Carbon Dioxide Capture by Niobium Polyoxometalate Fragmentation.

High oxidation state metal cations in the form of oxides, oxoanions, or oxoperoxoanions have diverse roles in carbon dioxide removal (direct air capture and point source). Features include providing basic oxygens for chemisorption reactions, direct binding of carbonate, and catalyzing low-temperature CO2 release to regenerate capture media. Moreover, metal oxides and aqueous metal-oxo species are stable in harsh, point-source conditions. Here, we demonstrate aqueous niobium polyoxometalate (POM) carbon capture ability, specifically [Nb6O19]8-, Nb6. Upon exposure of aqueous Nb6 to CO2, Nb6 fragments and binds chemisorbed carbonate, evidenced by crystallization of Nb-carbonate POMs including [Nb22O53(CO3)16]28-and [Nb10O25(CO3)6]12-. While Rb/Cs+ counter cations yield crystal structures to understand the chemisorption processes, K+ counter cations enable higher capture efficiency (based on CO3/Nb ratio), determined by CHN analysis and thermogravimetry-mass spectrometry of the isolated solids. Sum frequency generation spectroscopy also showed higher carbon capture efficiency of the K-Nb6 solutions at the air-water interface, while small-angle X-ray scattering (SAXS) provided insights into the role of the alkalis in influencing these processes. Tetramethylammonium counter cations, like K+, demonstrate high efficiency of carbonate chemisorption at the interface, but SAXS and Raman of the bulk showed a predominance of a Nb24-POM (HxNb24O72, x ∼ 9) that does not bind carbonate. Control experiments show that carbonate detected at the interface is Nb-bound, and the Nb-carbonate species are stabilized by alkalis, demonstrating their supporting role in aqueous Nb-POM CO2 chemisorption. Of fundamental importance, this study presents rare examples of directing POM speciation with a gas, instead of liquid phase acid or base.

Synthesis, Characterization, and Reactivity of a Synthetic End-On Cobalt(II) Alkyl Persulfide Complex as a Model Platform for Thiolate Persulfidation.

Persulfides (RSS-) are ubiquitous source of sulfides (S2-) in biology, and interactions between RSS- and bioinorganic metal centers play critical roles in biological hydrogen sulfide (H2S) biogenesis, signaling, and catabolism. Here, we report the use of contact-ion stabilized [Na(15-crown-5)][tBuSS] (1) as a simple synthon to access rare metal alkyl persulfide complexes and to investigate the reactivity of RSS- with transition metal centers to provide insights into metal thiolate persulfidation, including the fundamental difference between alkyl persulfides and alkyl thiolates. Reaction of 1 with [CoII(TPA)(OTf)]+ afforded the η1-alkyl persulfide complex [CoII(TPA)(SStBu)]+ (2), which was characterized by X-ray crystallography, UV-vis spectroscopy, and Raman spectroscopy. RSS- coordination to the Lewis acidic Co2+ center provided additional stability to the S-S bond, as evidenced by a significant increase in the Raman stretching frequency for 2 (vS-S = 522 cm-1, ΔvS-S = 66 cm-1). The effect of persulfidation on metal center redox potentials was further elucidated using cyclic voltammetry, in which the Co2+ → Co3+ oxidation potential of 2 (Ep,a = +89 mV vs SCE) is lowered by nearly 700 mV when compared to the corresponding thiolate complex [CoII(TPA)(StBu)]+ (3) (Ep,a = +818 mV vs SCE), despite persulfidation being generally seen as an oxidative post-translational modification. The reactivity of 2 toward reducing agents including PPh3, BH4-, and biologically relevant thiol reductant DTT led to different S2- output pathways, including formation of a dinuclear 2Co-2SH complex [CoII2(TPA)2(µ2-SH)2]2+(4).

3-Position Biaryl Endochin-like Quinolones with Enhanced Antimalarial Performance.

ELQ-300 is a potent antimalarial drug with activity against blood, liver, and vector stages of the disease. A prodrug, ELQ-331, exhibits reduced crystallinity and improved in vivo efficacy in preclinical testing, and currently, it is in the developmental pipeline for once-a-week dosing for oral prophylaxis against malaria. Because of the high cost of developing a new drug for human use and the high risk of drug failure, it is prudent to have a back-up plan in place. Here we describe ELQ-596, a member of a new subseries of 3-biaryl-ELQs, with enhanced potency in vitro against multidrug-resistant Plasmodium falciparum parasites. ELQ-598, a prodrug of ELQ-596 with diminished crystallinity, is more effective vs murine malaria than its progenitor ELQ-331 by 4- to 10-fold, suggesting that correspondingly lower doses could be used to protect and cure humans of malaria. With a longer bloodstream half-life in mice compared to its progenitor, ELQ-596 highlights a novel series of next-generation ELQs with the potential for once-monthly dosing for protection against malaria infection. Advances in the preparation of 3-biaryl-ELQs are presented along with preliminary results from experiments to explore key structure-activity relationships for drug potency, selectivity, pharmacokinetics, and safety.

Exome Sequencing for the Diagnostics of Osteogenesis Imperfecta in Six Russian Patients.

Osteogenesis imperfecta (OI) is a group of inherited disorders of connective tissue that cause significant deformities and fragility in bones. Most cases of OI are associated with pathogenic variants in collagen type I genes and are characterized by pronounced polymorphisms in clinical manifestations and the absence of clear phenotype-genotype correlation. The objective of this study was to conduct a comprehensive molecular-genetic and clinical analysis to verify the diagnosis of OI in six Russian patients with genetic variants in the COL1A1 and COL1A2 genes. Clinical and laboratory data were obtained from six OI patients who were observed at the Medical Genetics Center in Saint Petersburg from 2016 to 2023. Next-generation sequencing on MGISEQ G400 (MGI, China) was used for DNA analysis. The GATK bioinformatic software (version 4.5.0.0) was used for variant calling and hard filtering. Genetic variants were verified by the direct automatic sequencing of PCR products using the ABI 3500X sequencer. We identified six genetic variants, as follows pathogenic c.3505G>A (p. Gly1169Ser), c.769G>A (p.Gly257Arg), VUS c.4123G>A (p.Ala1375Thr), and c.4114A>T (p.Asn1372Tyr) in COL1A1; and likely pathogenic c.2035G>A (p.Gly679Ser) and c.739-2A>T in COL1A2. In addition, clinical cases are presented due to the presence of the c.4114A>T variant in the COL1A2 gene. Molecular genetics is essential for determining different OI types due to the high similarity across various types of the disease and the failure of unambiguous diagnosis based on clinical manifestations alone. Considering the variable approaches to OI classification, an integrated strategy is required for optimal patient management.

A High-Yielding Active Template Click Reaction (AT-CuAAC) for the Synthesis of Mechanically Interlocked Nanohoops.

Mechanically interlocked molecules (MIMs) represent an exciting yet underexplored area of research in the context of carbon nanoscience. Recently, work from our group and others has shown that small carbon nanotube fragments-[n]cycloparaphenylenes ([n]CPPs) and related nanohoop macrocycles-may be integrated into mechanically interlocked architectures by leveraging supramolecular interactions, covalent tethers, or metal-ion templates. Still, available synthetic methods are typically difficult and low yielding, and general methods that allow for the creation of a wide variety of these structures are limited. Here we report an efficient route to interlocked nanohoop structures via the active template Cu-catalyzed azide-alkyne cycloaddition (AT-CuAAC) reaction. With the appropriate choice of substituents, a macrocyclic precursor to 2,2'-bipyridyl embedded [9]CPP (bipy[9]CPP) participates in the AT-CuAAC reaction to provide [2]rotaxanes in near-quantitative yield, which can then be converted into the fully π-conjugated catenane structures. Through this approach, two nanohoop[2]catenanes are synthesized which consist of a bipy[9]CPP catenated with either Tz[10]CPP or Tz[12]CPP (where Tz denotes a 1,2,3-triazole moiety replacing one phenylene ring in the [n]CPP backbone).

Reversible Hydrosulfide (HS-) Binding Using Exclusively C-H Hydrogen-Bonding Interactions in Imidazolium Hosts.

H2S is a physiologically important signaling molecule with complex roles in biology and exists primarily as HS- at physiological pH. Despite this anionic character, few investigations have focused on the molecular recognition and reversible binding of this important biological anion. Using a series of imidazole and imidazolium host molecules, we investigate the role of preorganization and charge on HS- binding. Using a macrocyclic bis-imidazolium receptor, we demonstrate the unexpected 2:1 host-guest binding of HS-, which was characterized both in solution and by X-ray crystallography. To the best of our knowledge, this is the first example of this binding stoichiometry for HS- binding. Moreover, the short C-H···S distances of 2.53, 2.54, 2.76, and 2.79 Å are well within the sum of the van der Waals radii of the interacting atoms, which is consistent with strong C-H···S interactions.

Synthesis and Properties of Fluorenone-Containing Cycloparaphenylenes and Their Late-Stage Transformation.

Cycloparaphenylenes (CPPs) are the smallest possible armchair carbon nanotubes, the properties of which strongly depend on their ring size. They can be further tuned by either peripheral functionalization or by replacing phenylene rings for other aromatic units. Here we show how four novel donor-acceptor chromophores were obtained by incorporating fluorenone or 2-(9H-fluoren-9-ylidene)malononitrile into the loops of two differently sized CPPs. Synthetically, we managed to perform late-stage functionalization of the fluorenone-based rings by high-yielding Knoevenagel condensations. The structures were confirmed by X-ray crystallographic analyses, which revealed that replacing a phenylene for a fused-ring-system acceptor introduces additional strain. The donor-acceptor characters of the CPPs were supported by absorption and fluorescence spectroscopic studies, electrochemical studies (displaying the CPPs as multi-redox systems undergoing reversible or quasi-reversible redox events), as well as by computations. The oligophenylene parts were found to comprise the electron donor units of the macrocycles and the fluorenone parts the acceptor units.

2-λ5-Phosphaquinolin-2-ones as Non-cytotoxic, Targetable, and pH-Stable Fluorophores.

Several phosphaquinolinone derivatives have been synthesized and characterized to explore their usefulness in the realm of cell imaging. Solution-state photophysical properties in both aqueous and organic solutions were collected for these derivatives. Additionally, CCK-8 cell viability assays and fluorescent imaging in HeLa cells incubated with the new heterocyclic derivatives show evidence of favorable cell permeability, cell viability, and moderate intracellular localization when appended with the well-known morpholine targeting motif.

Satellite III (1q12) Copy Number Variation in Cultured Human Skin Fibroblasts from Schizophrenic Patients and Healthy Controls.

BACKGROUND: The chromosome 1q12 region harbors the genome's largest pericentromeric heterochromatin domain that includes tandemly repeated satellite III DNA [SatIII (1)]. Increased SatIII (1) copy numbers have been found in cultured human skin fibroblasts (HSFs) during replicative senescence. The aim of this study was to analyze the variation in SatIII (1) abundance in cultured HSFs at early passages depending on the levels of endogenous and exogenous stress. METHODS: We studied 10 HSF cell lines with either high (HSFs from schizophrenic cases, n = 5) or low (HSFs from healthy controls, n = 5) levels of oxidative stress. The levels of endogenous stress were estimated by the amounts of reactive oxygen species, DNA damage markers (8-hydroxy-2'-deoxyguanosine, gamma-H2A histone family member X), pro- and antioxidant proteins (NADPH oxidase 4, superoxide dismutase 1, nuclear factor erythroid 2-related factor 2), and proteins that regulate apoptosis and autophagy (B-cell lymphoma 2 [Bcl-2], Bcl-2-associated X protein, light chain 3). SatIII (1) copy numbers were measured using the nonradioactive quantitative hybridization technique. For comparison, the contents of telomeric and ribosomal RNA gene repeats were determined. RNASATIII (1 and 9) were quantified using quantitative Polymerase Chain Reaction (PCR). RESULTS: Increased SatIII (1) contents in DNA from confluent HSFs were positively correlated with increased oxidative stress. Confluent cell cultivation without medium replacement and heat shock induced a decrease of SatIII (1) in DNA in parallel with a decrease in RNASATIII (1) and an increase in RNASATIII (9). CONCLUSIONS: During HSF cultivation, cells with increased SatIII (1) content accumulated in the cell pool under conditions of exaggerated oxidative stress. This fraction of cells decreased after the additional impact of exogenous stress. The process seems to be oscillatory.

Benchmarking the placement of hydrosulfide in the Hofmeister series using a bambus[6]uril-based ChemFET sensor.

Hydrosulfide (HS-) is the conjugate base of gasotransmitter hydrogen sulfide (H2S) and is a physiologically-relevant small molecule of great interest in the anion sensing community. However, selective sensing and molecular recognition of HS- in water remains difficult because, in addition to the diffuse charge and high solvation energy of anions, HS- is highly nucleophilic and readily oxidizes into other reactive sulfur species. Moreover, the direct placement of HS- in the Hofmeister series remains unclear. Supramolecular host-guest interactions provide a promising platform on which to recognize and bind hydrosulfide, and characterizing the placement of HS- in the Hofmeister series would facilitate the future design of selective receptors for this challenging anion. Few examples of supramolecular HS- binding have been reported, but the Sindelar group reported HS- binding in water using bambus[6]uril macrocycles in 2018. We used this HS- binding platform as a starting point to develop a chemically-sensitive field effect transistor (ChemFET) to facilitate assigning HS- to a specific place in the Hofmeister series. Specifically, we prepared dodeca-n-butyl bambus[6]uril and incorporated it into a ChemFET as the HS- receptor motif. The resultant device provided an amperometric response to HS-, and we used this device to measure the response of other anions, including SO42-, F-, Cl-, Br-, NO3-, ClO4-, and I-. Using this response data, we were able to experimentally determine that HS- lies between Cl- and Br- in the Hofmeister series, which matches recent theoretical computational work that predicted a similar placement. Taken together, these results highlight the potential of using molecular recognition coupled with ChemFET architectures to develop new approaches for direct and reversible HS- detection and measurement in water and further advance our understanding of different recognition approaches for this challenging anion.

Topology of WC/Co Interfaces in Cemented Carbides.

WC-Co cemented carbides build one of the important classes of metal matrix composites. We show in this paper that the use of machine vision methods makes it possible to obtain sufficiently informative statistical data on the topology of the interfaces between tungsten carbide grains (WC) and a cobalt matrix (Co). For the first time, the outlines of the regions of the cobalt binder were chosen as a tool for describing the structure of cemented carbides. Numerical processing of micrographs of cross sections of three WC-Co alloys, which differ in the average grain size, was carried out. The distribution density of the angles in the contours of cobalt "lakes" is bimodal. The peaks close to 110° (so-called outcoming angles) correspond to the contacts between the cobalt binder and the WC/WC grain boundaries. The peaks close to 240° (or incoming angles) correspond to the WC "capes" contacting the cobalt "lakes" and are determined by the angles between facets of WC crystallites. The distribution density of the linear dimensions of the regions of the cobalt binder, approximated with ellipses, were also obtained. The distribution density exponentially decreases with the lengths of the semi-axes of the ellipsoid, approximating the area of the cobalt binder. The possible connection between the obtained data on the shape of cobalt areas and the crack trajectories in cemented carbides is discussed.

Antipsychotics Affect Satellite III (1q12) Copy Number Variations in the Cultured Human Skin Fibroblasts.

The fragment of satellite III (f-SatIII) is located in pericentromeric heterochromatin of chromosome 1. Cell with an enlarged f-SatIII block does not respond to various stimuli and are highly stress-susceptible. The fraction of f-SatIII in the cells of schizophrenia patients changed during antipsychotic therapy. Therefore, antipsychotics might reduce the f-SatIII content in the cells. We studied the action of haloperidol, risperidone and olanzapine (3 h, 24 h, 96 h) on human skin fibroblast lines (n = 10). The f-SatIII contents in DNA were measured using nonradioactive quantitative hybridization. RNASATIII were quantified using RT-qPCR. The levels of DNA damage markers (8-oxodG, γ-H2AX) and proteins that regulate apoptosis and autophagy were determined by flow cytometry. The antipsychotics reduced the f-SatIII content in DNA and RNASATIII content in RNA from HSFs. After an exposure to the antipsychotics, the autophagy marker LC3 significantly increased, while the apoptosis markers decreased. The f-SatIII content in DNA positively correlated with RNASATIII content in RNA and with DNA oxidation marker 8-oxodG, while negatively correlated with LC3 content. The antipsychotics arrest the process of f-SatIII repeat augmentation in cultured skin fibroblasts via the transcription suppression and/or through upregulated elimination of cells with enlarged f-SatIII blocks with the help of autophagy.

Taming the Dichalcogenides: Isolation, Characterization, and Reactivity of Elusive Perselenide, Persulfide, Thioselenide, and Selenosulfide Anions.

Reactive sulfur species (RSS) and reactive selenium species (RSeS) play integral roles in hydrogen sulfide (H2S) and hydrogen selenide (H2Se) biological signaling pathways, and dichalcogenide anions are proposed transient intermediates that facilitate a variety of biochemical transformations. Herein we report the selective synthesis, isolation, spectroscopic and structural characterization, and fundamental reactivity of persulfide (RSS-), perselenide (RSeSe-), thioselenide (RSSe-), and selenosulfide (RSeS-) anions. The isolated chalcogenides do not rely on steric protection for stability and have steric profiles analogous to cysteine (Cys). Simple reduction of S8 or Se by potassium benzyl thiolate (KSBn) or selenolate (KSeBn) in the presence of 18-crown-6 afforded [K(18-crown-6)][BnSS] (1), [K(18-crown-6)][BnSeSe] (2), [K(18-crown-6][BnSSe] (3), and [K(18-crown-6][BnSeS] (4). The chemical structure of each dichalcogenide was confirmed by X-ray crystallography and solution-state 1H, 13C, and 77Se NMR spectroscopy. To advance our understanding of the reactivity of these species, we demonstrated that reduction of 1-4 by PPh3 readily generates E═PPh3 (E: S, Se), and reduction of 1, 3, and 4 by DTT readily produces HE-/H2E. Furthermore, 1-4 react with CN- to produce ECN-, which is consistent with the detoxifying effects of dichalcogenide intermediates in the Rhodanese enzyme. Taken together, this work provides new insights into the inherent structural and reactivity characteristics of dichalcogenides relevant to biology and advances our understanding of the fundamental properties of these reactive anions.

Comparison of Antiaromatic Properties in a Series of Structurally Isomeric Naphthothiophene-Fused s-Indacenes.

Fusion of aromatic subunits to stabilize an antiaromatic core allows the isolation and study of otherwise unstable paratropic systems. A complete study of a series of six naphthothiophene-fused s-indacene isomers is herein described. Additionally, the structural modifications resulted in increased π-π overlap in the solid state, which was further explored through changing the sterically blocking mesityl group to (triisopropylsilyl)ethynyl in three derivatives. The computed antiaromaticity of the six isomers is compared to the observed physical properties, such as NMR chemical shift, UV-vis, and CV data. We find that the calculations predict the most antiaromatic isomer and give a general estimation of the relative degree of paratropicity for the remaining isomers, when compared to the experimental results.

Tunable Macrocyclic Polyparaphenylene Nanolassos via Copper-Free Click Chemistry.

Deriving diverse compound libraries from a single substrate in high yields remains to be a challenge in cycloparaphenylene chemistry. In here, a strategy for the late-stage functionalization of shape-persistent alkyne-containing cycloparaphenylene has been explored using readily available azides. The copper-free [3+2]azide-alkyne cycloaddition provided high yields (>90 %) in a single reaction step. Systematic variation of the azides from electron-rich to -deficient shines light on how peripheral substitution influences the characteristics of the resulting adducts. We find that among the most affected properties are the molecular shape, the oxidation potential, excited state features, and affinities towards different fullerenes. Joint experimental and theoretical results are presented including calculations with the state-of-the-art, artificial intelligence-enhanced quantum mechanical method 1 (AIQM1).

Association of NEF2L2 Rs35652124 Polymorphism with Nrf2 Induction and Genotoxic Stress Biomarkers in Autism.

Increased oxidative/genotoxic stress is known to impact the pathophysiology of ASD (autism spectrum disorder). Clinical studies, however, reported limited, heterogeneous but promising responses to treatment with antioxidant remedies. We determined whether the functional polymorphism of the Nrf2 gene, master regulator of anti-oxidant adaptive reactions to genotoxic stress, links to the genotoxic stress responses and to an in vitro effect of a NRF2 inductor in ASD children. Oxidative stress biomarkers, adaptive responses to genotoxic/oxidative stress, levels of master antioxidant regulator Nrf2 and its active form pNrf2 before and after inducing by dimethyl fumarate (DMF), and promotor rs35652124 polymorphism of NFE2L2 gene encoding Nrf2 were studied in children with ASD (n = 179). Controls included healthy adults (n = 101). Adaptive responses to genotoxicity as indicated by H2AX and cytoprotection by NRF2 contents positively correlated in ASD children with a Spearman coefficient of R = 0.479 in T+, but not CC genotypes. ASD children with NRF2 rs35652124 CC genotype demonstrated significantly higher H2AX content (0.652 vs. 0.499 in T+) and pNrf2 induction by DMF, lowered 8-oxo-dG concentration in plasma and higher cfDNA/plasma nuclease activity ratio. Our pilot findings suggest that in ASD children the NEF2L2 rs35652124 polymorphism impacts adaptive responses that may potentially link to ASD severity. Our data warrant further studies to reveal the potential for NEF2L2 genotype-specific and age-dependent repurposing of DMF and/or other NRF2-inducing drugs.

Bioprinted Schwann and Mesenchymal Stem Cell Co-Cultures for Enhanced Spatial Control of Neurite Outgrowth.

Bioprinting nerve conduits supplemented with glial or stem cells is a promising approach to promote axonal regeneration in the injured nervous system. In this study, we examined the effects of different compositions of bioprinted fibrin hydrogels supplemented with Schwann cells and mesenchymal stem cells (MSCs) on cell viability, production of neurotrophic factors, and neurite outgrowth from adult sensory neurons. To reduce cell damage during bioprinting, we analyzed and optimized the shear stress magnitude and exposure time. The results demonstrated that fibrin hydrogel made from 9 mg/mL of fibrinogen and 50IE/mL of thrombin maintained the gel's highest stability and cell viability. Gene transcription levels for neurotrophic factors were significantly higher in cultures containing Schwann cells. However, the amount of the secreted neurotrophic factors was similar in all co-cultures with the different ratios of Schwann cells and MSCs. By testing various co-culture combinations, we found that the number of Schwann cells can feasibly be reduced by half and still stimulate guided neurite outgrowth in a 3D-printed fibrin matrix. This study demonstrates that bioprinting can be used to develop nerve conduits with optimized cell compositions to guide axonal regeneration.

Impact of Internal Charge Transfer on the Photophysical Properties of Pyridine-Fused Phosphorus-Nitrogen Heterocycles.

The phosphaquinolinone scaffold has been previously studied as a modular core for a variety of fluorescent species where use of substituent effects has focused on increasing or decreasing electron density in the core rings. We now report the synthesis and analysis of several pyridine-containing phosphaquinolinone species exhibiting notable linear conjugation from the aryl-substituent to electron-withdrawing pyridyl nitrogen. Varying the nature of the aryl substituent from electron-withdrawing to electron-donating leads to the generation of an internal charge-transfer (ICT) band in the absorbance spectrum, which becomes the dominant absorbance in terms of intensity in the most electron-rich -NMe2 example. This heterocycle exhibits improved photophysical properties compared to others in the set including high quantum yield and considerably red-shifted emission. The enhanced ICT can be observed in the X-ray data where a rare example of molecule co-planarity is observed. Computational data show increased localization of negative charge on the pyridyl nitrogen as the electron-donating character of the aryl-substituent increases.

Active template strategy for the preparation of π-conjugated interlocked nanocarbons.

Mechanically interlocked carbon nanostructures represent a relatively unexplored frontier in carbon nanoscience due to the difficulty in preparing these unusual topological materials. Here we illustrate an active-template method in which a [n]cycloparaphenylene precursor macrocycle is decorated with two convergent pyridine donors that coordinate to a metal ion. The metal ion catalyses alkyne-alkyne cross-coupling reactions within the central cavity of the macrocycle, and the resultant interlocked products can be converted into fully π-conjugated structures in subsequent synthetic steps. Specifically, we report the synthesis of a family of catenanes that comprise two or three mutually interpenetrating [n]cycloparaphenylene-derived macrocycles of various sizes. Additionally, a fully π-conjugated [3]rotaxane was synthesized by the same method. The development of synthetic methods to access mechanically interlocked carbon nanostructures of varying topology can help elucidate the implications of mechanical bonding for this emerging class of nanomaterials and allow structure-property relationships to be established.

In Vitro Analysis of Biological Activity of Circulating Cell-Free DNA Isolated from Blood Plasma of Schizophrenic Patients and Healthy Controls-Part 2: Adaptive Response.

Oxidized in vitro genomic DNA (gDNA) is known to launch an adaptive response in human cell cultures. The cfDNA extracted from the plasma of schizophrenic patients (sz-cfDNA) and healthy controls (hc-cfDNA) contains increased amounts of 8-oxodG, a DNA-oxidation marker. The aim of the research was answering a question: can the human cfDNA isolated from blood plasma stimulate the adaptive response in human cells? In vitro responses of ten human skin fibroblasts (HSFs) and four peripheral blood mononuclear cell (PBMC) lines after 1-24 h of incubation with sz-cfDNA, gDNA and hc-cfDNA containing different amounts of 8-oxodG were examined. Expressions of RNA of eight genes (NOX4, NFE2L2, SOD1, HIF1A, BRCA1, BRCA2, BAX and BCL2), six proteins (NOX4, NRF2, SOD1, HIF1A, γH2AX and BRCA1) and DNA-oxidation marker 8-oxodG were analyzed by RT-qPCR and flow cytometry (when analyzing the data, a subpopulation of lymphocytes (PBL) was identified). Adding hc-cfDNA or sz-cfDNA to HSFs or PBMC media in equal amounts (50 ng/mL, 1-3 h) stimulated transient synthesis of free radicals (ROS), which correlated with an increase in the expressions of NOX4 and SOD1 genes and with an increase in the levels of the markers of DNA damage γH2AX and 8-oxodG. ROS and DNA damage induced an antioxidant response (expression of NFE2L2 and HIF1A), DNA damage response (BRCA1 and BRCA2 gene expression) and anti-apoptotic response (changes in BAX and BCL2 genes expression). Heterogeneity of cells of the same HSFs or PBL population was found with respect to the type of response to (sz,hc)-cfDNA. Most cells responded to oxidative stress with an increase in the amount of NRF2 and BRCA1 proteins along with a moderate increase in the amount of NOX4 protein and a low amount of 8-oxodG oxidation marker. However, upon the exposure to (sz,hc)-cfDNA, the size of the subpopulation with apoptosis signs (high DNA damage degree, high NOX4 and low NRF2 and BRCA1 levels) also increased. No significant difference between the responses to sz-cfDNA and hc-cfDNA was observed. Sz-cfDNA and hc-cfDNA showed similarly high bioactivity towards fibroblasts and lymphocytes. Conclusion: In cultured human cells, hc-cfDNA and sz-cfDNA equally stimulated an adaptive response aimed at launching the antioxidant, repair, and anti-apoptotic processes. The mediator of the development of the adaptive response are ROS produced by, among others, NOX4 and SOD1 enzymes.