Enhancer-promoter hubs organize transcriptional networks promoting oncogenesis and drug resistance.

Recent advances in high-resolution mapping of spatial interactions among regulatory elements support the existence of complex topological assemblies of enhancers and promoters known as enhancer-promoter hubs or cliques. Yet, organization principles of these multi-interacting enhancer-promoter hubs and their potential role in regulating gene expression in cancer remain unclear. Here, we systematically identify enhancer-promoter hubs in breast cancer, lymphoma, and leukemia. We find that highly interacting enhancer-promoter hubs form at key oncogenes and lineage-associated transcription factors potentially promoting oncogenesis of these diverse cancer types. Genomic and optical mapping of interactions among enhancer and promoter elements further show that topological alterations in hubs coincide with transcriptional changes underlying acquired resistance to targeted therapy in T cell leukemia and B cell lymphoma. Together, our findings suggest that enhancer-promoter hubs are dynamic and heterogeneous topological assemblies with the potential to control gene expression circuits promoting oncogenesis and drug resistance.

Unveiling the potential of a novel portable air quality platform for assessment of fine and coarse particulate matter: in-field testing, calibration, and machine learning insights.

Although low-cost air quality sensors facilitate the implementation of denser air quality monitoring networks, enabling a more realistic assessment of individual exposure to airborne pollutants, their sensitivity to multifaceted field conditions is often overlooked in laboratory testing. This gap was addressed by introducing an in-field calibration and validation of three PAQMON 1.0 mobile sensing low-cost platforms developed at the Mining and Metallurgy Institute in Bor, Republic of Serbia. A configuration tailored for monitoring PM2.5 and PM10 mass concentrations along with meteorological parameters was employed for outdoor measurement campaigns in Bor, spanning heating (HS) and non-heating (NHS) seasons. A statistically significant positive linear correlation between raw PM2.5 and PM10 measurements during both campaigns (R > 0.90, p ≤ 0.001) was observed. Measurements obtained from the uncalibrated NOVA SDS011 sensors integrated into the PAQMON 1.0 platforms exhibited a substantial and statistically significant correlation with the GRIMM EDM180 monitor (R > 0.60, p ≤ 0.001). The calibration models based on linear and Random Forest (RF) regression were compared. RF models provided more accurate descriptions of air quality, with average adjR2 values for air quality variables in the range of 0.70 to 0.80 and average NRMSE values between 0.35 and 0.77. RF-calibrated PAQMON 1.0 platforms displayed divergent levels of accuracy across different pollutant concentration ranges, achieving a data quality objective of 50% during both measurement campaigns. For PM2.5, uncertainty ( U r ) was below 50% for concentrations between 9.06 and 34.99 µg/m3 in HS and 5.75 and 17.58 µg/m3 in NHS, while for PM10, it stayed below 50% from 19.11 to 51.13 µg/m3 in HS and 11.72 to 38.86 µg/m3 in NHS.

Antimicrobial Resistance in Aquaculture: Risk Mitigation within the One Health Context.

The application of antimicrobials in aquaculture primarily aims to prevent and treat bacterial infections in fish, but their inappropriate use may result in the emergence of zoonotic antibiotic-resistant bacteria and the subsequent transmission of resistant strains to humans via food consumption. The aquatic environment serves as a potential reservoir for resistant bacteria, providing an ideal breeding ground for development of antimicrobial resistance (AMR). The mutual inter-connection of intensive fish-farming systems with terrestrial environments, the food processing industry and human population creates pathways for the transmission of resistant bacteria, exacerbating the problem further. The aim of this study was to provide an overview of the most effective and available risk mitigation strategies to tackle AMR in aquaculture, based on the One Health (OH) concept. The stringent antimicrobial use guidelines, promoting disease control methods like enhanced farm biosecurity measures and vaccinations, alternatives to antibiotics (ABs) (prebiotics, probiotics, immunostimulants, essential oils (EOs), peptides and phage therapy), feeding practices, genetics, monitoring water quality, and improving wastewater treatment, rather than applying excessive use of antimicrobials, can effectively prevent the development of AMR and release of resistant bacteria into the environment and food. The contribution of the environment to AMR development traditionally receives less attention, and, therefore, environmental aspects should be included more prominently in OH efforts to predict, detect and prevent the risks to health. This is of particular importance for low and middle-income countries with a lack of integration of the national AMR action plans (NAPs) with the aquaculture-producing environment. Integrated control of AMR in fisheries based on the OH approach can contribute to substantial decrease in resistance, and such is the case in Asia, where in aquaculture, the percentage of antimicrobial compounds with resistance exceeding 50% (P50) decreased from 52% to 22% within the period of the previous two decades.

Enhancer-promoter hubs organize transcriptional networks promoting oncogenesis and drug resistance.

Recent advances in high-resolution mapping of spatial interactions among regulatory elements support the existence of complex topological assemblies of enhancers and promoters known as enhancer-promoter hubs or cliques. Yet, organization principles of these multi-interacting enhancer-promoter hubs and their potential role in regulating gene expression in cancer remains unclear. Here, we systematically identified enhancer-promoter hubs in breast cancer, lymphoma, and leukemia. We found that highly interacting enhancer-promoter hubs form at key oncogenes and lineage-associated transcription factors potentially promoting oncogenesis of these diverse cancer types. Genomic and optical mapping of interactions among enhancer and promoter elements further showed that topological alterations in hubs coincide with transcriptional changes underlying acquired resistance to targeted therapy in T cell leukemia and B cell lymphoma. Together, our findings suggest that enhancer-promoter hubs are dynamic and heterogeneous topological assemblies with the potential to control gene expression circuits promoting oncogenesis and drug resistance.

Correlation between Radiological Characteristics, PET-CT and Histological Subtypes of Primary Lung Adenocarcinoma-A 102 Case Series Analysis.

Background and Objectives: Lung cancer is the second most common form of cancer in the world for both men and women as well as the most common cause of cancer-related deaths worldwide. The aim of this study is to summarize the radiological characteristics between primary lung adenocarcinoma subtypes and to correlate them with FDG uptake on PET-CT. Materials and Methods: This retrospective study included 102 patients with pathohistologically confirmed lung adenocarcinoma. A PET-CT examination was performed on some of the patients and the values of SUVmax were also correlated with the histological and morphological characteristics of the masses in the lungs. Results: The results of this analysis showed that the mean size of AIS-MIA (adenocarcinoma in situ and minimally invasive adenocarcinoma) cancer was significantly lower than for all other cancer types, while the mean size of the acinar cancer was smaller than in the solid type of cancer. Metastases were significantly more frequent in solid adenocarcinoma than in acinar, lepidic, and AIS-MIA cancer subtypes. The maximum standardized FDG uptake was significantly lower in AIS-MIA than in all other cancer types and in the acinar predominant subtype compared to solid cancer. Papillary predominant adenocarcinoma had higher odds of developing contralateral lymph node involvement compared to other types. Solid adenocarcinoma was associated with higher odds of having metastases and with higher SUVmax. AIS-MIA was associated with lower odds of one unit increase in tumor size and ipsilateral lymph node involvement. Conclusions: The correlation between histopathological and radiological findings is crucial for accurate diagnosis and staging. By integrating both sets of data, clinicians can enhance diagnostic accuracy and determine the optimal treatment plan.

FSP1 is a predictive biomarker of osteosarcoma cells' susceptibility to ferroptotic cell death and a potential therapeutic target.

Human osteosarcoma (OS) is a relatively rare malignancy preferentially affecting long body bones which prognosis is often poor also due to the lack of effective therapies. Clinical management of this cancer basically relies on surgical removal of primary tumor coupled with radio/chemotherapy. Unfortunately, most osteosarcoma cells are resistant to conventional therapy, with the undergoing epithelial-mesenchymal transition (EMT) giving rise to gene expression reprogramming, thus increasing cancer cell invasiveness and metastatic potential. Alternative clinical approaches are thus urgently needed. In this context, the recently described ferroptotic cell death represents an attractive new strategy to efficiently kill cancer cells, since most chemoresistant and mesenchymal-shaped tumors display high susceptibility to pro-ferroptotic compounds. However, cancer cells have also evolved anti-ferroptotic strategies, which somehow sustain their survival upon ferroptosis induction. Indeed, here we show that osteosarcoma cell lines display heterogeneous sensitivity to ferroptosis execution, correlating with the mesenchymal phenotype, which is consistently affected by the expression of the well-known anti-ferroptotic factor ferroptosis suppressor protein 1 (FSP1). Interestingly, inhibiting the activity or expression of FSP1 restores cancer cell sensitivity to ferroptosis. Moreover, we also found that: i) AKRs might also contribute to resistance; ii) NRF2 enhances FSP1 expression upon ferroptosis induction; while iii) p53 contributes to the regulation of FSP1 basal expression in OS cells.In conclusion, FSP1 expression can potentially be used as a valuable predictive marker of OS sensitivity to ferroptosis and as a new potential therapeutic target.

Microbial diversity in soils suppressive to Fusarium diseases.

Fusarium species are cosmopolitan soil phytopathogens from the division Ascomycota, which produce mycotoxins and cause significant economic losses of crop plants. However, soils suppressive to Fusarium diseases are known to occur, and recent knowledge on microbial diversity in these soils has shed new lights on phytoprotection effects. In this review, we synthesize current knowledge on soils suppressive to Fusarium diseases and the role of their rhizosphere microbiota in phytoprotection. This is an important issue, as disease does not develop significantly in suppressive soils even though pathogenic Fusarium and susceptible host plant are present, and weather conditions are suitable for disease. Soils suppressive to Fusarium diseases are documented in different regions of the world. They contain biocontrol microorganisms, which act by inducing plants' resistance to the pathogen, competing with or inhibiting the pathogen, or parasitizing the pathogen. In particular, some of the Bacillus, Pseudomonas, Paenibacillus and Streptomyces species are involved in plant protection from Fusarium diseases. Besides specific bacterial populations involved in disease suppression, next-generation sequencing and ecological networks have largely contributed to the understanding of microbial communities in soils suppressive or not to Fusarium diseases, revealing different microbial community patterns and differences for a notable number of taxa, according to the Fusarium pathosystem, the host plant and the origin of the soil. Agricultural practices can significantly influence soil suppressiveness to Fusarium diseases by influencing soil microbiota ecology. Research on microbial modes of action and diversity in suppressive soils should help guide the development of effective farming practices for Fusarium disease management in sustainable agriculture.

Outcome after Partial Pulpotomy: Long-term Results of the Prospective Clinical MMP-9 Study.

PURPOSE: While the objective of partial pulpotomy is to preserve the vitality and function of the pulp tissue, the preopera-tive pulp status is the main prognostic factor for its success. To date, however, there is little data on long-term success rates. Therefore, the aim of this prospective pilot study was to assess the long-term outcome of partial pulpotomy in per-manent teeth after carious pulp exposure without signs or symptoms of irreversible pulpitis, verified clinically, radio-graphically, and via MMP-9 levels. MATERIALS AND METHODS: Patients in whom permanent teeth with extremely deep carious lesions were diagnosed as com-pletely asymptomatic (n = 8) or with signs of reversible pulpitis (n = 10) underwent non-selective caries removal followed by a blood test to assess the level of MMP-9. The teeth were thereafter partially pulpotomised, MTA-capped, and immedi-ately restored with composite resin. Follow-up examinations were performed by endodontically experienced examiners focusing on clinical and radiographic assessment. RESULTS: One patient could not be contacted and was lost to follow-up. Overall, the follow-up period ranged from 2-8 years (mean = 4.4 years). The majority of teeth remained functional and without pathology; one tooth was classified as having failed because of a vertical root fracture. There was no statistically significant difference in the groups' success rate (p = 0.3). The estimated overall survival rate was 94.1% (95% CI: 0.84-1.00) after 4 years according to the Kaplan-Meier method. CONCLUSION: Pulp vitality in permanent teeth can be preserved with high success rates by means of partial pulpotomy after carious pulp exposure in asymptomatic teeth or in teeth with reversible pulpitis.

Magnesium suppresses in vivo oxidative stress and ex vivo DNA damage induced by protracted ACTH treatment in rats.

Oxidative stress, arising from disrupted balance between reactive oxygen/nitrogen species (ROS/RNS) and antioxidant defences, has been implicated in the pathogenesis of stress-related disorders. There is a growing body of evidence that supports the relationship between the activity of the hypothalamic-pituitary-adrenal (HPA) stress system, oxidative stress and magnesium (Mg) homeostasis. The present study aimed to explore the gap in our current understanding of antigenotoxic and protective effects of Mg supplementation against excessive ROS production in male rats during chronic treatment with adrenocorticotropic hormone (ACTH). Our findings show that exposure to exogenous ACTH (10 µg/day, s.c., for 21 days), as one of the key mediators of the HPA axis and stress response, produced an increase in superoxide anion levels and a decrease in superoxide dismutase activity in plasma. We observed that Mg supplementation, starting seven days prior to ACTH treatment and lasting 28 days (300 mg/L of drinking water, per os), abolished these effects in experimental animals. Moreover, our study reveals that ACTH increased the susceptibility of peripheral blood lymphocytes to ex vivo H2O2-induced total and high-level oxidative DNA damage, while Mg completely reversed these effects. Collectively, these results highlight the promising role of Mg in stress-related conditions accompanied by increased oxidative stress in animals and support further investigation using human dietary trials.

Discovery of a highly potent, selective, orally bioavailable inhibitor of KAT6A/B histone acetyltransferases with efficacy against KAT6A-high ER+ breast cancer.

KAT6A, and its paralog KAT6B, are histone lysine acetyltransferases (HAT) that acetylate histone H3K23 and exert an oncogenic role in several tumor types including breast cancer where KAT6A is frequently amplified/overexpressed. However, pharmacologic targeting of KAT6A to achieve therapeutic benefit has been a challenge. Here we describe identification of a highly potent, selective, and orally bioavailable KAT6A/KAT6B inhibitor CTx-648 (PF-9363), derived from a benzisoxazole series, which demonstrates anti-tumor activity in correlation with H3K23Ac inhibition in KAT6A over-expressing breast cancer. Transcriptional and epigenetic profiling studies show reduced RNA Pol II binding and downregulation of genes involved in estrogen signaling, cell cycle, Myc and stem cell pathways associated with CTx-648 anti-tumor activity in ER-positive (ER+) breast cancer. CTx-648 treatment leads to potent tumor growth inhibition in ER+ breast cancer in vivo models, including models refractory to endocrine therapy, highlighting the potential for targeting KAT6A in ER+ breast cancer.

Characterization of Thermoluminescent Dosimetry Systems According to the IEC 62387:2020 Standard.

ABSTRACT: A need for detailed testing of individual monitoring systems used in accredited service at the Vinca Institute of Nuclear Sciences was recognized following changes in individual, workplace, and environmental monitoring passive dosimetry systems acceptability criteria stated in IEC 62387:2020 and changes related to reference fields used in radiation protection defined in ISO 4037:2019. Reliability and accuracy of dosimetry data acquired by passive dosimetry systems used for individual monitoring is assured by carrying out type tests. In this manner, the effects of different radiation influence quantities are examined. Passive dosimetry systems comprised of an LiF:Mg,Ti (TLD-100) detector card placed in two different holder models (8814 and 8850) and the Harshaw TLD Model 6600 Plus Automated Reader were tested. Type tests were done in an extended range of photon energies from 40 keV up to 1.25 MeV, angle of incidence values of ±45° and ± 60° for both vertical and horizontal dosimeter orientation, and in the dose range from 0.05 mSv to 1 Sv. Both dosimetry system configurations perform in line with IEC 62387:2020 within mandatory range for tested influence quantities. Dosimeters that use the 8850 holder type showed less pronounced energy and angular dependence of the response in the low-energy range.

Two novel species isolated from wheat rhizospheres in Serbia: Pseudomonas serbica sp. nov. and Pseudomonas serboccidentalis sp. nov.

Pseudomonas strains IT-194P, IT-215P, IT-P366T and IT-P374T were isolated from the rhizospheres of wheat grown in soils sampled from different fields (some of them known to be disease-suppressive) located near Mionica, Serbia. Phylogenetic analysis of the 16S rRNA genes and of whole genome sequences showed that these strains belong to two potentially new species, one containing strains IT-P366T and IT-194P and clustering (whole genome analysis) next to P. umsongensis DSM16611T, and another species containing strains IT-P374T and IT-215P and clustering next to P. koreensis LMG21318T. Genome analysis confirmed the proposition of novel species, as ANI was below the threshold of 95% and dDDH below 70% for strains IT-P366T (compared with P. umsongensis DSM16611T) and IT-P374T (compared with P. koreensis LMG21318T). Unlike P. umsongensis DSM16611T, strains of P. serbica can grow on D-mannitol, but not on pectin, D-galacturonic acid, L-galactonic acid lactone and α-hydroxybutyric acid. In contrary to P. koreensis LMG21318T, strains of P. serboccidentalis can use sucrose, inosine and α-ketoglutaric acid (but not L-histidine) as carbon sources. Altogether, these results indicate the existence of two novel species for which we propose the names Pseudomonas serbica sp. nov., with the type strain IT-P366T (=CFBP 9060 T = LMG 32732 T = EML 1791 T) and Pseudomonas serboccidentalis sp. nov., with the type strain IT-P374T (=CFBP 9061 T = LMG 32734 T = EML 1792 T). Strains from this study presented a set of phytobeneficial functions modulating plant hormonal balance, plant nutrition and plant protection, suggesting a potential as Plant Growth-Promoting Rhizobacteria (PGPR).

African Swine Fever Outbreak in an Enclosed Wild Boar Hunting Ground in Serbia.

African swine fever (ASF) has been detected in many European countries since its introduction in Georgia in 2007. Serbia suffered its first case of ASF in the domestic pig population in 2019. At the beginning of 2020, ASF was detected in wild boars in open hunting grounds in the southeastern region of the country in districts along the country's borders with Romania and Bulgaria. Since then, all ASF outbreaks in wild boar were clustered in the population located in the same bordering areas. Despite the newly implemented biosecurity protocols for hunters in 2019, ASF was detected for the first time in June 2021 in the wild boar population located in an enclosed hunting ground in the northeast region of the country. In this study, we reported the first ASF outbreak in a wild boar population located in an enclosed hunting ground in close proximity to the Serbian-Romanian border. The epizootiological data on the field investigation of the ASF outbreak, with descriptions of the clinical signs and gross pathological lesions detected, including the total number as well as the estimated age, sex, and postmortem interval, were analyzed. Clinical signs were detected only in nine diseased wild boars, while in total, 149 carcasses were found in the open and enclosed part of the hunting ground. In addition, 99 carcasses from which samples (parts of spleen or long bones) were collected for molecular diagnostics (RT-PCR) were confirmed as ASF-positive. The results of the epidemiological investigations indicate the central role of wild boar movements as well as the constant risk of human-related activities in the countries bordering area.

Fiber-based optrode with microstructured fiber tips for controlled light delivery in optogenetics.

Objective.Optogenetic modulation of neuronal activity requires precise and flexible light delivery to deep brain regions. Flat cleaved optical fibers combined with electrodes are widely used in implantable optogenetic devices for light delivery and electrical monitoring of neural activity. However, the flat fiber tip geometry induces serious tissue damage upon insertion, and makes it difficult to adjust and control the spatial extent of illumination within the brain. With their strongly increased tissue-compatibility and the possibility of spatial illumination control, tapered fibers outperform cleaved fibers in targeted neural photo-stimulation.Approach.In this work, we describe our device concept, and present a novel approach for reproducible fabrication of tapered fiber tips via grinding. Furthermore, we characterize recording electrodes by commenting data obtained from electrochemical impedance spectroscopy (EIS). We also investigate the impact of different cone angles (14°, 30°, 60°, and 90°) on the illumination profile and optical throughput.Main results. We fabricated a fiber-based optrode with cone tip and two deposited electrodes. Custom grinding setup for fabrication of tapered fiber tips with various cone angles is developed as a part of our research. Microscope images showed very good optical quality of cone tips. The results of transmitted optical power measurements performed with integrating sphere suggest that, compared to the flat cleaved optical fiber, transmitted power decreases exponentially with cone angle reduction. Obtained emission profiles (as induced fluorescence in Rhodamine 6G water solution) indicate very strong effect of cone angle on shape and size of illumination volume. Results obtained from EIS show the effect of electrode size on its recording capability.Significance. Compared to optrodes with flat cleaved optical fiber, the demonstrated fiber-based optrode with cone tip allows controlled light delivery with reduced invasiveness. The possibility to fabricate reproducible fiber tips with various cone angles enables control of light delivery in optogenetic experiment. The results presented here give neuroscientists the possibility to choose the appropriate tissue-compatible cone geometry depending on their stimulation requirements.

Different Alterations of Hippocampal and Reticulo-Thalamic GABAergic Parvalbumin-Expressing Interneurons Underlie Different States of Unconsciousness.

We traced the changes in GABAergic parvalbumin (PV)-expressing interneurons of the hippocampus and reticulo-thalamic nucleus (RT) as possible underlying mechanisms of the different local cortical and hippocampal electroencephalographic (EEG) microstructures during the non-rapid-eye movement (NREM) sleep compared with anesthesia-induced unconsciousness by two anesthetics with different main mechanisms of action (ketamine/diazepam versus propofol). After 3 h of recording their sleep, the rats were divided into two experimental groups: one half received ketamine/diazepam anesthesia and the other half received propofol anesthesia. We simultaneously recorded the EEG of the motor cortex and hippocampus during sleep and during 1 h of surgical anesthesia. We performed immunohistochemistry and analyzed the PV and postsynaptic density protein 95 (PSD-95) expression. PV suppression in the hippocampus and at RT underlies the global theta amplitude attenuation and hippocampal gamma augmentation that is a unique feature of ketamine-induced versus propofol-induced unconsciousness and NREM sleep. While PV suppression resulted in an increase in hippocampal PSD-95 expression, there was no imbalance between inhibition and excitation during ketamine/diazepam anesthesia compared with propofol anesthesia in RT. This increased excitation could be a consequence of a lower GABA interneuronal activity and an additional mechanism underlying the unique local EEG microstructure in the hippocampus during ketamine/diazepam anesthesia.

Enhanced Degradation of Mutant C9ORF72-Derived Toxic Dipeptide Repeat Proteins by 20S Proteasome Activation Results in Restoration of Proteostasis and Neuroprotection.

A hexanucleotide repeat expansion (HRE) in an intron of gene C9ORF72 is the most common cause of familial amyotrophic lateral sclerosis and frontotemporal dementia. The HRE undergoes noncanonical translation (repeat-associated non-ATG translation) resulting in the production of five distinct dipeptide repeat (DPR) proteins. Arginine-rich DPR proteins have shown to be toxic to motor neurons, and recent evidence suggests this toxicity is associated with disruption of the ubiquitin-proteasome system. Here we report the ability of known 20S proteasome activator, TCH-165, to enhance the degradation of DPR proteins and overcome proteasome impairment evoked by DPR proteins. Furthermore, the 20S activator protects rodent motor neurons from DPR protein toxicity and restores proteostasis in cortical neuron cultures. This study suggests that 20S proteasome enhancers may have therapeutic efficacy in neurodegenerative diseases that display proteostasis defects.

Compounding of Liquid and Solid Dose Adjustable Formulations with Pantoprazole: Comparison of Stability, Applicability and Suitability.

Pantoprazole is a model substance that requires dosage form adjustments to meet the needs of all patients. Pediatric pantoprazole formulations in Serbia are mostly compounded as capsules (divided powders), while in Western Europe liquid formulations are more common. The aim of this work was to examine and compare the characteristics of compounded liquid and solid dosage forms of pantoprazole. Three syrup bases were used: a sugar-free vehicle for oral solution (according to USP43-NF38), a vehicle with glucose and hydroxypropyl cellulose (according to the DAC/NRF2018) and a commercially available SyrSpend Alka base. Lactose monohydrate, microcrystalline cellulose and a commercially available capsule filler (excipient II, composition: pregelatinized corn starch, magnesium stearate, micronized silicon dioxide, micronized talc) were used as diluents in the capsule formulations. Pantoprazole concentration was determined by the usage of the HPLC method. Pharmaceutical technological procedures and microbiological stability measurements were performed according to the recommendations of the EP10. Although dose appropriate compounding with pantoprazole is suitable using both liquid vehicles as well as solid formulations, chemical stability is enhanced in solid formulation. Nevertheless, according to our results, if liquid formulation is a pH adjusted syrup, it could be safely kept in a refrigerator for up to 4 weeks. Additionally, liquid formulations could be readily applied, while solid formulation should be mixed with appropriate vehicles with higher pH values.

Endorhizosphere of indigenous succulent halophytes: a valuable resource of plant growth promoting bacteria.

The adaptability of halophytes to increased soil salinity is related to complex rhizosphere interactions. In this study, an integrative approach, combining culture-independent and culture-dependent techniques was used to analyze the bacterial communities in the endorizosphere of indigenous succulent halophytes Salicornia europaea, Suaeda maritima, and Camphorosma annua from the natural salt marshes of Slano Kopovo (Serbia). The 16 S rDNA analyses gave, for the first time, an insight into the composition of the endophytic bacterial communities of S. maritima and C. annua. We have found that the composition of endophyte microbiomes in the same habitat is to some extent influenced by plant species. A cultivable portion of the halophyte microbiota was tested at different NaCl concentrations for the set of plant growth promoting (PGP) traits. Through the mining of indigenous halotolerant endophytes, we obtained a collection representing a core endophyte microbiome conferring desirable PGP traits. The majority (65%) of the selected strains belonged to the common halotolerant/halophilic genera Halomonas, Kushneria, and Halobacillus, with representatives exhibiting multiple PGP traits, and retaining beneficial traits in conditions of the increased salinity. The results suggest that the root endosphere of halophytes is a valuable source of PGP bacteria supporting plant growth and fitness in salt-affected soils.

Heavy Metals Content in Selected Medicinal Plants Produced and Consumed in Serbia and Their Daily Intake in Herbal Infusions.

The heavy metals content (HMs) was investigated in 14 different medicinal plants collected from the three regions in Central Serbia, Zlatar, Sokobanja, and Kopaonik. The concentrations of Cd, Cr, Ni, Hg and Pb were determined: Cd (<0.03-2.72 mg/kg); Cr (<0.08-12.1 mg/kg); Ni (<0.08-12.2 mg/kg); Pb (0.6-49.0 mg/kg); the Hg concentration was below the detection limit of 0.06 mg/kg in all samples. The daily intake of HMs due to ingestion of 200 mL of herbal infusion was in all cases below the recommended limit prescribed by the World Health Organization. The estimated daily intake values were below the values for the oral reference dose regulated by the U.S. Environmental Protection Agency (USA EPA). The target hazard quotient and hazard index for Cd, Cr Ni, and Pb were below 1. Nevertheless, due to the tendency of heavy metals to accumulate in the organism, attention should be paid to the daily intake of herbal infusion during long-term usage. Specifically, it is recommended to consume not more than one cup (200 mL) of infusion per day made from thyme (Mt. Zlatar) and blueberry (Mt. Kopaonik), and not more than two cups per day for other herbs.