug monitoring.

Introduction: Elevated albuminuria is an important outcome of diabetic complications and metabolic syndrome (MetS), the complex metabolic abnormalities manifested as glucose intolerance, hypertension, and dyslipidemia and enlarged waist circumference. These coexisting cardio-metabolic abnormalities are also associated with oxidative stress and low grade inflammation. Vitamin C (vitC) has long been recognized as hydrophilic antioxidant and blocker of oxidative stress which also has a protective role of MetS and kidney disease. Objective: The aim of this study was to identify the predictive effect of vitC deficiency on kidney disease among patients who developed metabolic syndrome. Method and procedures: To meet this objective, the National Health and Nutrition Examination Survey (NHANES) 2007-2008 data were used. NHANES represents the civilian, non-institutionalized US population data implemented for continuous system of monitoring health, nutritional status and well-being in the US. The predictive power of MetS on AU and vitC deficiency (vitC < 0.25 mg/dl) as effect modifier was assessed with binary logistic regression. Age, gender, race and BMI were used as covariates. Results: Among the respondents, 1.9% of the US population had risk of kidney damage, whereas 14.5 % of respondents had MetS. MetS was significantly positively correlated with AU (p < 0.01). Higher elevation of albuminuria creatinine ratio (ACR) was found in participants with VCD. The regression models developed in this study showed that the severity of kidney disease measured by ACR was increased among individuals who developed both VCD and MetS compared with individuals who developed MetS only (AOR=5.53; 95% CI: 2.73, 11.21). Increasing age and being African-American in race were independently associated with elevated AU. Conclusion: Specific considerations tailored to metabolic syndrome, vitamin C and kidney diseases measured by ACR screening and monitoring mechanisms at the community level is critical to tackle further medical complications. Moreover, the role of VitC fortified foods on prevention of kidney diseases among patients with MetS warrant further investigation.

Multisystem inflammatory syndrome related to SARS-CoV-2 infection (MIS-C) is a rare severe illness affecting pediatric patients. No data are available in literature about the presence of SARS-CoV-2 RNA in faeces in patients with MIS-C. The SARS-CoV-2 positivity was evaluated in fecal samples obtained in a prospective cohort of pediatric patients admitted to our tertiary Hos-pital and diagnosed with MIS-C or COVID-19 between April 15, 2020, and February 29, 2021. The real-time RT-PCR was performed using a validated kit. The assay measures 3 target genes: SARS-CoV-2 gene E, gene N, gene ORF1ab. Overall, 16/63 (25%) fecal samples revealed the pres-ence of SARS -CoV-2 RNA. No differences were detected about time from presumptive viral ex-posure and the time of stool collection (14 vs 8 days, p> 0,05) as well as about the presence of gas-trointestinal symptoms (p>0.05) between patients with positive (+) stools for SARS-CoV-2 RNA and patients tested negative (-). Among children with MIS-C, stools were collected 27.5 days as median (95% CI 14-34) after presumed contact and the positivity rate was 12.5% (4/32). According to our data, we could suggest contact precautions with all patients with MIS-C. Further sample collection is ongoing to verify our preliminary data.

In this era of technology, programming has become more significant than ever before. Python and C++ are both widely used programming languages. Python, the most popular programming language in today’s world, is a high-level object-oriented language whereas C++, the language behind most operating systems, is a low-level object-oriented language. In this paper, we present a comparative study of Python and C++. This paper discusses the introduction to these languages, their memory management techniques, and the reasons behind their program execution speed. Furthermore, we analyzed the execution time and memory used by multiple algorithms in both the languages with best, average, and worst cases. They are also compared with respect to the benefits and issues related to them. Results indicate that C++ is faster than Python in execution speed but Python serves as a better language for beginners due to its simplicity. Moreover, for the best results, the language should be selected according to the type of project.

Introduction: Elevated albuminuria is an important outcome of diabetic complications and metabolic syndrome (MetS), the complex metabolic abnormalities manifested as glucose intolerance, hypertension, and dyslipidemia and enlarged waist circumference. These coexisting cardio-metabolic abnormalities are also associated with oxidative stress and low grade inflammation. Vitamin C (vitC) has long been recognized as hydrophilic antioxidant and blocker of oxidative stress which also has a protective role of MetS and kidney disease. Objective: The aim of this study was to identify the predictive effect of vitC deficiency on kidney disease among patients who developed metabolic syndrome. Method and procedures: To meet this objective, the National Health and Nutrition Examination Survey (NHANES) 2007-2008 data were used. NHANES represents the civilian, non-institutionalized US population data implemented for continuous system of monitoring health, nutritional status and well-being in the US. The predictive power of MetS on AU and vitC deficiency (vitC < 0.25 mg/dl) as effect modifier was assessed with binary logistic regression. Age, gender, race and BMI were used as covariates. Results: Among the respondents, 1.9% of the US population had risk of kidney damage, whereas 14.5 % of respondents had MetS. MetS was significantly positively correlated with AU (p < 0.01). Higher elevation of albuminuria creatinine ratio (ACR) was found in participants with VCD. The regression models developed in this study showed that the severity of kidney disease measured by ACR was increased among individuals who developed both VCD and MetS compared with individuals who developed MetS only (AOR=5.53; 95% CI: 2.73, 11.21). Increasing age and being African-American in race were independently associated with elevated AU. Conclusion: Specific considerations tailored to metabolic syndrome, vitamin C and kidney diseases measured by ACR screening and monitoring mechanisms at the community level is critical to tackle further medical complications. Moreover, the role of VitC fortified foods on prevention of kidney diseases among patients with MetS warrant further investigation.

Standard evolutionary theory, supported by mathematical modelling of outbred, dispersed populations predicts that ageing is not an adaptation. We recently argued that in clonal, viscous populations, programmed organismal death could promote fitness through social benefits and has, in some organisms (e.g. Caenorhabditis elegans), evolved to shorten lifespan. Here we review previous adaptive death theory, including consumer sacrifice, biomass sacrifice, and defensive sacrifice types of altruistic adaptive death. In addition we discuss possible adaptive death in semelparous fish, coevolution of reproductive and adaptive death, and adaptive reproductive senescence in C. elegans. We also describe findings from recent tests for the existence of adaptive death in C. elegans using computer modelling. Such models have provided new insights into how trade-offs between fitness at the individual and colony levels mean that senescent changes can be selected traits. Exploring further the relationship between adaptive death and social interactions, we consider examples where adaptive death results more from action of kin than from self-destructive mechanisms and, to describe this, introduce the term adaptive killing of kin.

Umbu is a tropical fruit with high content of bioactive compounds. However, maturation causes significant losses on nutrient density reducing the nutritional value of this highly appreciated fruit. Thus, the objective of the present work was to encapsulate the Umbu fruit bioactive compounds using spray drying and identify the variables affecting the biomolecules preservation. A Box-Behnken experimental design with 3 factors was set varying inlet temperature, atomization flow rate, and maltodextrin concentration for process otimization. Then the powder physicochemical and chemical properties were characterized, and results were modeled using a polynomial equation. Results revealed that the droplet size and maltodextrin concentration had a significant influence on the conservation of the biomolecules. Drying kinetics favoring fast formation of a particle crust increases encapsulation efficiency. Bioactive compounds retention was achieved by increasing maltodextrin even at high temperatures, where a matrix is formed hindering chemical degradation. Process optimization was validated and revealed low inlet temperatures (122ºC), high atomization flow rate (5kg/h) and high maltodextrin concentration (20%) to be the most desirable conditions for bioactive compounds retention.

We describe the innate and adaptive immune system trajectory in Multi-system inflammatory syndrome of childhood (MIS-C), at acute(within 72 hours of hospitalization), resolution (at clinical improvement) and convalescent phase. In our cohort, in the acute phase, 68% of the children were SARS-CoV-2 seropositive, with hypercytokinenemia (high interleukin(IL)-1beta,IL-6,IL-8,IL-10,IL-17, interferon gamma), procoagulant state, myocardial dysfunction, activated neutrophils and monocytes; differential T and B cell subset lymphopenia; activated chemokine receptor type-7 positive and gamma-delta T cell subsets; antigen presenting cells had reduced HLA-DR expression; and B-cell class-switch responses occurred with illness resolution. MIS-C is an immunopathogenic illness associated with SARS-CoV-2 infections in children.

The delivery of Cytochrome c (Cyt c) to the cytosol stimulates apoptosis in cells were its release from mitochondria and apoptosis induction is inhibited. We developed a drug delivery system consisting of Cyt c nanoparticles decorated with folate-poly(ethylene glycol)-poly(lactic-co-glycolic acid)-thiol (FA-PEG-PLGA-SH) to deliver Cyt c into cancer cells and test their targeting in the Lewis Lung Carcinoma (LLC) mouse model. Cyt c-PLGA-PEG-FA nanoparticles (NPs) of 253 ± 55 and 354 ± 11 nm were obtained by Cyt c nanoprecipitation, followed by surface decoration with the co-polymer SH-PLGA-PEG-FA, and compared to a nanoparticle-free formulation. Overexpression of FA in LLC cells and internalization of Cyt c-PLGA-PEG-FA nanoparticles (NPs) was confirmed by confocal microscopy. Caspase activation assays show NPs retain 88-96% Cyt c activity. The NP formulations were more efficient in decreasing LLC cell viability than the NP-free formulation, with IC50: 49.2 to 70.1 μg/ml versus 129.5 μg/ml, respectively. Our NP system is thrice as selective towards cancerous than normal cells. In-vivo studies using tagged nanoparticles show accumulation in mouse LLC tumor 5 min post-injection. In conclusion, our NP delivery system for Cyt c shows superiority over the NP-free formulation and reaches a folic acid-overexpressing tumor in an immune-competent animal model.

I have recently reiterated that the cross-bridge is a calcium ATPase that is inhibited by magnesium and this arises because in normal hearts Myosin binding Protein-C prevents the use of MgATP as rate limiting substrate ensuring that Ca²⁺ replaces Mg²⁺ in the excitation pathway. Here I revisit the studies on [Ca²⁺] dependency of ATPase and tension under diastolic stretch with a different conclusion on Hill coefficients. This reveals the underlying mechanisms of the Frank-Starling Law and Hypertrophic myopathy are not the same, the former being kinase controlled.

In an attempt to correct misunderstandings this article brings together the observations on Calcium, Myosin Binding Protein-C and Hypertrophic Cardiomyopathy in the basic function of cardiac muscle. A finding of many years ago is reiterated in a novel enzyme kinetic format with defined rate limiting step which makes CaATP the apparent substrate of the actomyosin cross-bridge. The relationship of these kinetics to recent observations on disruption of myosin binding protein-C is described along with how this bears on the understanding of the related cardiomyopathies.

Sickle cell disease (SCD) is an inherited disorder of major health challenge in Nigeria. Micronutrients deficiencies often associated with the disorder may cause inflammation and abnormal metabolisms in the body. The copper-to-zinc ratio is a more important assessment than the concentrations of either of the metals in clinical practice. This study seeks to evaluate serum levels of c-reactive protein (CRP), copper, zinc and copper-to-zinc ratio and to correlate copper-to-zinc ratio with CRP in adult subjects with SCD. Serum copper, zinc, CRP and plasma fibrinogen were assayed in 100 confirmed SCD patients in steady clinical state and 100 age and sex matched subjects with normal haemoglobin. Serum copper and zinc were assayed by colorimetric method using reagents supplied by Centronic, Germany while CRP and fibrinogen were assayed using reagents supplied by Sigma (St. Louis, MO, USA) and Anogen (Ontario, Canada), respectively. The copper to zinc ratio was calculated from serum levels of copper and zinc. The measured parameters were compared between the groups using Students t-test and Pearson correlation coefficient was used to relate CRP with the other parameters. Serum copper, CRP, fibrinogen and copper-to-zinc ratio were significantly higher (p < 0.001) while zinc level was lower in SCD patients than controls. Serum CRP concentration correlated with copper (r = 0.10; p < 0.02), zinc (r = −0.199; p < 0.05) and Copper-to-zinc ratio (r = 0.312; p < 0.002) but the correlation between CRP and fibrinogen was not significant. Inflammatory condition may modulate copper and zinc homeostasis and copper-to-zinc ratio may be used as marker of nutritional deficiency and inflammation in SCD patients.

From single-cell organisms to complex neural networks, all evolved to provide control solutions to generate context and goal-specific actions. Neural circuits performing sensorimotor computation to drive navigation employ inhibitory control as a gating mechanism, as they hierarchically transform (multi)sensory information into motor actions. Here, we focus on this literature to critically discuss the proposition that prominent inhibitory projections form sensorimotor circuits. After reviewing the neural circuits of navigation across various invertebrate species, we argue that with increased neural circuit complexity and the emergence of parallel computations inhibitory circuits acquire new functions. The contribution of inhibitory neurotransmission for navigation goes beyond shaping the communication that drives motor neurons, instead, include encoding of emergent sensorimotor representations. A mechanistic understanding of the neural circuits performing sensorimotor computations in invertebrates will unravel the minimum circuit requirements driving adaptive navigation.

Sepsis is a devastating disease that carries an enormous toll in terms of human suffering and lives lost. Over 100 novel pharmacologic agents which targeted specific molecules or pathways have failed to improve the outcome of sepsis. Preliminary data suggests that the combination of Hydrocortisone, Ascorbic Acid and Thiamine (HAT therapy) may reduce organ failure and mortality in patients with sepsis and septic shock. HAT therapy is based on the concept that a combination of readily available, safe and cheap agents which target multiple components of the host’s response to an infectious agent will synergistically restore the dysregulated immune response and thereby prevent organ failure and death. This paper reviews the rationale for HAT therapy with a focus on vitamin C.

Centralized/Cloud Radio Access Networks (C-RAN) are deployed in converged fixed-mobile networks to exploit the flexibility coming from joint application of Network Function Virtualization (NFV) and Software Defined Networking (SDN). In this context, optical links connecting C-RAN nodes, possibly based on the Ethernet standards, may carry traffic with different requirements in terms of latency and throughput. This paper considers the problem of traffic aggregation on C-RAN optical Ethernet links with latency control for fronthaul traffic and throughput capability for backhaul traffic. Integrated hybrid nework technique is applied to show how time transparency can be enforced for Ethernet encapsulated Common Public Radio Interface (CPRI) traffic while allowing statistical multiplexing of backhaul traffic. Simulation results show the effectiveness of segmentation of backhaul traffic to allow exploitation of the available bandwidth even with high capacity CPRI options.

Hepatitis C virus (HCV) represents a challenging global health threat in ~200 million infected individuals. Clinical data suggests that only ~10-15% of acutely HCV-infected individuals will achieve spontaneous viral clearance despite exuberant virus-specific immune responses, which is largely attributed to difficulties in recognizing the pathognomonic symptoms during the initial stages of exposure to the virus. Given the paucity of a suitable small animal model, it is also equally challenging to study the early phases of viral establishment. Further, the host factors contributing to HCV chronicity in a vast majority of acutely HCV-infected individuals largely remain unexplored. The last few years have witnessed a surge in studies showing that HCV adopts a myriad mechanisms to disconcert virus-specific immune responses in the host to establish persistence that includes, but not limited to viral escape mutations, viral growth at privileged sites, and antagonism. Here, we discussed a few hitherto poorly explained mechanisms employed by HCV that are believed to lead to chronicity in infected individuals. A better understanding of these mechanisms would aid the design of improved therapeutic targets against viral establishment in susceptible individuals.

Lectins are carbohydrate-interacting proteins playing a pivotal role in multiple physiological and developmental aspects of all organisms. They can specifically interact with different bacterial and viral pathogens through the carbohydrate-recognition domains (CRD). In addition, lectins are also of biotechnological interest because of their potential use as biosensor for capturing and identification of bacterial species. In this work, we have characterized the bacterial agglutination properties of three C-type lectins from the Lepidoptera Spodoptera exigua. One of these lectins, BLL2, was able to agglutinate cells from a broad range of bacterial species at an extremely low concentration, becoming a very interesting protein to be used as biosensor or other biotechnological applications involving bacterial capturing.

The title compound, trans-11-(3,4-dimethoxyphenyl)-2,3,8,9-tetramethoxy-6-oxo-11,12-dihydro-6H-dibenzo[c,h]chromene-12-carboxylic acid (4), was synthesized for the first time via a two-step protocol from 3,4-dimethoxyhomophthalic anhydride (1) and 3,4-dimethoxybenzaldehyde (DMBA). In the first step, 1 reacts with DMBA to give trans-3-(3,4-dimethoxyphenyl)-6,7-dimethoxy-1-oxo-3,4-dihydro-1H-2-benzopyran-4-carboxylic acid (2), which further reacts with additional two equivalents of 1 to give 4. Compound 4 was characterized by means of spectral methods - 1H-, 13C-, DEPT-135-NMR, and HRMS.

Lymphadenomegaly is well described in dogs with neoplastic diseases, but it can also reflect in-flammation. However, its role in assessments of inflammation is little reported in the veterinary literature. Lymph nodes are most easily assessed superficially through palpation, but computed tomography (CT) enables evaluation of deep lymph nodes. Accordingly, we investigated associ-ations between maximal lymph node diameter and plasma concentrations of C-reactive protein (CRP), a sensitive inflammatory marker, targeting three deep lymph nodes (sternal, cranial me-diastinal, and internal iliac). We evaluated data from small dogs with non-neoplastic diseases that underwent synchronous CT and blood biochemistry at our institution. We found that cranial mediastinal lymph node diameter was significantly greater in dogs with clinically elevated CRP than those with clinically unremarkable CRP (CRP 0.7-7.0< mg/dL vs.

A new tetracyclic morpholine-fused [5,1-c]-triazole, (4aS,5S,6aR,10aR,10bR)-5-methoxy-9,9-dimethyl-4a,5,6a,7,10a,10b-hexahydro-12H-[1,3]dioxino[4',5':5,6]pyrano[4,3-b][1,2,3]triazolo[1,5-d][1,4]oxazine, was synthesized via a five-step sequence starting from methyl α-D-glucopyranoside by using as a key step an intramolecular copper(I) cat-alyzed alkyne-azide cycloaddition (CuAAC). The synthesized compound was fully characterized by 1H and 13C NMR, FT-IR, and HRMS.

The use of C-type natriuretic peptide (CNP) in the interaction with the oocyte and in the temporary postponement of spontaneous meiosis resumption has already been well described. However, its action in pre-implantation developmental stage embryos remains to be understood. Thus, our study aimed to detect the presence of the canonical CNP receptor (natriuretic peptide receptor, NPR2) in germinal vesicle (GV), metaphase II (MII), presumptive zygotes (PZ), morula (MO), and blastocyst (BL) stage embryos and, later, to observe possible modulations on the embryos when co-cultured with CNP. In the Experiment I, we detected and quantified the NPR2 on the above-mentioned embryo stages. Following, Experiment II, intended to test different concentrations (100, 200, or 400 nM of CNP) at different times of inclusion in the in vitro culture (IVC; inclusion from the beginning, i.e. day 1, or from day 5). In Experiment III, it was used 400 nM of CNP on day 1 (D1) in the IVC, which did no demonstrate to be embryotoxic, and it showed potentially promising results in blastocyst production rate, when compared to the control. Thus, we analyzed the embryonic development rates of bovine embryos (D7) and hatching kinetics (D7, D8, and D9). Subsequently, morula and blastocyst were collected and evaluated for transcript abundance to competence and quality (apoptosis, oxidative stress, proliferation and differentiation) and lipid metabolism. Differences with probabilities less than P < 0.05, and/or Foldchange (FC) ˃1.5 were considered significant. We demonstrate the presence of NPR2 until the blastocyst development stage when there was a significant decrease in membrane receptors. There was no statistical difference in production rate after co-culture with 400 nM CNP. However, when we evaluated the abundance of morula transcripts, there was an upregulated transcription in ADCY6 (P=0.057), and downregulated transcripts, in BMP15 (P= 0.013), ACAT1 (P= 0.040), CASP3 (P=0.082). In addition, a total of 12 transcriptions in morula presented variation FC ˃1.5. In blastocysts, the treatment with CNP induced upregulation in BID, CASP3, SOX2, HSPA5 transcripts, and downregulation in BDNF, NLRP5, ELOVL1, ELOVL4, IGFBP4, and FDX1 transcripts (FC >1.5). Thus, our study identified and quantified the presence of NPR2 in bovine pre-implantation embryos. Furthermore, 400 nM of CNP in IVC, a concentration not previously described in the literature, modulated some transcripts related to embryonic metabolism and it was not embryotoxic morphologically.

With advancements in remote sensing technology and affordable design, uncrewed aerial systems (UAS), commonly known as drones, have become prevalent in both civil and military applications, such as agriculture, public safety, and aerial imaging. However, the rise in unlawful UAS activities, such as non-compliance with legal standards and potential terrorist attacks, has raised significant public concern, necessitating effective detection and mitigation solutions. Despite the growing importance of this issue, comprehensive and detailed examinations of existing counter-UAS solutions are lacking. To address this gap, this study conducts a bibliometric analysis and scoping review of the current literature to identify key topics and emerging trends in counter-UAS approaches. Utilizing co-word and social network analyses, the study identifies strong and weak connections between selected keywords from academic articles. This study summarizes the limitations and potential opportunities within counter-UAS research, suggesting an increasing focus on multisensory fusion and machine-learning approaches for drone detection and mitigation. Additionally, areas such as swarm drone operations, UAS traffic management (UTM), and UAS networks are identified as important but promising fields for further investigation. The findings of this study provide a foundation for enhancing air and ground safety through improved counter-UAS applications.

Carbon (C) losses due to the conversion of natural forests adversely affect the abiotic components of terrestrial ecosystems. In tropical China, rubber cultivation often extends from its traditional range to elevations of up to 1400 m. However, C storage in rubber plantations across elevation gradients is poorly understood. In this study, we investigated biomass and C storage along elevation gradients in two age groups (8- and 12-year-old) of rubber monoculture plantations in Xishuangbanna, Southwest China. We investigated the C distribution across various tree sections, ranging from aboveground biomass (AGB) to belowground biomass (BGB), including litter, big dead branches, and different soil depths. A significant negative correlation was observed between total ecosystem C stocks and elevation in both age groups of rubber plantations. The highest ecosystem C stock of 197.90 Mg C ha–1 was recorded at 900 m in 8-year-old plantations, whereas in 12-year-old rubber plantations, the highest value of 183.12 Mg C ha–1 was found at 700 m. The total ecosystem C stocks decreased to its lowest level at 1000 m in both the 8-year-old and 12-year-old plantations, ranging between 113.05 Mg C ha–1 and 125.75 Mg C ha–1, respectively. We concluded that the total ecosystem C stocks were negatively correlated with elevation and significantly decreased from 8.05% to 51.55% and 11.46% to 42.96% between 700 m and 1100 m in both 8-year-old and 12-year-old plantations, respectively. However, no correlation was observed between the total soil C stocks and elevation in either age group of rubber plantations. Regardless of elevation gradient, the total ecosystem C stock of 12-year-old rubber plantations was 1.98% greater than that of 8-year-old rubber plantations. Biomass was the second largest contributor, while soil accounted for 82% to 90%, and the other factors contributed less than 2% of the total ecosystem C stock in both age groups. These fluctuations in C stocks along elevation gradients in both 8- and 12-year-old plantations suggested that rubber growth, biomass and C storage capacity decreased above 900 m and that age and elevation are key factors for biomass and C storage in monoculture rubber plantations.

Hepatitis C virus (HCV) is an oncogenic virus that causes chronic liver disease in more than 80% of patients. During the last decade, efficient direct acting antivirals were introduced into clinical practice. However, clearance of the virus does not reduce risk of end-stage liver diseases to the level observed in patients that have never been infected. So, investigation of HCV pathogenesis is still warranted. Virus-induced changes in cell metabolism contribute to the development of HCV-associated liver pathologies. Here we studied the impact of the virus on the metabolism of polyamines and proline as well as on the urea cycle, which plays a crucial role in liver function. It was found that HCV strongly suppresses the expression of arginase, a key enzyme of the urea cycle, leading to accumulation of arginine and upregulates proline oxidase with a concomitant decrease in proline concentrations. Addition of exogenous proline moderately suppressed viral replication. HCV upregulated transcription but suppressed protein levels of polyamine-metabolizing enzymes. This resulted in a decrease in polyamine content in infected cells. Finally, compounds targeting polyamine metabolism demonstrated pronounced antiviral activity pointing to spermine and spermidine as compounds affecting HCV replication. These data expand our understanding of HCV’s imprint on cell metabolism.

Quasi-solid composited electrolytes were produced by LiFSI initiated polymerized poly-(Dioxolane) (PDOL) with garnet-LLZO (Li7La2Zr3O12) nanofibers and used in lithium-metal batteries. Linear sweep voltammetry shows that the initial oxidation voltage of 4.6 V for Gel-10% (G10, 10% wt. LLZO in PDOL) vs Li/Li+. EIS test of stainless steel// stainless steel symmetric cells for Gel-1% (G1), Gel-5% (G5) and Gel-10% (G10) show ion conductivity (5*10-5 S/cm). Li/G10/Li symmetric cells have stable stripping-plating cycling performance over 1300 hours continuously with the current density of 0.1 mA/cm2 at 25 oC, indicating a good interface contact and stable lithium-ion transport pathway through the composite electrolytes. LFP/G10/Li batteries have stable charge-discharge plateau, low polarization voltage of 0.07-volt, energy efficiency of 95% and coulombic efficiency of ~99% at current density of 26.3 mA/g at 25 oC for over 100 cycles.

Dengue is one the most significant mosquito-borne viral diseases globally, with its prevalence extending across tropical and subtropical regions, exerting a considerable financial strain on health systems. Despite decades of research leading to the development of a vaccine implemented in endemic countries, its usage remains restricted to a fraction of the population at risk of contracting dengue. Due to these limitations, there is a growing focus on research aimed at unraveling the cellular mechanisms crucial for Dengue virus (DENV) infection to pinpoint potential host targets. Multiple studies propose a pivotal role of cytoskeletal remodeling in DENV infection. Specifically, DENV alters the organization of actin to facilitate viral entry, replication, and release. In this study, we investigated the involvement of the protein c-Abl, a kinase crucial in actin dynamics, in the context of DENV infection. Our findings suggest that either silencing or pharmacological inhibition of the kinase c-Abl leads to accumulation of dengue ENV protein in vitro, associated with actin remodeling. These results illuminate cellular mechanisms that could serve as potential therapeutic alternatives for dengue management.

Cervical cancer is caused by a persistent and high-grade infection, caused by the Human Papilloma Virus (HPV), which, when entering cervical cells, alters their physiology and generates serious lesions. HPV 18 - is among those most involved in carcinogenesis in this region, but there are still no drug treatments that cause cure or total remission of lesions caused by HPV. Knowing that L-Asparaginase is an amidohydrolase, which plays a significant role in the pharmaceutical industry, particularly in the treatment of specific cancers, due to its antitumor properties, some studies have demonstrated its cytotoxic effect against cervical cancer cells. However, the commercial version of this enzyme has side effects, such as hypersensitivity, allergic reactions and silent inactivation due to the formation of antibodies. To mitigate these adverse effects, several alternatives have been explored, including the use of L-asparaginase from other microbiological sources, which is the case with the use of the fungus Aspergillus niger, a high producer of L-asparaginase. The study investigated the influence of the type of fermentation, precipitant, purification, characterization and in vitro cytotoxicity of L-asparaginase. The results revealed that semisolid fermentation produced higher enzymatic activity and protein concentration of A. niger. The characterized enzyme showed excellent stability at pH 9.0, temperature of 50ºC, resistance to surfactants and metallic ions, and an increase in enzymatic activity was also noted with the organic solvent ethanol. Furthermore, it exhibited low cytotoxicity in GM and RAW cells, and significant cytotoxicity in HeLa cells. These findings indicate that L-asparaginase derived from Aspergillus niger may be a promising alternative for pharmaceutical production. Its attributes, including stability, activity and low toxicity in healthy cells, suggest that this modified enzyme could overcome challenges associated with antitumor therapy.

This study focused on the investigation of myeloperoxidase through a Molecular Docking approach with various natural compounds to identify potential substances for cardiovascular research. Recent research has linked elevated myeloperoxidase levels to the severity of coronary artery disease. The results of the docking analysis revealed Polydatin, Daidzin, Astringin, Ginkgetin, and Amentoflavone as promising compounds with excellent binding capacity. To complement this, toxicity prediction studies were conducted using pkCSM. Overall, all four investigated molecules (Amentoflavone, Daidzin, Ginkgetin, and Astringin) were found to be non-toxic, exhibiting high maximum tolerated doses (human) and favorable values for Oral Rat Acute Toxicity and Oral Rat Chronic Toxicity. Moreover, they showed non-AMES toxicity and non-hepatotoxicity. Astringin, in particular, stood out with the highest positive effects, including a high maximum tolerated dose (human) and favorable values for Oral Rat Chronic Toxicity, along with dual inhibition of hERG II and hERG I. These findings suggest the potential utility of these compounds in cardiovascular research with minimized unwanted effects.

Background: Inflammation is an important mechanism in atherosclerosis and plaque formation. C-reactive protein (CRP) is a common inflammatory biomarker associated with the risk of coro-nary heart disease. We investigated the relationship of CRP with findings from myocardial per-fusion imaging (MPI). Methods: In this retrospective study, 102 consecutive patients (mean age 71 years, 68% males) that underwent MPI (for diagnostic reasons or quantification of myocardial ischemia) and CRP determination (upper limit: 6mg/L) within 1 month from MPI, were included. Patients had no infection or recent acute coronary syndrome. Results: the median CRP level was 4mg/L (2,10) among the study population. Patients with raised CRP had higher summed stress score (SSS) (P = 0.006) and summed rest score (SRS) (P = 0.001) and higher risk for SSS > 3 (OR 9.25, 95% CI 2.03-42.13, P = 0.001) compared to those with low CRP. The association of SSS and SRS with CRP levels was more evident in patients over 70 years (P = 0.027 and P = 0.005 respectively). No significant difference in summed difference score was shown. The two groups had no difference in other risk factors (p > 0.05 for all comparisons). Conclusion: A high level of CRP was associated with the presence and extent of stress-induced myocardial ischemia in MPI.

Febrile infections are a common cause of presentation to the emergency department (ED) in chil-dren. While viral infections are usually self-limiting, sometimes bacterial illnesses may lead to sepsis and severe complications. Inflammatory biomarkers such as C reactive protein (CRP) and procalcitonin are usually the first blood exams performed in the ED to differentiate bacterial and viral infections; the better understanding of immunochemical pathways has nowadays led to the discovery of new and more specific biomarkers that could play a role in the emergency setting. The aim of this narrative review is to provide the most recent evidence on biomarkers and predictor models combining them for serious bacterial infections (SBI) diagnosis in febrile children. Litera-ture analysis showed that inflammatory response is a complex mechanism in which many bio-chemical and immunological factors contribute to host response in SBI. CRP and procalcitonin still represent the most used biomarkers in the pediatric ED for the diagnosis of SBI. Their sensibility and sensitivity increase when combined and for this reason it is reasonable to take them both into consideration in the evaluation of a febrile children. The potential of machine learning tools, who represent a real novelty in medical practice, in conjunction with routine clinical and biological in-formation, may improve accuracy of diagnosis and target therapeutic options in SBI. However, studies on this matter are not yet validated in younger populations, making their relevance in pe-diatric precision medicine still uncertain. More data from further researches are needed to improve clinical practice and decision making using these new technologies.

Space exploration introduces astronauts to many challenges such as space radiation and microgravity. Researchers have investigated vitamin C as a potential radiation mitigator and antioxidants for sustaining astronaut health. Building on our own studies, which indicate vitamin C's life-saving radioprotective effects and its potential as a radiation mitigator, our research highlights its promise, even when administered 24 h post-exposure. This is particularly relevant in scenarios where astronauts may be exposed to sudden large solar particle events, potentially resulting in lethal doses of space radiation. The success of vegetable cultivation on the International Space Station using NASA's Veggie system offers fresh, vitamin C-rich food. While approved supplements address somatic function, further research is needed to optimize vitamin C's efficacy in humans and develop antioxidant cocktails for space missions. The variable vitamin C content in vegetables underscores the necessity for utilization of artificial intelligence (AI) to assist astronauts in selecting and cultivating vitamin C-rich vegetables that are best suited to combat high levels of space radiation and microgravity. Particularly, AI algorithms can be utilized in analyzing various factors such as nutritional content, growth patterns, and cultivation methods. In conclusion, vitamin C shows significant potential for mitigating space radiation, and ongoing research aims to enhance astronaut health through optimal dietary strategies.

Background: Polycystic ovary syndrome is a common reproductive and endocrinological disease characterized by ovulatory dysfunction, polycystic ovaries, and hyperandrogenism. Adipokines are believed to contribute to developing polycystic ovary syndrome and its accompanying metabolic complications such as dyslipidemia, insulin resistance, and cardiovascular diseases. Oncostatin M, a novel adipokine, plays a role in oogenesis, lipogenesis, and inflammation and may contribute to polycystic ovary syndrome pathogenesis and its related metabolic problems. Methods: In this case-control study, the patients were grouped in a 1:1 ratio into either the polycystic ovary syndrome (n = 32) or the control group (n = 32). Blood samples were obtained between the third and fifth days of the menstrual cycle. Serum levels of fasting glucose, insulin, C-reactive protein, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, white blood cell count, thyroid-stimulating hormone, luteinizing hormone, follicle-stimulating hormone, total testosterone, prolactin, estradiol, homeostasis model assessment of insulin resistance and oncostatin M were analyzed. Results: Oncostatin M levels were significantly lower, but C-reactive protein levels were substantially higher in the polycystic ovary syndrome group than in the control group (p = 0.002, p = 0.001, respectively). Oncostatin M was inversely correlated with total cholesterol, non-high-density lipoprotein cholesterol, fasting glucose, and the luteinizing hormone/follicle-stimulating hormone ratio (ρ = -0.329, p =0 .017; ρ = -0.386, p = 0.005; ρ = -0.440, p = 0.001; ρ = -0.316, p = 0.023, respectively). Conversely, there was no correlation between oncostatin M and total testosterone level (ρ = 0.220; p = 0.118). In the context of inflammation and metabolic parameters, oncostatin M was inversely correlated with C-reactive protein, homeostatic model assessment for insulin resistance score, and low-density lipoprotein cholesterol (ρ = -0.353, p = 0.019; ρ = -0.275, p = 0.048; ρ = -0.470, p &lt; 0.001, respectively). The diagnostic performance of oncostatin M, C-reactive protein, homeostasis model assessment of insulin resistance, and non-high-density lipoprotein cholesterol for polycystic ovary syndrome is as follows: Oncostatin M, sensitivity: 50%, specificity: 75%, Accuracy: 63%, p = 0.009; C-reactive protein, sensitivity: 84%, specificity: 61%, Accuracy: 74%, p = 0.004; homeostasis model assessment of insulin resistance, sensitivity: 72%, specificity: 81%, Accuracy: 77%, p &lt; 0.001; and non-high-density lipoprotein cholesterol; sensitivity: 72%, specificity: 75%, accuracy: 73%, p &lt; 0.001. Conclusions: Plasma oncostatin M levels were considerably lower in patients with polycystic ovary syndrome than in the control group, and this was inversely correlated with the hormonal and metabolic parameters of polycystic ovary syndrome. Thus, oncostatin M may be a novel therapeutic target for polycystic ovary syndrome and its metabolic complications.

An undescribed diterpene, stellerterpenoid A (1) and two undescribed sesquiterpenoids, stellerterpenoids B and C (2-3), together with six known compounds, were isolated from the roots of Stellera chamaejasme L. Their structures were elucidated by extensive spectroscopic data (1D, 2D NMR, IR, UV and HR-ESI-MS). The absolute configuration of 1-3 were elucidated based on ECD calculation. Among of them, stellerterpenoid A was a rare 13, 14 - seco nortigliane diterpenoid and stellerterpenoid B was a guaiacane type sesquiterpenoid with an unusual 1, 2-diketone moiety. The known stelleraguaianone B (5) exhibited moderate activity to suppress NO production in LPS - simulated macrophages with an IC50 value of 24.76 ± 0.4 μM. None of the compounds showed inhibitory influenza virus and tumor activity.

CD8+ cytotoxic T lymphocytes (CTLs) play a crucial role in anti-tumor immunity. In a previous study, we identified a subset of murine effector CTLs expressing the hepatocyte growth factor (HGF) receptor c-Met (c-Met+ CTLs) that are endowed with enhanced cytolytic capacity. HGF directly inhibited the cytolytic function of c-Met+ CTLs, both in 2D in vitro assays and in vivo, leading to reduced T cell responses against metastatic melanoma. To further investigate the role of c-Met+ CTLs in a three-dimensional (3D) setting, we studied their function within B16 melanoma spheroids and examined the impact of cell-cell contact on the modulation of inhibitory checkpoint molecules expression such as KLRG1, PD-1 and CTLA-4. Additionally, we evaluated the cytolytic capacity of human CTLs clones expressing c-Met (c-Met+) and compared it to c-Met− CTLs clones. Our results indicated that, similar to their murine counterparts, c-Met+ human CTLs clones exhibited increased cytolytic activity compared to c-Met− CTLs clones, and this enhanced function was negatively regulated by the presence of HGF. Taken together, our findings highlight the potential of targeting the HGF/c-Met pathway to modulate CTL-mediated anti-tumor immunity. This research holds promises for developing strategies to enhance the effectiveness of CTL-based immunotherapies against cancer.

Ustekinumab, a new anti-interleukin-12/23 antibody, is an effective treatment for ulcerative colitis; however, data regarding predictive factors of its efficacy are limited. This study aimed to identify biomarkers that can predict the long-term outcome of ustekinumab treatment. We retrospectively reviewed the records of patients with active ulcerative colitis treated with ustekinumab at our hospital from June 2020 to January 2023. We divided patients into non-remission and remission groups, and examined whether baseline biomarkers, including C-reactive protein-to-lymphocyte ratio, and early treatment response could predict clinical remission at week 48 of ustekinumab treatment. Of the 33 patients included in the study, 21 (63.6%) were in clinical remission at week 48 of ustekinumab treatment. The baseline C-reactive protein-to-lymphocyte ratio value was identified as an independent prognostic factor for clinical remission at week 48 (odds ratio: 10, 95% confidence interval: 1.6–62.4, p=0.014), with the cutoff value of 3.353 showing excellent prognostic performance (sensitivity: 71.4%, specificity: 83.3%). Furthermore, the clinical response at week 4 (p=0.009) and that at week 8 (p=0.005) were significantly associated with clinical remission at week 48. The baseline C-reactive protein-to-lymphocyte ratio value and early treatment response are useful biomarkers to predict the long-term efficacy of ustekinumab treatment.

Campylobacter is one of the most commonly reported foodborne bacteria worldwide. Although C. jejuni and C. coli have been reported to be responsible for the great majority of campylobacterio-sis, the burden of infections by species other than C. jejuni and C. coli have been increasing as a result of a transition to diagnostic test methods that enable the isolation of emerging species. The aim of the present study was to recover C. jejuni, C. coli, and emerging species from the stool samples of 500 patients with gastroenteritis and 100 healthy subjects by use of a filtration meth-od and culture techniques using Butzler agar and mCCDA under microaerophilic or hydrogen enriched atmosphere, identify the species by multiplex PCR methods and assess the significance of emerging species in enteric diseases. Thirty-one (6.2%) Campylobacter spp. were isolated from the stool samples of diarrheic patients but none from healthy individuals. Of 31 isolates, 21 (67.8%), 9 (29%) and 1 (3.2%) were identified as C. jejuni, C. coli and C. concisus by multiplex PCR, respectively. Filtration method was superior to the culture technique using mCCDA under mi-croaerophilic atmosphere. C. concisus was evaluated as the etiology of gastroenteritis as a result of laboratory and clinical evaluations. The present study was the first to indicate that emerging Campylobacter species are rarely detected and C. concisus is linked to acute gastroenteritis in Tur-key where additional studies are warranted to clarify the significance of emerging species in gastroenteritis.

The growing worldwide cancer incidence, coupled to the increasing occurrence of multidrug cancer resistance, requires a continuous effort towards the identification of new leads for cancer management. In this work, two C-scorpionate complexes, [FeCl2(κ3-Tpm)] (1) and [Co(κ3-TpmOH)2] (2), (Tpm = hydrotris(pyrazol-1-yl)methane and TpmOH = 2,2,2-tris(pyrazol-1-yl)ethanol), are studied as potential scaffolds for future anti-cancer drug development. Their cytotoxicity and cell migration inhibitory activity are analyzed, and an untargeted metabolomics approach is em-ployed to elucidate the biological processes significantly affected by these two complexes, using two tumoral cell lines (B16 and HCT116) and a non-tumoral cell line (HaCaT). While [FeCl2(κ3-Tpm)] did not display a significant cytotoxicity, [Co(κ3-TpmOH)2] was particularly cy-totoxic against the B16 cell line. While [Co(κ3-TpmOH)2] significantly inhibited cell migration in all tested cell lines, [FeCl2(κ3-Tpm)] displayed a mixed activity. From a metabolomics perspective, exposure to [FeCl2(κ3-Tpm)] is associated with changes in various metabolic pathways involving tyrosine, where iron-dependent enzymes are particularly relevant. On the other hand, [Co(κ3-TpmOH)2] is associated with dysregulation of cell adhesion and membrane structural pathways, suggesting its antiproliferative and anti-migration properties can be due to changes in the overall cellular adhesion mechanisms.

Prolonged fatigue is associated with non-pathological causes, and lacks an established therapeutic approach. The current study is aimed at assessing the efficacy of a new food supplement (Improve® Response) based on a chemically characterized pomegranate extract and hydro-soluble vitamins (B complex and C). UHPLC-HRMS analysis of pomegranate extract showed the presence of 59 compounds, with gallotannins and ellagitannins being the most abundant phytochemicals. For the clinical study, 58 subjects were randomized into two groups, 1 and 2 (n = 29, each), which received either the food supplement or placebo. The effects of the food supplement against fatigue were assessed via validated questionnaires, recorded at time intervals t0 (at baseline), t1 (after 28 days), t2 (56 days), and t3 (after follow-up) in combination with the analysis of biochemical markers at t0 and t2. Fatigue Severity Scale (FSS) questionnaire scores were significantly decreased at the t2 and t3 time intervals in subjects treated with the food supplements, while the effect of the food supplement on a 12-Item Short Form Survey (SF-12) was not considerable. Moreover, the food supplement did not significantly affect biochemical parameters associated with fatigue and stressed conditions. This study shows that the food supplement tested reduces prolonged fatigue following two months supplementation in healthy subjects with mild prolonged fatigue.

Unhealthy diet can lead to the development of metabolic disorders, and studies have shown strong associations between those conditions, c-reactive protein (CRP) and adiponectin. We report on associations between targeted metabolic markers and active nutrients from diet and Sujiaonori algal supplement (SBM), a natural adiponectin modulation inducer (NAMI) containing 60% of bioactive ulvan-rich fiber, in Japanese women. The study comprised dietary survey and intervention conducted in Kochi, Japan (2016-2017), involving 31 women who completed a dietary survey and provided biospecimen for CRP and adiponectin measurement using ELISA. Sixteen women received 3g SBM daily for one month and 15 others (controls) received 3g of corn starch. In SBM group, mean age was 23.06 (2.21) years [vs. 23.06 (1.55)], BMI was 21.11 (0.59) kg/m2 [vs. 21.43 (0.60) in controls], and daily intake of n3-PUFA [3.83 (0.24) vs. 2.21 (0.33) mg/day; p=0.042] and total fiber [364.12 (2.45) vs. 48.13 (1.57) mg/day in controls; p=0.000] were markedly higher. Furthermore, CRP was inversely associated with total fiber, total n3-PUFA, SBM-n3PUFA, vitamin D and vitamin B6, whereas adiponectin was strongly and positively associated with SBM-fiber and total n3-PUFA. Thus ulvan-rich SBM supplement, which contains ulvan-rich fiber and n3-PUFA, might be beneficial in reducing metabolic risk.

Unhealthy diet can lead to the development of metabolic disorders, and studies have shown strong associations between those conditions and biomarkers, such as c-reactive protein (CRP) and adiponectin. Recently, marine algal biomaterials have been investigated extensively due to their health benefits. We report on associations between metabolic markers and bioactive nutrients from diet and Sujiaonori algal biomaterial (SBM), a natural adiponectin modulation inducer (NAMI) containing 60% of ulvan-rich fiber, in a sample of Japanese women. The study comprised dietary survey and intervention conducted in Kochi, Japan (2016-2017), involving 31 women who completed a dietary survey and provided biospecimen for CRP and adiponectin measurement using ELISA. Sixteen women received 3g SBM daily for one month and 15 others (controls) received 3g of corn starch. In SBM group, mean age was 23.06 (2.21) years [vs. 23.06 (1.55)], BMI was 21.11 (0.59) kg/m² [vs. 21.43 (0.60) in controls], and daily intake of n3-PUFA [3.83 (0.24) vs. 2.21 (0.33) mg/day; p=0.042] and total fiber [364.12 (2.45) vs. 48.13 (1.57) mg/day in controls; p=0.000] were markedly higher. Furthermore, CRP was inversely associated with total fiber, total n3-PUFA, SBM-n3PUFA, vitamin D and vitamin B6, whereas adiponectin was strongly and positively associated with SBM-fiber and total n3-PUFA. Thus ulvan-rich SBM supplement, which contains ulvan-rich fiber and n3-PUFA, might be beneficial in reducing metabolic risk.

The Ramazzottius varieornatus tardigrade is an extremotolerant terrestrial invertebrate belonging to the phylum of Tardigrada. At a length of 0.1-1.0 mm, tardigrades are small animals with an exceptional tolerance to extreme conditions such as high pressure, chemicals and irradia-tion. These properties have been attributed to the recently-discovered Dsup protein. Dsup is a nucleosome-binding protein that prevents DNA damage against X-ray and oxidative stress without impairing cell life, also in Dsup-transfected animal and plant cells. However, the precise “protective” role of this protein is still under study. We performed experiments on human cells and shows that, as compared to control cells, Dsup+ cells are more resistant to UV-C exposure and H2O2. Real-time PCR identified different expression patterns of endogenous genes involved in apoptosis, cell survival and DNA damage repair in Dsup+ cells in response to H2O2 and UV-C. While H2O2 treatment in Dsup+ cells only marginally involved the activation of pathways responsible for DNA repair reinforcing the idea of a direct protective effect of the protein on DNA, in UV-C exposed cells, Dsup efficiently upregulates DNA damage repair genes. In conclusion, our data may help to delineate the different mechanisms by which the Dsup protein operates in response to different insults.

We studied the prognostic impact of tumor immunoglobulin kappa C (IGKC) mRNA expression as a marker of the humoral immune system in the FinHer trial patient population, where 1,010 patients with early breast cancer were randomly allocated to either docetaxel-containing or vinorelbine-containing adjuvant chemotherapy. HER2-positive patients were additionally allocated to either trastuzumab or no trastuzumab. Hormone receptor-positive patients received tamoxifen. IGKC was evaluated in 909 tumors using quantitative real-time polymerase chain reaction, and the influence on distant disease-free survival (DDFS) was examined using univariable and multivariable Cox regression and Kaplan-Meier estimates. Interactions were analyzed using Cox regression. IGKC expression, included as continuous variable, was independently associated with DDFS in a multivariable analysis including also age, molecular subtype, grade, and pT and pN stage (HR 0.930, 95% CI 0.870 – 0.995, P = 0.034). An independent association with DDFS was also found in a subset analysis of triple-negative breast cancers (TNBC) (HR 0.843, 95% CI 0.724 – 0.983, P = 0.029), but not in luminal (HR 0.957, 95% CI 0.867 – 1.056, P = 0.383) or HER2-positive (HR 0.933, 95% CI 0.826 – 1.055, P = 0.271) cancers. No significant interaction between IGKC and chemotherapy or trastuzumab administration was detected (Pinteraction = 0.855 and 0.684, respectively). These results show that humoral immunity beneficially influences the DDFS of patients with early TNBC.

Cordia dichotoma Forst. (F. Boraginaceae) has been traditionally used for the management of a variety of human ailments. In our earlier work, the antidiabetic activity of methanolic bark extract of C. dichotoma (MECD) has been reported. In this paper, two flavonoid molecules were isolated (by column chromatography) and identified (by IR, NMR and Mass spectroscopy/spectrometry) from the MECD with an aim to investigate their antidiabetic effectiveness. Molecular docking and ADMET studies were carried out using AutoDock Vina software and Swiss ADME online tool, respectively. The isolated flavonoids were identified as 3,5,7,3’,4’-tetrahydroxy-4-methoxyflavanone-3-O-L-rhamnopyranoside and 5,7,3’-trihydroxy-4-methoxyflavanone-7-O-L-rhamnopyranoside (quercitrin). Docking and ADMET studies revealed the promising binding affinity of flavonoid molecules for human lysosomal alpha-glucosidase and human pancreatic alpha-amylase with acceptable ADMET properties. Based on computational studies, our study reports the antidiabetic potential of the isolated flavonoids with predictive pharmacokinetics profile.

Cytochrome-c-oxidase (COX) subunit 4 (COX4) plays important roles in the function, assembly and regulation of COX (mitochondrial respiratory complex 4), the terminal electron acceptor of the oxidative phosphorylation (OXPHOS) system. The principal COX4 isoform, COX4-1, is expressed in all tissues, whereas COX4-2 is mainly expressed in the lungs, or under hypoxia and other stress conditions. We have previously described a patient with a COX4-1 defect with a relatively mild presentation compared to other primary COX deficiencies, and hypothesized that this could be the result of compensatory upregulation of COX4-2. To this end, COX4-1 was downregulated by shRNAs in human foreskin fibroblasts (HFF), and compared to patient's cells. COX4-1, COX4-2 and HIF-1α were detected by immunocytochemistry. The mRNA transcripts of both COX4 isoforms and HIF-1 target genes were carried out by RT-qPCR. COX activity and OXPHOS function were measured by enzymatic and oxygen consumption assays, respectively. Pathways were analyzed by CEL-Seq2 and by RT-qPCR. We demonstrate elevated COX4-2 levels in the COX4-1-deficient cells with a concomitant HIF-1α stabilization, nuclear localization and upregulated hypoxia and glycolysis pathways. We suggest that COX4-2 and HIF-1α has the are upregulated, also in normoxia as a compensatory mechanism in COX4-1 deficiency.

Let G be a graph with n vertices and let 1; 2; : : : ; n be the eigenvalues of Randic matrix. The Randic Estrada index of G is REE(G) = Ón i=1 ei . In this paper, we establish lower and upper bounds for Randic index in terms of graph invariants such as the number of vertices and eigenvalues of graphs and improve some previously published lower bounds.

In some species of salmon, reproductive maturity triggers the development of massive pathology resulting from reproductive effort, leading to rapid post-reproductive death. Such reproductive death, which occurs in many semelparous organisms (with a single bout of reproduction), can be prevented by blocking reproductive maturation, and this can increase lifespan dramatically. Reproductive death is often viewed as distinct from senescence in iteroparous organisms (with multiple bouts of reproduction) such as humans. Here we review the evidence that reproductive death occurs in C. elegans and discuss what this means for its use as a model organism to study aging. Inhibiting insulin/IGF-1 signaling and germline removal suppresses reproductive death and greatly extends lifespan in C. elegans, but can also extend lifespan to a small extent in iteroparous organisms. We argue that mechanisms of senescence operative in reproductive death exist in a less catastrophic form in iteroparous organisms, particularly those involving costly resource reallocation, and exhibiting endocrine-regulated plasticity. Thus, mechanisms of senescence in semelparous organisms (including plants) and iteroparous ones form an etiological continuum. Therefore understanding mechanisms of reproductive death in C. elegans can teach us about some mechanisms of senescence that are operative in iteroparous organisms.

Tenascin C (TNC) is an element of the extracellular matrix (ECM) of various tissues, including the skin, and is involved in modulating ECM integrity and cell physiology. Although skin aging is apparently associated with changes in the ECM, little is known about the role of TNC in skin aging. Here we found that Tnc mRNA level was significantly reduced in the skin tissues of aged mice compared with young mice, consistent with reduced TNC protein expression in aged human skin. TNC-large (TNC-L; 330-kDa) and -small (TNC-S; 240-kDa) polypeptides were observed in conditional media from primary dermal fibroblasts. Both recombinant TNC polypeptides, corresponding to TNC-L and TNC-S, increased the expression of type I collagen and reduced the expression of matrix metalloproteinase-1 in fibroblasts. Treatment of fibroblasts with a recombinant TNC polypeptide, corresponding to TNC-L, induced phosphorylation of SMAD2 and SMAD3. TNC increased the level of TGF-β1 mRNA and upregulated the expression of type I collagen by activating the TGF-β signaling pathway. In addition, TNC also promoted the expression of type I collagen in fibroblasts embedded in a three-dimensional collagen matrix. Our findings suggest that TNC contributes to the integrity of ECM in young skin and to prevention of skin aging.

In this paper, the computational fluid dynamics (CFD) method has been used to simulate the gas flow and the catalytic hydrogenation process of the C-2 hydrogenation adiabatic reactor in a practical ethylene production unit of a chemical plant. The laminar finite-rate model was used for the chemical reaction model. The standard two-equation model was used for the turbulence model. The exponent-function kinetic model was used for the reaction dynamics model. The simulation results were in good agreement with the actual industrial data obtained from the C-2 hydrogenation reactor, and the distributions of reaction parameters such as temperature and component concentrations in the reactor were further analyzed. Based on the validated CFD models, the structure and operating conditions of the reactor, as well as hydrogen load distribution ratios, are simulated for comparing the comprehensive performance metrics of ethylene selectivity and acetylene conversion rate; as a result, we can obtain the optimal temperature of 312 K, the optimal hydrogen/acetylene ratio of 0.10 as well as the optimal hydrogen load distribution ratio of 4:4:2, and the diameter/height ratio exerts a marginal effect on the selectivity, conversion rate and harmonic mean of the reactor.

Introduction: Dental health care workers, particularly dental medicine students (DMS), are at an increased risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. The aim of our study was to assess the level of knowledge on HBV and HCV, estimate needlestick injury (NSI) prevalence and reporting practice in DMS at the University of Zagreb and analyze how enrolment in obligatory and supplemental courses affects knowledge and needlestick injury reporting practice. Materials and methods: The knowledge was assessed by our questionnaires based on Centers for Disease Control general handouts. Additional information was collected to examine the prevalence and reporting practice of NSI. Data was analyzed by descriptive statistical analysis, independent-samples t-tests, proportion analyses and combined factor analyses of categorical and quantitative variables in SPSS and R. Results: In total, 206 students participated. The overall level of HBV and HCV-related knowledge was poor with average scores being 61.90% and 51.35% respectively. Moreover, students enrolled in the first year demonstrated significantly lower levels of knowledge in comparison with their older peers. Of all participants 18.2% sustained a needlestick injury, and majority of them (78.95%) never reported the injury. Conclusion: In conclusion, DMS have low levels of knowledge on important occupational pathogens and poor NSI reporting practice. Moreover, formal education in the current form failed to significantly improve competence of students and theoretical knowledge translates poorly into more conscientious injury reporting practice. We should look for a better way to increase student awareness and level of knowledge on this topic.