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Abstract Nanostructured surfaces are effective at physically killing bacterial cells, highlighting their prospective application as biomaterials. The benefits of application of mechano‐bactericidal nanostructures as an alternative to chemical functionalisation are well documented, however, the effects of protein adsorption are not well understood. In this work, theoretical and experimental analyses are conducted by studying the adsorption of human serum proteins (HSP) to nanosheet titanium (Ti) and its subsequent effect on the mechano‐bactericidal efficacy toward Staphylococcus aureus and Pseudomonas aeruginosa cells. The nanosheet pattern exhibits enhanced antibiofouling behaviour mantaining high bactericidal efficiency toward both Gram‐negative and Gram‐positive cells in the presence of adsorbed HSP. To ascertain the immunomodulatory response, S. aureus cells are introduced to protein‐conditioned Ti nanosheet surfaces prior to introducing RAW 264.7 macrophages. On the pre‐infected nanostructured surfaces, macrophages exhibit wound healing behaviour with superior activation of M2‐like macrophage polarization and secretion of anti‐inflammatory cytokines. By contrast, macrophages attached to infected smooth surfaces activated the M1‐like polarized phenotype via the high expression of pro‐inflammatory cytokines, indicating persistent inflammation. The outcomes of this work demonstrate the suitability of Ti nanosheets as a potential biomaterial surface whereby the mechano‐bactericidal activity is not compromised by HSP adsorption and, furthermore, positively influenced an anti‐inflammatory immune response.

Objective. To determine incidence rate and risk factors for the development of venous thromboembolism in complicated cervical spine injury. Material and Methods. The study included 34 patients with acute complicated cervical spine injury. Inclusion criteria were newly diagnosed venous thromboembolic complications, and application of low-frequency piezothromboelastography to study the hemostasis system. All patients received standard drug thromboprophylaxis. Patients were divided into two study groups: Group I included 21 patients with venous thromboembolic complications, and Group II – 13 patients without thromboembolic complications. Results. The incidence of venous thromboembolism in the total sample was 61.8 %. Pulmonary artery embolism developed in 4.7 % of cases. In 91,0 % of cases, thrombosis was asymptomatic. The state of the hemostatic system in Group I before the start of thromboprophylaxis was characterized by chronometric hypocoagulation, and structural hypercoagulation with a 2.6-fold increase in the intensity of clot retraction and lysis. In Group II, there was chronometric and structural hypercoagulation with a 14.4-fold increase in the intensity of clot retraction and lysis. The main significant predictors of the development of venous thromboembolism were identified as intestinal paresis (p = 0.004), absence of changes in neurological status (p = 0.012), length of stay in the ICU (p = 0.025), and length of hospital stay (p = 0.039). The building of a multivariate logistic regression model revealed multiplicative significant predictors of the development of thromboembolism. It has been shown that the presence of intestinal paresis is associated with a 25.07-fold increase in the chances of developing DVT of lower extremities. Conclusion. Considering the high incidence of venous thromboembolic complications in patients with complicated cervical spine injury, further research is required to study the effectiveness and safety of correction of drug thromboprophylaxis regimens in the form of increasing doses of anticoagulants or the frequency of their administration.

Abstract One of the major hurdles that has hindered the success of chimeric antigen receptor (CAR) T cell therapies against solid tumors is on-target off-tumor (OTOT) toxicity due to sharing of the same epitopes on normal tissues. To elevate the safety profile of CAR-T cells, an affinity/avidity fine-tuned CAR was designed enabling CAR-T cell activation only in the presence of a highly expressed tumor associated antigen (TAA) but not when recognizing the same antigen at a physiological level on healthy cells. Using direct stochastic optical reconstruction microscopy (dSTORM) which provides single-molecule resolution, and flow cytometry, we identified high carbonic anhydrase IX (CAIX) density on clear cell renal cell carcinoma (ccRCC) patient samples and low-density expression on healthy bile duct tissues. A Tet-On doxycycline-inducible CAIX expressing cell line was established to mimic various CAIX densities, providing coverage from CAIX-high skrc-59 tumor cells to CAIX-low MMNK-1 cholangiocytes. Assessing the killing of CAR-T cells, we demonstrated that low-affinity/high-avidity fine-tuned G9 CAR-T has a wider therapeutic window compared to high-affinity/high-avidity G250 that was used in the first anti-CAIX CAR-T clinical trial but displayed serious OTOT effects. To assess the therapeutic effect of G9 on patient samples, we generated ccRCC patient derived organotypic tumor spheroid (PDOTS) ex vivo cultures and demonstrated that G9 CAR-T cells exhibited superior efficacy, migration and cytokine release in these miniature tumors. Moreover, in an RCC orthotopic mouse model, G9 CAR-T cells showed enhanced tumor control compared to G250. In summary, G9 has successfully mitigated OTOT side effects and in doing so has made CAIX a druggable immunotherapeutic target.

Affinity chromatography is a widely used technique for antibody isolation. This article presents the successful synthesis of a novel affinity resin with a mutant form of protein A (BsrtA) immobilized on it as a ligand. The key aspect of the described process is the biocatalytic immobilization of the ligand onto the matrix using the sortase A enzyme. Moreover, we used a matrix with primary amino groups without modification, which greatly simplifies the synthesis process. The resulting resin shows a high dynamic binding capacity (up to 50 mg IgG per 1 mL of sorbent). It also demonstrates high tolerance to 0.1 M NaOH treatment and maintains its effectiveness even after 100 binding, elution, and sanitization cycles.

This article discusses the mountain metonymy of the Urals, i.e. the designation of supernatural anthropomorphic creatures that store the riches of the subsoil (minerals and metals) and contribute to or hinder their discovery, extraction, and processing. Russian mountain mythology has been studied by folklorists, but the linguistic aspect is only beginning to be explored. The material for the article was collected in the field between 2020 and 2023, and derived from dictionaries, folklore texts, and authorial literature. The author mostly focuses on Middle Ural and South Ural mythonyms; for comparison, the article draws on material of other zones connected with the Urals geographically or historically (Bashkiria, Siberia). The article provides detailed descriptions of the motivations of mythonyms and the conditions for the appearance of nominations. Mountain mythonymy can be divided into several groups depending on the motivation, i. e. the thematic group of vocabulary underlying the mythonym. This article analyses mythonyms motivated by social vocabulary, namely, denoting a person or kinship: золотая девка (golden girl), каменная девка (stone girl), горная девка (mountain girl), чудская девица (Chudskaya maiden), горный батюшка (mountain father), горная матка (mountain mother), Шубин (Shubin), etc. The article reveals and explains the specificity of Ural mountain mythonymy: thus, the девка token is used for the nomination of female spirits, whereas the баба nomination is characteristic of traditional Russian peasant mythology. An expressive feature of Ural mountain mythonymy is the presence of mythonyms formed from toponyms (девка Азовка, девка Дедюрка). The article proves that the formation of mountain mythonymy was influenced by the mythology of the Russian peasantry, the mythology of the autochthonous peoples of the Urals (Turkic and Finno-Ugric), as well as the terminology of mining actively developing in the Urals in the eighteenth and nineteenth centuries.