Androgen Insensitivity Syndrome with Bilateral Gonadal Sertoli Cell Lesions, Sertoli-Leydig Cell Tumor, and Paratesticular Leiomyoma: A Case Report and First Systematic Literature Review.

Androgen insensitivity syndrome (AIS) is a rare Mendelian disorder caused by mutations of the androgen receptor (AR) gene on the long arm of the X chromosome. As a result of the mutation, the receptor becomes resistant to androgens, and hence, karyotypically male patients (46,XY) carry a female phenotype. Their cryptorchid gonads are prone to the development of several types of tumors (germ cell, sex cord stromal, and others). Here, we report a 15-year-old female-looking patient with primary amenorrhea who underwent laparoscopic gonadectomy. Histologically, the patient's gonads showed Sertoli cell hamartomas (SCHs) and adenomas (SCAs) with areas of Sertoli-Leydig cell tumors (SLCTs) and a left-sided paratesticular leiomyoma. Rudimentary Fallopian tubes were also present. The patient's karyotype was 46,XY without any evidence of aberrations. Molecular genetic analysis of the left gonad revealed two likely germline mutations-a pathogenic frameshift deletion in the AR gene (c.77delT) and a likely pathogenic missense variant in the RAC1 gene (p.A94V). Strikingly, no somatic mutations, fusions, or copy number variations were found. We also performed the first systematic literature review (PRISMA guidelines; screened databases: PubMed, Scopus, Web of Science; ended on 7 December 2023) of the reported cases of patients with AIS showing benign or malignant Sertoli cell lesions/tumors in their gonads (n = 225; age: 4-84, mean 32 years), including Sertoli cell hyperplasia (1%), Sertoli cell nodules (6%), SCHs (31%), SCAs (36%), Sertoli cell tumors (SCTs) (16%), and SLCTs (4%). The few cases (n = 14, 6%; six SCAs, four SCTs, two SLCTs, and two SCHs) with available follow-up (2-49, mean 17 months) showed no evidence of disease (13/14, 93%) or died of other causes (1/14, 7%) despite the histological diagnosis. Smooth muscle lesions/proliferations were identified in 19 (8%) cases (including clearly reported rudimentary uterine remnants, 3 cases; leiomyomas, 4 cases). Rudimentary Fallopian tube(s) were described in nine (4%) cases. Conclusion: AIS may be associated with sex cord/stromal tumors and, rarely, mesenchymal tumors such as leiomyomas. True malignant sex cord tumors can arise in these patients. Larger series with longer follow-ups are needed to estimate the exact prognostic relevance of tumor histology in AIS.

Study on Syntaxonomic Diversity of Algal Cenoses in Soils of the Russian Far East, Using an Integrative Taxonomic Approach.

Soil is a unique ecosystem with peculiar biodiversity that includes cyanobacteria and algae. Traditionally, cyanobacterial and algal cenoses were described mainly using the dominance approach, rarely based on the Braun-Blanquet method (floristic classification). More importantly, in both cases, the species of cyanobacteria and algae in communities were identified using classical methods (light microscopy) only. In this study, we present results of soil algal cenoses classification using the Braun-Blanquet approach based on species composition data obtained via an integrative approach. Characteristic tables include 19 out of 108 samples collected in the Jewish Autonomous Region, Primorsky Territory, and Sakhalin Region (Iturup Island) in 2018 and in 2020-2021. Twenty-five species of algae from four classes were identified in these sites. We described three new associations of algal communities-Coelastrelletum aeroterrestricae ass. nova, Vischerietum magnae ass. nova, Bracteacoccetum bullati ass. nova. PCA analysis corroborated the results of syntaxonomic analysis and revealed that Coelastrelletum aeroterrestricae inhabit soils with a high value of P; Vischerietum magnae inhabit soils with high value of soil organic carbon (SOC), N, and higher humidity; and Bracteacoccetum bullati inhabit soils with high K values.

The Effect of Mice Adaptation Process on the Pathogenicity of Influenza A/South Africa/3626/2013 (H1N1)pdm09 Model Strain.

Influenza virus strain A/South Africa/3626/2013 (H1N1)pdm09 (SA-WT) is a non-mouse-adapted model strain that has naturally high pathogenic properties in mice. It has been suggested that the high pathogenicity of this strain for mice could be due to the three strain-specific substitutions in the polymerase complex (Q687R in PB1, N102T in PB2, and E358E/K heterogeneity in PB2). To evaluate the role of these replacements, SA-WT was passaged five times in mouse lungs, and the genome of the mouse-adapted version of the SA-WT strain (SA-M5) was sequenced. SA-M5 lost E358E/K heterogeneity and retained E358, which is the prevalent amino acid at this position among H1N1pdm09 strains. In addition, in the hemagglutinin of SA-M5, two heterogeneous substitutions (G155G/E and S190S/R) were identified. Both viruses, SA-M5 and SA-WT, were compared for their toxicity, ability to replicate, pathogenicity, and immunogenicity in mice. In mice infected with SA-M5 or SA-WT strains, toxicity, virus titer in pulmonary homogenates, and mouse survival did not differ significantly. In contrast, an increase in the immunogenicity of SA-M5 compared to SA-WT was observed. This increase could be due to the substitutions G155G/E and S190S/R in the HA of SA-M5. The prospects for using SA-M5 in studying the immunogenicity mechanisms were also discussed.

Biochemical Responses to the Long-Term Impact of Copper Sulfate (CuSO4) in Tobacco Plants.

Metabolic changes under stress are often studied in short-term experiments, revealing rapid responses in gene expression, enzyme activity, and the amount of antioxidants. In a long-term experiment, it is possible to identify adaptive changes in both primary and secondary metabolism. In this study, we characterized the physiological state of tobacco plants and assessed the amount and spectrum of phenolic compounds and the lignification of axial organs under excess copper stress in a long-term experiment (40 days). Plants were treated with 100 and 300 µM CuSO4, as well as a control (Knop solution). Copper accumulation, the size and anatomical structure of organs, stress markers, and the activity of antioxidant enzymes were studied. Lignin content was determined with the cysteine-assisted sulfuric method (CASA), and the metabolite profile and phenolic spectrum were determined with UHPLC-MS and thin-layer chromatography (TLC). Cu2+ mainly accumulated in the roots and, to a lesser extent, in the shoots. Copper sulfate (100 µM) slightly stimulated stem and leaf growth. A higher concentration (300 µM) caused oxidative stress; H2O2 content, superoxide dismutase (SOD), and guaiacol peroxidase (GPOX) activity increased in roots, and malondialdehyde (MDA) increased in all organs. The deposition of lignin increased in the roots and stems compared with the control. The content of free phenolics, which could be used as substrates for lignification, declined. The proportions of ferulic, cinnamic, and p-coumaric acids in the hydrolysate of bound phenolics were higher, and they tended toward additional lignification. The metabolic profile changed in both roots and stems at both concentrations, and changed in leaves only at a concentration of 300 µM. Thus, changes in the phenolic spectrum and the enhanced lignification of cell walls in the metaxylem of axial (root and stem) organs in tobacco can be considered important metabolic responses to stress caused by excess CuSO4.

Female Sex Hormones Upregulate the Replication Activity of HIV-1 Sub-Subtype A6 and CRF02_AG but Not HIV-1 Subtype B.

More than 50% of all people living with HIV worldwide are women. Globally, HIV/AIDS is the leading cause of death among women aged 15 to 44. The safe and effective methods of hormonal contraception are an essential component of preventive medical care in order to reduce maternal and infant mortality. However, there is limited knowledge regarding the effect of hormones on the rate of viral replication in HIV infection, especially non-B subtypes. The goal of the present work was to study in vitro how the female hormones ß-estradiol and progesterone affect the replication of the HIV-1 subtypes A6, CRF02_AG, and B. The findings show that high doses of hormones enhanced the replication of HIV-1 sub-subtype A6 by an average of 1.75 times and the recombinant variant CRF02_AG by 1.4 times but did not affect the replication of HIV-1 subtype B. No difference was detected in the expression of CCR5 and CXCR4 co-receptors on the cell surface, either in the presence or absence of hormones. However, one of the reasons for the increased viral replication could be the modulated TLRs secretion, as it was found that high doses of estradiol and progesterone upregulated, to varying degrees, the expression of TLR2 and TLR9 genes in the PBMCs of female donors infected with HIV-1 sub-subtype A6.

Properties of recombinant extracellular N-terminal domain of human high-affinity copper transporter 1 (hNdCTR1) and its interactions with Cu(II) and Ag(I) ions.

High-affinity copper transporter 1 (CTR1) is a key link in the transfer of copper (Cu) from the extracellular environment to the cell. Violation in the control system of its expression, or mutations in this gene, cause a global copper imbalance. However, the mechanism of copper transfer via CTR1 remains unclear. It has been shown that transformed bacteria synthesizing the fused GB1-NdCTR become resistant to toxic silver ions. According to UV-Vis spectrophotometry and isothermal titration calorimetry, electrophoretically pure GB1-NdCTR specifically and reversibly binds copper and silver ions, and binding is associated with aggregation. Purified NdCTR1 forms SDS-resistant oligomers. The link between nontrivial properties of NdCTR1 and copper import mechanism from extracellular space, as well as potential chelating properties of NdCTR1, are discussed.

Biofertilizer Based on Biochar and Metal-Tolerant Plant Growth Promoting Rhizobacteria Alleviates Copper Impact on Morphophysiological Traits in Brassica napus L.

Metal tolerant plant growth-promoting (PGP) rhizobacteria are promising for enhancing plant productivity under copper (Cu) stress. Present pot scale experiment was conducted on Brassica napus L. to check the efficiency of rhizobacteria isolated from the rhizosphere of Tussilago farfara L. growing on Cu-contaminated soils. Out of fifty Cu tolerant strains, three isolates which showed multiple PGP traits such as indole-3-acetic acid (IAA) synthesis, phosphate (PS) solubilization, siderophore and ammonia production were identified preliminarily by morphological and physiological characteristics followed by 16S rRNA gene sequencing. The best Bacillus altitudinis strain TF16a which showed IAA: 15.5 mg L-1, PS: 215 mg L-1, siderophore halo zone ratio of 3.0 with high ammonia production was selected to prepare a biochar-based biofertilizer (BF). Seedling test showed maximum growth of B. napus shoot and root in presence of 5% of BF and this concentration was selected for further experiment. The pot experiment included four treatments: control (soil), 100Cu (100 mg Cu kg-1 soil), 5%BF (v/v), and 5%BF+100Cu, which were carried out for 30 days, after which the morphological, physiological, and biochemical parameters of B. napus were studied. The Cu treatment caused its accumulation in shoot and root up to 16.9 and 30.4 mg kg-1 DW, respectively, and increased malondialdehyde (MDA) content by 20%. Application of BF with copper led to the decrease in the Cu accumulation by 20% for shoot and 28% for root while MDA content was the same as in the control. Both treatments of BF with and without Cu increased chlorophyll a and b content by 1.3 times on average as well as non-enzymatic antioxidants such as soluble phenolic compounds (1.3 times) and free proline (1.6 times). Moreover, BF + Cu led to the increase in the biomass of shoot and root by 30 and 60%, respectively, while there was no significant effect on the growth characteristics of plants after the addition of BF without Cu. The study elucidates that BF based on B.altitudinis strain TF16a and biochar can be a promising bioformulation which could increase rapeseed growth under the moderate Cu concentration in soil.

Current Opinion in LAIV: A Matter of Parent Virus Choice.

Influenza is still a frequent seasonal infection of the upper respiratory tract, which may have deadly consequences, especially for the elderly. This is in spite of the availability of vaccines suggested for persons above 65 years of age. Two types of conventional influenza vaccines are currently licensed for use-live attenuated and inactivated vaccines. Depending on local regulatory requirements, live attenuated vaccines are produced by the reverse genetics technique or by classical reassortment in embryonated chicken eggs. Sometimes, the efficiency of classical reassortment is complicated by certain properties of the wild-type parent virus. Cases of low efficacy of vaccines have been noted, which, among other reasons, may be associated with suboptimal properties of the wild-type parent virus that are not considered when recommendations for influenza vaccine composition are made. Unfortunately, knowledge surrounding the roles of properties of the circulating influenza virus and its impact on the efficacy of the reassortment process, vaccination efficiency, the infectivity of the vaccine candidates, etc., is now scattered in different publications. This review summarizes the main features of the influenza virus that may dramatically affect different aspects of the preparation of egg-derived live attenuated vaccine candidates and their effectiveness. The author expresses her personal view, which may not coincide with the opinion of other experts in the field of influenza vaccines.

Variable Clinical Appearance of the Kir2.1 Rare Variants in Russian Patients with Long QT Syndrome.

BACKGROUND: The KCNJ2 gene encodes inward rectifier Kir2.1 channels, maintaining resting potential and cell excitability. Presumably, clinical phenotypes of mutation carriers correlate with ion permeability defects. Loss-of-function mutations lead to QTc prolongation with variable dysmorphic features, whereas gain-of-function mutations cause short QT syndrome and/or atrial fibrillation. METHODS: We screened 210 probands with Long QT syndrome for mutations in the KCNJ2 gene. The electrophysiological study was performed for the p.Val93Ile variant in the transfected CHO-K1 cells. RESULTS: We found three rare genetic variants, p.Arg67Trp, p.Val93Ile, and p.R218Q, in three unrelated LQTS probands. Probands with p.Arg67Trp and p.R218Q had a phenotype typical for Andersen-Tawil (ATS), and the p.Val93Ile carrier had lone QTc prolongation. Variant p.Val93Ile was initially described as a gain-of-function pathogenic mutation causing familial atrial fibrillation. We validated electrophysiological features of this variant in CHO-K1 cells, but no family members of these patients had atrial fibrillation. Using ACMG (2015) criteria, we re-assessed this variant as a variant of unknown significance (class III). CONCLUSIONS: LQT7 is a rare form of LQTS in Russia, and accounts for 1% of the LQTS cohort. Variant p.Val93Ile leads to a gain-of-function effect in the different cell lines, but its clinical appearance is not so consistent. The clinical significance of this variant might be overestimated.

Understanding the Variability of Certain Biological Properties of H1N1pdm09 Influenza Viruses.

The influenza virus continually evolves because of the high mutation rate, resulting in dramatic changes in its pathogenicity and other biological properties. This study aimed to evaluate the evolution of certain essential properties, understand the connections between them, and find the molecular basis for the manifestation of these properties. To that end, 21 A(H1N1)pdm09 influenza viruses were tested for their pathogenicity and toxicity in a mouse model with a ts/non-ts phenotype manifestation and HA thermal stability. The results demonstrated that, for a strain to have high pathogenicity, it must express a toxic effect, have a non-ts phenotype, and have a thermally stable HA. The ancestor A/California/07/2009 (H1N1)pdm influenza virus expressed the non-ts phenotype, after which the cycling trend of the ts/non-ts phenotype was observed in new strains of A(H1N1)pdm09 influenza viruses, indicating that the ratio of the ts phenotype will increase in the coming years. Of the 21 tested viruses, A/South Africa/3626/2013 had the high pathogenicity in the mouse model. Sequence alignment analysis showed that this virus has three unique mutations in the polymerase complex, two of which are in the PB2 gene and one that is in the PB1 gene. Further study of these mutations might explain the distinguishing pathogenicity.

Efficacy of the Endolysin-Based Antibacterial Gel for Treatment of Anaerobic Infection Caused by Fusobacterium necrophorum.

Abscess formation is a common complication of severe life-threatening infections caused by obligate anaerobes. Fusobacterium necrophorum is among the frequently detected anaerobic pathogens from clinical specimens associated with liver abscesses, skin and soft tissue infections, or oral abscesses. The antimicrobial therapy for this kind of infection needs to be optimized. Here, we examined the possibility of treating F. necrophorum-induced abscess wound infections with candidate therapeutics based on three endolysins with activity against a broad spectrum of aerobe Gram-negative pathogens. Antibacterial gel containing three Gram-negative bacteria-targeting endolysins, LysAm24, LysAp22, and LysECD7, was formulated for topical use. Abscess formation was induced in rabbits with F. necrophorum and caused systemic infection. The survival and lifespan of the animals, general parameters, and biochemical and hematological blood tests were analyzed to assess the effectiveness of the gel treatment for the wound infection. The administration of the investigated gel twice per day for 5 days resulted in less acute inflammation, with decreased leukocytes and segmented neutrophils in the blood, retardation of infection progression, and an almost two-fold increase in the lifespan of the animals compared to the placebo group. The results indicate that endolysin-based therapy is an effective approach to treat anaerobic bacterial infections. The use of endolysins as independent pharmaceuticals, or their combination with antibiotics, could significantly reduce the development of complications in infectious diseases caused by sensitive bacterial species.

COVID-19 Shuts Doors to Flu but Keeps Them Open to Rhinoviruses.

It is well known that rhinoviruses are distributed across the globe and are the most common cause of the common cold in all age groups. Rhinoviruses are widely considered to be harmless because they are generally perceived as respiratory viruses only capable of causing mild disease. However, they may also infect the lower respiratory tract, inducing chronic obstructive pulmonary disease and exacerbations of asthma, bronchiolitis, etc. The role of rhinoviruses in pathogenesis and the epidemiological process is underestimated, and they need to be intensively studied. In the light of recent data, it is now known that rhinoviruses could be one of the key epidemiological barriers that may influence the spread of influenza and novel coronaviruses. It has been reported that endemic human rhinoviruses delayed the development of the H1N1pdm09 influenza pandemic through viral interference. Moreover, human rhinoviruses have been suggested to block SARS-CoV-2 replication in the airways by triggering an interferon response. In this review, we summarized the main biological characteristics of genetically distinct viruses such as rhinoviruses, influenza viruses, and SARS-CoV-2 in an attempt to illuminate their main discrepancies and similarities. We hope that this comparative analysis will help us to better understand in which direction research in this area should move.

The Crossroads between Host Copper Metabolism and Influenza Infection.

Three main approaches are used to combat severe viral respiratory infections. The first is preemptive vaccination that blocks infection. Weakened or dead viral particles, as well as genetic constructs carrying viral proteins or information about them, are used as an antigen. However, the viral genome is very evolutionary labile and changes continuously. Second, chemical agents are used during infection and inhibit the function of a number of viral proteins. However, these drugs lose their effectiveness because the virus can rapidly acquire resistance to them. The third is the search for points in the host metabolism the effect on which would suppress the replication of the virus but would not have a significant effect on the metabolism of the host. Here, we consider the possibility of using the copper metabolic system as a target to reduce the severity of influenza infection. This is facilitated by the fact that, in mammals, copper status can be rapidly reduced by silver nanoparticles and restored after their cancellation.

Nickel and copper accumulation strategies in Odontarrhena obovata growing on copper smelter-influenced and non-influenced serpentine soils: a comparative field study.

The present investigation is the first in situ comparative study for the identification of Ni and Cu accumulation strategies involved in Odontarrhena obovata (syn. Alyssum obovatum (C.A. Mey.) Turcz.) growing in Cu-rich smelter-influenced (CSI) and non-Cu-influenced (NCI) sites. The total and Na2EDTA (disodium ethylenediaminetetraacetic acid)-extractable metal concentration in soils and plant tissues (roots, stem, leaves and flowers) were determined for CSI and NCI sites. High concentrations of total Ni, Cr, Co and Mg in the soil suggest serpentine nature of both the sites. In spite of high total and extractable Cu concentrations in CSI soil, majority of its accumulation was restricted to O. obovata roots showing its excluder response. Since the translocation and bioconcentration factors of Ni > 1 and the foliar Ni concentration > 1000 µg g-1, it can be assumed that O. obovata has Ni hyperaccumulation potential for both the sites. No significant differences in chlorophyll content in O. obovata leaves were observed between studied sites, suggesting higher tolerance of this species under prolonged heavy metal stress. Furthermore, this species from CSI site demonstrated rather high viability under extreme technogenic conditions due to active formation of antioxidants such as ascorbate, free proline and protein thiols. The presence of Cu in higher concentration in serpentine soil does not exert detrimental effect on O. obovata and its Ni hyperaccumulation ability. Thus, O. obovata could act as a putative plant species for the remediation of Cu-rich/influenced serpentine soils without compromising its Ni content and vitality.

Anti-Influenza Effect of Nanosilver in a Mouse Model.

The present study assesses copper metabolism of the host organism as a target of antiviral strategy, basing on the "virocell" concept. Silver nanoparticles (AgNPs) were used as a specific active agent because they reduce the level of holo-ceruloplasmin, the main extracellular cuproenzyme. The mouse model of influenza virus A infection was used with two doses: 1 LD50 and 10 LD50. Three treatment regimens were used: Scheme 1-mice were pretreated 4 days before infection and then every day during infection development; Scheme 2-mice were pretreated four days before infection and on the day of virus infection; Scheme 3-virus infection and AgNP treatment started simultaneously, and mice were injected with AgNPs until the end of the experiment. The mice treated by Scheme 1 demonstrated significantly lower mortality, the protection index reached 60-70% at the end of the experiment, and mean lifespan was prolonged. In addition, the treatment of the animals with AgNPs resulted in normalization of the weight dynamics. Despite the amelioration of the infection, AgNP treatment did not influence influenza virus replication. The possibility of using nanosilver as an effective indirectly-acting antiviral drug is discussed.

COVID-19 in Light of Seasonal Respiratory Infections.

A wide diversity of zoonotic viruses that are capable of overcoming host range barriers facilitate the emergence of new potentially pandemic viruses in the human population. When faced with a new virus that is rapidly emerging in the human population, we have a limited knowledge base to work with. The pandemic invasion of the new SARS-CoV-2 virus in 2019 provided a unique possibility to quickly learn more about the pathogenesis of respiratory viruses. In this review, the impact of pandemics on the circulation of seasonal respiratory viruses is considered. The emergence of novel respiratory viruses has often been accompanied by the disappearance of existing circulating strains. Some issues arising from the spread of pandemic viruses and underlying the choices of a strategy to fight the coronavirus infection are discussed.

New Points of Departure for More Global Influenza Vaccine Use.

Each year, influenza causes a significant acute respiratory disease burden. In addition, influenza pandemics periodically occur. Annual vaccination is the best tool for influenza prevention, but its effectiveness can vary from year to year. The narrow specificity of conventional vaccines and the drug resistance of currently circulating viruses reduce the effectiveness of prophylaxis and treatment and require the development of new broad-spectrum preparations. Furthermore, the challenge of creating a highly effective universal influenza vaccine takes on renewed intensity in the face of the COVID-19 pandemic.

Non-Mouse-Adapted H1N1pdm09 Virus as a Model for Influenza Research.

The number of lung-adapted influenza viruses is limited. Most of them are not antigenically related to current circulating viruses. Viruses similar to recent strains are required for screening modern antiviral compounds and studying new vaccine candidates against novel influenza viruses. The process by which an influenza virus adapts to a new host is rather difficult. The aim of this study was to select a non-adapted current virus whose major biological properties correspond to those of classical lab-adapted viruses. Mice were inoculated intranasally with non-lung-adapted influenza viruses of subtype H1N1pdm09. They were monitored closely for body weight loss, mortality outcomes and gross pathology for 14 days following inoculation, as well as viral replication in lung tissue. Lung-adapted PR8 virus was used as a control. The tested viruses multiplied equally well in the lower respiratory tract of mice without prior adaptation but dramatically differed in lethality; the differences in their toxicity and pathogenicity in mice were established. A/South Africa/3626/2013 (H1N1)pdm09 virus was found to be an appropriate candidate to replace PR8 as a model virus for influenza research. No prior adaptation to the animal model is needed to reach the pathogenicity level of the classical mouse-adapted PR8 virus.

A Phase 1 Randomized Placebo-Controlled Study to Assess the Safety, Immunogenicity and Genetic Stability of a New Potential Pandemic H7N9 Live Attenuated Influenza Vaccine in Healthy Adults.

This study describes a double-blind randomized placebo-controlled phase I clinical trial in healthy adults of a new potential pandemic H7N9 live attenuated influenza vaccine (LAIV) based on the human influenza virus of Yangtze River Delta hemagglutinin lineage (ClinicalTrials.gov Identifier: NCT03739229). Two doses of H7N9 LAIV or placebo were administered intranasally to 30 and 10 subjects, respectively. The vaccine was well-tolerated and not associated with increased rates of adverse events or with any serious adverse events. Vaccine virus was detected in nasal swabs during the 6 days after vaccination or revaccination. A lower frequency of shedding was observed after the second vaccination. Twenty-five clinical viral isolates obtained after the first and second doses of vaccine retained the temperature-sensitive and cold-adapted phenotypic characteristics of LAIV. There was no confirmed transmission of the vaccine strain from vaccinees to placebo recipients. After the two H7N9 LAIV doses, an immune response was observed in 96.6% of subjects in at least one of the assays conducted.

Toxic metal(loid)s contamination and potential human health risk assessment in the vicinity of century-old copper smelter, Karabash, Russia.

Active smelters release high concentration of multiple toxic metal(loid)s into the environment, degrading the soil cover and posing high risks to human health. The present study investigates Cu along with other metal(loids) such as As, Cd, Hg, Co, Mn, Pb and Zn in the soil collected from the vicinity of Cu smelter, Karabash, Russia, and potential health risks to local children and adults were assessed. The average concentrations of Cu, Zn, Pb, As, Cd, and Hg in the exposed soil were 2698, 1050, 702, 392, 9 and 2 mg kg-1, respectively, which was significantly (p < 0.05) much higher than reference soil: Cu(107), As(18), Cd(0.3), Hg(0.2), Pb(54) and Zn(125) mg kg-1. The enrichment factor (EF) for Cu, Hg, Pb and Zn showed significant enrichment, whereas very high enrichment was recorded for As (20.0) and Cd (27.6) suggesting the soil was severely affected by smelting activities. The pollution load index was tenfold higher than the acceptable level of one, whereas potential ecological risk factor showed very high potential risks of Cd and Hg, along with a considerable ecological risk of As and Cu. Very high ecological risk index of 1810 indicates severe degradation of environmental ecosystem. The results of EF, Pearson correlation and principle component analysis were complementary and suggest the anthropogenic source of contamination for Cu, As, Pb, Hg and Cd. The present result suggests As > Pb > Cu in the exposed soil were the major contributors for the health risks and account for 81%, 12% and 5%, and 77%, 12% and 8% of hazard quotient for children and adults, respectively. Noticeably, the health risks to local children dwelling in the vicinity of Cu smelter were 12 and 20 times higher than to adult and the acceptable level of one, respectively. Therefore, in order to reduce the health risk due to metal(loid)s, mitigation measures are needed to remediate the pollution of the exposed soil.