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The application of digital technologies in the tax domain represents a confirmation of modernization and the turning point in the development of the state's tax function. Digitalization establishes a new paradigm of managing the tax system and significantly changes the tax-political reality. The potential of digital technologies is expressively transformative for proceedings of tax relation subjects and offers numerous possibilities for advancing the implementation of taxes and protection of the state's fiscal interest. The alterations brought about by digital technologies affect tax relations and the perception of the taxation phenomenon in the tax public opinion. The resulting digital innovations of the organization and business model of tax administration generate prerequisites for basic modification of tax procedures and taxpayers' behaviour in relation to tax compliance. Since the process of digitalizing the tax domain is complex and it seeks to raise taxation to a significantly higher level of development, it is necessary to timely discern, understand, and accept the advantages of this process, but also the accompanying difficulties and challenges, in order to adequately treat them. Digitalization of the taxation domain facilitates the work of tax authorities and compliance with tax regulations, strengthens the state's digital tax power, empowers the function of tax control of taxpayers, digitally and technologically shapes the tax reality, and gradually paves the "path" for a wider and deeper presence of tax authority in the taxpayer's life and business. By glorifying the positive points of digitalizing the tax domain and by expecting taxpayers to accept the projected digital-technological novelties in the tax sphere and to model the existing ways of fulfilling tax obligations, the need for a more comprehensive examination of the reverse side of tax digital novelties, the perception of unknown issues and a more subtle analysis of the uncertainty of their impact on our contemporary tax society and accepted democratic principles and social values, have generally been marginalized. More daring digressions from the discourse of the inevitability of digitalizing taxation which has become almost monopolistically established in numerous countries of the world are less represented, despite the well-known fact that with the increase of digital capacity, the tax domain becomes more exposed to risks. Superficial and uncritical adherence to digital-technological trends initiates a series of serious socio-ethical dilemmas in the tax area, which will most certainly be resolved only in the coming years. In the meantime, in circumstances in which the realization of extensive and substantive legal regulation of the use of digital achievements is incomparably slower than the dynamics of their creation for application in administering taxes, the position of taxpayers in the tax procedure will change significantly. The crucial question is whether taxpayers will accept this state of affairs with complete confidence in tax authorities or with an explicit prior request for a more detailed explanation of the effect of digital-technological changes, as a condition for accepting the remodelling of traditional tax relations and avoiding potential misunderstandings, uncertainties and problems.

Instrument transformers are a critical component of power plants, widely distributed due to their essential role in measuring and protecting the entire power system. Given their continuous exposure to environmental and electrical stresses, and the potential for explosive failures that can jeopardize power facility operations and disrupt power supply, regular electrical testing is crucial to assess their condition and operational reliability. One non-invasive testing method for instrument transformers is acoustic (ultrasound) analysis. This technique involves placing an acoustic piezo-sensor on the grounded wall of the transformer tank, at a safe distance from high-voltage components. Short-term data acquisition and subsequent analysis are then performed. This method is particularly advantageous for power plants as it requires minimal intervention and does not necessitate disconnecting the transformer from operation. Acoustic detection of partial discharges is often complemented by gas chromatographic analysis of insulating oil. This combined approach provides robust confirmation of partial discharge activity within the transformer's insulation system. This paper will present case studies of ultrasonic detection of partial discharges on 110 kV instrument transformers, where chemical analysis of oil samples corroborated the presence of these detrimental discharges.

The subject matter of analysis in this paper is the importance, value and reach of the principles of monetary law which are observed through the prism of their original field of application and social justification in the period of early development, and the subsequent establishment of this positive law branch in the legal order, which indisputably determined the axiology and confirmed the validity of the academic and practical study of this scientific discipline. The paper further examines the theses on the (un)sustainability of the original principles (lex monetae) in the circumstances of accession to the monetary union, as well as today's monetary flows that increasingly rely on the use of digital technologies and the advantages of monetary innovations. It inevitably raises the question of redefining the form, the content and reach of the principle of lex monetae to maintain monetary stability as a public good, but also to preserve monetary sovereignty protected by the central bank as the supreme monetary institution. In the process of implementing the principles of monetary law, in the circumstances of the information revolution, the legislator may face not only the challenges related to the impact of decentralized financial technologies on the protection of the rights of monetary users and public monetary management but also the challenges related to monetary innovations carried out by the central bank itself as the bearer of monetary sovereignty. In the author's opinion, central bank digital money represents an ingenious solution, a compromise that will simultaneously allow the central bank to preserve its position as the guardian of monetary sovereignty while at the same time legalizing the use of private digital money that is already accepted in some monetary jurisdictions as a legal tender. A big challenge in preserving the principle of lex monetae is the idea of a kind of incorporation of software code into a legal norm, which is a complex multidisciplinary issue that lawyers cannot resolve alone but in close cooperation with other experts in the economic and technical professions. At the same time, this process must take the form of a specific and legally rounded international initiative because only by the simultaneous application of primary monetary legislation (which has been regulating lex monetae in an identical way for decades) and secondary monetary legislation (which deals with the issue of its digitization) at all levels of state management can ensure monetary stability as a global public good. In the absence of coordinated international cooperation between central banks and other subjects of international monetary law, monetary instability would easily spill to another monetary jurisdiction.

Knowledge transfer is a key determinant of the development and implementation of innovations. It has not yet been sufficiently investigated how knowledge transfer can influence the environmental innovations of acquired companies in Serbia. This study investigates the role of knowledge transfer in acquired companies in Serbia and examines the impact of knowledge transfer on environmental innovation, i.e. on environmental innovation activities and strategy. The research was conducted based on the answers of 91 respondents, i.e. employees from five companies that were part of the acquisition process in Serbia. Collected primary data were processed in the SPSS program, using statistical analysis such as descriptive statistical analysis, correlational statistical analysis, and regression statistical analysis. Empirical results show that knowledge transfer in acquisition processes has a positive impact on the environmental innovations of acquired companies. The results show that knowledge transfer activities encourage the development and implementation of environmental innovations in those acquired companies. Since there is a lack of studies investigating the environmental orientation of acquired companies, this study contributes to the understanding of how knowledge sharing promotes the development of environmental innovations in acquired companies.

The subject of this paper is the introduction of the environmental protection concept in the central banking law to preserve natural resources and contribute to ensuring sustainable economic development. In that sense, the author will attempt to describe the potential contribution of green Central Bank legislation in managing and mitigating environmental issues, aiming to identify the ecological dimension of the European Central Bank (ECB) mandate, as the supreme monetary institution of the European Union (EU). The following text focuses on the functional analysis of the ECB's potential legal mandate for environmental activities, their scope, limitations, and practical justification where the introduction of these new activities must be carefully managed without creating a collision with its primary task of maintaining monetary and financial stability.

Basal cell carcinoma (BCC) is one of the most common malignant tumors in human medicine and the most common skin malignancy, with the largest number of lesions found on exposed parts of the skin, on the face, head, and neck. The average age of the patients is 60 years, with an increasing incidence in younger ages and an increased incidence in males. The incidence of BCC is increasing and doubles every 25 years. Annually, there are approximately 1,000,000 newly diagnosed cases worldwide. The frequency of malignant skin tumors depends on the influence of external factors such as ultraviolet radiation and other biological properties of the skin with a higher incidence in fair-skinned people (Fitzpatrick type I and type II skin types). BCC is a slow-growing malignant tumor that arises from the basal layer of the epidermis, the outer layer of hair follicles, or the sebaceous glands. BCC can be locally invasive and, if neglected, can infiltrate surrounding structures (muscles and cartilage) and vital structures, which can ultimately lead to death. The clinical presentation is very diverse and dependent on the histological subtype. Prevention is the most important and effective approach towards reducing the burden of BCC. The best treatment for BCC is surgical excision with confirmation and verification of surgical margins. The therapeutic goal is oncologic radical resection of the tumor, followed by reconstruction of the affected area for structure and optimal aesthetic result.

The competitiveness of the agri-food products is one of the key factors for promoting export and economic development, especially in developing countries. Competitiveness can be influenced by increasing productivity, applying modern knowledge, innovating processing capacities and producing a high-quality final product with high added value. The agriculture of Serbia is very important for economic growth. In order to improve the competitive advantage of the agri-food sector in foreign markets, it is important to increase its efficiency by introducing modern technologies and approaches. The subject of the paper is to examine the most important export agri-food products of Serbia, as well as the most important markets for their exports. Using the RCA and ARCA indices, the comparative advantages of these products in trade were examined, which is the goal of the research. Multiple regression was then also used to examine the impact on exports. Although significant agri-food products achieve comparative advantages, the decline in their competitiveness has a negative impact on exports. Low pricing policies, as well as inadequate product quality cannot maintain competitiveness in the long run. The structure of the export of agricultural products is also unsatisfactory, bearing in mind that they are products with a low level of processing, and low added value. Therefore, it is necessary to invest in modern equipment, develop innovative approaches, such as organic production and the introduction of innovations to improve quality standards, differentiate products and create a final product with high added value, as important prerequisites for improving competitiveness and promoting the export of the agri-food sector.

Introduction. Myocarditis is not a rare diagnosis, but its etiology often remains unknown as it requires extensive diagnostic work. Eosinophilic granulomatosis with polyangiitis (EGPA) or Churg-Strauss syndrome is a very rare systemic disease that is not easy to diagnose. Myocarditis in EGPA is uncommon and usually occurs in the late stages of the disease. Case report. A 22-year-old man was admitted with acute coronary syndrome. Using coronary angiography, the presence of stenoses on the epicardial coronary arteries was ruled out, and a working diagnosis of myocardial infarction with non-obstructive coronary arteries (MINOCA) was established. Then, we found inflammatory syndrome, eosinophilia, and a lot of systemic symptoms and signs. The diagnostic work included extensive laboratory tests, which ruled out infectious agents. Then, immunological tests, a computed tomography scan of the chest, cardiac magnetic reso-nance imaging (MRI) and a biopsy of the bone marrow, nasal mucosa, and skin were performed. We managed to establish the diagnosis of myopericarditis by cardiac MRI. The cause of myocarditis – EGPA, was found only after the histopathological finding of the skin biopsy, which enabled ad-equate immunosuppressive therapy. Conclusion. The accurate diagnosis was crucial for the correct, causal treatment of the patient, especially because he needed life-long immunosuppressive therapy. In order for such complex patients to receive adequate treatment, a multidisciplinary approach and perseverance in the diagnostic evaluation of the etiology of myocarditis are necessary.

The subject matter of analysis in this paper is the concept of monetary credibility and its important place in the normative framework of contemporary monetary law. The emphasis on the importance of credibility in public monetary management has been present as a basic axiological subordinate to the norms of monetary law since it was established as an independent and independent branch of the legal order. The content and direction of the monetary activities of the central bank, as the basic subject of monetary law, were mixed over time and adapted to new circumstances, which resulted in the expansion of the regulatory competences of the central bank, the emergence of new theories about the legal custody of money and establishing limits of legal responsibility in the work of monetary agents. Notably, the meaning of credibility has remained the same, being the final monetary legal thought of each epoch, the ideal and the ultimate purpose of this branch of law with all its institutes, principles and categories. Contemporary monetary law, which has sui generis legal sources, proves to be extremely flexible even in today's unstable social conditions and suitable for transformation into the law of necessity. In extraordinary circumstances, when it is required in a value context, it does not make credibility the primordial value of public management of every institution. Thus, the central bank remains in the central position.

Power transformers represent one of the most important components in terms of generation, transmission and distribution of electrical power. Precisely for this reason, it is necessary to pay some attention in terms of preventive electrical measurements that should be done in order to have an adequate insight into their condition, avoid unwanted breakdowns and thus ensure stable and reliable operation of the entire power system. However, there are situations when power transformers fail due to various factors. In such cases, depending on which protection has reacted and preemptively switched off the observed transformer, and especially in the case of an outage due to the differential protection of the transformer, it is necessary to carry out certain tests before possible reconnection in order to assess the reason for the outage and the continued ability of the transformer itself to work. Electrical tests should be preceded by sampling oil from the transformer (and/or gas and oil from the Buchholz relay) for chemical analysis by the gas chromatography method. The results of the chemical analysis of the oil sample can express doubts about possible irregularities that may be a problem for further normal operation of the transformer and such situations are followed by certain electrical tests whose results in most cases will give a better insight into the state of the transformer itself. This paper will give examples of the results of electrical measurements (most often insulation resistance and dielectric loss factor of windings, magnetizing currents and ohmic resistance of windings) made after power transformers were out of operation and measurements after bad results of chemical analysis of oil samples.

In recent years, there has been an increase in the agrarian budget and subsidies in agriculture, as well as lending to farmers by commercial banks. The goal of the work is to shed light on trends that indicate importance of financing agriculture for the economic development of the Republic of Serbia. The Kruskal-Wallis test was used to compare subsidies in agriculture in relation to other economic activities, as well as to compare agricultural lending between commercial banks, while the Friedman test was used to examine the lending of observed banks. The results showed that subsidies in agriculture are higher compared to other economic activities, and that they are growing, as well as the entire agricultural budget, especially in recent years, when they reach record amounts. The same case was recorded in lending to farmers by commercial banks. The increase in agricultural financing and lending was accompanied by an increase in agricultural production and GVA of agriculture. It is concluded that adequate financing of agriculture has a positive impact on both agriculture and the overall economic development of the Republic of Serbia.

Introduction/Objective. Artificial enamel caries lesions are commonly created to simulate in vivo caries development and to examine the effect of non-invasive and microinvasive approaches in treatment of initial caries lesions. The objective of the present study was to compare three different demineralizing solutions and exposing times in terms of the formation of artificial white spot lesions and to evaluate their demineralization effect through scanning electron microscopy observations. Methods. Twenty intact human premolars, extracted for orthodontic reasons, were thoroughly cleaned, stored in 0.1% thymol solution at room temperature and cut at the cementoenamel junction before demineralizing process. The specimens were randomly divided into three experimental groups, according to the used demineralization agent and the time of exposure: Group I (acetic acid; pH = 4.4; 96 hours); Group II (lactic acid; pH = 4.5; 120 hours); Group III (Lactic acid; pH = 4.3; 504 hours) and one control group (saline). After demineralisation, macroscopic appearance was checked and all specimens were observed under scanning electron microscope to evaluate the enamel characteristics and caries lesion depths. Results. In Group I and II enamel subsurface porosity with dissolution of enamel crystals is detected and the mean depths of white spot lesions were 48.55 μm (SD = 1.11) and 43.23 μm (SD = 6.74), respectively. In Group III structural integrity of enamel surface was not preserved. Conclusion. Demineralizing solutions used in experimental groups I and II resulted in artificial initial caries lesions with satisfactory characteristics and similar appearance on scanning electron microscopy. The outcome of demineralizing process which lasted 504 hours were cavitated enamel lesions.

Polysynaptic activity is necessary to engage the neural circuitry that controls the motor behaviour and is crucial to the recovery after spinal cord injury (SCI) [1]. Polysynaptic responses can be elicited with spinal cord stimulation, and there are few reports on these types of responses in human electrophysiology, most of them describing them as constant to fixed stimuli. However, we have observed that the responses fluctuate in amplitude and time. Amplitude variations can be analysed with statistical methods. However, time fluctuations are more complex due to the multiple parameters involved. This work describes a methodology to analyse the time fluctuation in the responses of each pulse. It is based on the calculation of the signal temporal centroid, representing the whole activity, weighted by its latency, in a single time value. This value is then used to model the temporal fluctuation with linear regression. The methodology was verified with an electromyography dataset from a discomplete spinal cord injured patient with spinal cord stimulation. The parameter is able to follow small changes in the responses' distribution. Examples of how the temporal centroid and linear model identify the fluctuations are presented. Once fitted in a linear model, the fluctuation coefficient describes time fluctuations in the interneuron processing and, together with amplitude metrics, can characterise changes in polysynaptic responses during the application of fixed stimulation parameters.

Purpose: The intestinal immune compartment is increasingly recognized as an important player in central nervous system (CNS) autoimmunity. We have recently reported that oral administration of the free fatty acid receptor 2 (FFAR2) agonist Cpd1 in the inductive phase of experimental autoimmune encephalomyelitis (EAE) in rats ameliorates the disease by stimulating the regulatory immune response in the intestine., Method: Here, the effects of Cpd1 on the gut microbiota and short-chain fatty acid (SCFA) composition were investigated in the same experimental system., Finding: Increased levels of the phylum Proteobacteria, the class Gammaproteobacteria, the orders Burkholderiales and Erysipelotrichales, the families Sutterellaceae and Erysipelotrichaceae, and the genera Parasutterella and Faecalibaculum were observed in agonist-treated rats. The genera Allobaculum and Ileibacterium were only detected in the agonist-treated group. The treatment led to changes in the functional profile of the gut microbiota both in the KEGG orthologous pathways and in the clusters of orthologous genes. In addition, an altered profile of intestinal SCFA content was observed in the agonist-treated group., Conclusion: The effects of Cpd1 on the gut microbiota and SCFA composition are relevant to the observed treatment benefit of FFAR2 agonism in the EAE model during the inductive phase of the disease., (© 2025 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

This study aimed to determine the prevalence of carcass bruising in Simmental cross-breed bulls and to characterize the bruises in terms of number, size, shape, severity, and the affected region of the carcass. In addition, the risk factors related to the pre-harvested and harvested phase of beef production and meat quality parameters, as well, were investigated. The prevalence of bruised carcasses was 40.6% (95% confidence interval, CI = 35.4-46.0%). The main risk factors related to carcass bruising were procurement of the bulls from the auction markets (odds ratio, OR = 2.94, 95% CI = 1.65-5.26) compared to the bulls that came directly from the farms and inadequate practice in the combined type of slaughterhouses (type A: OR = 6.86, 95% CI = 3.53-13.37; type B: OR = 4.76, 95% CI = 2.26-10.01) relative to the beef-only slaughterhouses (P = 0.0001). Out of the total investigated bruises, 40.7% were severe, affecting muscular parts and mainly localized on the rear parts of the carcasses. The probability of severe bruises was higher in bulls with at least one large-sized bruise than in bulls without bruises of that size (OR = 3.10, 95% CI = 1.42-6.78, P = 0.005). Concerning the risk factors, the dark cutting occurrence was significantly lower in the bull's carcasses originating from the farms and completely absent in beef-only slaughterhouses (P = 0.001). Improvement of facilities and equipment, avoiding transport through markets, and training of staff in terms of animal welfare are crucial in obtaining a concept of safe and better quality food., Competing Interests: Declarations. Competing interests: The authors declare no competing interests.. Animal ethics declaration: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Recurrent vulvovaginal candidosis (RVVC) is a chronic infection affecting 8-10% of women worldwide. Biofilm production of the infecting species and reduced sensitivity to antimycotics could contribute to the recurrence of this infection. This study aimed to examine the biofilm production ability and antifungal susceptibility of genital yeast isolates to determine their virulence potential., Methods: Matrix-assisted laser desorption in ionization-time of flight mass spectrometry (MALDI-TOF MS) was used to identify 300 Candida species. Using crystal violet method, strains were categorized into non-producers, weak, moderate, and strong biofilm producers (BFP). Antifungal susceptibility testing was performed using commercial Integral System YEASTS Plus test (ISYPT) and broth microdilution method (BMM)., Results: MALDI-TOF MS identified 150 Candida albicans, 124 non-albicans Candida (NAC), and 26 Saccharomyces cerevisiae strains. Within 138 (46.0%) BFP, 23 (16.7%) were strong, 44 (31.9%) moderate, and 71 (51.4%) weak. BMM was done for 43 BFP selected isolates with nystatin MIC ˃1.25 μl, fluconazole MIC ˃64 μl, and clotrimazole MIC ˃1.0 μl determined by ISYPT. Compared to all examined isolates, BMM confirmed that: i) C. albicans and NAC BFP showed low sensitivity to fluconazole (12% and 4%, respectively); ii) all BFP showed low sensitivity to nystatin (12.7% C. albicans, 14.5% NAC, and 23.1% S. cerevisiae); iii) clotrimazole in vitro was the most efficient regarding C. albicans and S. cerevisiae strains, but in 4.0% NAC BFP for this antimycotic higher MIC was established., Conclusion: Novel antimycotics or possible combinations of antifungal agents and natural products could be a new treatment option for RVVC., Competing Interests: Declarations. Conflict of interest: The authors have no conflict of interest., (© 2024. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

This study aimed to determine concentrations of 29 elements in the gills and liver as well as biomarker response in gills, liver, and blood of European chub from Pek River (exposed to long-term mining activities), and to compare these findings with individuals from Ibar River (influenced by emission of treated municipal wastewater) and Kruščica reservoir (source of drinking water) using inductively-coupled plasma optical emission spectrometry (ICP-OES). The metal pollution index (MPI) was also calculated. Supporting analyses for the detection of the municipal wastewater presence at investigated localities included analyses of microbiological indicators (total coliforms and Escherichia coli) of faecal pollution. We have assessed biomarker responses from molecular to organism level using the condition index, comet assay, micronucleus test, oxidative stress parameters, histopathological alterations, and fluorescence spectroscopy parameters. Multibiomarker analysis was summarized by Integrated Biomarker Response v2 (IBRv2). Among these locations, Kruščica exhibited the lowest, whereas the Pek River displayed the highest values for both categories of indicator bacteria. Due to the porphyry copper ores mining, individuals from Pek River had several times higher Cu concentrations in both gills and liver compared to the other localities which was confirmed by biomarker responses and IBRv2 value. On the contrary, fish from Kruščica reservoir were the least affected by elemental pollution which is also confirmed by low MPI and IBRv2 values. Responses of biomarkers correspond to the elemental accumulation in the liver and gills of the Ibar River are positioned between the Pek River and Kruščica reservoir. Of all the biomarkers analyzed in this study, the condition index was the least sensitive. The results of this study showed that fluorescence spectroscopy may be a method for fast screening of structural changes in gills caused by the pollution burden., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Type 1 diabetes (T1D) is an autoimmune disease with a strong chronic inflammatory component. One possible strategy for the treatment of T1D is to stimulate the regulatory arm of the immune response, i.e. to promote the function of tolerogenic dendritic cells (tolDC) and regulatory T cells (Treg). Since both cell types have been shown to be responsive to the aryl hydrocarbon receptor (AHR) activation, we used a recently characterized member of a new class of fluorescent AHR ligands, AGT-5, to modulate streptozotocin-induced T1D in C57BL/6 mice. Prophylactic oral administration of AGT-5 reduced hyperglycemia and insulitis in these mice. Phenotypic and functional analysis of cells in the pancreatic infiltrates of AGT-5-treated mice (at the early phase of T1D) revealed a predominantly anti-inflammatory environment, as evidenced by the upregulation of tolDC and Treg frequency, while CD8 + cell, Th1 and Th17 cells were significantly reduced. Similarly, AGT-5 enhanced the proportion of Treg and tolDC in small intestine lamina propria and suppressed the activation status of antigen-presenting cells through down-regulation of co-stimulatory molecules CD40, CD80 and CD86. The expression levels of Cyp1a1, controlled by the AHR, were increased in CD4 + , CD8 + and Treg, confirming the AHR-mediated effect of AGT-5 in these cells. Finally, AGT-5 stimulated the function of regulatory cells in the pancreatic islets and lamina propria by upregulating indoleamine 2,3-dioxigenase 1 (IDO1) in tolDC. These findings were supported by the abrogation of AGT-5-mediated in vitro effects on DC in the presence of IDO1 inhibitor. AGT-5 also increased the expression of CD39 or CD73 ATP-degrading ectoenzymes by Treg. The increase in Treg is further supported by the upregulated frequency of IL-2-producing type 3 innate lymphoid cells (ILC3) in the lamina propria. Anti-inflammatory effects of AGT-5 were also validated on human tonsil cells, where in vitro exposure to AGT-5 increased the proportion of immunosuppressive dendritic cells and ILC3. These results suggest that AGT-5, by stimulating AHR, may promote a general immunosuppressive environment in the pancreas and small intestine lamina propria at the early phase of disease, and thereby inhibit the severity of T1D in mice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jonić, Koprivica, Kyrkou, Bistas, Chatzigiannis, Radulović, Pilipović, Jovanović, Jovanović, Dimitrijević, Tzakos and Stojanović.)

Algal biomass is a viable source of chemicals and metabolites for various energy, nutritional, medicinal and agricultural uses. While stresses have commonly been used to induce metabolite accumulation in microalgae in attempts to enhance high-value product yields, this is often very detrimental to growth. Therefore, understanding how to modify metabolism without deleterious consequences is highly beneficial. We demonstrate that low-doses (1-5 Gy) of ionizing radiation in the X-ray range induces a non-toxic, hormetic response in microalgae to promote metabolic activation. We identify specific radiation exposure parameters that give reproducible metabolic responses in Chlorella sorokiniana caused by transcriptional changes. This includes up-regulation of >30 lipid metabolism genes, such as genes encoding an acetyl-CoA carboxylase subunit, phosphatidic acid phosphatase, lysophosphatidic acid acyltransferase, and diacylglycerol acyltransferase. The outcome is an increased lipid yield in stationary phase cultures by 25% in just 24 hours, without any negative effects on cell viability or biomass., (© 2024. The Author(s).)

Aryl Hydrocarbon Receptor (AHR) ligands, upon binding, induce distinct gene expression profiles orchestrated by the AHR, leading to a spectrum of pro- or anti-inflammatory effects. In this study, we designed, synthesized and evaluated three indole-containing potential AHR ligands (FluoAHRL: AGT-4, AGT-5 and AGT-6). All synthesized compounds were shown to emit fluorescence in the near-infrared. Their AHR agonist activity was first predicted using in silico docking studies, and then confirmed using AHR luciferase reporter cell lines. FluoAHRLs were tested in vitro using mouse peritoneal macrophages and T lymphocytes to assess their immunomodulatory properties. We then focused on AGT-5, as it illustrated the predominant anti-inflammatory effects. Notably, AGT-5 demonstrated the ability to foster anti-inflammatory regulatory T cells (Treg) while suppressing pro-inflammatory T helper (Th)17 cells in vitro. AGT-5 actively induced Treg differentiation from naïve CD4 + cells, and promoted Treg proliferation, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) expression and interleukin-10 (IL-10) production. The increase in IL-10 correlated with an upregulation of Signal Transducer and Activator of Transcription 3 (STAT3) expression. Importantly, the Treg-inducing effect of AGT-5 was also observed in human tonsil cells in vitro. AGT-5 showed no toxicity when applied to zebrafish embryos and was therefore considered safe for animal studies. Following oral administration to C57BL/6 mice, AGT-5 significantly upregulated Treg while downregulating pro-inflammatory Th1 cells in the mesenteric lymph nodes. Due to its fluorescent properties, AGT-5 could be visualized both in vitro (during uptake by macrophages) and ex vivo (within the lamina propria of the small intestine). These findings make AGT-5 a promising candidate for further exploration in the treatment of inflammatory and autoimmune diseases.

Ethyl pyruvate (EP) is a redox-active compound that has been previously shown to be effective in restraining immune hyperactivity in animal models of various autoimmune and chronic inflammatory diseases. Importantly, EP has also been proven to have a potent tolerogenic effect on dendritic cells (DCs). Here, the influence of EP on the signaling pathways in DCs relevant for their tolerogenicity, including anti-inflammatory NRF2 and pro-inflammatory NF-κB, was explored. Specifically, the effects of EP on DCs obtained by GM-CSF-directed differentiation of murine bone marrow precursor cells and matured under the influence of lipopolysaccharide (LPS) were examined via immunocytochemistry and RT-PCR. EP counteracted LPS-imposed morphological changes and down-regulated the LPS-induced expression of pro-inflammatory mediators in DCs. While it reduced the activation of NF-κB, EP potentiated NRF2 and downstream antioxidative molecules, thus implying the regulation of NRF2 signaling pathways as the major reason for the tolerizing effects of EP on DCs.

We have recently characterized experimental autoimmune encephalomyelitis (EAE) induced in DA rats with spinal cord homogenate without complete Freund's adjuvant (CFA). The main advantage of this multiple sclerosis model is the lack of CFA-related confounding effects which represent the major obstacles in translating findings from EAE to multiple sclerosis. Here, antigen specificity of the cellular and humoral immune response directed against the central nervous system was explored. The reactivity of T and B cells to myelin basic protein, myelin oligodendrocyte glycoprotein, and β-synuclein was detected. Having in mind that reactivity against β-synuclein was previously associated with autoimmunity against the brain, the infiltration of immune cells into different brain compartments, i.e. pons, cerebellum, hippocampus, and cortex was determined. T cell infiltration was observed in all structures examined. This finding stimulated investigation of the effects of immunization on DA rat behavior using the elevated plus maze and the open field test. Rats recovered from EAE displayed increased anxiety-like behavior. These data support CFA-free EAE in DA rats as a useful model for multiple sclerosis research., Competing Interests: Declaration of competing interest None., (Copyright © 2024 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)

In this study, the concentrations of metals and trace elements (As, Cd, Co, Cr, Cu, Hg, Ni, Pb and Zn) were determined in the muscle tissue of adult roach and white bream at two different sites in the Belgrade section of the Danube. Twenty-six fatty acids, consisting of nine saturated FA (SFAs), seven monosaturated FA (MUFAs) and ten polysaturated FA (PUFAs), were identified. The analysis of the concentration of metals and trace elements of the roach and white bream showed species-specific differences in their bioaccumulation. Four of all elements analyzed (As, Hg, Ni and Pb) correlated significantly with the changes in FA profiles in fish from both sampling sites, with the exception of Cu, which correlated with the FA profile at the site before, and Zn, whose concentration influenced the FA profile at the site after wastewater discharges. The lower PUFA content in the fish from a site under higher environment pressure could indicate that the fish are stressed. The results suggest that changes in lipid composition may be one of the protective mechanisms of cells to cope with anthropogenic stressors.

Complete Freund's adjuvant (CFA) is used as a standard adjuvant for the induction of experimental autoimmune encephalomyelitis (EAE), the most commonly used animal model in multiple sclerosis studies. Still, CFA induces glial activation and neuroinflammation on its own and provokes pain. In addition, as CFA contains Mycobacteria, an immune response against bacterial antigens is induced in parallel to the response against central nervous system antigens. Thus, CFA can be considered as a confounding factor in multiple sclerosis-related studies performed on EAE. Here, we discuss the effects of CFA in EAE in detail and present EAE variants induced in experimental animals without the use of CFA. We put forward CFA-free EAE variants as valuable tools for studying multiple sclerosis pathogenesis and therapeutic approaches., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lazarević, Stanisavljević, Nikolovski, Dimitrijević and Miljković.)

The goal of this study conducted in Serbia was to detect HEV in pig liver samples from slaughterhouses, retail outlets, and environmental swabs over the course of a year. All positive HEV samples were measured and expressed as HEV gene copy numbers per gram of sample, and a representative number of samples were sequenced using the Sanger approach. A total of 45 HEV-positive samples were re-amplified using nested RT-PCR employing CODEHOP primers targeting ORF2 (493 nucleotides). The average prevalence of the HEV genotype 3 in all pig liver samples from the slaughterhouses was 29%, while HEV prevalence was 44% in liver samples from animals younger than 3 months. HEV RNA was found in thirteen out of sixty (22%) environmental swab samples that were taken from different surfaces along the slaughter line. Our findings confirmed seasonal patterns in HEV prevalence, with two picks (summer and winter periods) during the one-year examination. Among HEV-positive samples, the average viral particles for all positive liver samples was 4.41 ± 1.69 log 10 genome copies per gram. Phylogenetic analysis revealed the majority of HEV strains (43/45) from Serbia were grouped in the HEV-3a subtype, while two strains were classified into the HEV-3c subtype, and one strain could not be classified into any of the HEV-3 subtypes.

Experimental autoimmune encephalomyelitis (EAE) induced in inbred rodents, i.e., genetically identical animals kept under identical environmental conditions, shows variable clinical outcomes. We investigated such variations of EAE in Dark Agouti rats immunized with spinal cord homogenate and identified four groups: lethal, severe, moderate, and mild, at day 28 post immunization. Higher numbers of CD4 + T cells, helper T cells type 1 (Th1) and 17 (Th17) in particular, were detected in the spinal cord of the severe group in comparison with the moderate group. In addition, increased proportion of Th1 and Th17 cells, and heightened levels of interferon (IFN)-γ and interleukin (IL)-6 were detected in the small intestine lamina propria of the severe group. A selective agonist of free fatty acid receptor type 2 (Ffar2) applied orally in the inductive phase of EAE shifted the distribution of the disease outcomes towards milder forms. This effect was paralleled with potentiation of intestinal innate lymphoid cells type 3 (ILC3) regulatory properties, and diminished Th1 and Th17 cell response in the lymph nodes draining the site of immunization. Our results suggest that different clinical outcomes in DA rats are under determinative influence of intestinal ILC3 activity during the inductive phase of EAE., (© 2024. The Author(s).)

Iridoids, a class of atypical monoterpenes, exhibit exceptional diversity within the Nepeta genus (subfam. Nepetoidae, fam. Lamiaceae).The majority of these plants produce iridoids of the unique stereochemistry, with nepetalactones (NLs) predominating; however, a few Nepeta species lack these compounds. By comparatively analyzing metabolomics, transcriptomics, gene co-expression, and phylogenetic data of the iridoid-producing N. rtanjensis Diklić & Milojević and iridoid-lacking N. nervosa Royle & Bentham, we presumed that one of the factors responsible for the absence of these compounds in N. nervosa is iridoid synthase (ISY). Two orthologues of ISY were mined from leaves transcriptome of N. rtanjensis ( Nr PRISE1 and Nr PRISE2), while in N. nervosa only one ( Nn PRISE) was identified, and it was phylogenetically closer to the representatives of the Family 1 isoforms, designated as P5βRs. Organ-specific and MeJA-elicited profiling of iridoid content and co-expression analysis of IBG candidates, highlighted NrPRISE2 and NnPRISE as promising candidates for ISY orthologues, and their function was confirmed using in vitro assays with recombinant proteins, after heterologous expression of recombinant proteins in E. coli and their His-tag affinity purification. Nr PRISE2 demonstrated ISY activity both in vitro and likely in planta , which was supported by the 3D modeling and molecular docking analysis, thus reclassification of Nr PRISE2 to Nr ISY is accordingly recommended. Nn PRISE also displays in vitro ISY-like activity, while its role under in vivo conditions was not here unambiguously confirmed. Most probably under in vivo conditions the Nn PRISE lacks substrates to act upon, as a result of the loss of function of some of the upstream enzymes of the iridoid pathway. Our ongoing work is conducted towards re-establishing the biosynthesis of iridoids in N. nervosa ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Aničić, Matekalo, Skorić, Gašić, Nestorović Živković, Dmitrović, Božunović, Milutinović, Petrović, Dimitrijević, Anđelković and Mišić.)

(1) Background: Vulvovaginal candidosis (VVC) is a major therapy issue due to its high resistance rate and virulence factors such as the ability to form biofilms. The possibility of combining commonly used antifungals with natural products might greatly improve therapeutic success. (2) Methods: A total of 49 vulvovaginal isolates, causative agents of recurrent VVC, were tested for their susceptibility to fluconazole, nystatin, and Melissa officinalis essential oil (MOEO). This examination included testing the antibiofilm potential of antifungals and MOEO and the determination of their types of interaction with mature biofilms. (3) Results: Antimicrobial testing showed that 94.4% of the Candida albicans isolates and all the Candida krusei isolates were resistant to fluconazole, while all strains showed resistance to nystatin. The same strains were susceptible to MOEO in 0.156-2.5 mg/mL concentrations. Additionally, the results revealed very limited action of fluconazole, while nystatin and MOEO reduced the amount of biofilm formed by as much as 17.7% and 4.6%, respectively. Testing of the combined effect showed strain-specific synergistic action. Furthermore, the lower concentrations exhibited antagonistic effects even in cases where synergism was detected. (4) Conclusions: This study showed that MOEO had a very good antibiofilm effect. However, combining MOEO with antimycotics demonstrated that the type of action depended on the choice of antifungal drugs as well as the applied concentration.

The interactions of drugs with iron are of interest in relation to the potential effects of iron-rich foods and iron supplements on sorption and bioavailability. Doxycycline (DOX), a member of the tetracycline class of broad-spectrum antibiotics, is frequently administered by oral route. In the digestive tract, DOX can be exposed to iron at different pH values (stomach pH 1.5-4, duodenum pH 5-6, distal jejunum and ileum pH 7-8). In relation to this, we analyzed the impact of pH on Fe 3+ -DOX complex formation. The optimal conditions for Fe 3+ -DOX complex formation are pH = 4 and [Fe 3+ ]/[DOX] = 6 molar ratio. HESI-MS showed that Fe 3+ -DOX complex has 1:1 stoichiometry. Raman spectra of Fe 3+ -DOX complex indicate the presence of two Fe 3+ -binding sites in DOX structure: tricarbonylamide group of ring A and phenolic-diketone oxygens of BCD rings. The Fe 3+ -DOX complex formed at pH = 4 is less susceptible to oxidation than DOX at this pH. The increase of pH induces the decomposition of Fe 3+ -DOX complex without oxidative degradation of DOX. The pH dependence of Fe 3+ -DOX complex formation may promote unwanted effects of DOX, impeding the absorption that mainly takes place in duodenum. This could further result in higher concentrations in the digestive tract and to pronounced impact on gut microbiota., (© 2023. The Author(s), under exclusive licence to Society for Biological Inorganic Chemistry (SBIC).)

Background: The goal of this research is to identify correlations of motivation and physical self-concept with physical activity among students of younger school age, as well as the level of prediction of motivation and physical self-concept with physical activity of students in physical education classes., Methods: The sample of respondents consisted of 411 students of the third and fourth grades from the territory of the Zlatibor district. A modified Self-Regulation Questionnaire was used to assess students' motivational orientations, while appropriate subscales of the Self-perception Profile for Children measuring instrument were used to assess physical self-concept. Physical activity is shown as volume and intensive physical activity (vigorous physical activity (VPA)), measured with a Suunto memory belt pedometer and heart-rate monitor., Results: Boys' motivational predictor variables accounted for 14% (volume) and 28% (VPA) of their physical activity in class, with intrinsic motivation, introjective regulation (just for the level of physical activity), and identified regulation as the most important determinants of physical activity. For girls, the identified regulation variable (from the system of motivational predictor variables) was shown to be the primary predictor variable on both criterion variables (R2 = 0.34 and 0.36)., Conclusion: The teaching of physical education for students of younger school age should be conceived by creating a motivational climate, in order to encourage physical activity.

Herein, upgraded chloroquine (CQ) derivatives capable of overcoming Plasmodium resistance and, at the same time, suppressing excessive immune response and risk of concurrent bacteremia were developed. Twelve new ferrocene- CQ hybrids tethered with a small azathia heterocycle (1,3-thiazolidin-4-one, 1,3-thiazinan-4-one, or 5-methyl-1,3-thiazolidin-4-one) were synthesized and fully characterized. All hybrids were evaluated for their in vitro antiplasmodial, antimicrobial, and immunomodulatory activities. Additional assays were performed on selected hybrids to gain insights into their mode of action. Although only hybrid 4a was more potent than the parent drug toward CQ -resistant Dd2 Plasmodium falciparum strain, several other hybrids (such as 6b , 6c , and 6d ) manifested substantially improved antimicrobial and immunomodulatory properties. Interesting structure-activity relationship data were obtained, hinting at future research for the development of new multitarget chemotherapies for malaria and other infectious diseases complicated by drug resistance, bacterial co-infection, and immune-driven pathology issues.

Metabolism of metals in microalgae and adaptation to metal excess are of significant environmental importance. We report a three-step mechanism that the green microalga Chlorella sorokiniana activates during the acquisition of and adaptation to manganese (Mn), which is both an essential trace metal and a pollutant of waters. In the early stage, Mn2+ was mainly bound to membrane phospholipids and phosphates in released mucilage. The outer cell wall was reorganized and lipids were accumulated, with a relative increase in lipid saturation. Intracellular redox settings were rapidly altered in the presence of Mn excess, with increased production of reactive oxygen species that resulted in lipid peroxidation and a decrease in the concentration of thiols. In the later stage, Mn2+ was chelated by polyphosphates and accumulated in the cells. The structure of the inner cell wall was modified and the redox milieu established a new balance. Polyphosphates serve as a transient Mn2+ storage ligand, as proposed previously. In the final stage, Mn was stored in multivalent Mn clusters that resemble the structure of the tetramanganese-calcium core of the oxygen-evolving complex. The present findings elucidate the bioinorganic chemistry and metabolism of Mn in microalgae, and may shed new light on water-splitting Mn clusters., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The aim of this study was to determine accumulation of heavy metals and metalloids which are widely distributed in the environment and in food chain using wild edible mushrooms belonging to the Boletaceae family mushrooms. In addition, methanol extracts of mushrooms were tested for in vitro protective effect by the cytochalasin-B blocked micronucleus (CBMN) assay using chromosome aberrations in human peripheral lymphocytes as a model. The genotoxic activity of methanol extracts prepared at 4 different concentrations (1, 2, 3 or 6 µg/ml) was examined using amifostine and mitomycin C as positive controls. Extracts of species B. regius and B. edulis exhibited the greatest reduction in the frequency of micronuclei (MN). Extract of B. regius at concentrations of 2 µg/ml showed the highest decrease in number of MN. In comparison, extract of mushroom B. edulis at a concentration of 3 µg/ml displayed less reduction. However, as heavy metals and metalloids are found in mushrooms, another aim was to examine whether these agents affected genotoxicity. Principal component analysis (PCA) identified clustering differences between control and heavy metals and metalloids groups and might explain the influence of heavy element content and genotoxic activity in mushrooms.

A survey was undertaken to determine the overall prevalence of Yersinia enterocolitica in pigs of slaughter age and to characterize the isolates in relation to bio-serotype, the presence of virulence genes, genetic diversity, and antimicrobial resistance. Moreover, possible risk factors associated with Y. enterocolitica infection during the pre-harvested and harvested phase of pig production were studied. The overall Y. enterocolitica prevalence in the pigs was 10.4% (95% confidence interval, CI = 8.5-12.3%). The most common Y. enterocolitica bio-serotype was 4/O:3, accounting for 81.6% of investigated isolates. The pathogenicity of 63 Y. enterocolitica 4/O:3 isolates, originating from all infected farms, was confirmed by the presence of both the ail and ystA virulence-associated genes and the absence of ystB gene (100%). Characterization with PFGE of 63 confirmed Y. enterocolitica 4/O:3 isolates identified five different genotypes with shared identical genetic profiles (100% similarity) within each genotype. Isolates originating from farrow-to-finish farms were only resistant to ampicillin, while resistance to nalidixic acid, tetracycline, and chloramphenicol at fattening farms was also observed. Risk factors related to Y. enterocolitica pig infection include fattening farms (odds ratio, OR = 2.3, 95% CI = 1.4-3.8, P < 0.001), a 3-6 h lairage period (OR = 1.6, 95% CI = 1.0-2.6, P = 0.035) and winter season (OR = 3.8, 95% CI = 2.0-7.4, P < 0.001). In addition to the overall characterization of Y. enterocolitica isolates, identification of the main risks associated with infection allows better application of preventive measures to reduce the occurrence and distribution of Y. enterocolitica infection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Gallic acid is a phenolic acid present in various plants, nuts, and fruits. It is well known for its anti-oxidative and anti-inflammatory properties. The phenethyl ester of gallic acid (PEGA) was synthesized with the aim of increasing the bioavailability of gallic acid, and thus its pharmacological potential. Here, the effects of PEGA on encephalitogenic cells were examined, and PEGA was found to modulate the inflammatory activities of T cells and macrophages/microglia. Specifically, PEGA reduced the release of interleukin (IL)-17 and interferon (IFN)-γ from T cells, as well as NO, and IL-6 from macrophages/microglia. Importantly, PEGA ameliorated experimental autoimmune encephalomyelitis, an animal model of chronic inflammatory disease of the central nervous system (CNS)-multiple sclerosis. Thus, PEGA is a potent anti-inflammatory compound with a perspective to be further explored in the context of CNS autoimmunity and other chronic inflammatory disorders.

Rosmarinic acid is a polyphenolic compound, abundantly present in herbs of the Lamiaceae family. The aim of the study was to evaluate the immunomodulatory properties of a recently developed phenethyl ester derivative of rosmarinic acid (PERA), with enhanced ability of diffusion through biological membranes, in an animal model of the central nervous system (CNS) autoimmunity. To this end, experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis was used. Daily subcutaneous administration of PERA (30 mg/kg) from day 7 to day 22 after immunization successfully ameliorated EAE induced in Dark Agouti rats, shortening the disease duration and reducing maximal, cumulative and mean clinical score. PERA efficiently reduced production of major encephalitogenic cytokines, interferon (IFN)-γ and interleukin (IL)-17, in immune cells from the CNS or the lymph nodes draining the site of immunization of EAE rats, as well as in CD4 + T cells purified from the lymph nodes. Also, PERA inhibited NO production in the CNS and the lymph nodes, as well as in macrophages and microglial cells. Finally, microglial ability to produce pro-inflammatory cytokines IL-6, and tumor necrosis factor (TNF) were also reduced by PERA. Our results clearly imply that PERA possesses anti-encephalitogenic properties. Thus, further studies on the relevance of the observed effects for the therapy of multiple sclerosis are warranted., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2022 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)

Prostate cancer is the second most commonly occurring cancer in men. Regardless of statistics, screening for prostate cancer is an individual decision and most male patients come for their first examination with an already developed disease, as they are not adequately informed. The study aimed to emphasize the importance of preventive tests for urological diseases in the Republic of Serbia, raise awareness about urinary problems, and present social marketing strategies for prevention. The results confirm the generally lower awareness of respondents under the age of 30, followed by those who finished university, go to the doctor two or three times a year, and receive information other than by watching TV. Implemented research indicates the influence of the marketing principles and social marketing strategies on possible target groups of the male population over 50, which is aimed at raising awareness of the importance of prevention of urological diseases and the expected changes in the health behavior of the target population., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Tamara Panajotović et al.)

It is well-known that mushrooms of the genus Lactarius constitute a natural food resource providing health benefits as a nutritient. This genus contains 4 mushrooms identified as L. deliciosus, L. volemus, L. sanguifluus, L. semisanguifluus and L. piperatus which were collected in Serbia. The aim of this study aimed was to identify and characterize the content of phenolic compounds and examine the antioxidant potential of 5 wild edible mushrooms. L. sanguifluus contained the highest content of total phenol compounds (75.25 mg gallic acid equivalents (GAE) per g dry extract weight (GAE/g DE) and exhibited the greatest antioxidant activity through the ability to remove radicals as evidenced by ABTS assay (8.99 mg of trolox equivalents (TE) per g dry extract weight (mg TE/g DE); total reducing power (TRP) assay mg ascorbic acid equivalents per mg of dry extract weight (0.42 mg AAE/g DE) and CUPRAC (14.23 mg TE /g DE). L. deliciosus methanolic extract produced greatest scavenging of the DPPH radical (46%). The methanol mushroom extracts were screened for in vitro antimicrobial activity against a panel of pathogenic bacterial strains using the microdilution method. Of all the extracts tested, L. sanguifluus extract showed the best antibacterial properties. The cytokinesis block micronucleus assay results for the examined mushrooms demonstrated that extracts at a concentration of 3 μg/ml decreased the number of micronuclei (MN) in the range of 19-49% which is significant bearing in mind that radioprotectant amifostine reduced the frequency of MN by only 16.3%. Data thus demonstrate that the 5 wild edible mushrooms of genus Lactarius contain constituents that are beneficial not only as nutrients but also have the potential as antioxidants, antibacterial and antigenotoxic properties.

The effects of a fructose-rich diet and chronic stress on copper metabolism in the kidneys are still understudied. We investigated whether fructose and/or chronic unpredictable stress modulate copper metabolism in a way that affects redox homeostasis, thus contributing to progression of metabolic disturbances in the kidney. We determined protein level of copper transporters, chaperones, and cuproenzymes including cytochrome c oxidase, as well as antioxidant enzymes function in the kidneys of male Wistar rats subjected to 20% liquid fructose supplementation and/or chronic stress. Liquid fructose supplementation increased level of copper chaperone of superoxide dismutase and decreased metallothionein level, while rendering the level of copper importer and copper chaperones involved in copper delivery to mitochondria and trans Golgi network unaffected. Stress had no effect on renal copper metabolism. The activity and expression of renal antioxidant enzymes remained unaltered in all experimental groups. In conclusion, fructose, independently of stress, decreased renal copper level, and modulated renal copper metabolism as to preserve vital cellular function including mitochondrial energy production and antioxidative defense, at the expense of intracellular copper storage.