Milk fat globule membrane (MFGM) is a complex tri-layer membrane that wraps droplets of lipids in milk. In recent years, it has attracted widespread attention due to its excellent bioactive functions and nutritional value. The milk fat globule membrane contains a diverse array of bioactive lipids, including cholesterol, phospholipids, and sphingolipids, which play pivotal roles in mediating the bioactivity of the milk fat globule membrane. We sequentially summarize the main lipid types in milk fat globule membrane in this comprehensive review and outline the characterization methods used to employed them. In this comprehensive review, we sequentially describe the types of major lipids found in the milk fat globule membrane and outline the characterization methods employed to study them. Additionally, we compare the structural disparities among glycerophospholipids, sphingolipids, and gangliosides, while introducing the formation of lipid rafts facilitated by cholesterol. The focus of this review revolves around an extensive evaluation of current research on lipid isolates from the milk fat globule membrane, as well as products containing milk fat globule membrane lipids, with respect to their impact on human health. Notably, we emphasize clinical trials encompassing a large number of participants. The summarized bioactive functions of milk fat globule membrane lipids encompass regulation of human growth and development, influence on intestinal health, inhibition of cholesterol absorption, enhancement of exercise capacity, and anti-cancer effects. By offering a comprehensive overview, the aim of this review is to provide valuable insights into the diverse biologically active functions exhibited by lipids in milk fat globule membrane.

The trials were performed on 20 multiparous cows of Holstein breed (39.7 ± 0.75 kg of milk) at the end of the first phase of lactation this different milk fat (4.1-2.8%). The aim of the research was to study the characteristics of nutrition, metabolism and biosynthesis of milk components in highly productive dairy cows with normal and low milk fat levels and the timing of their productive use. Study the characteristics of fermentation of scar formation substrates and their use in energy metabolism and biosynthesis of the milk components. Found that low fat milk is not associated with a lack of formation of acetate in the rumen (6.1 vs. 6.6 mmol/dl in the contents of the rumen, р>0.05) and the non change in the hormonal profile, but depends on the reduction of fatty acids synthesis de novo in mammary gland, regulated by conjugated higher fatty acids. The result is a reduction in the need of cows in the exchange energy (reduction of heat transfer by 6.2 MJ), a shorter service period (109.5 vs.139 days) and the prolongation of their productive use (the number of lactations correlated back with the level of fat in milk (r=-0.68, p<0.05, n=1300).

Milk fat production is important in the New Zealand (NZ) dairy industry. Elsewhere, an amino acid substitution (K232A) in the enzyme diacylglycerol acyl-CoA acyltransferase (DGAT1) has been reported to explain variation in some milk traits, including variation in milk fatty acid (FA) profile. In this study, associations between K232A, and milk traits including milk FA composition, were studied in wholly pasture-fed NZ Holstein-Friesian × Jersey (HF×J) cross-bred dairy cows. With a high frequency of K variant (61.9%), the KK cows produced more milk fat than the AA cows (5.41 ± 0.04 % vs 4.42 ± 0.05 %). The milk volume, fat concentration and protein concentration of AK cows were between the genotypes, AA and KK. More C16:0, CLA and C18:3 cis-9, 12, 15 FA were found in the milk of Kiwi-cross cows feed in outdoor pasture grazing system., and the influence of DGAT1 K232A, on these FAs from mid- and late lactation stages were significant. The AA cows produced (P < 0.001) more CLA and C18:3 cis-9, 12, 15, but less C16:0 (1.137 ± 0.047, 0.855 ± 0.015 and 35.170 ± 0.355) than the KK cows (0.934 ± 0.025, 0.778 ± 0.009 and 38.010 ± 0.250).

Maternal milk, from well-nourished and healthy mothers, is a source of several bioactive compounds and balanced nutrients required for proper growth and development of the infant. Hence it is regarded as the optimal form of nourishment. Human milk fat from human milk is the most crucial component and is a necessity for the growing infant. However, in certain cases, the breast milk may fulfill the nutritional needs or the breast-feeding of the infant is not feasible; infant formulae are then considered as the best alternative as nutritional support. It becomes essential for the infant formula to behave and provide nutritive support in the same way as human milk. In order to achieve so, the most crucial components of all should also be prepared precisely, i.e., the analogue of human milk fat. This analogue, which mimics the actual human milk fat, can be then used as a prime ingredient while designing the infant formula. Significant research and several advances have been made in preparing the infant formula enriched with adequate fat content, and more studies are still being conducted in order to achieve a more sound product in the most economical and simplest way possible.

Dysregulation of the Cyclin-dependent kinase 8 (CDK8) activity has been associated to many diseases including the colorectal and breast cancer. As usual in the CDK family, the activity of CDK8 is controlled by a regulatory protein called cyclin C (CycC). But while human CDK family members are generally activated in two steps that is, the binding of the cyclin to CDK and the phosphorylation of a residue in the CDK activation loop, CDK8 does not require the phosphorylation step to be active. Another peculiarity of CDK8 is its ability to be associated to CycC while adopted an inactive form. These specificities raise the question of the role of CycC in the complex CDK8-CycC, which appears to be more complex than for the other members of CDK family. Through MD simulations and binding free energy calculations, we investigated the effect of CycC on the structure and dynamics of CDK8 on the one hand, and the structural molecular basis of the protein-protein interaction between the two partners on the other hand. We found that CycC has a stabilizing effect on CDK8 and identified specific interaction hotspots within its interaction surface compared to other human CDK/Cyc pairs. Targeting these specific interaction hotspots could be a promising approach in terms of specificity, to effectively disrupt the interaction between CDK8. The simulation of the conformational transition from the inactive to the active form of CDK8 suggests that the residue Glu99 of the CycC may assume the role of the missing phosphorylation step in the activation mechanism of CDK8. In a more general view, these results point the importance of keeping the CycC in computational studies when studying the human CDK8 protein in both the active and the inactive form.

The Italian herbal products market is the most prosperous in Europe. The proof is represented by the use of these products in several marketing categories, ranging from medicine to nutrition and cosmetics. Market and legislation in Italy are at the same time cause and consequence of this peculiar situation. In fact, the legislation on botanical food supplements in Italy is very permissive and at the same time the market shows an overall satisfaction of users and strong feedback in terms of consumption, which brings a widening use of medicinal plants, formerly the prerogative of pharmaceuticals, to other fields such as nutrition. This review summarizes the market and normative panorama of herbal products in Italy, highlighting the blurred boundaries of health indications, marketing authorizations and quality controls between herbal medicines and non pharmaceutical products, such as food supplements, cosmetics and other herbal-based “parapharmaceuticals”.

Arylmagnesium and -calcium reagents are easily accessible, however, ether degradation processes limit the storability especially of the calcium-based heavy Grignard reagents. Ortho-bound substituents with phosphanyl donor sites usually block available coordination sites and stabilize such complexes. The reaction of bromo-2,6-bis(diphenylphosphanylmethyl)benzene (1a) with magnesium in tetrahydrofuran yields [Mg{C₆H₃-2,6-(CH₂PPh₂)₂}₂] (2) after recrystallization from 1,2-dimethoxyethane. However, the similarly performed reduction of bromo- (1a) and iodo-2,6-bis(diphenylphosphanylmethyl)benzene (1b) with calcium leads to ether cleavage and subsequent degradation products. α-Deprotonation of THF yields 1,3-bis(diphenylphosphanylmethyl)benzene. Furthermore, the insoluble THF adducts of dimeric calcium diphenylphosphinate halides, [(thf)₃Ca(X)(µ-O₂PPh₂)]₂ [X = Br (3a), I (3b)], precipitate verifying ether decomposition and cleavage of P-C bonds. Ether adducts of calcium halides [such as [(dme)₂(thf)CaBr₂] (4)] form supporting the initial Grignard reaction and a subsequent Schlenk-type dismutation reaction.

Water samples for bacterial microbiome studies undergo a biomass concentration, DNA extraction and taxonomic identification steps. Through benchmarking, we studied the applicability of Skimmed milk flocculation (SMF) for bacterial enrichment, an adapted in-house DNA extraction protocol, and six 16S rRNA databases (16S-DBs). Surface water samples from two rivers were treated with SMF and Vacuum filtration (VF) and subjected to amplicon or shotgun metagenomics. A mock community standard underwent five DNA extraction protocols, taxonomical identification with six different 16S-DBs and evaluated by the Measurement Integrity Quotient (MIQ) score. In SMF samples, the skimmed milk was metabolized by members of lactic acid bacteria or genera such as Polaromonas, Macrococcus, and Agitococcus, resulting in increased relative abundance (p &lt; 0.5) up to 5.0 log fold change compared to VF, rendering SMF inapplicable for bacterial microbiome studies. The best performing DNA extraction protocols were FastSpin Soil, the in-house method and EurX. All 16S-DBs yielded comparable MIQ scores within each DNA extraction kit, ranging from 61-66 (ZymoBIOMICs) up to 80-82 (FastSpin). DNA extraction kits exert more bias to the composition than the 16S-DBs. This benchmarking study presented valuable insights to inform future water metagenomic study designs.

The main focus of the in vitro toxicity assessment methods is on the viability of the cells, which is usually based on metabolism changes. Yet, when exposed to toxic substances, the cell triggers multiple signals in response. With this in mind, we have developed a promising cell-based toxicity method that observes various cell responses when exposed to toxic substances (either death, division or remaining viable). Based on the collective cell response, we observed and predicted the dynamics of the cell population to determine the toxicity of the toxicant. The method was tested with two different conformations: In the first conformation, we exposed a monoculture model of blood macrophages to UV light, hydrogen peroxide, nutrient deprivation, tetrabromobisphenol A, fatty acids and 5-fluorouracil. In the second, we exposed a coculture liver model consisting of hepatocytes, hepatic stellate cells, Kupffer cells and liver sinusoidal endothelial cells to rifampicin, ibuprofen and 5-fluorouracil. The method showed good accuracy compared to established toxicity assessment methods. In addition, this approach provided more representative information on the toxic effects of the compounds as it considers the different cellular responses induced by toxic agents.

Analysing the human body by direct observation can lead to misinterpretation of underlying trends, whereas in vitro organ models facilitate their understanding. Likewise, in vitro organ models serve as valuable tools for assessing the toxicity of compounds. However, none of the existing models had the features we considered critical for toxicity assessment, so we developed an in vitro liver model for toxicity assessment. We used four different types of primary liver cells: Hepatic sinusoidal endothelial cells, hepatic stellate cells, Kupffer cells and hepatocytes. We cultured them in different combinations of composition and volume of cell medium, hepatocyte proportion of total cells, and addition of extracellular matrix. We added rifampicin, ibuprofen and 5-fluorouracil to this model and observed the microanatomy and physiology changes for a week with preclinical and clinical instruments. Among the different model configurations, we selected the feature combination of the in vitro model that had similar biomarker values to those measured by the clinical instruments used in clinical diagnostics. When we exposed the selected model configuration to rifampicin, ibuprofen and 5-fluorouracil, the viability of Kupffer cells and liver sinusoidal endothelial cells was significantly lower than in the untreated samples. In contrast, we observed negligible viability of hepatocytes compared to the untreated samples. We have built an in vitro liver model that resembles the liver microenvironment and we have analysed it with clinical instrumentation to facilitate the data translation. In this sense, we have established that Kupffer and LSEC cells are suitable candidates for the search for clinical diagnostic markers of liver function.

The photosystem I (PSI) of the green alga Chlamydomonas reinhardtii associates with 10 light-harvesting proteins (LHCI) to form the PSI-LHCI complex. Binding of LHCII to PSI may also occur and is controlled by a process called state transitions. Hereby, two LHCII trimers bind to the PSAL, PSAH and PSAO side of PSI to produce the PSI-LHCI-LHCII complex. In this work, we took advantage of chemical crosslinking of proteins in conjunction with mass spectrometry to identify protein-protein interactions between the light-harvesting proteins of PSI and PSII. We detected binding of LHCBM proteins to the LHCA1-PSAG side of PSI and identified protein-protein interactions of LHCSR3 with LHCA5 and LHCA3. Our data indicate that the binding of LHCII to PSI is more versatile as anticipated and reveal that LHCSR3 likely regulates excitation energy transfer to the PSI core via LHCA5/LHCA3.

Drug-induced liver injury (DILI) stands as a significant cause of drug attrition. To mitigate clinical DILI risks, assessing drugs using human liver models is crucial since animal studies may fall short due to species-specific liver pathway variations. Cell-based preclinical hepatotoxicity testing is often pertinent. In the present study, cells from a human liver cancer line (HepG2, HepaRG) were cultured in both formats of 2D and 3D spheroids to explore their responses to drugs. Liver-specific marker expressions across cell lines and culture formats were also examined to assess disparities in drug-induced liver injury marker expressions. In cytotoxicity assays, HepG2 cells exhibited heightened sensitivity to amiodarone HCl, while HepaRG cells showed greater sensitivity to acetaminophen. Generally, 2D cultures were more responsive to drugs than 3D cultures. Consistency was observed between cytotoxicity assays and liver injury markers AST and ALT. Variations were also noted in liver cell marker secretion, with albumin and urea concentrations declining post-drug treatment, particularly with higher baseline expression in HepaRG cells and 3D cultures. Additionally, mRNA expression levels of CYP enzymes involved in hepatocellular drug metabolism were compared following treatment with enzyme inducers. CYP1A2 and CYP2C9 were not expressed in HepG2 cells. On the other hand, CYP3A4 was expressed higher in 3D culture than in 2D culture. HepaRG cells exhibited significantly increased expression of all three enzymes post-treatment. Notably, enzyme expression was notably higher in 3D cultures than in 2D cultures. Collectively, these findings suggest that HepaRG cells and 3D cultures hold promise for evaluating DILI during early-stage drug development.

Small interfering RNA (siRNA) holds significant therapeutic potential by silencing target genes through RNA interference. Current clinical applications of siRNA have been primarily limited to liver diseases, while achievements in delivery methods are expanding its applications to various organs, including the lungs. Cholesterol-conjugated siRNA emerges as a promising delivery approach due to its low toxicity and high efficiency. This study focuses on developing a cholesterol-conjugated anti-Il6 siRNA and the evaluation of its potency for the potential treatment of inflammatory diseases using the example of acute lung injury (ALI). The biological activities of different Il6-targeted siRNAs containing chemical modifications were evaluated in J774 cells in vitro. The lead cholesterol-conjugated anti-Il6 siRNA after intranasal instillation demonstrated dose-dependent therapeutic effects in a mouse model of ALI induced by lipopolysaccharide (LPS). The treatment significantly reduced Il6 mRNA levels, inflammatory cell infiltration, and the severity of lung inflammation. IL6 silencing by cholesterol-conjugated siRNA proves to be a promising strategy for treating inflammatory diseases, with potential applications beyond the lungs.

Introduction: maxillary hypoplasia and mandibular asymmetry may be corrected with orthognathic surgery at the completion of growth. Many patients require segmental Le Fort I osteotomies to obtain the most stable results. Unfortunately, if Invisalign is chosen for pre-surgical preparation, ClinCheck © software does not allow for prediction when these complex surgeries are planned. The objective of this paper was to show the potential of aligners beyond its software in most complex cases like multiple-piece maxillary osteotomies in cleft and non-cleft patients. Method: Thirteen patients who underwent pre-surgical treatment with clear aligners-Invisalign (study group) were matched in terms of diagnosis, surgical procedure, and orthodontic complexity with thirteen patients treated using fixed appliances (control group). A technique based on simple superimposition was devised to enhance the software for creating a suitable occlusion for segmental pre-surgical treatments. Virtual curves following the lower arch were employed to guide the correct pre-surgical positions of the upper teeth. The amount of impressions required in both groups to achieve satisfactory pre-surgical alignment of the segmented arches was compared. Results: one or no refinement phase were needed in the Invisalign group to reach an acceptable pre-surgical occlusion while the amount of pre-surgical impressions taken in order to reach adequate coordination with fixed appliance treatment was slightly higher. The average overall treatment duration did not show a statistically significant variation between the groups. Conclusions: it appears that clear aligner could serve as an effective treatment for individuals with skeletal discrepancies, including cleft and craniofacial anomalies, necessitating segmental Le Fort I osteotomies when aided by the suggested superimposition approach during digital pre-surgical movement simulations. More sophisticated softwares will certainly be implemented in the future.

Abstract: Background: The analysis of vitamins in baby food is a challenging task given the com-plexity of the food matrix, vitamin stability, and strict regulations of the European Union regarding permissible deviations from declared values. Vitamins in food exist in different concentrations and forms and have different stabilities, and it is not straightforward to prepare samples for reliable analysis using the same procedure. Therefore, significant attention has been devoted to optimizing sample preparation in the analysis of vitamins. Methods: This study aims to determine which of the seven applied extraction methods is the most efficient for the simultaneous extraction and deter-mination of A, D, E, and K vitamins in milk and baby food using high-performance liquid chro-matography (HPLC). Different samples of baby food were prepared in seven different ways based on four methods (saponification, enzymatic hydrolysis, solvent extraction, and solid-phase extrac-tion). Results and Conclusion: The best preparation method proved to be solid-phase extraction with a C18 stationary phase, and HPLC with a UV-VIS detector was identified as a sufficiently sensitive technique for the identification and quantification of fat-soluble vitamins in milk and baby food.

From experimental studies of protein folding, it is now clear that there are two types of folding behavior, i.e., two-state folding and non-two-state folding, and understanding the relationships between these apparently different folding behaviors is essential for fully elucidating the molecular mechanisms of protein folding. This article describes how the presence of the two types of folding behavior has been confirmed experimentally, and discusses the relationships between the two-state and the non-two-state folding reactions, on the basis of available data on the correlations of the folding rate constant with various structure-based properties, which are determined primarily by the backbone topology of proteins. Finally, a two-stage hierarchical model is proposed as a general mechanism of protein folding. In this model, protein folding occurs in a hierarchical manner, reflecting the hierarchy of the native three-dimensional structure, as embodied in the case of non-two-state folding with an accumulation of the molten globule state as a folding intermediate. The two-state folding is thus merely a simplified version of the hierarchical folding caused either by an alteration in the rate-limiting step of folding or by destabilization of the intermediate.

Human serum albumin (HSA) corona formation at polymer microparticles of a spheroidal shape was studied using dynamic light scattering and laser Doppler velocimetry (LDV). Physicochemical characteristics of the albumin comprising, the zeta potential and the isoelectric point were determined as a function of pH for various ionic strengths. Analogous characteristics of the polymer particles were carried out. The adsorption of albumin on the particles was monitored by electrophoretic mobility measurements (LDV). The stability of the HSA functionalized particle suspensions under various pHs and their electrokinetic properties were determined. The deposition kinetics of the particles on mica, silica and gold sensors were determined in situ by optical microscopy, AFM and by the quartz microbalance (QCM) under diffusion and flow conditions. The obtained results were interpreted in terms of the coarse-grained random sequential adsorption model that allowed to estimate the range of applicability of QCM for determining deposition kinetics of virus and bacteria at abiotic surfaces.

The increasing frequency and severity of phytoplankton blooms worldwide highlight the need for advancements in monitoring technologies. Optical remote sensors, such as Landsat, have proven to be a cost-effective method for large-scale, near-real-time assessments of phytoplankton biomass in lakes. However, its effectiveness is often compromised by atmospheric interferences like clouds, dust, and wildfire smoke, which can obscure the clear-sky conditions essential for accurate remote sensing. While partial atmospheric correction (removing only the Rayleigh effect) is commonly applied to address these interferences, it remains inadequate for mitigating the impact of wildfire smoke. This study investigates the potential of Landsat's coastal/aerosol band (B1) for assessing wildfire smoke interference effects on Chlorophyll-a (Chl-a) retrieval models, which serve as proxies for phytoplankton biomass. We employed cluster analysis of B1 values to create a screening system based on aerosol reflectance, categorizing smoke interference into low, moderate, and high levels. Subsequently, we applied both partial (Rayleigh-corrected reflectance) and full (Landsat 8 Level 2 surface reflectance) atmospheric corrections before developing the Chl-a retrieval models. Excluding high wildfire smoke interference (B1 &gt; 0.07) from the Chl-a calibration dataset significantly enhanced model performance, increasing the r-squared value from approximately 0.55 to 0.80. Moderate smoke interference (0.05 &lt; B1 &lt; 0.07) yielded results comparable to low-interference conditions. Notably, Rayleigh-corrected reflectance, even without additional aerosol band filtering, achieved higher r-squared values for the Chl-a retrieval model than full atmospheric correction. B1 thus proves to be a valuable tool for identifying low smoke-impacted observations, offering an effective method to monitor phytoplankton biomass amid increasing wildfire activity and improving the capacity to monitor aquatic environments in a changing global landscape.

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

This study investigates the optical properties of Yttrium Orthoferrite thin films fabricated via plasma laser deposition. Yttrium Orthoferrite, a ferrimagnetic material known for its potential applications in spintronics and photonics, was deposited on single-crystal substrates under controlled conditions to analyze its optical characteristics. The influence of deposition time, on the film quality and optical properties was examined.

The article considers the issues of ensuring operational performance and environmental sustainability of marine diesel engines by using biodiesel fuel. The research was conducted on 5S60ME-C8 MAN-B&W Diesel Group and 6DL-16 Daihatsu Diesel marine diesel engines, which were operated using RMG380 petroleum fuel and B10 and B30 biodiesel fuels. The efficiency of biofuel usage was assessed based on environmental (reduced nitrogen oxide concentration in exhaust gases) and economic (increased specific effective fuel consumption) criteria. It was found out that the use of B10 and B30 biofuels provides reduction of nitrogen oxides concentration in exhaust gases by 14.71–25.13 %, but at the same time increases specific effective fuel consumption by 1.55–6.01 %. Optimum fuel injection advance angles were determined that ensure the best thermal energy, economic and environmental performance of diesel engines. The optimum angle of biofuel supply advance is determined experimentally and should correspond to the limits recommended by the diesel engine operating instructions. It has been proven experimentally that the use of biofuel increases the environmental sustainability of marine diesel engines by 13.75–29.42 %. It increases the diesel engines environmental safety in case of emergency situations, as well as accidental and short-term emissions of exhaust gases with an increased content of nitrogen oxides into the atmosphere - phenomena that are possible in starting modes of diesel engine operation, as well as in modes of sudden load changes. It is the increase in the environmental friendliness of marine diesel engines in the case of using biofuel that is the most positive criterion and contributes to the intensity of biofuel use in power plants of sea vessels.

Modern automotive systems should must satisfy strict reliability requirements. Most of the real vehicle systems and safety-critical networks have complex interconnections. Sensitivities and probabilistic uncertainties of reliability of System with Complex Interconnections (SwCI) can be investigated by the Monte-Carlo Simulation (MCS). The paper focuses on sensitivities and parametrical uncertainties of SwCIs reliability. The proposed method can be used forimplemented in the investigation of uncertainties of SwCIs reliability – in other wordsi.e., for in the determination of critical system elements and to estimateion of the Required Number of Spare Parts (RNSP) of the system, which depends on the probability of allowable spare equipment shortage.

Aflatoxins (AF), secondary metabolites produced by fungi, pose significant health risks, especially to children and adults. In developing countries like Nepal, the tropical climate promotes fungal growth, leading to high levels of AF in animal feed and milk. In this study, we investigated the incidence of aflatoxin M1 (AFM1) contamination in 84 milk samples collected from the Kathmandu district using the competitive enzyme-linked immunosorbent assay (c-ELISA) technique. We also interviewed farmers to gather information on feeding and storage practices. . All the collected milk samples were contaminated with AFM1, with 97.6% of the samples exceeding the European Union (EU) maximum permissible limit of 50 ppt. The majority (98.5%) of the farms included paddy straw, and all farms (100%) included concentrate in their feed regimen. Only half (52%) of the farms had proper storage facilities. Straw was mostly stored in sacks outdoors or left open in a shed, while concentrates were stored in a closed room or shed. The study reports very high contamination levels of AFM1 in the milk samples, presenting a serious public health issue, and recommends comprehensive surveillance and further investigation across the country, especially given the limited research and literature available.

Objective: Evaluation of patients with prosthetic valves who developed infective endocarditis by comparing treatment outcomes in both early- and late-onset IE episodes following prosthetic valve replacement surgery. This study sought to conduct a comprehensive assessment of the efficacy of these methodologies. The insights derived from this assessment will be utilized to enhance the quality of care for individuals with infective endocarditis who have received prosthetic valve replacement surgery. Results: During the period of investigation (January 2018 - December 2022), 78 patients diagnosed with infective endocarditis (IE) on prosthetic valve were admitted to the Infectious Diseases Department of the "Dr. Carol Davila" Central Military Emergency University Hospital in Bucharest. In 28 cases (35.8%), the onset of PVE occurred within 12 months of surgery (early onset), whereas in 50 patients (64.2%), the onset occurred more than 12 months after surgery (late onset). The mortality rate was 35.9% (53.6% among the early onset patients and 26% among the late-onset patients). Among patients who received surgical and medical therapy, the mortality rate was 29.6%, whereas among those who underwent only medical therapy, a 39.2% mortality rate was reported. According to the extracted data, antibiotic therapy was successful in 72.6% of patients. In contrast, a combination of surgical and drug-based approaches resulted in a cure in 76.1% of the patients. The most common etiological agent was Staphylococcus aureus (38.5%), followed by Enterococcus faecalis (26.9%), and Streptococcus mitis (10.3%). The mortality rate of patients with S. aureus was 29.2%, indicating the severity of this infectious agent. Conclusions: Prosthetic valve endocarditis (PVE) is a serious condition associated with a high mortality rate both in the short and long term. Regardless of the therapy used, the risk of death remains high. All patients with PVE who survived received effective early treatment, highlighting the need for prophylactic measures.

This paper focus on the modeling and time-domain analyzing method of piecewise-smooth fractional-order circuit systems. Firstly, an analytical framework is constructed based on a generalized piecewise-smooth two-port impedance network model, which takes the topological characteristics of Dickson type switched-capacitor converters (SCCs) as examples, and considers the fractional-order characteristics of class-2 X7R ceramic capacitors, which are widely used in SCCs. Secondly, the time-domain analyzing method for such a piecewise-smooth fractional-order circuit system is developed, numerical solutions are obtained, and the influence of the fractional-order capacitor on the power conversion efficiency of the system are revealed. Finally, in order to validate the analysis, both numerical simulation and experiments are provided in the work, the results of which confirm that, the proposed fractional-order analytical framework can capture the power loss mechanism of piecewise-smooth fractional-order circuit systems more effectively than the traditional integer-order based approach, thus benefiting the design of circuit systems.

Maternal diet plays a significant role in the fatty acid composition of breast milk. Natural trans fatty acids (TFAs) are generated through the biohydrogenation of unsaturated fatty acids (FAs) in the rumen of animals by bacterial isomerases and are consequently found in milk, dairy products, and meat from ruminant animals. Dietary products such as milk and meat are the primary sources of natural TFAs for humans, derived from rumen fermentations. These peculiar fatty acids hold nutritional significance as they not only lack the detrimental effects on endothelium characteristic of industrially produced trans fat, but also exhibit anti-inflammatory properties. The relationship between the presence in breast milk of eight fatty acids (including natural TFAs trans-vaccenic and conjugated linoleic acid) and maternal diet has been explored, and their abundance has been compared to that of infant formulas. Two cohorts of lactating women participated in this study, originating from a Spanish region adhered to the Southern European Atlantic Diet or Atlantic Diet. While the consumption of conventional meat or dairy products does not seem to increase the abundance of trans fatty acids in breast milk, trans-vaccenic and oleic acid are among the most distinctive features of breast milk fat in mothers consuming naturally improved dairy products, with an improved fatty acid profile. The most significant differences between natural breastfeeding and formula feeding lie in natural trans fatty acids, since formula are notably deficient, while overfortified in alpha-linolenic acid in comparison to breast milk.

Abstract: Conventional antibiotic and multidrug treatments become less and less effective and a discovery of new effective and safe antibacterial agents got a global priority. The returning to the natural antibacterial product is relatively new current trend. Terrestrial biota is a rich source of biologically active substances whose antibacterial potential was not fully utilized. Aim of this review is to present the current state-of-the art of terrestrial biota-derived antibacterial agents and inspired by nature treatments. It is a summary of the most important sources and new identified or modified antibacterial agents and treatments during the last 5 years. It focuses on the significance of plants- animals- and bacteria-derived biologically active agents as powerful alternatives to antibiotics as well as on the advantages of utilizing natural antibacterial molecules alone or in combinations with antibiotics. The main conclusion is that the terrestrial biota derived antibacterial products and substances open variety of new ways to modern improved therapeutic strategies. New terrestrial sources of known antibacterial agents and new antibacterial agents from terrestrial biota were discovered during the last 5 years, which are under investigation together with some long ago known but now surviving their renaissance for the development of new medical treatments. Use of natural antibacterial peptides as well as combinational therapy by commercial antibiotics and natural products outlines as the most promising for treating of bacterial infections. In vivo testing and clinical trials are necessary to reach clinical application.

Cell viability refers to the proportion of living, healthy cells within a given population. This information is crucial in any cell-based research, especially in toxicology. Over the past century, numerous methods for assessing cell viability have been developed. These methods can be categorized into five main types: non-invasive cell structure damage, invasive cell structure damage, cell growth, cellular metabolism, and cell membrane potential. Each method operates on different principles and has its own advantages and disadvantages, making it essential for researchers to choose the method that best fits their experimental design. Despite the variety of cell viability methods available, most rely on indirect measurements of cell viability, which may compromise their accuracy. In this sense, there is insufficient information regarding their accuracy, highlighting the need for researchers to investigate the accuracy of both existing and future methods.

Tumor necrosis factor (TNF) inhibitors (anti-TNFs) represent a cornerstone of the treatment of various immune-mediated inflammatory diseases and are among the most commercially successful therapeutic agents. Knowledge of TNF binding partners is critical for identification of the factors able to affect clinical efficacy of the anti-TNFs. Here we report that among eighteen representatives of the multifunctional S100 protein family only S100A11, S100A12 and S100A13 interact with the soluble form of TNF (sTNF) in vitro. The lowest equilibrium dissociation constants (Kd) for the complexes with monomeric sTNF determined using surface plasmon resonance spectroscopy range from 2 nM to 28 nM. The apparent Kd values for the complexes of multimeric sTNF with S100A11/A12 estimated from fluorimetric titrations are 0.1-0.3 µM. S100A12/A13 suppress the cytotoxic activity of sTNF against Huh-7 cells, as evidenced by the MTT assay. Structural modeling indicates that the sTNF-S100 interactions may interfere with the sTNF recognition by the therapeutic anti-TNFs. Bioinformatic analysis reveals dysregulation of TNF and S100A11/A12/A13 in numerous disorders. Overall, we have shown a novel potential regulatory role of the extracellular forms of specific S100 proteins that may affect efficacy of anti-TNF treatment in various diseases.

Histological evidence of active prosthetic valve endocarditis (PVE) in cardiac valve tissue is widely regarded as a criterion established by Duke to confirm the presence of this condition, although the histological characteristics of mechanical prosthetic valve endocarditis have not yet been definitively established. The primary objective of this study was to determine the histologic differences in mechanical PVE in individuals with either early- or late-onset PVE, with the aim of distinguishing the unique aspects of this rare condition. Histological analysis of mechanical cardiac valve tissue was conducted in 27 patients who underwent surgical valve removal, comprising individuals with early onset and late-onset PVE. The findings were compared between the two groups. Histopathologically, PVE in individuals with mechanical heart valves is typically associated with the formation of vegetation and considerable neutrophil-rich infiltrates. In cases of early onset PVE, the affected valve tissue displays intense inflammation predominantly consisting of lymphocytes. In contrast, valve tissue samples from patients with late-onset PVE exhibit extensive fibrosis and inflammation, comprising macrophages, which are specialized immune cells and calcifications.

Goat milk is a nutritious food, with high levels of vitamins and minerals. In this context, there is a growing need to improve preservation techniques. Thus, the present work was developed with the aim of drying goat milk using a spray dryer. Chemical, physical, and physicochemical analyses of powdered goat milk and reconstituted goat milk were performed, as well as the characterization of raw goat milk. The statistical model used was the full factorial design 2³ + 3, observing the Pareto Diagram and Analysis of Variance to study the effect of atomization frequency (Hz), inlet temperature (°C), and peristaltic pump rotation (rpm) on the responses for the powdered and reconstituted product. The planning was executed with eleven trials, including nine different trials and three central points. For the analysis of the planning at a 95% confidence level, the Statistica 8.0 software was used. The results showed that atomization frequency and inlet temperature had the greatest effect on the powdered product and the reconstituted food, respectively. Therefore, the importance of drying this food is evident as it offers several advantages for the food industry and consumers.

A field experiment was conducted for 2 years in Green Tea Laboratory of Saitama Prefectural Agriculture and Forestry Research Center, Iruma, Saitama, Japan from March 2014 to December 2015. Controlled release fertilizers (CRF) or organic fertilizers (ORG) which is the mixture of chicken manure and oil cakewere applied with the amount of 450 kg N ha^-1 yr^-1 in 2014 and 397 kg N ha^-1 yr^-1 in 2015. Nitrous oxide (N₂O) emissionsfrom soil in green tea fields were measured by closed chamber method. The results showed that CRF has significantly lower N₂O compared to ORG. The cumulative N₂O emissions from CRF accounted for 51% of N₂O emissions from ORG fields and 138% of control with no fertilizer treatment. The N₂O flux from the row was higher than that of under the canopy, since fertilizer were applied on the row. However the total emission from the area between the rows was lower than that under the canopy because of the area ratio of row and canopy was 1:5.

This paper presents the deformation of the joined sheet after the clinch-riveting process. The DX51D steel sheet with zinc coating was used. The samples to be joined with clinch riveting technology had a thickness of 1±0.05 mm and 1.5±0.1 mm. The sheet deformation was measured before and after the joining process. The rivet was pressed in the sheets with the same dimension between the rivet axis and three sheet edges: 20, 30 and 40 mm. For fixed segments of the die, from the rivet side close to the rivet, the sheet deformation was greater than that of the area with movable segments. The movement of die sliding element caused more sheet material to flow in the space between the fixed part of the die and movable segments. Hence, the sheet deformation in these places was smaller than for the die fixed element – sheet material was less compressed. For sheets thickness 1.5 mm and width 20 mm, the bulk of the sheet was observed. For a sheets width of 20 mm, it was observed that the deformation of the upper and lower sheets in the area of the rivet is greater than for sheets width of 30 or 40 mm.

The reasons for the circular sense of human color perception generated by two sorts of color opponent neurons and three cone types are not well understood. Here we use geometrical analysis to examine the hypothesis that opponency, the recursive nature of color perception, and trichromacy arise as the most efficient ways of distinguishing spectrally different points on a plane using a minimum of color classes and receptor types.

For very first time, we report the synthesis of 8-(2-methoxyphenyl)-6-methyl-2-(1-methyl-1H-benzo[d]imidazol-2-yl)quinoline 1. This was achieved in several steps, including usage of Suzuki reaction for functionalization of 2-(1H-benzo[d]imidazol-2-yl)quinoline moiety. The new compound exhibits blue fluorescence. Its structure was confirmed with 1D- and 2D-NMR spectroscopy, IR-spectroscopy, high-resolution mass spectrometry and X-ray analysis.

Hydration and fluids detected with bioimpdance can be confounderdby ecw expansion and overload. to estimates with sufficient accuracy body fat A confrontation with imaging and dxa is confirmatory

The systematic sampling is used as a method to get the quantitative results from the tissues and the radiological images. Systematic sampling on real line (R) is a very attractive method within which the biomedical imaging is consulted by the practitioners. For the systematic sampling on R, the measurement function (MF) is occurred by slicing the three-dimensional object equidistant systematically. The currently used covariogram model in variance approximation proposed by [28,29] is tested for the different measurement functions in a class to see the performance on the variance estimation of systematically sampled R. This study is an extension of [17], and an exact calculation method is proposed to calculate the constant λ(q,N) of confidence interval in the systematic sampling. The exact value of constant λ(q,N) is examined for the different measurement functions as well. As a result, it is observed from the simulation that the proposed MF should be used to check the performances of the variance approximation and the constant λ(q,N). Synthetic data can support the results of real data.

Previously, we described a 19-base pair double-stranded RNA with 3'-trinucleotide overhangs, acting as immunostimulatory RNA (isRNA). This molecule demonstrated notable antiproliferative effects on cancer cells, inhibited tumor growth, and elicited immunostimulatory and antiviral responses by inducing cytokine and interferon production. Within this study, we compared the efficiency of lung fibrosis development, initiated in mice by BLM or LPS using different schemes of induction. Then we compared the effect of isRNA used in a preventive or therapeutic regimen on the development of fibrosis in selected BLM- and LPS-induced mouse models and showed that isRNA can be used in pathological conditions accompanied by the development of inflammation and the risk of fibrosis formation, without adverse side effects. Prophylactic regimen of isRNA application is beneficial for prevention of the development of pulmonary fibrosis.

This study aimed to evaluate the fatty acid (FAs) profile in milk from commercial farms with varying pasture levels in the diet during spring and fall, and to investigate the physical and chemical properties of butter to assess the impact of FAs on technological and nutritional properties. Milk sampling was conducted biweekly from six farms, categorized into high (HP) and low (LP) pasture treatments based on pasture intake: &gt;60% and &lt;35%, respectively. Butter was made from a pasture-based system (GRZ) and a confined system (C). No differences were observed in milk fat percentage between HP and LP in either season. High pasture had 85-66% more conjugated linoleic acid (CLA, p=0.01), 74-48% more trans-vaccenic acid (TVA, p=0.01), and 21-15% more branched- chain FAs (BCFA, p=0.006) than LP in spring and fall, respectively. In fall, butter from C had lower saturated FAs (SFA, p=0.005), higher unsaturated FAs (UFA, p=0.008), and a lower spreadability index (SI, p=0.005) than GRZ, resulting in softer butter. In conclusion, HP in both seasons had higher contents of FAs considered healthy for consumers compared to LP. Contrary to expectations, in fall, C showed higher UFATVA and lower SFA in butter, leading to better technological characteristics than GRZ.

Naturally fermented dairy products are an important component of the human diet. They are a valuable source of nutrients as well as vitamins and minerals. Their importance as a source of probiotic bacterial strains should not be overlooked. A number of studies highlights the positive effects of species of the Lactobacillacea on the intestinal microbiota, the overall homeostasis of the body, as well as a complementary treatment for some diseases. However, data on the effects on intestinal epithelial cells of postmetabolites released by bacteria are incomplete. This is likely due to the fact that these effects are species and strain specific. In the present study, we investigated the effects of postmetabolites produced by a pre-selected candidate probiotic strain Limosilactobacillus fermentum on HT-29 intestinal epithelial cells. Our data showed a pronounced proliferative effect, evaluated by flow cytometry, quantification of cell population, and determination of mitotic index. This was accompanied by stabilization of the cell monolayer, measured by increase of TEER (trans epithelial electric resistance) and reorganization of actin filaments. The data obtained are a clear indication of the positive effects, that the products secreted by L. fermentum strain 53 have on the intestinal epithelial cells.

The recent increase in global consumption of rice has led to increased demand for sustainable water management in paddy cultivation. In this study, we propose an enhanced paddy simulation module to be introduced to Soil and Water Assessment Tool (SWAT) to evaluate the sustainability of paddy cultivation. The enhancements added to SWAT include: (1) modification of water balance calculation for impounded fields, (2) addition of an irrigation management option for paddy fields that are characterized by flood irrigation with target water depth, and (3) addition of a puddling operation that influences the water quality and infiltration rate of the top soil layer. In a case study, the enhanced model, entitled SWAT-Paddy, was applied to an agricultural watershed in Japan. The results showed that the SWAT-Paddy successfully represented paddy cultivation, water management, and discharge processes. Simulated daily discharge rates with SWAT-Paddy (R² = 0.8) were superior to the SWAT result (R² = 0.002). SWAT-Paddy allows the simulation of paddy management processes realistically, and thus can enhance model accuracy in paddy-dominant agricultural watersheds.

The diagnosis and management of cow's milk allergy (CMA) is a topic of debate and controversy. We aimed to compare the opinions of expert groups from the Middle East (n=14) and the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) (n=13). These Expert groups voted on statements developed by the ESPGHAN group and published in a recent position paper. The voting outcome was compared. Overall, there was consensus amongst both groups of experts. Most experts agreed that symptoms of crying, irritability and colic, as single manifestations, do not suggest CMA. They agreed that amino-acid-based formula (AAF) should be reserved for severe cases (e.g. malnutrition and anaphylaxis) and that there is insufficient evidence to recommend a step-down approach. There was no consensus on the statement that a cow’s milk-based extensively hydrolysed formula (eHF) should be the first choice as a diagnostic elimination diet in mild/moderate cases. Although the statements regarding the role of hydrolysed rice formula as a diagnostic and therapeutic elimination diet were accepted, 3/27 disagreed. The votes regarding soy formula highlight the differences in opinion in the role of soy protein in CMA dietary treatment. Generally, soy-based formula is seldom available in the Middle East region. All ESPGHAN experts agreed that there was no added value of probiotics, prebiotics, and synbiotics to the efficacy of elimination diets, whereas 3/14 of the Middle East group thought there was sufficient evidence. Therefore, there is not a consensus on the optimal diagnostic and therapeutic elimination diet for CMA, but the first-choice elimination diet and the stepwise management approach reveal some differences.

The objective of this study is to determine the relationship between body condition score (BCS) and body carcass fat (BCF) of ewes at two key stages of the production cycle. Data were collected from 88 Coopworth ewes including BCS measurements manually evaluated by the farm manager, BCF measurements determined by computerized tomography (CT) and body parameter measurements automatically determined by an image processing application. Artificial neural network (ANN) statistical analysis method was used to develop a relationship between the body parameters and the BCF with an r2=0.96 and RMSE=1.01 using all top and side variables.

Cannabis sativa is one of the oldest plants utilized by humans for both economic and medical purposes. Although the use of cannabis started millennia ago in the Eastern part of the hemisphere, its use has moved and flourished in the Western Nations in more recent centuries. C. sativa is the source of psychoactive cannabinoids that are consumed as recreational drugs worldwide. The C21 aromatic hydrocarbons are restricted in their natural occurrence to cannabis (with a few exceptions). Delta-9-tetrahydrocannabinol (Δ9-THC) is the main psychoactive component in cannabis with many pharmacological effects and various approved medical applications. However, a wide range of side effects are associated with the use of Δ9-THC, limiting its medical use. In 1966, another psychoactive cannabinoid, Delta-8-tetrahydrocannabinol (Δ8-THC) was isolated from marijuana grown in Maryland but in very low yield. Δ8-THC is gaining increased popularity due to its better stability and easier synthetic manufacturing procedures compared to Δ9-THC. Passing the U.S. Farm Bill in 2018 led to an increase in the sale of Δ8-THC in the United States. The marketed products contain Δ8-THC from synthetic sources. In this review, methods of extraction, purification, and structure elucidation of Δ8-THC will be presented. The issue of whether Δ8-THC is a natural compound or an artifact will be discussed, and the different strategies for its chemical synthesis will be presented. Δ8-THC of synthetic origin is expected to contain some impurities due to residual amounts of starting materials and reagents as well as side products of the reactions. The various methods of analysis and detection of impurities present in the marketed products will be discussed. The pharmacological effects of Δ8-THC, including its interaction with CB1 and CB2 cannabinoid receptors in comparison with Δ9-THC, will be reviewed.

Clinical and laboratory diagnostics are particularly important in monitoring the internal homeostasis of the body in high-yielding animals, especially in dairy cows, whose metabolism is under constant pressure to obtain high parameters of milk production and reproduction. Knowledge of laboratory test results and relationships based on significant correlations between various milk and blood parameters may be very useful in veterinary diagnostics and helpful in cattle practice in order to protect animal health and the quality of milk production. The aim of the study was to analyze the correlation between selected hematological biomarkers such as white blood corpuscles (WBC), red blood corpuscles (RBC), hemoglobin concentration (HGB), hematocrit (HCT), platelets (PLT), erythrocyte mean corpuscular volume (MCV), mean corpuscular hemoglobin content (MHC), mean corpuscular hemoglobin concentration (MCHC) and selected quantitative-qualitative parameters of cow’s milk such as current milk production, somatic cells count (SCC), colony of bacteria forming units (CFU), milk fat (MF), milk protein (MP), milk lactose (ML), milk solids (S), solids non-fat in milk (SNF), daily milk production. Samples were collected three times at daily intervals from 11 clinically healthy late-lactation dairy cows obtaining 33 sets of test results. This repeated study of cows allowed for obtaining a homogeneous group in order to determine statistical correlations between selected blood and milk parameters. Many significant correlations were found between the examined parameters. In cows, significant positive correlations were recorded between milk production and HGB, HCT, MCV or MHC. Significant negative correlations were also found between SCC and HGB, SCC and HCT, SNF and MCV, SNF and MHC, and between MF and RBC.

The viticulture sector, spanning over 7.3 million hectares worldwide, plays a crucial economic role but faces challenges such as labor shortages, rising production costs, market competition, and climate change stresses. Addressing these issues requires monitoring the spatial and temporal variability in vineyard productivity. Traditional ground-based observations, though accurate, are time-consuming and limited in scope. Precision viticulture, leveraging technologies like GPS, remote sensing, and artificial intelligence, offers efficient, non-destructive monitoring tools. This study aims to develop and test a technological workflow using the mobile app Digivit, integrated with the AgroSat platform, to estimate yield variability in vineyards. The workflow was performed during the 2023 growing season in a series of vineyards near Siena (Italy) and involved two main steps: spatial variability characterization using AgroSat and yield estimation using the mobile Digivit app. AgroSat processed Sentinel-2 NDVI data to identify homogeneous zones, while Digivit used smartphone images of grape clusters to estimate yields. The field campaign, performed three weeks before harvest, involved monitoring representative vines within identified zones and uploading georeferenced images for cluster segmentation analysis. Yield estimates were validated against measured weights, showing a strong linear correlation (R²=0.85, RMSE=43.74g). Excluding one outlier improved correlation to R²=0.95, RMSE=14.58g. Vineyard-level yield predictions were compared with harvest data, achieving an overall error of approximately 7%, in agreement with other methods in the literature. The study demonstrates that the Digivit app provides accurate, timely yield prediction, supporting farmers in harvest planning and winemaking management. The user-friendly mobile app approach facilitates a broader adoption of precision viticulture technologies among farmers, overcoming barriers related to technical expertise.

Chronic joint inflammatory disorders such as osteoarthritis and rheumatoid arthritis have in common an upsurge of inflammation, and oxidative stress, resulting in progressive histological alterations and disabling symptoms. Currently used conventional medication (ranging from pain-killers to biological agents) is potent, but frequently associated with serious, even life-threatening side effects. Used for millennia in traditional herbalism, medicinal plants are a promising alternative, with lower rate of adverse events and an efficiency frequently comparable with that of conventional drugs. Nevertheless, their mechanism of action is in many cases elusive and/or uncertain. Even many of them have been proved effective in studies done in vitro or on animal models, there is a scarcity of human clinical evidence. The purpose of this review is to summarise the available scientific information on these joint-friendly medicinal plants, which have been already tested in human studies: Arnica montana, Boswelliaspp., Curcuma spp., Equisetum arvense, Harpagophytumprocumbens, Salix spp., Sesamumindicum, Symphytumofficinalis, Zingiberofficinalis, Panaxnotoginseng, Whitaniasomnifera.

Excess consumption of a high-fat diet has been identified as one of the contributing factors for obesity. Women are at higher risk for adult obesity than men, predisposing them to a different set of detrimental disease conditions. Furthermore, aging studies show that physiological decline also has a serious impact on changes in the endocrine properties of white adipose tissue. Howev-er, there is still relatively little known about the factors associated with obesity and aging and their compounding impact on women’s health. To investigate adipocytokine secretion profile changes, female C3H/HeJ mice were induced to obesity through long-term consumption of a high-fat diet. Weight gain measurements and Echo MRI analysis of fat composition showed in-creases were a due solely to the high fat content in the diet. Adipocytokine secretions were ana-lyzed in media conditioned from harvested visceral fat tissue that was organ cultured ex-vivo. Adipocytokine analysis across diets and age showed significant increases in Adiponectin and Leptin secretion in high-fat diets, accelerated increases in Resistin secretion with high-fat diets. Aging induced increased secretion of Lipcalin-2, Pentraxin-3 and Serpin E1, MCP-1 and ICAM-1, regardless of diet. Furthermore, comparisons of organoid cultured protein secretions and flash-frozen tissue samples differed greatly, suggesting the WAT organoid cultures may yield information more reflective of in situ conditions. Taken together, our results show that diet and aging significantly impact secretions from adipose tissue, that may contribute to women’s health issues.

(1) Background: The rapid development of information technology has changed the traditional concept of space, gradually shifting the "container space" to the "relational space" . The constraints of geographical spatial elements are diminishing, and the theory of virtual agglomeration is gaining attention. (2) Methods: In this study, we constructed an evaluation system for virtual agglomeration, comprising four primary indicators: virtual infrastructure level, virtual output level, virtual input level, and virtual service level. The TOPSIS method was used to calculate the virtual agglomeration level for each province, and the DEA-Malmquist method was employed to measure provincial total factor productivity (TFP) in China. Using panel data from 30 provincial regions in China from 2013 to 2021, we examined the mechanism and impact path of virtual agglomeration on TFP. (3) Result: There is an inverted U-shaped relationship between virtual agglomeration and TFP in China. The overall development level of virtual agglomeration is relatively low, within the range where the marginal effect of virtual agglomeration on TFP is positive but diminishing, indicating significant potential for further development. The impact of virtual agglomeration on TFP is stronger in the Yangtze River Economic Belt compared to non-Yangtze River areas, and the highest stable point of TFP is higher in central provinces than in eastern and western provinces. (4) Conclusions: This study provides a theoretical basis and practical reference for improving the level of virtual agglomeration.

Obesity is a highly prevalent chronic disease characterized by excessive weight gain and fat accumulation. There is growing evidence that Lactiplantibacillus plantarum strains with bile salt hydrolase (BSH) activity are effective in preventing and alleviating obesity. However, few of them has confirmed the anti-obesity effect of BSH by gene deletion. In this study, 23 BSH-positive Lp. plantarum strains were screened by bile salt precipitation halo assay. Among these strains, Lp. plantarum Lp20 showed the highest BSH activity with a hydrolysis rate to glycodeoxycholic acid (GDCA) by 91.62%. Genomic sequencing and bioinformatics analysis indicated that gene bsh1 was associated with BSH activity of Lp. plantarum Lp20 and gene deletion of bsh1 confirmed the role of Bsh1 in GDCA hydrolysis. To investigate if the Bsh1 from Lp. plantarum Lp20 could alleviate obesity, the wild type and bsh1 deletion mutant strains were administered daily for 8 weeks to diet-induced obese mice, respectively. Compared with mutant strain, the wild type strain Lp20 significantly reduced body weight gain, inguinal white adipose tissue and mesenteric fat mass in obese mice. In addition, Lp20 also reduced serum total cholesterol levels and LDL-C by 20.8% and 33.3%, respectively. Furthermore, the recovered liver steatosis was only observed in Lp. plantarum Lp20 treated mice. Taken together, the bile salt hydrolase Bsh1 from Lp. plantarum Lp20 was a key functional factor on ameliorating HFD-induced obesity by reducing cholesterol levels and suppressing adipogenesis in mice.

Research into lightweight structural concrete using volcanic tuff is of great importance to the construction industry. These materials have excellent thermal insulation properties, which helps improve the energy efficiency of buildings. A three-factor experimental design was used to build the statistical model. The test methods used were methods for determining the crushability of volcanic tuff, determining the average density, compressive strength and thermal conductivity of lightweight structural concrete. The influence of basalt fiber on the properties of lightweight structural concrete has been determined. The optimal compositions of lightweight structural concrete using tuff have been selected. The compressive strength of lightweight structural concrete reached 32.0 MPa. The average density range is 1754.6-2114.0 kg/m³. Good thermal conductivity values ​​were obtained in the range of 0.653-0.818 W/m·K. The article obtained the optimal compositions of lightweight structural concrete using volcanic tuff as a filler.

Endometriosis is known to be a chronic, debilitating disease. The pathophysiological mechanisms of endometriosis development include local chronic inflammation and a certain degree of local immune deficit. We investigated the relationship between the endometriosis severity, IL-8, IL-10, BDNF, VEGF-A serum and tissue levels, patient-related pain, and physical activity in a cohort of 46 patients diagnosed with endometriosis who underwent surgery. The same panel of biomarkers was investigated in a control group of 44 reproductive-aged patients with non-endometriotic gynecological pathology who underwent surgical intervention. Our data show a high statistical significance between tissue expression of IL-8, IL-10, patient-related pain and the severity of endometriosis. No relationship was identified between serum or tissue levels of VEGF-A and BDNF and the severity of endometriosis. These results validate the presence of local chronic inflammation and immune deficit, thereby creating, alongside other studies in the field, an opportunity for the development of innovative and personalized treatment approaches in endometriosis.

Pasteurized milks are still causing food borne illness. Milk contamination can occur at any stage from its way from cow to our tables. Usually milk is pure and sterile when produced in udder of a healthy cow. Like humans, cow are reservoirs of bacteria which are harmless to humans and some cows can harbour few bacteria that are harmful to humans even though they are not harmful to the cow. Milk can be contaminated during or after milking. Also, cow feeds can be contaminated with mycotoxins such as aflatoxins produced by the fungi, Aspergillus flavus. Four types of aflatoxins are known which are; aflatoxin B1, B2, G1, G2. Cows comsuming feeds contaminated with aflatoxin B1 leads to secretion in the milk of aflatoxin M1 and M2 causing aflatoxicosis. Microbial contamination of milk and dairy products is a universal problem and foodborne infections accounting for 20 million cases annually in the world have been identified as an important public health and economic problem in developed as well as developing nations. The main objective of this study was to determine milk microbial quality in Kicukiro district. The specific objectives are to identify bacteria pathogens in milk collected in Kicukiro district, to compare milk quality among sectors of Kicukiro district, to compare milk processed by industries and home-processed milk. The methodology employed in this research was cross-sectional and experimental as the study began with collection of raw data and went through laboratory analysis from July–August, 2018. The findings showed that 59.56% of the milk fell within Grade I – Grade III (< 200,000 ≤ 2,000,000 cfu/ml) and 40.42 % of the milk samples were not within the acceptable limit of total count quality as per COMESA and EAS, non-lactobacilli and fungi were present in most samples as examined through microscope and no Staphylococcus aureus was present in any sample as examined by catalase and coagulase tests.

Spermatogenesis is critical for insect reproduction and is regulated by many different genes. In this study, we found that Forkhead transcription factor Fd59a functions as a key factor in spermatogenesis of Drosophila melanogaster. Fd59a contains a conversed Forkhead domain, and it is clustered to the FoxD subfamily with other FoxD members from some insect and vertebrate species. Mutation in Fd59a caused swelling in the apical region of the testis. More importantly, only a few mature sperm were present in the seminal vesicle of Fd59a mutant flies compared to the control flies, and the fertility of Fd59a2/2 mutant males was significantly lower than that of the control flies. Immunofluorescence staining showed that the homeostasis of testis stem cell niche in Fd59a2/2 mutant and Fd59a RNAi flies was disrupted, and apoptosis of sperm bundles was increased. Furthermore, results from RNA-sequencing and qRT-PCR suggest that Fd59a can regulate expression of genes related to reproductive process and cell death. Taken together, our results indicated that Fd59a plays a key role in the spermatogenesis of Drosophila.

Surface water distribution extracted from remote sensing data has been used in water resource assessment, coastal management, and environmental change studies. Traditional manual methods for extracting water bodies cannot satisfy the requirements for mass processing of remote sensing data; therefore, accurate automated extraction of such water bodies has remained a challenge. The histogram bimodal method (HBM) is a frequently used objective tool for threshold selection in image segmentation. The threshold is determined by seeking twin peaks, and the valley values between them; however, automatically calculating the threshold is difficult because complex surfaces and image noise which lead to not perfect twin peaks (single or multiple peaks). We developed an operational automated water extraction method, the modified histogram bimodal method (MHBM). The MHBM defines the threshold range of water extraction through mass static data; therefore, it does not require the identification of twin histogram peaks. It then seeks the minimum values in the threshold range to achieve automated threshold. We calibrated the MHBM for many lakes in China using Landsat 8 Operational Land Imager (OLI) images, for which the relative error (RE) and squared correlation coefficient (R2) for threshold accuracy were found to be 2.1% and 0.96, respectively. The RE and root-mean-square error (RMSE) for the area accuracy of MHBM were 0.59% and 7.4 km2. The results show that the MHBM could easily be applied to mass time-series remote sensing data to calculate water thresholds within water index images and successfully extract the spatial distribution of large water bodies automatically.

Cascading landslides represent a dynamic and hazardous geological phenomenon, char-15 acterized by a sequential chain of slope failures triggered by various factors such as heavy rainfall, 16 seismic activity, or anthropogenic activities. These events can amplify the damage caused by the 17 initial trigger and propagate instability along a slope, often resulting in significant environmental 18 and societal impacts. The Morino-Rendinara cascading landslide, situated in the Ernici mountains 19 along the border of Abruzzo and Lazio region (Italy), serves as a notable example of the complexities 20 and devastating consequences associated with such events. In March 2021, a substantial debris flow 21 event in Morino obstructed the Liri River, marking the latest step in a series of landslide events 22 characterized by a complexity far beyond initial expectations. This study employs a multidiscipli-23 nary approach, combining conventional techniques and advanced technologies, to understand the 24 complexities of the Morino-Rendinara landslide. Field activities, UAV image acquisition, SAR inter-25 ferometry based on SENTINEL-1 images and pixel offset analysis based on high-resolution Google 26 Earth images, offer insights into the geological and hydrogeological setting of the unstable slope, 27 landslide geometry, mechanism and kinematics. To supplement the analysis a specific FEM slope 28 stability analyses is used to reconstruct the deep geometry of the system emphasizing the modula-29 tion action of groundwater flow to the slope stability

Long COVID, a name often given to the persistent symptoms following acute SARS-CoV-2 infection, poses a multifaceted challenge for health. This review explores the intrinsic relationship between comorbidities and autoimmune responses in shaping the trajectory of long COVID. Autoantibodies have emerged as significant players in COVID-19 pathophysiology, with implications for disease severity and progression. Studies show immune dysregulation persisting months after infection, marked by activated innate immune cells and high cytokine levels. The presence of autoantibodies against various autoantigens suggests their potential as comorbid factors in long COVID. Additionally, the formation of immune complexes may lead to severe disease progression, highlighting the urgency for early detection and intervention. Furthermore, long COVID is highly linked to cardiovascular complications and neurological symptoms, posing challenges in diagnosis and management. Multidisciplinary approaches, including vaccination, tailored rehabilitation, and pharmacological interventions, are used for mitigating long COVID's burden. However, numerous challenges persist, from evolving diagnostic criteria to addressing the psychosocial impact and predicting disease outcomes. Leveraging AI-based applications holds promise in enhancing patient management and improving our understanding of long COVID. As research continues to unfold, unravelling the complexities of long COVID remains paramount for effective intervention and patient care.

Background: A significant proportion of SARS-CoV-2-infected patients develops respiratory failure. Thromboembolism is also prevalent in coronavirus disease 2019 (Covid-19). Vitamin K plays a role in coagulation and possibly also in lung diseases. We therefore hypothesized that vitamin K is implicated in Covid-19 pathogenesis. Methods: 134 Covid-19 patients and 184 controls were included. Inactive vitamin K-dependent matrix Gla protein (i.e.dp-ucMGP) and prothrombin (i.e. PIVKA-II) were measured, which are inversely related to respectively extrahepatic and hepatic vitamin K status. Desmosine was measured to quantify elastic fiber degradation. Lung involvement and arterial calcifications severity were assessed by computed tomography. Results Dp-ucMGP was elevated in Covid-19 patients compared to controls (P=0.001). Higher dp-ucMGP was found in Covid-19 patients with poor compared to better outcomes (P=0.002). PIVKA-II was normal in 81.8%, mildly elevated in 14.0% and moderately elevated in 4.1% of Covid-19 patients not using vitamin K antagonists. Dp-ucMGP in Covid-19 patients was correlated with desmosine (P<0.001), thoracic aortic calcification (P<0.001) but not with pneumonia severity. Conclusions: Extrahepatic vitamin K status was severely reduced in Covid-19 patients, as reflected by elevated inactive MGP, and related to poor outcome. Procoagulant prothrombin activity remained preserved in the majority of Covid-19 patients, which is compatible with the increased thrombogenicity that is frequently observed in severe Covid-19. Impaired MGP activation was linked to accelerated elastic fiber degradation and premorbid vascular calcifications. A trial should assess whether increasing MGP and protein S activity by vitamin K administration improves Covid-19 outcomes.

Employing remote sensing techniques to evaluate crop residue cover (CRC) enables rapid mapping of tillage practices over large cropland areas, which has significant practical implications for monitoring the implementation of conservation tillage practices. This research utilized Sentinel-2 MSI and Landsat-8 OLI remotely sensed data, various spectral indices were calculated and the datasets were correlated with the field-measured CRC data. Selected spectral indices, highly significantly correlated, were chosen to build a correlation model between the indices and the CRC. Considering Sentinel-2 MSI and Landsat 8 OLI remotely sensed data variations in spectral and spatial scales, the accuracy of CRC models was evaluated using R2 and RMSE values. From the results, it's evident that all six spectral indices, including STI, NDTI, SRNDR, NDI5, NDI7 and NDSVI, registered correlation coefficients with the CRC exceeded 0.3 in the study area. STI and NDTI showed a stronger correlation to CRC, with coefficients of 0.810 and 0.803, respectively. For the Landsat 8 data, the lowest correlation obtained was for NDSVI with the Landsat 8 data with a correlation coefficient of 0.358. Applying the linear regression technique, STI and NDTI obtained higher accuracy compared to other indices in the Sentinel-2 MSI data. For NDTI and STI, The R2 values were 0.650 and 0.665, respectively, while their corresponding RMSE values were 3.96% and 4.03%. The highest model accuracy was obtained for the STI and NDTI constructed from the Landsat 8 OLI data (R2 values 0.41 and 0.40; RMSE values 5.25% and 5.27%, respectively). The CRC model built using partial least squares regression (PLSR) exhibited greater precision when applied to the Sentinel-2 MSI data (R2 value 0.894; RMSE value 2.18%) in comparison to the Landsat 8 OLI data (R2 value 0.695; RMSE value 3.70%). PLSR has the potential to enhance the precision of the model. In addition, the study area shows that the estimation of the CRC is better in the one-dimensional linear regression model and the PLSR model created with the Sentinel-2 MSI optical data compared to the Landsat 8 OLI optical remotely sensed data. The validation suggests that the CRC estimation in the study area is more precise when using the model relying on Sentinel-2 satellite imagery rather than the Landsat 8 OLI imagery.

The pervasive use of plastic for milk packaging has raised significant health concerns, despite its advantages in terms of cost-effectiveness, convenience, and durability. The potential correlation between cancer and plastic packaging is one of these concerns. This mini-review examines the health implications of plastic materials used in milk packaging, with a particular emphasis on their carcinogenic hazards. This work endeavors to summarize the current state of knowledge regarding the influence of plastic components on human health and underscore the importance of ongoing research in this field by utilizing insights from a comprehensive review article. Harmful chemicals have been observed to leach into milk from plastics used in milk packaging, including high-density polyethylene (HDPE), low-density polyethylene (LDPE), and polyethylene terephthalate (PET), particularly under conditions of protracted storage and heat. Bisphenol A (BPA), phthalates, and styrene are among the most prevalent leachates. These chemicals have been associated with a variety of health issues, such as an elevated risk of cancer, and are recognized for their endocrine-disrupting properties. BPA and phthalates, in particular, have the potential to disrupt hormone function, which may result in breast cancer, prostate cancer, and other hormone-related malignancies.This review emphasizes the significance of comprehending the precise components of plastics utilized in milk packaging and their potential health consequences. It advocates for more rigorous research to completely elucidate the long-term health impacts of these materials by emphasizing the current state of knowledge and regulatory initiatives. Additionally, it underscores the necessity of innovative packaging technologies to guarantee consumer protection and mitigate the risk of exposure to carcinogenic substances.

Background: Obesity remains a widely debated issue, often criticized for the limitations in its identification and classification. This study aims to compare two distinct systems for classifying obesity: Body Mass Index (BMI) and body fat percentage (BFP) as assessed by bioelectrical impedance analysis (BIA). By examining these measures, the study seeks to clarify how different metrics of body composition influence the identification of obesity-related risk factors. Methods: The study enrolled 1255 adults, comprising 471 males and 784 females, with a mean age of 36 ± 11.90 years. Participants exhibited varying degrees of weight status, including optimal weight, overweight, and obesity. Body composition analysis was conducted using the TANITA Body Composition Analyzer BC-418 MA III device (T5896, Tokyo, Japan), evaluating the following parameters: current weight, basal metabolic rate (BMR), adipose tissue (%), muscle mass (%), and hydration status (%). Results: Age and psychological factors like cravings, fatigue, stress, and compulsive eating were significant predictors of obesity in the BMI model but not in the BFP model. Additionally, having a family history of diabetes was protective in the BMI model (OR: 0.33) but increased risk in the BFP model (OR: 1.66). The BMI model demonstrates exceptional predictive ability (AUC=0.998). In contrast, the BFP model, while still performing well, exhibits a lower AUC (0.975), indicating slightly reduced discriminative power compared to the BMI model. Conclusions:BMI classification demonstrates superior predictive accuracy, specificity, and sensitivity. This suggests that BMI remains a more reliable measure for identifying obesity-related risk factors compared to the BFP model.

In this study, an alternative method to conventional production methods involving thin section copper permanent mould casting (rapid solidification), hot rolling and heat treatment processes to manufacture AISI DC 53 cold work tool steel, has been investigated. In this new method, solidification of the AISI DC 53 was done in the thin section copper mould instead of traditional ingot casting. After solidification, thin slabs obtained was homogenized to 1150 ^oC and hold at this temperature for one hour and then hot rolling was be applied. During hot rolling process, about % 30 reduction in thickness of slab was obtained. After hot rolling, heat treatment (austenitizing, quenching and tempering) have been applied to thin slab. The samples have been taken as cast, as rolled and as heat treated (austenitized and tempered) and the microstructural analysis, hardness tests, retained austenite quantity measurement by XRD method have been performed. The heat treatment and tests have been performed for a commercially available AISI DC 53 which is manufactured by thick section ingot casting and rolling. Hardness values of the AISI DC 53 steels produced by traditional route is in the range of 52-54 HRC after austenitization at 1025 ^oC for one hour and quenched in compressed air and tempered twice at 525 ^oC for 120 mins. On contrary the permanent mould cast AISI DC 53 after homogenization at 1150 ^oC and immediately hot rolling then air cooling and austenitized at 1025 ^oC for one hour then quenched by compressed air and tempered twice at 525 ^oC for 120 mins have hardness valeus in the range of 55-57 HRC. Experiments have revealed that the properties of new rapid solidified steel in permanent copper mould are better than the commercially available steel and have a more refined microstructure than commercially produces alternative. Therefore, the new proposed method can be used as an alternative manufacturing method for cold-work tool steels.

Solar pasteurization, as a means of treating milk in remote rural areas without electrical power, is based on using solar energy to thermally inactivate pathogenic microorganisms at temperatures below the boiling point to maintain or improve milk quality. A solar milk pasteurizer of flat‐plate water‐heating glass acting as the solar collector, connected to a stainless-steel cylindrical milk vat, was constructed and evaluated in Navrongo, in the tropical savanna zone of Ghana, West Africa. The novel approach taken in this project is to integrate the solar collection and heat exchanger into a single unit using materials and fabrication techniques readily available in the developing world. The vat comprises a 1.5 mm thick stainless steel cylindrical tank, a 2.2 cm wide hot water jacket, and an outer layer of 5.0 mm thick aluminium foil insulation. Hot water produced by the collector was used for pasteurizing milk. The optimum quantity of milk that this device could pasteurize under the study conditions was 8 L. The device could pasteurize raw milk to a maximum temperature of 74 °C at 14:00 h GMT. The ambient temperature during the pasteurization ranged from 30 °C to 43 °C. The microbial analysis before and after the pasteurization was done, and the result shows that the total bacteria count before pasteurization was 6.6x10⁶ log CFU/mL per unit volume, and the total bacteria count after pasteurization was 1.0x10² log CFU/mL. By acceptable standards, the total bacteria count after pasteurization is within a safe range for consumption, and coliform counts were negative. The solar milk pasteurization system is cost-effective. Hence, it is appropriate for milk producers in arid pastoral areas without electricity to adopt the solar pasteurizer as an alternative to firewood as a fuel source for milk pasteurization. This approach can potentially create a cottage industry that may also play a crucial role as a water treatment technology that will improve the health of rural populations.

The past few decades have brought tremendous insight into the molecular and pathophysiological mechanisms responsible for thrombus generation. For the clinician it is usually sufficient to explain the incident deep vein thrombosis (DVT) with provoking factors such as trauma with vascular injury, immobilization, hormonal factors, or inherited or acquired coagulation defects. About half of the DVTs are, however, lacking such triggers and are called unprovoked. Venous stasis and hypoxia at the valve sinus level may start a chain of reactions. In order to better understand the mechanisms behind DVT and reach beyond the above-mentioned simplifications animal models and clinical epidemiological studies have informed of the complex interplay between leukocytes, platelets, endothelium, cytokines, complements and coagulation factors and inhibitors. These pathways and the interplay will be reviewed here.

This study examines the relationship between teleworking, gender roles and happiness of couples using data from the British Household Panel Survey (BHPS) and the Understanding Society Survey (USS) during the period 1991-2012. Various approaches are followed, including Probit-adapted fixed effects, multinomial Logit and Instrumental variables (IV). The results support that both men and women who are teleworkers spend more time on housework, while teleworking increases the probability that the household chores examined in this study, such as cooking, cleaning ironing and childcare, will be shared relatively to those who are non-teleworkers. In addition, women are happier when they or their spouse is teleworker, as well as, both men and women are happier when they state that the specific household chores are shared. Thus, women teleworkers may be happier because they can face the family demands and share the household chores with their spouse, increasing their fairness belief about the household division allocation and improving their well-being, expressed by happiness.

Patients with a psychotic disorder frequently report oral health problems, while mental health nurses (MHNs) seem not to be fully aware of these problems and the risk factors. Therefore, this study aims to develop supportive tools for MHNs regarding oral health to increase sensitization among MHNs and to provide MHNs with knowledge to recognize (potential) oral health problems in patients with a psychotic disorder. We used a human-centered design in which the user, MHNs as well as experts by experience, were placed in the centre of the research process. Problems and needs in MHNs working with patients with a psychotic disorder were addressed. To identify key issues of problem as well as the needs in terms of resources, we started with focus groups (n = 9). We analysed the data thematically based on context of patients and MHNs in practice regarding oral health, preferred oral health tools focused on MHN, and intended outcomes of tools. A Multi Criteria Decision Matrix was developed and analysed (n = 9) to identify the most optimal and viable solution based on established criteria and issues that are prevalent in the work of MHNs. Most promising result was the development of a brochure with an awareness screener. The brochure with awareness screener was developed as a low-fidelity prototype for MHNs regarding oral health in patients with a psychotic disorder, based on the latest scientific evidence. After testing it, the feasibility was tested through semi-structured interviews (n=19). MHNs and experts by experience were satisfied with the tool and provided recommendations for adjustments to the content. Significant augmentations to the brochure include a clinical lesson and a toothbrush with toothpaste for patients. We can conclude that a brochure with an awareness screener is feasible for MHNs. Future steps aiming to further refine and optimize care processes for oral health tools in MHNs, should take refining eligibility criteria for psychiatric populations and the language level of the target group of a tool into account.

Greenhouse gas (GHG) emission-induced climate change, particularly occurring since the mid-20th century has been considerably affecting short-term weather conditions, such as increasing weather variability, and incidence of extreme weather-related events. Milk production is sensitive to such changes. In this study, we use spatial panel econometric models, Spatial Error Model (SEM) and Spatial Durbin Model (SDM), with a panel dataset at the state-level varying over seasons, to estimate the relationship between weather indicators and milk productivity, in an effort to reduce the bias of omitted climatic variables that can be time-varying and spatially correlated and cannot be directly captured by conventional panel data models. We find an inverse U-shaped effect of summer heat stress on milk production per cow (MPC), indicating that milk production reacts positively to a low-level increase in summer heat stress, and then MPC declines as heat stress continues increasing beyond a threshold value of 72. Additionally, fall precipitation exhibits an inverse U-shaped effect on MPC, showing that milk yield increases at a decreasing rate until fall precipitation rises to 14 inches and then over that threshold milk yield declines at an increasing rate. We also find that, relative to conventional panel data models, spatial panel econometric models could improve prediction performance by leading to smaller in-sample and out-sample root mean squared errors. Our study contributes to the literature by exploring the feasibility of promising spatial panel models and resulting in estimating weather influences on milk productivity with high model predicting performance.

The collection of forty-nine 8-hydroxyquinoline derivatives, substituted at C5, C6 or C7, was designed and studied by computational methods of modified POM analysis, using SwissADME, Osiris and Molinspiration tool. POM analysis (Petra/Osiris/Molinspiration) and its modified version using SwissADME instead of Petra software are indisputably tools of modern chemoinformatics, often published in the professional literature as well as in the field of research of new antibacterial active compounds, developed to replace existing antibiotics that fail due to increased resistance of bacteria. NitroxolineTM and the group of 8-hydroxyquinoline derivatives with their broad antibacterial effect and the possibility of extensive derivatization of the skeleton, represent a promising direction in the research of new antibacterial active substances. Twenty 8-hydroxyquinoline derivatives were also evaluated on their antibacterial activity against eight selected G+ and G- bacterial strains with a defined resistance mechanism. All structures were in accordance with Lipinski's criteria, twenty-one structures were interesting from the point of view of individual or average value of the bioactivity prediction score and fourteen structures showed one or more mechanisms of toxicity prediction. Furthermore, eleven structures showed a low rate of GI absorption or the inability to cross the BBB barrier, fourteen substances showed a BRENK or PAIN warning, eleven substances are an undesirable substrate of P-glycoprotein and all structures predicted the same level of bioavailability and a relatively low rate of metabolism in the liver. Five structures were selected by the intersection of the POM criteria. The virtual structures 17, 25, 35 and 43 can be favored for the continuity of next study. The resulting scores of bioactivity can indicate the potential of studied structures to be used for the design and development of new active antibacterial agents.

Chronic inflammatory diseases are considered the most significant cause of death worldwide. Current treatments for inflammatory diseases are limited due to the lack of understanding of the biological factors involved in early-stage disease progression. Nerve growth factor (NGF) is a neurotrophic factor directly associated with inflammatory and autoimmune diseases like osteoarthritis, multiple sclerosis, and rheumatoid arthritis. It has been shown that NGF levels are significantly upregulated at the site of inflammation and play a crucial role in developing a robust inflammatory response. However, little is known about NGF's temporal expression profile during the initial progressive phase of inflammation. This study aimed to determine the temporal expression pattern of NGF in rat skin during Adjuvant-Induced Arthritis (AIA). Sprague Dawley rats were randomly divided into control and Complete Freund's Adjuvant (CFA) treated groups. Levels of NGF were evaluated following unilateral AIA at different time points and it was found that peripheral inflammation due to AIA significantly upregulated the expression of NGF mRNA and Protein in a biphasic pattern. These results suggest that NGF signaling is crucial for initiating and maintaining peripheral neurogenic inflammation in rats during AIA.

This study investigates the effect of altitude on the fatty acid composition of grass, yak milk, and yak ghee on the Qinghai-Tibet Plateau, aiming to understand how environmental factors influence the nutritional quality of these products. Samples were collected from four different altitudes and analyzed for fatty acid profiles using gas chromatography. The findings reveal significant differences in fatty acid profiles, with notably higher concentrations of lauric acid (C12:0) and myristic acid (C14:0) at altitude A2 compared to others (p＜ 0.001). Furthermore, the fatty acid composition in yak milk and ghee is influenced by the grass consumed and the metabolism of rumen microorganisms. The results indicate that yaks adapt their lipid biosynthesis to high-altitude conditions, as evidenced by a significant increase in stearic acid (C18:0) levels at higher altitudes, which subsequently affects the nutritional value of their milk and ghee. These insights are crucial for improving yak breeding and dairy production practices, ultimately enhancing food security and nutritional health for local communities residing in high-altitude areas. The study underscores the necessity for further research on optimizing these natural resources for better health outcomes.

This study sought to investigate the problem of losses along the milk value chain in Nandi and Kakamega Counties in Kenya. Using semi structured questionnaire, quantitative data were collected from different stages of the value chain consisting of 400 dairy farmers proportionally and randomly selected in Chesumei and Ikolomani sub counties; 15 cooperatives, 40 transporters, 20 milk bars, 17 supermarkets. Additionally Key informant interviews and focus group discussions we held with extension staff and farmers, respectively.The results showed losses occurred at all stages of the value chain in Nandi and Kakamega Counties with the highest losses at Cooperative (50.6%), collection centres (33.7%) and milk bars (7.5%). Annual milk loss was estimated to be 260,000 litres and 20,000 litres in Nandi and Kakamega counties respectively. The economic value of losses per year was estimated at KES 13 million (USD 100 000). Significant factors (P<0.001) influencing milk losses at farm level were: type of cow housing, level of training of milker, mixing morning and evening milk and Lack of cooling facilities. In cooperatives, poor roads, poor preservation of milk and mastitis influenced post harvest losses (PHL) causing milk rejection due to spoilages; while transporters attributed PHL to storage during transportation. Inadequate storage facilities and milk handling practices influenced PHL in milk bars while supermarkets attributed PHL to poor packaging materials and short shelf life. The most important causes of milk PHL along the chain were spoilages, spillages, adulteration and physical dirt. Key interventions to minimize PHL should target improvement of rural road infrastructure connecting farmers to markets; milk storage facilities and capacity building on milk handling practices for all actors. A sustainable PHL reduction should entail policy dialogue on milk payment system based on quality rather than quantity.

Aflatoxin M1 (AFM1), a carcinogenic toxin, mainly contaminates cow milk and poses significant challenges to the dairy industry and, thereby, public health in most tropical countries, including Ethiopia. This study aimed to investigate the prevalence and level of AFM1 in raw cow milk collected from Specialized Dairy Farms and Milk Vendors in three Urban Centers: Chiro town, Dire Dawa, and Harar cities in Eastern Ethiopia. 180 milk samples were collected from two major Milk Sources: Specialized Dairy Farms (N=90) and Milk Vendors (N=90) using a simple random sampling technique. AFM1 was analyzed using high-performance liquid chromatography. The study revealed that, 63.9% (115/810) prevalence and 0.179±0.48µg/L mean of AFM1 level in milk, which 39.13% and 26.08% exceed the tolerable limits of EU and FDA respectively. A 40.0% prevalence and 0.344±0.72µg/L average of AFM1 in the milk from Dire Dawa city was significantly higher than the samples from other Urban Centers. However, 30.43% and 29.57% prevalence as well as 0.055±±0.13µg/L and 0.140±0.33µg/L average of AFM1 in milk from Chiro town and Harar city, respectively were not significant. Furthermore, milk samples from Dairy Farms revealed a higher prevalence (57.39%) and level (0.252±0.64µg/L) of AFM1 than Milk Vendors, with a prevalence of 42.61% and an average of 0.107±0.21µg/L. Therefore, this study concludes that substantial milk samples were contaminated by AFM1 and urges the need to enhance farmers' awareness on mitigation.

Objectives: The study aimed to develop a deep learning-based edge AI model deployed on electrocardiograph (ECG) devices for real-time detection of atrial fibrillation (AF)-risk during sinus rhythm (SR) using standard 10-second 12-lead electrocardiograms (ECGs). Methods: A novel approach was used to convert standard 12-lead ECGs into binary images for model input, and a lightweight convolutional neural network (CNN)-based model was trained using data collected by the Japan Agency for Medical and Research Development (AMED) between 2019 and 2022. Patients over 40 years old with digital, SR ECGs were retrospectively enrolled and divided into AF and non-AF groups. Data labeling was supervised by cardiologists. The dataset was randomly allocated into training, validation, and internal testing datasets. External testing was conducted on data collected from other hospitals.　Results: The best-trained model achieved an AUC of 0.82 and 0.80, sensitivity of 79.5% and 72.3%, specificity of 77.8% and 77.7%, precision of 78.2% and 76.4%, and overall accuracy of 78.6% and 75.0% in the internal and external testing datasets, respectively. The deployed model and app package utilized 2.5MB and 40MB of the available ROM and RAM capacity on the edge ECG device, correspondingly. Processing time for AF-risk detection was approximately 2 seconds.　Conclusion: The model maintains comparable performance and improves its suitability for deployment on resource-constrained ECG devices, thereby expanding its potential impact to a wide range of healthcare settings. Its successful deployment enables real-time AF-risk detection during SR, allowing for timely intervention to prevent AF-related serious consequences like stroke and premature death.

Buckwheat is important not only as a crop that improves soil quality and reduces erosion, but its excellent nutritional profile for usage in functional foods. This study aimed to investigate how long-term storage (3, 6, and 9 months) affects Novosadska variety buckwheat's chemical, nutritional, and antioxidative properties, phenolic acids and bioflavonoids profiles. Standard traditional methods were used for quality determinations, and instrumental (spectrophotometry, reverse-phase high performance liquid chromatography) for antioxidant activity and bioactive compounds determination. One-way ANOVA, and Tukey’s HSD post-hoc were performed for statistical data processing. Throughout the storage period, proximate composition and starch content significantly decreased (p&lt;0.05), while total carbohydrates, β-glucan, and energy value significantly increased (p&lt;0.05). Significant decrease in pH and alcoholic acidity of 0.55 pH units, and 0.33% DM, were observed. Total phenol content and antioxidant activity decrease to 5.57 mg GAE/g DM TPC, 22.20 μmol Fe2+/g DM FRAP and 8.12 μmol TE/g DM DPPH, during the storage (p&lt;0.05). Of fifteen phytochemical compounds, gallic, p-coumaric, trans-cinnamic acids, and epicatechin were in high abundance, with a notable decrease in epicatechin (38%). To the authors' knowledge, dihydrocaffeic and phloretic acids, daidzein, naringin, and naringenin were quantified in buckwheat flour for the first time. Easy adaptability to the environment, ability to attract various insects, speedy short-season growing plant for food, many nutritional and health benefits, gives buckwheat potential to be sustainable and biodiversity-friendly crops.

During the last few decades, the main focus of numerus studies has been on the human breast milk microbiota and its influence on the infant intestinal microbiota and overall health. The presence of lactic acid bacteria in breast milk affects both the quantitative and qualitative composition of the infant gut microbiota. The aim of this study was to assess the dominant cultivable rod-shaped lactic acid bacteria, specific for breast milk of healthy Bulgarian women and fecal samples of their infants over the first month of life, in 14 mother-infant tandem pairs. Additionally, we evaluated strain diversity among the dominant newly isolated species. 68 gram-positive and catalase negative strains were subjected to identification by using MALDI-TOF technique. Predominant culturable populations belonging to the rod-shaped lactic acid bacteria have been identified as Lacticaseibacillus rhamnosus, Limosilactobacillus fermentum, Lacticaseibacillus paracasei and Limosilactobacillus reuteri. Also, we confirmed the presence of Lactiplantibacillus plantarum and Lactobacillus gasseri. 27 isolates were selected as representatives and analyzed by 16S rDNA sequencing for strain identity confirmation and a phylogenetic tree based on 16S rDNA gene sequence was constructed. Comparative analysis by four RAPD primers revealed genetic differences between newly isolated L. rhamnosus strains. This pilot study provides data for the current first report concerning investigation on characteristic microbiota of human breast milk and infant feces in Bulgaria.

Succinate is proposed to be a mediator of muscle exercise-induced adaptations. We studied metabolic health and changes of muscle mass in 6-month-old male mice after 12 weeks of feeding regular diet (RD, 13.4 kcal% fat, 66.8 kcal% carbohydrate, 29.8 kcal% protein), high fat diet (HFD, 60 kcal% fat, 20 kcal% carbohydrates, 20 kcal% protein) and ketogenic diet (KD, 80 kcal% fat, &lt;1 kcal% carbohydrates, 20 kcal% protein) with or without 2% succinate supplements (SUS) in drinking water (n=8-12 per group). Functional overloading of the plantaris muscle (PL) was induced in a group of mice by denervation of the gastrocnemius and soleus muscles at week 6 of feeding different diets. HFD induced the greatest (p &lt; 0.001) increase in body and fat mass. HFD and KD lead to significant (p &lt; 0.01) impairment in glucose tolerance compared to RD. SUS blunted (p &lt; 0.01) initial surge in energy intake when mice were switched from RD to HFD, but did not influence any measures of metabolic health after 12 weeks of the study. Functional overloading lead to ~25% increase in PL mass which was not affected by diet or SUS. In conclusion, SUS does not have a long-term effect on metabolic health or muscle mass.

A method for estimating river water surface elevation (WSE) from Landsat imagery using the river inundation area - water surface elevation (RIA-WSE) rating curve constructed from the U.S. Geological Survey Topobathymetric Elevation Model (TEM) data was developed and tested at six gauging stations along the upper Mississippi River. The Otsu's automatic threshold selection algorithm was employed for the image classification and estimation of inundation areas within each pre-defined polygon around each gauging station. In addition to the commonly used green-band based water indices, Landsat 8 and 9 OLI's ultra-blue, blue, and red band-based water indices were also tested in this study, which resulted in twenty different water indices: NDWIv (Normalized Difference Water Index), MNDWI1v and MNDWI2v (Modified Normalized Difference Water Index), AWEIsv (Automatic Water Extraction Index with shadow), and AWEInsv (AWEI without shadow), where v represents the visible light band used in the water index. At each station, about 60-80 Landsat 8 or 9 images during 2013-2023 were used for assessing the performances of the twenty water indices through comparing the estimated WSEs with the measured WSEs. Results showed that the ultra-blue or red band-based AWEIs yielded the most accurate estimations of WSEs among the twenty tested water indices.

Hereditary hemochromatosis (HH) is the main genetic cause of iron overload and is regarded as metal-related human toxicosis. HH may result from HFE and non-HFE gene mutations causing hepcidin deficiency or hepcidin resistance. The disorder has a high biochemical penetrance, but a low clinical prevalence. Unfortunately, the majority of patients with HH remain undiagnosed at their disease-curable stage. The main aim of HH therapy is to prevent iron overload in the early-phase disease and elimination of excess iron from the body by phlebotomy in its late stage. Raising global awareness of HH among health professionals, their training to pay attention to early HH signs and symptoms, and strict patient monitoring are critical management strategies for preventing treatment delays, upgrading its efficacy, and improving patient prognosis.

(1) The purpose of this study was to compare the percentages of quarterly change for each of the variables analysed (height, weight, body fat percentage and muscle mass) as a function of the quarter in a sample of adolescent football players. (2) The sample consisted of young male football players of different categories belonging to a high-performance football academy, (more than 5 years in football and have spent 1 full year at the academy). (3) Two-way repeated measures ANOVA revealed for the anthropometric variable, P_value

This study aimed to evaluate the effect of incorporating linseed oil and fish oil in the diet on intake, ruminal fermentation milk yield and milk fatty acid profile in dairy goats. Four crossbred Saanen lactating goats in mid-lactation and milking 1.30±0.28 g/day were used in a 4 × 4 Latin square design. The basal diet consisted of concentrate and Para grass (C:F 40:60). Treatments included the basal diet without oil supplement (Ctrl) or with 2.5% linseed oil (LO2.5), 2.5% linseed oil and fish oil (3:2, w/w, LFO2.5), and 4.16% linseed oil and fish oil (3:2, w/w, LFO4.16). Diets had no effect on intake, milk yield, milk composition and ruminal fermentation patterns (P > 0.05). The lower (P < 0.05) proportions of C10:0-C14:0 in milk fat were observed with LFO4.16 compared with Ctrl. Compared with the Ctrl and linseed oil added alone, feeding LFO4.16 resulted in a 589% and 303% increase in C18:1 t11, respectively. Milk c9,t11 CLA was markedly increased with the LFO4.16 diet, accounting for 4.53 and 2.94 times greater concentrations than those in Ctrl and LO2.5 diets, respectively (P < 0.01). Goats fed LFO2.5 and LFO4.16 had greater levels of C22:6n-3 (0.63% and 0.87%; P < 0.001) compared with those fed Ctrl and LO2.5 diets (0.06% and 0.08%). Overall, the combined data suggested that including 4.16% linseed oil and fish oil in the diet of dairy goats is effective for improving the concentrations of healthy fatty acids in milk, without affecting milk production.

Promoting green development has become an important way to optimize the ecological and economic structure and promote sustainable development. The Yangtze River Economic Belt is an important economic corridor in China, and it remains to be examined whether the implementation of environmental regulations has enhanced the green total factor productivity (GTFP) of cities. This paper calculates the green total factor productivity of 107 cities within the Yangtze River Economic Belt by using the super-efficient SBM model and the GML index with Chinese city panel data from 2007-2019 and measures the intensity of environmental regulations through textual analysis. The bidirectional fixed-effects model constructed in this paper suggests an inverted U-shaped relationship between environmental regulation and GTFP, which is confirmed by a series of robustness tests. Green technology innovation and advanced industrial structure play a mechanism role in this. In regions with lower levels of green technology and industrial structure, the inverted U-shaped relationship between environmental regulation and green total factor productivity is more significant. In addition, the phenomenon of GTFP rising and then falling because of environmental regulation is more obvious in cities in the middle and upper reaches of the Yangtze River and outside the urban agglomerations. Therefore, when formulating environmental regulation policies, it is necessary to balance the relationship between economic development and environmental protection and harmonize the environment and economic development of the entire Yangtze River Basin.

The aim of this work is to compare two softwares (MAUD and TOPAS) based on the Rietveld algorithm and to test the concept of tolerance factor using the dissolution at high temperature of yttrium into BaTiO₃. In general, both softwares give up different values of the crystalline parameters however the trends are similar in most cases but the analysis of the strain and crystallite size in the BaTiO₃ crystals suggests that, in this particular case, MAUD offered results more consistent with the expected behavior. Using the crystalline parameters calculated by Rietveld, the tolerance factor values were obtained and these data suggest even better stability in the crystalline structure than that expected using theoretical parameters. Tolerance factor concept also indicates that Ti⁴⁺ should be preferred.

Tamil Nadu, a state in southern India, is bereft of any native milch or dual-purpose cattle breed and the state depends chiefly on crossbred cattle for milk production. As most (90 percent) of the milk production in the state was contributed by Jersey crossbred cattle, the genetic evaluation study was intended to assess the milk production traits viz., test-day milk yields (TDMYs), total milk yield (TMY) and 305-day milk yield (305MY) in these crossbred cattle reared under farmers’ rearing environment. Data on monthly TDMYs (TDMY1 to TDMY10) of Jersey crossbred cows (n=81,653) reared by the farmers over 24 years (1999-2022) were collected for evaluation. The influence of non-genetic factors viz., location (agroclimatic zones), period and season of calving, and parity on TDMYs, TMY, and 305MY were assessed, and the variance and covariance components for genetic parameters (heritability and genetic correlation) of the traits were estimated by the method of restricted maximum likelihood (REML) under multivariate animal model and by random regression model (RRM). The overall means of various TDMYs ranged from 4.98 (TDMY10) to 9.95 kg (TDMY2) and, for TMY and 305MY the means were 2480.33 and 2393.71 kg respectively. The heritabilities estimated by animal model for TDMYs were high and ranged from 0.39 ± 0.01 to 0.47 ± 0.01 and were fairly less variable throughout the lactation while the estimates obtained by RRM were medium to high and ranged between 0.28 ± 0.01 and 0.65 ± 0.02 for different days in milk (DIMs). The heritability estimated for TMY and 305MY were 0.48 ± 0.01 and 0.49 ± 0.01 respectively. The estimates of heritability in mid-lactation yields were comparatively little less than those at the beginning and the end of lactation. The high estimates of heritabilities for TDMYs, TMY, and 305MY obtained in the present study offered an ample scope for improving milk production through selective breeding. Genetic correlations between TDMYs estimated by animal model were positive and moderate to high, with a range between 0.47 ± 0.01 and 0.99 ± 0.00. Considerably higher estimates (0.97-0.99) were observed between adjacent TDMYs showing strong genetic associations. By RRM, genetic correlations estimated between DIMs were positive, except for a few estimates and the magnitude of genetic correlation decreased with an increase in the interval between the DIMs. The high genetic correlation observed between the TDMYs in early and mid stages of lactation with TMY and 305MY suggested that these test day yields could be used favorably for the early selection of cows for milk production which facilitates reduction in the generation interval and consequently increase the annual genetic gain for the milk production traits.

The number of physical devices connected to the Internet such as vehicles, household appliances and other "things" has been steadily increasing in recent years, thus forming the basis for the Internet of Things (IoT). IoT ecosystem extends beyond country borders and application domains, combining thousands of versatile devices that differ in terms of their structures, capabilities, and available resources. It is therefore not surprising that the landscape of wireless communication technologies and the degree of IoT devices available today is excessively broad and diverse. Interference between networks leads to frame collisions and consequent packet loss. Frame collisions occur when two or more packets overlap in time and frequency and use the same Long Range (LoRa) parameters, i.e. the same Spreading Factor (SF), Bandwidth (BW) and Carrier Frequency (CF). When most devices use the same configuration, collision probability is higher. The probability of frame collisions is also affected by traffic characteristics, particularly the periodicity of the transmission and the payload size. Larger payload sizes and more frequent transmissions accumulate with higher Time on Air (ToA) and channel occupancy [1]. Transmission powers and the location of the gateways also influences this situation. The aim of this experimental work is to verify the effects of collisions and interference in Long Range Wide Area Network (LoRaWAN), regarding the periodicity of transmissions and the payload sizes in a context of an inter-SF interference scenario. And to validate measuring tools like Received Signal Strength Indicator (RSSI), ToA and Packet Delivery Ratio (PDR) in the reliability of a network. We validate our conclusions by analyzing ToA according with RSSI and different data sizes, the RSSI for different SFs and different data sizes and finally the packet loss through the PDR for a better understanding of the reliability of packet transmission in our link. In the end we conclude that in an environment with inter-SF interference, the choice of SFs and packet lengths impacts ToA. When dealing with multiple devices near gateways, different SFs and varying packet lengths can lead to increased latency and longer ToA. Consequently, the risk of packet loss becomes more significant, especially if the signal-to-interference ratio (SIR) is low. This limitation will therefore affect scalability, particularly in Non-Line-Of-Sight (NLOS) scenarios.

Energy from biogas is one of the most promising renewable energy sources. Significant, for technical, economic, and environmental reasons, is the construction of agricultural microgas plants next to households specialising in cattle rearing. The availability of free substrate makes it possible not only to produce one's electricity and heat but also to produce a more environmentally and human-friendly manure. The operation of biogas plants is, unfortunately, associated with technical problems. This paper presents the results of a study of the quality of electricity generated in an agricultural biogas plant built at a farm specialising in dairy cows, where the owner reported a problem with the voltage in the power supply network. Therefore, selected power quality parameters occurring at the connection point of the biogas plant were analysed in detail. As the authors' research showed, in the case in question, the agricultural biogas plant was connected via a cable with too small a conductor cross-section, which resulted in significant voltage exceedances, making it impossible to switch on the second of the biogas plant's generators. Replacement of the feed-in cable has enabled both generators to run, but significant fluctuations in the feed-in voltage values were still noticeable. Analysis of the subsequent measurements revealed the need for changes in the design of the digester itself. The proposal for change is to replace the two current digester mixers (each rated at 9 kW) with more mixers of lower power. The new mixers would operate in an alternating system, where only one would always be activated.

We have previously shown that the transmembrane protein ODZ1 promotes cytoskeletal remodelling of glioblastoma (GBM) cells and invasion of the surrounding parenchyma through activation of a RhoA-ROCK pathway. We also described that GBM cells can control the expression of ODZ1 through transcriptional mechanisms triggered by binding of IL-6 to its receptor and a hypoxic environment. Epidermal growth factor (EGF) plays a key role in the invasive capacity of GBM. However, the molecular mechanisms that enable tumor cells to acquire the morphological changes to migrate out from the tumor core have not been fully characterized. Here we show that EGF is able to induce the expression of ODZ1 in primary GBM cells. We analysed the levels of EGF receptor (EGFR) in 20 GBM primary cell lines and found expression in 19 of them by flow cytometry. We selected two cell lines that do or do not express EGFR and found that EGFR-expressing cells responded to EGF ligand by increasing ODZ1 at the mRNA and protein level. Moreover, blockade of EGF-EGFR binding by Cetuximab, inhibition of the p38 MAPK pathway or siRNA-mediated knockdown of MAPK11 (p38 MAPK) reduced the induction of ODZ1 in response to EGF. Overall, we show that EGF may activate an EGFR-mediated signalling pathway through p38 MAPK, to upregulate the invasion factor ODZ1, which may initiate morphological changes for tumor cells to invade the surrounding parenchyma. These data identify a new candidate of the EGF-EGFR pathway for novel therapeutic approaches.

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

POGZ (Pogo transposable element derived with ZNF domain) is known to function as a regulator of gene expression. While variations in the POGZ gene have been associated with intellectual disabilities and developmental delays in humans, the exact pathophysiological mechanisms re-main unclear. To shed light on this, we created two lines of conditional knockout mice for Pogz, one specific to excitatory neurons (Emx1-Pogz mice) and the other to inhibitory neurons (Gad2-Pogz mice) in the brain. Emx1-Pogz mice showed a decrease in body weight, similar to total Pogz knockout mice. Although the two lines did not display significant morphological ab-normalities in the telencephalon, impaired POGZ function affected the electrophysiological prop-erties of both excitatory and inhibitory neurons differently. These findings suggest that these mouse lines could be useful tools for clarifying the precise pathophysiological mechanisms of neurodevelopmental disorders associated with POGZ gene abnormalities.

Background: The modified Duke index derived from coronary computed tomography angiography (CCTA) was designed to predict cardiovascular outcomes based on the severity of coronary ste-nosis. However, it does not take into consideration the presence or severity of peri-coronary in-flammation. The peri-coronary fat attenuation index (FAI) is a novel imaging marker determined by CCTA which reflects the degree of inflammation in the coronary tree in patients with coronary artery disease. Purpose: To assess the association between the modified Duke index assessed by CCTA, cardiovascular risk factors and peri-coronary inflammation in the coronary arteries of pa-tients with coronary artery disease. Methods: One hundred seventy-two patients who underwent CCTA for typical angina were assigned into two groups based on the modified Duke index: group 1 – patients with low index ≤ 3 (n=107) and group 2 – patients with high index > 3 (n=65). Demo-graphic, clinical and CCTA data were collected for all patients, and FAI analysis of coronary in-flammation was performed. Results: Patients with increased values of the modified Duke index were significantly older compared to those with a low index (61.83 ± 9.89 vs. 64.78 ± 8.9; p = 0.002). No differences were found between the two groups in terms of gender distribution, hypertension, hypercholesterolemia or smoking history (all p > 0.5). The FAI score was significantly higher in patients from group 2, who presented a significantly higher score of inflammation compared to the patients in group 1, especially at the level of the right coronary artery (FAI score 20.85 ± 15.80 vs. 14.61 ± 16.66; p = 0.01 for the right coronary artery, 13.85 ± 8.04 vs. 10.91 ± 6.5; p = 0.01 for the circumflex artery, and 13.26 ±10.18 vs. 11.37 ± 8.84; p = 0.2 for the left anterior descending artery). CaRi-Heart® analysis identified a significantly higher risk of future events among patients with a high modified Duke index (34.84 % ± 25.86 % versus 16.87 % ± 15.80 %; p

Many anti-tumor effects of group-specific component-derived macrophage-activating factors (GcMAFs) have been reported; however, the specific mechanisms remain unclear. Controlling tumor-associated macrophages (TAMs) in the tumor microenvironment is essential for cancer treatment. This study assessed the role of GcMAF in macrophage activation, elucidated the mechanisms by which it exerts its anti-tumor effects, and determined its effects on TAMs in the tumor microenvironment. GcMAF-stimulated RAW264.7 macrophages and EMT6 breast tumor cells were co-cultured in a 0.4-µm pore cell culture insert, and gene and protein expression and cell viability were evaluated. DNA microarray analysis of GcMAF-stimulated RAW264.7 cells was conducted. The induction of M2 RAW264.7 cells by interleukin (IL)-4 and IL-13 was analyzed. GcMAF stimulation increased the tumor necrosis factor-α and inducible nitric oxide synthase mRNA and protein levels in RAW264.7 cells but decreased the viability of co-cultured EMT6 cells. These results were confirmed in the M2 RAW264M2.7 cells, suggesting that GcMAF exerts anti-tumor effects by inducing the differentiation of macrophages into the M1 type and reprogramming M2 macrophages to the M1 type. The anti-tumor activity of GcMAF via M2-to-M1 macrophage reprogramming could aid in developing novel cancer immunotherapies.

Neurosteroids are pleiotropic molecules involved in various neurodegenerative diseases with neuroinflammation. We assessed neurosteroids serum levels in a cohort of Parkinson’s Disease (PD) patients with heterozygous glucocerebrosidase (GBA) mutations (GBA-PD) compared with matched cohorts of consecutive non-mutated PD (NM-PD) patients, and healthy subjects with (GBA-C) and without (NM-HC) GBA mutations. A consecutive cohort of GBA-PD was paired for age, sex, disease duration, Hoehn &amp; Yahr stage, and comorbidities with a cohort of consecutive NM-PD. Two cohorts of GBA-C and HC were also considered. Clinical assessment included the MDS-UPDRS and the Montreal Cognitive Assessment (MoCA). Serum samples were processed and analyzed by liquid chromatography coupled with triple quadrupole mass spectrometry. Twenty-two GBA-PD (males: 11, age: 63.68), 22 NM-PD (males: 11, age: 63.05), 14 GBA-C (males: 8; age: 49.36), and 15 HC (males: 4; age: 60.60) were studied. Compared to NM-PD, GBA-PD showed more hallucinations and psychosis (p&lt;0.05, Fisher’s exact test) and higher MDS-UPDRS part-II (p&lt;0.05). Most of the serum neurosteroids were reduced in both GBA-PD and NM-PD compared to the respective control cohorts, except for 5α-DHP. Allopregnanolone was the only neurosteroid significantly lower (p&lt;0.01, Dunn’s test) in NM-PD compared to GBA-PD patients. Only in GBA-PD, allopregnanolone, and pregnanolone levels correlated (Spearman) with a more severe MDS-UPDRS part-III. Allopregnanolone levels also negatively correlated with MoCA scores, and pregnanolone levels correlated with more pronounced bradykinesia. This pilot study provides the first observation of changes in neurosteroid peripheral levels in GBA-PD. The involvement of the observed changes in the development of neuropsychological and motor symptoms of GBA-PD deserves further attention.

Milk consumption is crucial for a balanced diet, yet recent trends indicate a decline, especially in Italy. A significant factor in this decline is the altered perception of milk quality among consumers, creating a communication gap between them and other stakeholders. This study aimed to explore the discourse on social media and sentiment towards the concept of milk quality among consumers, farmers, and processors. The research adopted a Social Media Analysis to examine online community messages. A sample of 19,906 Italian comments and posts mentioning keywords Milk, Quality, Cow, and Vaccine was collected and categorized using term frequency analysis, correspondence analysis, and sentiment analysis. Results highlighted gaps in the perceptions of milk quality: farmers focused on economic issues, consumers on animal welfare and health, and processors on lactose content. For farmers, almost all comments were negative, while for processors, nearly all comments were positive. Consumers presented a more mixed picture. This work contributes to the literature by expanding research on milk quality using social media as a source of information. The findings suggest that enhancing communication and understanding among these groups could lead to more effective strategies for addressing consumer concerns, potentially reversing the declining of milk consumption.

This study analyzed methodologies for identifying β-casein genotypes in dairy cows and the purity of A2 fermented milk. The research was justified by the need for quick and accurate techniques for herd screening and A2 milk quality control. The methodology included the development of an ELISA test to detect β-casein A1 in fermented milk and the evaluation of a commercial Lateral Flow Immuno Assay (LFIA) to identify A2A2 genotypes and the purity of A2 milk. The results showed that the ELISA test had high sensitivity and specificity (100%) in detecting β-casein A1. The LFIA test was 100% effective in identifying A2A2 genotypes and verifying the purity of A2 milk with a minimum detectable contamination of 5% for raw milk and 10% for fermented milk. Compared to traditional genotyping, these methods proved to be highly reliable and more practical for large-scale screening. It was concluded that the ELISA and LFIA were valuable tools for ensuring the quality and authenticity of A2 milk, meeting the demands of producers and consumers for safe and healthy dairy products.

“Pecorino” is a typical semi-hard cheese obtained with raw or heat-treated sheep milk using procedures to valorize the raw material's chemical and microbiological properties. In the present study, using a high throughput method of 16S rRNA gene sequencing, we assessed the evolution of the microbiome composition from milk to Pecorino cheese in artisanal processes using milk from Comisana and Lacaune sheep breeds. The comparative analysis of the bacterial com-munity composition revealed significant differences in the presence and abundance of specific taxa in the milk microbiome of the Comisana and Lacaune breeds. NGS analysis also revealed differences in the curd microbiome related to dairy farming practices, which have a relevant effect on the final structure of the Pecorino-cheese microbiome.

This study investigated the effects of fish oil (FO) treatment, particularly enriched with eicosapentaenoic acid (EPA), on obesity induced by a high-fat diet (HFD) in mice. The investigation focused on elucidating the impact of FO on epigenetic modifications in white adipose tissue (WAT) and the involvement of adipose-derived stem cells (ASCs). C57BL/6j mice were submitted to a control diet or a HFD for 16 weeks, treated (or not) with FO for the last 8 weeks. WAT was removed for RNA and protein extraction, while ASCs were isolated, cultured, and treated with Leptin. All samples were analyzed using functional genomics tools, including PCR-array, RT-PCR and Western Blot assays. Mice receiving HFD displayed increased body mass, fat accumulation, and altered gene expression associated with WAT inflammation and dysfunction. FO supplementation attenuated these effects, a potential protective role against HFD-induced obesity. Analysis of H3K27 revealed HFD-induced changes in histone, which were partially reversed by FO treatment. The study further explored leptin signaling in ASCs, suggesting a potential mechanism for ASC dysfunction in the leptin-rich environment of obese WAT. Overall, FO supplementation demonstrated efficacy in mitigating HFD-induced obesity, influencing epigenetic and molecular pathways, and shedding light on the role of ASCs and leptin signaling in WAT dysfunction associated with obesity.

The theory of water transport in trees, according to which the main driving force of water movement is the suction created by the evaporation of water by the meniscus (the curved surface of the capillary liquid column) on the evaporating elements, supported from below by root pressure, is flawed. The capillary effect in nature is around one meter. In the case of open-air gaps, the leaf cannot suck in the water against gravity because, in this case, the plant would not be sucking in water, but air through the open-air gap. If not, how do trees transport water? When evaporation occurs, there is no suction towards the canopy, but pressure is due to a reduction in the cross-section of the water pipe caused by heat loss through evaporation. At night, when evaporation stops, a thermal equilibration process is triggered, which restores the original cross-section of the pipe. This generates suction and draws water from the soil. As the hydrostatic pressure in the pipe is high for tall trees, the pipe is cut off. To prove my theory, I have given several examples. Water transport is not based on physical mechanical laws alone. There may be complex physiological, biochemical, and biophysical processes behind the operation of the pipe system.

Polyetheretherketone (PEEK) in the last few years emerged as an exceedingly promising material for craniofacial defect, due to its biocompatibility and mechanical properties. However, its utilization remains controversial due to its inertness and low osteoinductivity. This study aimed to investigate the postoperative outcomes of patients undergoing maxillo-facial and neurosurgical procedures with PEEK implants. The focus is on evaluating bone regrowth on the surface and edges of the implant, periosteal reactions, and implant positioning. A retrospective analysis of 12 maxillo-facial surgery patients and 10 neurosurgery patients who received PEEK implants was conducted. CT scans performed at least one-year post-operation, were examined for bone regrowth, periosteal reactions, and implant positioning. In maxillo-facial cases, the analysis included mandibular angle and fronto-orbital reconstruction, while neurosurgical cases involved cranioplasty. In maxillofacial surgery, 11 out of 12 patients showed radiological evidence of bone regrowth around PEEK implants, with favorable outcomes observed in craniofacial reconstruction. In neurosurgery, 9 out of 10 patients exhibited minimal or none bone regrowth, while one case demonstrated notable bone regeneration beneath the PEEK implant interface. The study highlights the importance of implant design and patient-specific factors in achieving successful outcomes, providing valuable insights for future implant-based procedures.

The species Lactococcus lactis is the bacterium extensively used in dairy industry. This bacterium is generally recognized as safe which was added to the European Food Safety Authority Qualified Presumption of Safety list. The major functions of this species in dairy fermentation are production of lactic acid from lactose, citric acid fermentation and hydrolysis of casein. But the representatives of this species producing bacteriocin substances can exert an inhibitory effect against spoilage bacteria. The aim of this study was to test three lactococcal strains isolated from raw goat milk for their postbiotic activity and to test their stability in goat milk yogurts in encapsulated form for further application. To reach the aims, validated methods were used. Three postbiotic active Lactococcus lactis subsp. lactis strains (identified by Blastn 16S rRNA analysis) from raw goat milk produced bacteriocin substances which in their concentrated form inhibited the growth of indicator enterococci and staphylococci up to 97.8 % with inhibitory activity up to 800 AU/mL. The encapsulated (freeze dried) lactococci fortified goat milk yogurts showed sufficient stability and survival in yogurts. The highest amount was reached using the strain MK2/8 (8.1 ± 0.0 cfu/g log 10) not influencing yogurt pH.

Since the 1980s, a growing interest in goat milk was noticed due to the nutritional values and health benefits of this milk, which resulted in increasing goat populations and milk production worldwide. This comprehensive review elaborates on goat milk composition compared to other types of milk. It is also an overview of goat milk production, properties, nourishment-value, applications in dairy products, and potential health benefits. Goat milk composition and its characteristics are slightly different from other types of milk and can be utilized to manufacture many dairy products. Fresh goat milk and goat milk products (e.g., yogurt and kefir were found to provide various potential health benefits, such as anti-inflammatory, prevent cardiovascular disease, anti-diabetic and antihypertensive, strengthen bones, boost immunity, and improve metabolism.

Abstract:This study aimed to explore the effects of supplementary feeding on milk yield, blood biochemical indexes, milk components, and fecal microflora diversity of Yili horses under grazing condition.18 grazing Yili mare horses with physiological condition consistent were randomly assigned to three groups with six mare horses each. The control group normal grazing, whereas the test group I and II were provided with supplemented with 1 kg/d of concentrate and 1 kg/d of concentrate + 0.4 kg/d coated fatty acids, respectively. After 3 days of pre-feeding, begin the experiment.Horse milk was collected every 7 days, and 10% of the milk yield of each horse was mixed in 100 mL milk sample bottles and stored in -20℃ refrigerator.Which blood samples were collected from the jugular vein before morning feeding (0 h) and at 1,2,3,4,6,9 and 12 h after morning feeding on day 40, and the plasma were centrifuged at 4000 rpm for 15 min and conservation at-20℃. Excrement was collected within 8 h on days 45 and 46 of the test, mixed with 5g of fresh fecal samples in a 5 mL frozen storage tubes and stored in liquid nitrogen. Compared with the control group, the lactation volume of Yili horses in test groups I and II was significantly higher throughout the trial period (P <0.05), and the late test group II was significantly higher than test group I (P <0.05). The yield of milk fat, lactose, and milk protein in test group II was significantly higher than that in test group I and control group (P <0.05); the urea nitrogen content in test group I was significantly lower than the control group (P <0.01). The lauric acid, tetradecanoic acid, cis-11,14,17-eicosotrienic acid, total saturated fatty acid, and total saturated fatty acid/total unsaturated fatty acid in test group II were significantly higher than those in the control group and test group I (P <0.05); The plasma glucose concentration of mares in test group II was significantly higher than that of control group and test group I at 1, 2 and 9 h after feeding (P <0.05), and significantly higher at 4 h after feeding (P <0.05); At 3 h and 6 h after feeding, test group II mares had significantly higher plasma free fatty acids and triglycerides concentrations than the control and test group I (P <0.05), at 4 h after feeding, the plasma triglyceride concentrations were significantly higher than the control and test I groups (P <0.05). Plasma low density lipoprotein and very low density lipoprotein concentrations were significantly higher in mares at 3 h and 9 h after feeding than in control and group I (P <0.05). The total number of OTUs was 3483, and the number of OTUs was 4984,5487, and 5158 in the control and test I and II, respectively. At the phylum level, the total abundance of Bacteroidetes and Firmicutes was more than 75%, and the test group Verrucomicrobia was significantly higher than the control group (P <0.05), and the test group II was significantly higher than the test group I (P <0.05). The Treponema_saccharophilum was significant difference in the feces of the control group (P <0.05); WCHB 1_41, kiritimatiellae, and Verrucomicrobia were significant difference of the test group II (P <0.05) and the fecal flora was mainly related to lipid synthesis, metabolism, and energy metabolism (P <0.05). Supplemental feeding can improve lactation volume of grazing Yili horses, improve the absorption and utilization of fatty acids, and improve the composition and diversity of horse milk and fecal flora to a certain extent.