Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal oncological diseases, with a 5-year survival rate of approximately 13%-among the lowest in oncology. Poor survival is driven by aggressive tumor progression and metastasis, which may be influenced by the tumor microbiome. This study aimed to evaluate the role of microbiome in PDAC progression and metastasis. First, we assessed the microbial composition of control samples (surface swabs, empty paraffin, extraction controls, and sequencing controls) and removed contaminant taxa. Overall bacterial biomass was extremely low, with no significant differences in alpha or beta-diversity between tumor and normal tissue. Kocuria rosea was significantly enriched in tumors compared to normal tissue, and this difference persisted after decontamination. Metastatic tumors showed altered abundance of K. rosea and Herbaspirillum huttiense, whereas non-metastatic tumors differed in Lysobacter bugurensis, Caulobacter ginsengisoli, and H. huttiense relative to normal tissue. No global compositional differences were observed between KRAS-mutant and wild-type tumors; however, KRAS-mutant tumors exhibited differential enrichment of K. rosea and L. bugurensis relative to adjacent normal tissue. The PDAC microbiome harbors very low bacterial biomass and does not robustly distinguish tumor from normal tissue at the community level. Nonetheless, K. rosea emerges as a candidate taxon differentially enriched in PDAC, with potential stage- and KRAS-associated patterns. These findings highlight the need for orthogonal validation (qPCR, FISH, culture) and larger prospective cohorts to differentiate true biological associations from residual contamination or stochastic noise in low-biomass settings.

Our analysis of metabolic and ecological features of fungi indicates a high bioremediation potential of fungal mycelium. The relevance of the problems solved in this work is conditioned by insufficiently studied mechanisms and conditions of micromycetal activity on heavy metal detoxication. The effect of copper on the development of two micromycete species, namely, melanised Alternaria alternata (Fr.) Keissl., 1912 and hyaline Fusarium oxysporum Schltdl., 1824 cultivated on Czapek agar (with 2 or 3% sucrose) was compared; the ability of mycelium to sorb copper cations when grown in a liquid culture with 0, 0.05, 0.1, 0.25, and 0.5 mg Cu2+ / L was evaluated. F. oxysporum had noticeable advantages in terms of growth rate, tolerance, conidia production on medium with Cu2+. The effective concentration of copper (EC50), indicating the resistance of the fungus, increased for F. oxysporum by 1.5 times with increasing sucrose content in the medium. The melanised culture of A. alternata was superior to F. oxysporum in terms of sorption capacity. The percentage of Cu2+ extraction by fungal mycelium from the medium reached 40% in the case of F. oxysporum and twice as much in the case of A. alternata . The vast majority of copper was sorbed by the cell walls of hyphae and washed away by water. A small amount (a maximum of 0.16 µg Cu2+ /g dry mycelium of A. alternate ) penetrated inside the mycelial cells. F. oxysporum, which had no intracellular protective melanins, accumulated Cu2+ (2 to 14 times) less. The results show that the mechanisms of resistance to Cu2+ and sorption are different in the studied species: in Fusarium they are determined mainly by the barrier functions of hyphae cell walls, while in Alternaria melanin plays a significant role in protection against Cu toxic action.

Given the high growth rates of cognitive decline among the elderly population and the lack of effective etiological treatments, early diagnosis of cognitive impairment progression is an imperative task for modern science and medicine. It is of particular interest to identify predictors of an unfavorable subsequent course of cognitive disorders, specifically, rapid progression. Our study assessed the informative role of various risk factors on the dynamics of cognitive impairment among mild cognitive impairment (MCI) patients. The study included patients with MCI (N = 338) who underwent neuropsychological assessment, magnetic resonance imaging (MRI) examination, blood sampling for general and biochemical analysis, APOE genotyping, and polygenic risk score (PRS) evaluation. The APOE ε4/ε4 genotype was found to be associated with a diminished overall cognitive scores initial assessment and negative cognitive dynamics. No associations were found between cognitive changes and the PRS. The progression of cognitive impairment was associated with the width of the third ventricle and hematological parameters, specifically, hematocrit and erythrocyte levels. The absence of significant associations between the dynamics of cognitive decline and PRS over three years can be attributed to the provided suitable medical care for the prevention of cognitive impairment. Adding other risk factors and their inclusion in panels assessing the risk of progression of cognitive impairment should be considered.

The specific features of halotolerant fungi are analyzed to assess their potential for indicating chemical contamination of saline soils and to search for the promising test species for laboratory mycotesting. The listed halophile and halotolerant micromycete genera comprise the representatives suitable as indicators of pollution by heavy metals, oil products, and other toxicants on the background of increased salinity of soil substrates. The moderately halotolerant species of micromycetes are proposed as promising for biotesting of the soils with moderate salinity. Morphological, physiological, and molecular mechanisms underlying the adaptation of halophilic and halotolerant fungi to an increased salinity of habitats are analyzed. The responses of fungal communities to the combined impact of salinization and toxic substances of different natures are discussed. The methodological aspects of the application of halotolerant fungi for biotesting the degree of disturbance of saline soils are considered, including the composition of media, cultivation conditions, and test responses of fungal cultures optimal for an adequate assessment of the degree of fungal halotolerance and the ecotoxicity of soil samples.

The polygenic risk score (PRS), together with the ɛ4 allele of the APOE gene (APOE-ɛ4), has shown high potential for Alzheimer’s disease (AD) risk prediction. The aim of this study was to validate the model of polygenic risk in Russian patients with dementia. A microarray-based assay was developed to identify 21 markers of polygenic risk and ɛ alleles of the APOE gene. This case–control study included 348 dementia patients and 519 cognitively normal volunteers. Cerebrospinal fluid (CSF) amyloid-β (Aβ) and tau protein levels were assessed in 57 dementia patients. PRS and APOE-ɛ4 were significant genetic risk factors for dementia. Adjusted for APOE-ɛ4, individuals with PRS corresponding to the fourth quartile had an increased risk of dementia compared to the first quartile (OR 1.85; p-value 0.002). The area under the curve (AUC) was 0.559 for the PRS model only, and the inclusion of APOE-ɛ4 improved the AUC to 0.604. PRS was positively correlated with tTau and pTau181 and inversely correlated with Aβ42/Aβ40 ratio. Carriers of APOE-ɛ4 had higher levels of tTau and pTau181 and lower levels of Aβ42 and Aβ42/Aβ40. The developed assay can be part of a strategy for assessing individuals for AD risk, with the purpose of assisting primary preventive interventions.

The review is devoted to the analysis of information on aquatic fungi as potential agents of bioremediation of aquatic environments under chemical pollution. Approaches to the classification of groups of aquatic mycobiota based on the duration of existence in aquatic environments and morphophysiological features of species are considered. The known mechanisms of interaction between fungi and pollutants, which result in biodegradation or biosorption of pollutants, and ultimately a decrease in the concentration of chemicals available to other inhabitants of aquatic environments, are outlined. Specific examples illustrating the role of fungal enzymes in these processes are considered. Data are given on the use of fungal strains isolated from marine and fresh waters for the purpose of mycoremediation, and the effectiveness of fungi of different origin in bioremediation is characterized. It is concluded that a more promising direction of microremediation seems to be the orientation towards the choice of biodestructor fungi species that have specific enzymes that can lead to the degradation of pollutants.

Известные факты повышения доли фитопатогенных форм микромицетов в почвах, загрязненных тяжелыми металлами (ТМ), делают актуальными исследования механизмов их резистентности, что важно для выбора эффективных средств борьбы с возбудителями болезней растений. Не менее актуальными и нуждающимися в изучении остаются вопросы взаимодействия металл-резистентных фитопатогенов с непатогенными видами на фоне загрязнения. В лабораторных экспериментах с чистыми культурами четырех видов грибов (фитопатогенные штаммы Alternaria alternata и Fusarium oxysporum и непатогенные Trichoderma harzianum и Clonostachys rosea) исследовали резистентность к катионам Cu, Zn, Pb, по отдельности добавленных в питательную среду с разным содержанием доступного углерода (сахарозы). Измеряли рост колоний, активность спорообразования и накопление биомассы. Рассчитывали эффективные концентрации, приводящие к 50%-му ингибированию параметров роста, - EC50. Исследуемые грибы проявляли различную устойчивость к ТМ. T. harzianum и C. rosea были более устойчивы к Zn и Pb при любом содержании доступного углерода. Наиболее устойчивы к Cu были пары A. alternata - C. rosea и T. harzianum - C. rosea на средах с меньшим и большим содержанием углерода соответственно. При этом для всех грибов Zn и Pb оказались менее токсичны, чем Сu. Антагонистическая активность, оцененная методом встречных культур на средах с добавлением ТМ, зависела как от ростовых характеристик, так и от выявленной устойчивости вида к ТМ. Активность быстрорастущего T. harzianum как территориального антагониста стимулировалась внесением Zn и Pb. Медленнорастущий C. rosea проявлял конкурентоспособность благодаря высокой устойчивости к ТМ. Сделан вывод о необходимости учета видовой устойчивости к ТМ для прогноза развития взаимоотношений патогенных и непатогенных видов в грибных сообществах на фоне загрязнения почвы. The facts of an increase in the proportion of phytopathogenic forms of micromycetes in soils contaminated with heavy metals (HM) make it relevant to study the mechanisms of their resistance, which is important to choose effective phytopathogen control methods. The issues of interaction between metal-resistant phytopathogens and non-pathogenic species against the background of pollution remain no less relevant and need to be studied. In laboratory experiments with pure cultures of four fungal species (phytopathogenic strains Alternaria alternata and Fusarium oxysporum and non-pathogenic strains Trichoderma harzianum and Clonostachys rosea), the resistance to Cu, Zn, Pb cations, separately added to nutrient medium with different content of available carbon (sucrose), was studied. Colony growth, sporulation activity, and biomass accumulation were measured. The effective concentrations, resulting in 50 % inhibition of growth parameters (EC50), were calculated. The studied fungi showed different resistance to HM. T . harzianum and C. rosea were more resistant to Zn and Pb at any available carbon content. The pairs A. alternata-C. rosea and T. harzianum-C. rosea were the most resistant to Cu on media with lower and higher carbon contents, respectively. At the same time, Zn and Pb turned out to be less toxic than Cu for all fungi. The antagonistic activity, assessed by the dual culture method on media supplemented with HM cations, depended both on the growth characteristics and on the revealed resistance to HM. The activity of fast growing T. harzianum as a territorial antagonist was stimulated by the addition of Zn and Pb. The slow-growing C. rosea showed competitiveness due to its high resistance to HM. It is concluded that it is necessary to take into account species resistance to HM in order to predict the development of relationships between pathogenic and non-pathogenic species in fungal communities against the background of soil pollution.

Many studies aim to detect the early phase of dementia. One of the major ways to achieve this is to identify corresponding biomarkers, particularly immune blood biomarkers. The objective of this study was to identify such biomarkers in patients with mild cognitive impairment (MCI) in an experiment that included cognitive training. A group of patients with MCI diagnoses over the age of 65 participated in the study (n = 136). Measurements of cognitive functions (using the Mini-Mental State Examination scale and Montreal Cognitive Assessment) and determination of 27 serum biomarkers were performed twice: on the first visit and on the second visit, one year after the cognitive training. APOE genotypes were also determined. Concentrations of EGF (F = 17; p = 0.00007), Eotaxin (F = 7.17; p = 0.008), GRO (F = 13.42; p = 0.0004), IL-8 (F = 8.16; p = 0.005), MCP-1 (F = 13.46; p = 0.0001) and MDC (F = 5.93; p = 0.016) increased after the cognitive training in MCI patients. All these parameters except IL-8 demonstrated a weak correlation with other immune parameters and were poorly represented in the principal component analysis. Differences in concentrations of IP-10, FGF-2, TGFa and VEGF in patients with MCI were associated with APOE genotype. Therefore, the study identified several immune blood biomarkers that could potentially be associated with changes in cognitive function.

Heavy metals (HM) in the soil cause changes in the ratio of resistant and susceptible fungal species, the mechanisms of interaction between which are not well understood. The aim of this work is to study the resistance to Cu and Pb cations and the antagonistic properties of two species of soil micromycetes Alternaria alternata and Trichoderma viride. Fungal resistance was assessed by the following test functions: biomass accumulation, colony diameter, and sporulation activity. The antagonistic activity of fungal species was assessed by competition test. The calculated effective concentrations and tolerance indices made it possible to conclude that A. alternata and T. viride are highly resistant to the investigated HMs. At the same time, species differences in the patterns of reactions were found. The growth of A. alternata colonies was inhibited to a greater extent than T. viride, however at the same HM concentration, the stimulation of sporulation in Alternaria was more pronounced than in the rapidly growing Trichoderma. The studied strain T. viride turned out to be quite competitive with respect to the phytopathogenic fungus A. alternata, and its antagonistic properties were well pronounced in the medium with HM. The data obtained can be useful for predicting the phytopathogenic activity of micromycetes against the background of chemical pollution and the dynamics of accumulation of various fungal species under adverse environmental conditions.

Experimentally substantiated assessment of the remediation properties of humic products is an important condition for their safe and effective use. The review provides an analysis of existing approaches to biotesting of humic products, which enable us to draw a conclusion about the efficiency of detoxification of soils and adjacent media and about ensuring the viability of biocenoses, when using humic products. The advantages and disadvantages of traditional approaches to biotesting of humic products in soil media based on well-known reactions of higher plants and microorganisms, as well as the possibility of algotesting, using fluorescent methods, and mycotesting of humic products in aqueous and artificial nutrient media are discussed. The results of the experimental verification of the remediating ability of humic products during biotesting in media rich in organic substances indicate the need to standardize the conditions for the quantitative assessment of the quality of humic products. Standard artificial soil (according to ISO 11268-2) may be used as a universal soil matrix for the initial assessment of humic products. To summarize their quality as potential soil improvers, the proposed remediation index is calculated by the data of chemical, bioindication, and ecotoxicological studies of soil treated with humic products.

Dementia has enormous implications for patients and the health care system. Genetic markers are promising for detecting the risk of cognitive impairment. We hypothesized that genetic variants associated with suicide risk might significantly increase the risk of cognitive decline because suicide in older adults is often a consequence of cognitive impairment. We investigated several single-nucleotide polymorphisms that were initially associated with suicide risk in dementia older adults and identified the APOE gene alleles. The study was performed with subjects over the age of 65: 112 patients with dementia and 146 healthy volunteers. The MMSE score was used to assess cognitive functions. Study participants were genotyped using real-time PCR (APOE: rs429358, rs7412; genes associated with suicide: rs9475195, rs7982251, rs2834789, rs358592, rs4918918, rs3781878, rs10903034, rs165774, rs16841143, rs11833579 rs10898553, rs7296262, rs3806263, and rs2462021). Genotype analysis revealed the significance of APOEε4, APOEε2, and rs4918918 (SORBS1) when comparing dementia and healthy control groups. The association of APOEε4, APOEε2, and rs10903034 (IFNLR1) with the overall MMSE score was indicated. The study found an association with dementia of rs4918918 (SORBS1) and rs10903034 (IFNLR1) previously associated with suicide and confirmed the association of APOEε4 and APOEε2 with dementia.

Fungal contamination of aquatic environments can lead to an adverse impact on the environment and human health. (1) The search for fast, inexpensive and appropriate methods for detection of fungi is very moving rapidly due to their significant impact on ecosystem functions and human health. (2) We focused on examination of fluorescence proxies able to distinguish chromophoric matter occurring in different fungi. Spectroscopic studies were performed on five strains of filamentous fungi: Trichoderma harzianum, Fusarium solani, Alternaria alternata, Cladosporium cladosporioides and Aspergillus terreus. (3) The results showed that most of the fungal autofluorescence was emitted by amino acids, melanin-like compounds, NAD(P)H and flavins. The spectra of five fungal species cultivated as planktonic or surface-associated forms turned out to be different. Protein fluorescence can be used to detect general microbial contamination. Presence of excitation wavelength dependent mode and the “blue shift” of fluorescence (emission bands 400–500 nm) can be suggested as specific feature of fluorescence of fungal melanin-containing samples. (4) The determination based on fluorescence spectra obtained at a certain excitation/emission wavelengths pair and at whole excitation-emission matrices (EEMs) coupled to principal component analysis (PCA) algorithms as a tool of improving detection capabilities can be suggested to enable fast and inexpensive monitoring of fungal contamination of aquatic environments.

Bioassay is a popular method for assessing the ecotoxicological state of different components of urban ecosystems: soils, water bodies, and air. However, little is known about the potential of bioassay application to determine the ecotoxicity of urban dust, which is a complex heterogeneous medium composed of natural and technogenic particles. Many components of urban dust are known to have toxic effects on living organisms. The purpose of this paper is to review the existing practices for assessing the ecotoxicity of urban dust and identifying the key trends in the development of the bioassay method. Analysis of the existing studies has revealed a high potential of bioassay methods, since they are sensitive to a wide range of pollutants that are contained in dust and can selectively reflect dust toxicity depending on environmental factors and be implemented using organisms of different trophic levels. The following dust characteristics should be taken into account for proper choice of the bioassay method: sample weight, wettability, pH, and content of water-soluble ions and organic matter. Due to the complexity of the composition of urban dust and different potentials for the transition of its components into water extracts, it is recommended to prioritize contact bioassay based on solid dust substrates instead of extracts. For comprehensive assessment of dust impact on an urban ecosystem, it is reasonable to test a set of organisms of different trophic levels. Standards should be developed for dust bioassay to unify the results of different studies. One of the most important methodological questions is the choice of the control sample.

(1) Background: Older people suffer from cognitive decline; several risk factors contribute to greater cognitive decline. We used acquired (COVID-19 infection) and non-modifiable (presence of APOE rs429358 and rs7412 polymorphisms) factors to study the progression of subjective cognitive impairment while observing patients for one year. Cognitive training was used as a protective factor. (2) Methods: Two groups of subjects over the age of 65 participated in the study: group with subjective cognitive decline receiving cognitive training and individuals who did not complain of cognitive decline without receiving cognitive training (comparison group). On the first visit, the concentration of antibodies to COVID-19 and APOE genotype was measured. At the first and last point (1 year later) the Mini-Mental State Examination scale and the Hospital Anxiety and Depression Scale were performed. (3) Results: COVID-19 infection did not affect cognitive function. A significant role of cognitive training in improving cognitive functions was revealed. Older adults with APOE-ε4 genotype showed no positive effect of cognitive training. (4) Conclusions: Future research should focus on cognitive dysfunction after COVID-19 in long-term follow-up. Attention to the factors discussed in our article, but not limited to them, are useful for a personalized approach to maintaining the cognitive health of older adults.

In a model vegetation experiment (30 days), the responses of microbial communities of agro soddy-podzolic soil of two sites (Chashnikovo, Moscow oblast) with different organic carbon content (Corg 3.86 and 1.30%) to polymetallic pollution with heavy metals (HM) (Cu 660, Zn 1100, Pb 650 mg/kg) and treatment with biochar (5%) and lignohumate (0.25%). Classical microbiological culture-dependent analysis using Czapek agar and analysis of soil lipid profiles by gas chromatography–mass spectrometry revealed the differences in abundance colony forming units (CFUs), fungal and bacterial biomass, as well as in the diversity of cultivated fungi both in humus-rich and humus-poor soil. HMs did not have a significant effect on the number of CFUs and the number of cultural-morphological types of colonies, but reduced fungal and bacterial biomass in both soils; this decrease was more significant in a humus-poor soil. In addition, differences between the soils in the increase in the proportion of resistant melanized forms of fungi under the influence of HM in humus-rich (by 25.9%) and in humus-poor soil (by 45.7%) were observed. The sensitivity and universal significance of structural indicators as indicators of the stability of microbial complexes under chemical contamination of soils with different humus content were discussed. It was shown that the most sensitive and reliable indicators among the studied included the proportion of melanized fungi.

Reliable stable indicators are very important for assessing soil quality. This paper compares the dynamics of microbial parameters in two different soils (rich/poor in organic carbon), contaminated in laboratory experiments with an equal dose of heavy metals (HMs) after 30 and 90 days. For this purpose, the changes in the number, biomass, and taxonomic structure of bacterial and fungal communities were assessed in microcosm experiments using an organic carbon–rich ordinary chernozem (Ch-humus-rich soil) and a depleted carbon agrozem (Ag-humus-poor soil), spiked with high concentrations of a zinc, lead, and copper solution (1100 Zn + 660 Cu + 650 Pb mg per kg soil). At the 30th and 90th day from HM contamination, soil samples were collected for analyzing microbial community lipid markers by gas chromatography-mass spectrometry. The results show how both biomass and taxonomic structure of the bacterial and fungal communities analyzed were differently sensitive to HM contamination, depending on the type of soil. The Ag-humus-poor soil microbial community was significantly affected by the HM pollution with an increase in both fungi and bacteria and inside the latter several species changed their percentages. Differently, the Ch-humus-rich soil microbial community was not influenced by the HM addition. However, the negative impact of HM can manifest itself over time, so the microbial structure and its functioning cannot represent accurate indicators of the quality of all soil types. The results show that microbial characteristics should be taken into account only in a comprehensive assessment of soil quality in accordance with ISO 19,204:2017—soil quality TRIAD approach. This approach to environmental risk assessment combines biological data (from bioassay and ecological observations) with chemical analysis.

Humic substances (HSs) support the sustainable functioning of soils. Filamentous fungi are involved in HSs turnover, demonstrating the ability to degrade and simultaneously synthesize HSs. The aim of the work was to study the transformation of HS samples by soil filamentous fungi using a set of spectral indices and to connect those findings to stability of soil biomes. We used three fungal strains: melanin containing Alternaria alternatа, non-pigmented Fusarium solani and Trichoderma harzianum. Absorption and fluorescence spectra were measured after cultivating fungi in various concentrations of HSs (200 mg/L for HPs and 100 mg/L for HAs) and sucrose (3 and 0.3 g/L). The transformations of HSs under cultivation of A alternatа led to increase of absorbance ratio A250/A365, shortening of the fluorescence emission wavelength, and growth in fluorescence quantum yield QY355. Under cultivation of F. solani and T. harzianum we did not observe these spectral changes. This indicates that among three strains studied, A. alternata degrades HSs the most actively. The data we obtained and principal component analysis showed that phytopathogenic A. alternata, F. solani and antagonistically active against alternaria and fusaria T. harzianum have different patterns of interaction with HSs; this should be considered when humic-based biostimulants are used.