Application of carbon nanostructures in biomedicine: realities, difficulties, prospects.

The review systematizes data on the wide possibilities of practical application of carbon nanostructures. Much attention is paid to the use of carbon nanomaterials in medicine for the visualization of tumors during surgical interventions, in the creation of cosmetics, as well as in agriculture in the creation of fertilizers. Additionally, we demonstrate trends in research in the field of carbon nanomaterials with a view to elaborating targeted drug delivery systems. We also show the creation of nanosized medicinal substances and diagnostic systems, and the production of new biomaterials. A separate section is devoted to the difficulties in studying carbon nanomaterials. The review is intended for a wide range of readers, as well as for experts in the field of nanotechnology and nanomedicine.

On Haptotropic Rearrangements of Diphosphene and Diarsene Ligands in Titanium Complexes.

Dipnictenes of the type RE=ER (E=P, As, Sb, Bi) are the isovalence electronic heavier analogs of alkenes. Although diphosphenes and dipnictenes in general show a variety of binding modes in metal complexes, little is known about haptotropic shift reactions involving these ligands. Herein, we report an unprecedented η2 to η1 rearrangement of the dipnictene ligands in titanocene complexes of the type Cp2Ti(Pn2Ar2) (Pn=P, As; Ar=2,4,6-Me3-C6H2, Mes; 2,6-iPr2-C6H3, Dip; 2,4,6-iPr3-C6H2, Tip), initiated by Lewis basic ligands (L=MeCN, PMe3, AdNC, CO). In the presence of L the dipnictene ligand changes its hapticity from η2 to η1 and complexes of the general form Cp2Ti(L)(Pn2Ar2) with a succinctly different electronic structure are obtained. Electronically, the new complexes are best described as biradicaloids with antiferromagnetically coupled (via a π-bond) [Cp2TiIII]⋅+ and [Pn2Ar2]⋅- fragments. However, the biradical character of these systems is affected by the electronic features of the co-ligand and significantly decreases moving from PMe3/MeCN (σ-donors) to CNAd/CO (σ-donors/π-acceptors).

AI-Based Approach to One-Click Chronic Subdural Hematoma Segmentation Using Computed Tomography Images.

This paper presents a computer vision-based approach to chronic subdural hematoma segmentation that can be performed by one click. Chronic subdural hematoma is estimated to occur in 0.002-0.02% of the general population each year and the risk increases with age, with a high frequency of about 0.05-0.06% in people aged 70 years and above. In our research, we developed our own dataset, which includes 53 series of CT scans collected from 21 patients with one or two hematomas. Based on the dataset, we trained two neural network models based on U-Net architecture to automate the manual segmentation process. One of the models performed segmentation based only on the current frame, while the other additionally processed multiple adjacent images to provide context, a technique that is more similar to the behavior of a doctor. We used a 10-fold cross-validation technique to better estimate the developed models' efficiency. We used the Dice metric for segmentation accuracy estimation, which was 0.77. Also, for testing our approach, we used scans from five additional patients who did not form part of the dataset, and created a scenario in which three medical experts carried out a hematoma segmentation before we carried out segmentation using our best model. We developed the OsiriX DICOM Viewer plugin to implement our solution into the segmentation process. We compared the segmentation time, which was more than seven times faster using the one-click approach, and the experts agreed that the segmentation quality was acceptable for clinical usage.

The Advantages of Non-Adhesive Gel-like Embolic Materials in the Endovascular Treatment of Benign Hypervascularized Lesions of the Head and Neck.

OBJECTIVES: The use of non-adhesive gel-like embolic materials (NAGLEMs) in the endovascular treatment of hypervascularized formations in the head and neck is gaining in popularity because of a number of important characteristics involved. Their primary benefits are their capacity to penetrate diseased vasculature, effectively distribute, and, most importantly, remain controllable during the process. We reviewed the literature and evaluated the results of using NAGLEMs in comparison to other embolizing substances (namely, coils, glue, and particles) as alternative embolizing agents for patients receiving care at our clinic. The process comprised evaluating the safety, effectiveness, and technological elements of endovascular therapy used to treat two categories of hypervascular pathological abnormalities that were surgically corrected between 2015 and 2023. Arteriovenous malformations (AVMs) located in the head, neck, and paragangliomas with jugular/carotid body localization are combined by intense shunting blood flow and shared requirements for the embolic agent used in endovascular treatment (such as penetration, distribution, delayed polymerization, and controllability). An analysis of the literature was also conducted. Results showed 18 patients diagnosed with neck paragangliomas of the carotid body and jugular type. Five patients with arteriovenous malformation (AVM) of the face and neck were included, consisting of sixteen females and seven males with an average age of 55 ± 13 years. Endovascular procedures were performed using NAGLEMs (ONYX (Medtronic, Irvine, CA, USA), SQUID (Balt, Montmorency, France), and PHIL (Microvention, Tustin, CA, USA)) and dimethyl sulfoxide (DMSO)-compatible balloon catheters. All patients achieved complete or partial embolization of hypervascularized formations using one or more stages of endovascular treatment. Additionally, three AVMs of the face and two paragangliomas of the neck were surgically excised following embolization. In other instances, formations were not deemed necessary to be removed. The patients' condition upon discharge was assessed by the modified Rankin Scale (mRs) and rated between 0 and 2. CONCLUSION: Currently, NAGLEMs are predominantly used to treat hypervascularized formations in the neck and head due to their fundamental properties. These properties include a lack of adhesion and a delay in predictable polymerization (after 30-40 min). NAGLEMs also exhibit excellent distribution and penetration throughout the vascular bed of the formation. Adequate controllability of the process is largely achieved through the presence of embolism forms of different viscosity, as well as excellent X-ray visualization.

Mathematical Method of Rational Placement of Gas Fire Sensors.

Ensuring fire safety is an important condition for the successful operation of industrial enterprises. It is necessary to detect the threat of fire before the ignition. An indicator of danger is the appearance of gas, which occurs as a result of unauthorized heating of the equipment. Gas sensors make it possible to detect the appearance of gases characteristic for the decomposition of materials at the stage of smouldering and pyrolysis, which cause a change in the composition of the atmosphere. This paper presents a mathematical method for the rational placement of gas analyzers in the premises of potentially hazardous industries. The rational placement of gas sensors ensures safety, taking into account economic feasibility. For the first time, an analysis of the accumulation of gas flow from the source to the ceiling, and then to the location of the sensors, was used to select the location of gas sensors. Depending on the permissible values of the gas volume, the placement and number of gas sensors are selected. The calculation of the conditions for the rational placement of gas sensors is carried out according to the most common indicators, such as carbon monoxide and hydrogen at different sizes and heights of premises.

C60 adduct with L-arginine as a promising nanomaterial for treating cerebral ischemic stroke.

The work aimed to investigate the biocompatibility and biological activity of the water-soluble fullerene adduct C60-Arg. It was found that the material is haemocompatible, is not cyto- and genotoxic, possesses pronounced antioxidant activity. Additionally, this paper outlines the direction of application of water-soluble fullerene adducts in the creation of neuroprotectors. It has been suggested that a putative mechanism of the protective action of the C60-Arg adduct is associated with its antioxidant properties, the ability to penetrate the blood-brain barrier, and release nitrogen monoxide as a result of the catabolism of L-arginine residues, which promote vascular relaxation. The action of the C60-Arg adduct was compared with the action of such an antioxidant as Edaravone, which is approved in Japan for the treatment of ischemic and haemorrhagic strokes.

Incorporating resilience when assessing pandemic risk in the Arctic: a case study of Alaska.

The discourse on vulnerability to COVID-19 or any other pandemic is about the susceptibility to the effects of disease outbreaks. Over time, vulnerability has been assessed through various indices calculated using a confluence of societal factors. However, categorising Arctic communities, without considering their socioeconomic, cultural and demographic uniqueness, into the high and low continuum of vulnerability using universal indicators will undoubtedly result in the underestimation of the communities' capacity to withstand and recover from pandemic exposure. By recognising vulnerability and resilience as two separate but interrelated dimensions, this study reviews the Arctic communities' ability to cope with pandemic risks. In particular, we have developed a pandemic vulnerability-resilience framework for Alaska to examine the potential community-level risks of COVID-19 or future pandemics. Based on the combined assessment of the vulnerability and resilience indices, we found that not all highly vulnerable census areas and boroughs had experienced COVID-19 epidemiological outcomes with similar severity. The more resilient a census area or borough is, the lower the cumulative death per 100 000 and case fatality ratio in that area. The insight that pandemic risks are the result of the interaction between vulnerability and resilience could help public officials and concerned parties to accurately identify the populations and communities at most risk or with the greatest need, which, in turn, helps in the efficient allocation of resources and services before, during and after a pandemic. A resilience-vulnerability-focused approach described in this paper can be applied to assess the potential effect of COVID-19 and similar future health crises in remote regions or regions with large Indigenous populations in other parts of the world.

Theoretical simulation and experimental design of selenium and gold incorporated polymer-based microcarriers for ROS-mediated combined photothermal therapy.

Recently, multi-modal combined photothermal therapy (PTT) with the use of photo-active materials has attracted significant attention for cancer treatment. However, drug carriers enabling efficient heating at the tumor site are yet to be designed: this is a fundamental requirement for broad implementation of PTT in clinics. In this work, we design and develop hybrid carriers based on multilayer capsules integrated with selenium nanoparticles (Se NPs) and gold nanorods (Au NRs) to realize reactive oxygen species (ROS)-mediated combined PTT. We show theoretically and experimentally that cooperative interaction of Se NPs with Au NRs improves the heat release efficiency of the developed capsules. In addition, after uptake by tumor cells, intracellular ROS level amplified by Se NPs inhibits the tumor growth. As a consequence, the synergy between Se NPs and Au NRs exhibits the advantages of hybrid carriers such as (i) improved photothermal conversion efficiency and (ii) dual-therapeutic effect. The results of in vitro and in vivo experiments demonstrate that the combination of ROS-mediated therapy and PTT has a higher tumor inhibition efficiency compared to the single-agent treatment (using only Se-loaded or Au-loaded capsules). Furthermore, the developed hybrid carriers show negligible in vivo toxicity towards major organs such as the heart, lungs, liver, kidneys and spleen. This study not only provides a potential strategy for the design of multifunctional "all-in-one" carriers, but also contributes to the development of combined PTT in clinical practice.

Development of Nanocarrier-Based Radionuclide and Photothermal Therapy in Combination with Chemotherapy in Melanoma Cancer Treatment.

Conventional cancer therapy methods have serious drawbacks that are related to the nonspecific action of anticancer drugs that leads to high toxicity on normal cells and increases the risk of cancer recurrence. The therapeutic effect can be significantly enhanced when various treatment modalities are implemented. Here, we demonstrate that the radio- and photothermal therapy (PTT) delivered through nanocarriers (gold nanorods, Au NRs) in combination with chemotherapy in a melanoma cancer results in complete tumor inhibition compared to the single therapy. The synthesized nanocarriers can be effectively labeled with 188Re therapeutic radionuclide with a high radiolabeling efficiency (94-98%) and radiochemical stability (>95%) that are appropriate for radionuclide therapy. Further, 188Re-Au NRs, mediating the conversion of laser radiation into heat, were intratumorally injected and PTT was applied. Upon the irradiation of a near-infrared laser, dual photothermal and radionuclide therapy was achieved. Additionally, the combination of 188Re-labeled Au NRs with paclitaxel (PTX) has significantly improved the treatment efficiency (188Re-labeled Au NRs, laser irradiation, and PTX) compared to therapy in monoregime. Thus, this local triple-combination therapy can be a step toward the clinical translation of Au NRs for use in cancer treatment.

Clinical and Morphological Evaluation of Erosive and Ulcerative Gastric Lesions in Patients with Rheumatoid Arthritis.

BACKGROUND: One of the most important problems associated with the treatment of Rheumatoid Arthritis (RA) is erosive-ulcerative lesions (EUL) of the gastroduodenal zone, which is associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs). AIMS: Our research aims to study the clinical and histo-morphological criteria for forming the EUL of the gastroduodenal zone in patients with RA. METHODS: Patients were divided into 3 groups, depending on the presence of an EUL, according to Fibrogastroduodenoscopy (FGDS) data with a negative test for H. pylori. Group 1 included RA patients without EUL (n = 18), group 2 RA patients with erosive lesions of the gastroduodenal zone (n = 57), and group 3 consisted of RA patients with ulcerative lesions (n = 17). As a norm, we used data from a survey of 18 healthy donors corresponding to RA patient's age and sex distribution, where no somatic pathology was revealed. GSRS questionnaire was used for assessment of subjective symptoms. For histomorphological studies, biopsy specimens were taken during FGDS using an Olympus Evis Exera II digital video endoscope. RESULTS: Patients of RA with EUL in the gastro-duodenal zone were significantly different from the group of healthy donors and patients of group 1 by the severity of 5 symptoms related to the upper gastrointestinal tract according to the GSRS questionnaire, including abdominal pain, heartburn, belching acid, a feeling of sucking and burning in epigastria, nausea and vomiting. In general, there were no clinically significant differences between the frequency of occurrence and the severity of symptoms on the GSRS scale between group 2 and group 3, except for complaints of heartburn. So, RA patients of group 3 had a higher rate of heartburn feeling of 3.0 (2.0-3.0) points than patients of group 2 with 2.0 (1.0-2.0) points. CONCLUSION: The development of a EUL of the gastroduodenal zone in patients with RA is associated with low activity of inflammation in all studied slides, regardless of structurally destructive changes in the stomach and duodenum and compensatory hyperplastic reactions in the superficial layer of mucosa membrane, which can be determined by minimal subjective sensations or even complete absence of clinical manifestations with the formation of "silent ulcers", complicated by bleeding and perforation.

Regional geographies and public health lessons of the COVID-19 pandemic in the Arctic.

Objectives: This study examines the COVID-19 pandemic's spatiotemporal dynamics in 52 sub-regions in eight Arctic states. This study further investigates the potential impact of early vaccination coverage on subsequent COVID-19 outcomes within these regions, potentially revealing public health insights of global significance. Methods: We assessed the outcomes of the COVID-19 pandemic in Arctic sub-regions using three key epidemiological variables: confirmed cases, confirmed deaths, and case fatality ratio (CFR), along with vaccination rates to evaluate the effectiveness of the early vaccination campaign on the later dynamics of COVID-19 outcomes in these regions. Results: From February 2020 to February 2023, the Arctic experienced five distinct waves of COVID-19 infections and fatalities. However, most Arctic regions consistently maintained Case Fatality Ratios (CFRs) below their respective national levels throughout these waves. Further, the regression analysis indicated that the impact of initial vaccination coverage on subsequent cumulative mortality rates and Case Fatality Ratio (CFR) was inverse and statistically significant. A common trend was the delayed onset of the pandemic in the Arctic due to its remoteness. A few regions, including Greenland, Iceland, the Faroe Islands, Northern Canada, Finland, and Norway, experienced isolated spikes in cases at the beginning of the pandemic with minimal or no fatalities. In contrast, Alaska, Northern Sweden, and Russia had generally high death rates, with surges in cases and fatalities. Conclusion: Analyzing COVID-19 data from 52 Arctic subregions shows significant spatial and temporal variations in the pandemic's severity. Greenland, Iceland, the Faroe Islands, Northern Canada, Finland, and Norway exemplify successful pandemic management models characterized by low cases and deaths. These outcomes can be attributed to successful vaccination campaigns, and proactive public health initiatives along the delayed onset of the pandemic, which reduced the impact of COVID-19, given structural and population vulnerabilities. Thus, the Arctic experience of COVID-19 informs preparedness for future pandemic-like public health emergencies in remote regions and marginalized communities worldwide that share similar contexts.

Biocompatibility and biological activity of C70 fullerene adduct with L-threonine (C70(C4H9NO3)2).

The aim of this work is to synthesise and study the biocompatibility and biological activity of the C70 fullerene adduct with l-threonine (C70-Thr). The obtained adduct was identified using a complex of physicochemical methods, namely, 13C NMR spectroscopy, IR spectroscopy, thermogravimetric analysis, electron spectroscopy, elemental analysis, and high-performance liquid chromatography. The study of biocompatibility and biological activity of the C70-Thr adduct included the study of haemocompatibility (haemolysis, platelet aggregation, plasma coagulation haemostasis, binding to human serum albumin, esterase activity), antiradical activity, cytotoxicity, cell proliferation, and interaction with DNA (determination of the DNA binding constant and genotoxicity).

Angiogenetic Factors in Chronic Subdural Hematoma Development.

The levels of angiogenic factors were analyzed in eight patients who underwent the embolization of chronic subdural hematoma (CSDH) with non-adhesive liquid embolic agents. Four of these patients had previously undergone surgical treatment for hematoma removal and had recurrences of a similar volume, and four had an increase in hematoma volume due to rebleeding. The levels of vascular endothelial growth factor (VEGF), matrix metallopeptidase 9 (MMP 9), angiopoietin-2 (Ang2), transforming growth factor beta 1 (TGF-ß1) and platelet-derived growth factor BB (PDGF-BB) in the arterial and venous blood were analyzed. The most significant results were obtained from the peripheral venous blood samples. The levels of VEGF in the samples of all the patients were close to normal or slightly decreased. There was an increase in the MMP9 levels (the factor that contributes to the disintegration of the vessel wall components) in all the patients. The Ang2 and especially the PDGF TGF-ß1 (the factor that plays an important role in the growth of the vessel wall from the already existing blood vessel tissue) levels were distinctly low in most of the cases and slightly elevated only in a number of patients who had previously been operated on. The results obtained show that there is an imbalance in the angiogenesis factors in patients with rebleeding CSDH. At the same time, the factors determining the formation of the vessel wall were reduced, and the levels of factors contributing to the degradation of extracellular matrix components were significantly increased. Such factors could help us to anticipate the increased risk of hemorrhages. Highlights: The levels of VEGF, MMP 9, Ang2, TGF-ß1 and PDGF-BB in the arterial and venous blood were analyzed. The most significant results were obtained from the peripheral venous blood samples. The results obtained show that there is an imbalance in the angiogenesis factors in patients with rebleeding CSDH. Such a profile of factors could help us to anticipate the increased risk of hemorrhages.

Reactivity of Sodium Pentaphospholide Na[cyclo-P5 ] towards C≡E (E=C, N, P) Triple Bonds.

A diglyme solution of Na[cyclo-P5 ] (1) reacts with alkynes and isolobal nitriles and phosphaalkynes to afford the otherwise elusive (aza)phospholide anions 2 a-c, 4 a,b, and 6. The reaction of Na[cyclo-P5 ] with alkynes and nitriles was studied by means of DFT methods, which suggested a concerted mechanism for the formation of 2 a and 4 b. The anions 2 a-c, 4 a,b, and 6 coordinate in an η5 -fashion towards FeII to give the sandwich (aza)phosphametallocenes 3 a-c, 5 a,b and 7 in moderate to good yields. The new compounds were characterized by means of multinuclear NMR spectroscopy, single-crystal X-ray diffraction and cyclic voltammetry.

Ultrafast signatures of magnetic inhomogeneity in Pd1- x Fe x (x ≤ 0.08) epitaxial thin films.

A series of Pd1- x Fe x alloy epitaxial films (x = 0, 0.038, 0.062, and 0.080), a material promising for superconducting spintronics, was prepared and studied with ultrafast optical and magneto-optical laser spectroscopy in a wide temperature range of 4-300 K. It was found that the transition to the ferromagnetic state causes a qualitative change of both the reflectivity and the magneto-optical Kerr effect transients. A nanoscale magnetic inhomogeneity of the ferromagnet/paramagnet type inherent in the palladium-rich Pd1- x Fe x alloys reveals itself through the occurrence of a relatively slow, 10-25 ps, photoinduced demagnetization component following a subpicosecond one; the former vanishes at low temperatures only in the x = 0.080 sample. We argue that the 10 ps timescale demagnetization originates most probably from the diffusive transport of d electrons under the condition of nanoscale magnetic inhomogeneities. The low-temperature fraction of the residual paramagnetic phase can be deduced from the magnitude of the slow reflectivity relaxation component. It is estimated as ≈30% for x = 0.038 and ≈15% for x = 0.062 films. The minimal iron content ensuring the magnetic homogeneity of the ferromagnetic state in the Pd1- x Fe x alloy at low temperatures is about 7-8 atom %.

Single and double deprotonation/dearomatization of the N,S-donor pyridinophane ligand in ruthenium complexes.

We report a series of ruthenium complexes with a tetradentate N,S-donor ligand, 2,11-dithia[3.3](2,6)pyridinophane (N2S2), that undergo single and double deprotonation in the presence of a base leading to the deprotonation of one or both pyridine rings. Both singly and doubly deprotonated complexes were structurally characterized by single-crystal X-ray diffraction. The NMR spectra are indicative of the dearomatization of one or both pyridine rings upon the deprotonation of the CH2-S arm, similar to the dearomatization of phosphine-containing pincer ligands. The deprotonated (N2S2)Ru complexes did not show appreciable catalytic or stoichiometric reactivity in transfer hydrogenation, hydrogenation and dehydrogenation of alcohols, and attempted activation of H2, CO2, and other substrates. Such a lack of reactivity is likely due to the low stability of the deprotonated species as evident from the structural characterization of one of the decomposition products in which shrinkage of the macrocyclic ring occurs via picolyl arm migration.