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PD-L1 immunohistochemical staining does not always predict whether a cancer will respond to treatment with PD-1 inhibitors. We sought to characterize immune cell infiltrates and the expression of T-cell inhibitor markers in PD-L1–positive and PD-L1–negative malignant pleural mesothelioma samples. We developed a method for immune cell phenotyping using flow cytometry on solid tumors that have been dissociated into single-cell suspensions and applied this technique to analyze 43 resected malignant pleural mesothelioma specimens. Compared with PD-L1–negative tumors, PD-L1–positive tumors had significantly more infiltrating CD45+ immune cells, a significantly higher proportion of infiltrating CD3+ T cells, and a significantly higher percentage of CD3+ cells displaying the activated HLA-DR+/CD38+ phenotype. PD-L1–positive tumors also had a significantly higher proportion of proliferating CD8+ T cells, a higher fraction of FOXP3+/CD4+ Tregs, and increased expression of PD-1 and TIM-3 on CD4+ and CD8+ T cells. Double-positive PD-1+/TIM-3+ CD8+ T cells were more commonly found on PD-L1–positive tumors. Compared with epithelioid tumors, sarcomatoid and biphasic mesothelioma samples were significantly more likely to be PD-L1 positive and showed more infiltration with CD3+ T cells and PD-1+/TIM-3+ CD8+ T cells. Immunologic phenotypes in mesothelioma differ based on PD-L1 status and histologic subtype. Successful incorporation of comprehensive immune profiling by flow cytometry into prospective clinical trials could refine our ability to predict which patients will respond to specific immune checkpoint blockade strategies. Cancer Immunol Res; 4(12); 1038–48. ©2016 AACR.

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PDF file - 74K, Table describing clinical and molecular characteristics of NSCLC patients

figure legends for supplementary Table S1-S3 and supplementary Figure S1-S13

Supplemental Figure 1. Difference in CD3+ immune cell infiltrates by histologic subtype of mesothelioma. Supplemental Figure 2. Comparison of immune cell infiltrates among patients who received or did not receive neoadjuvant chemotherapy prior to surgical resection of their tumor. Supplemental Figure 3. Quantification of monocyte subtypes in tumor samples. Supplemental Figure 4. Comparison of immune cell infiltrates by mutational subtype in mesothelioma samples. Supplemental Figure 5. Statistical analysis of t-SNE maps from Figure 6. Supplemental Figure 6. Kaplan-Meier overall survival analysis for patients according to histologic subtype, PD-L1 immunohistochemical status, and CD3 infiltration as assessed by either flow cytometry or immunohistochemistry.

Introduction. The development of modern equipment and technologies for geological exploration and mining processes raises the problem of ensuring the reliability and durability of mechanic units operating under the conditions of elevated temperatures and pressures in the presence of aggressive external environments. In this regard, there is a need to create functional coatings with unique physical, mechanical and operational properties.Aim. To improve the performance of electrospark coatings based on an analysis of a cause-andeffect diagram and a regression study of the technological modes of processing steel units of geological exploration equipment (on the example of hydraulic cylinder rods of drilling pumps).Materials and methods. To harden the steel surfaces of hydraulic equipment parts, the technology of electrospark deposition (ESD) was used on an IMES-1001 mechanized installation using carbide electrodes and various gas media. In order to identify causal relationships between the factors affecting the hardened surface and to establish the most important factors affecting the quality of the formed coating, the Ishikawa diagram method was used and a regression analysis was performed. The adhesion activity of the obtained coatings was assessed by atomic force microscopy on a Solver PRO scanning probe microscope in a semi-contact air scanning mode using NSG10probe sensors with a resonance frequency of 219 kHz and a radius of curvature of the probe tip of 10 nm. When determining the strength of the adhesive interaction of the probe and the surface at one point, the absolute error was 15 nN. Tribological tests were carried out on a 2070-СМТ-1 standard friction machine according to the “disk-shoe” scheme.Results. The obtained cause-and-effect diagram showed that the technological modes of an electrospark deposition installation comprise a determining factor affecting the quality of the formed layers and coatings. In order to identify those process parameters that had the greatest effect, a regression analysis was carried out. The capacitance of the unit capacitors was found to have the greatest impact on the adhesion force formed by the ESD coating. Therefore, in order to reduce the strength of the adhesive interaction of surfaces and, as a result, increase their wear resistance, it is necessary to increase the capacitance of capacitors while reducing the voltage and processing time when implementing the ESD technology. On the basis of tribological tests, it is concluded that the minimum wear rate of coatings can be obtained by alloying the steel surface in an oxygen environment with a carbide electrode based on tungsten carbide with additives of elements that form unlimited solid solutions with the surface material and perform the role of fluxes (Ni-Cr-B-Si).Conclusion. Due to strict requirements to the performance of metal surfaces of units that enter into frictional interaction during the implementation of mining and exploration processes, there is a need to improve existing technologies for creating functional (wear-resistant) coatings.

Subject. This article discusses the application of the tax equity principle in practice, which helps reduce social stratification, combat poverty, as well as replenish the budget at the expense of personal income tax. Objectives. The article aims to substantiate the need to apply progressive taxation of individuals in a modern socially-oriented State. Methods. For the study, we used analysis and synthesis, historical method, and the dialectical approach. Results. The article highlights differences in approaches to the implementation of the tax equity principle in foreign countries and Russia. Conclusions and Relevance. The excessive level of inequality in Russia requires the urgent introduction of tools of socially oriented tax policy based on the classical principles of taxation. The results of the study can be applied in the higher education, as well as serve as a scientific justification for updating the regulatory framework in the field of taxation of individuals.

Purpose The purpose of this study is to investigate a novel rotor design model to improve the technical performance of a superconducting synchronous generator. Design/methodology/approach Superconducting synchronous generators with a modular rotating cryostat for a single coil of the superconducting winding instead of an old-style single cryostat in which all rotor components are cold are briefly discussed. Subsequently, a new method of cryostat arrangement in the magnetic system of a rotor is considered. Different options were compared for the cryostat placement. The advantages of the novel rotor design model are noted. Findings In the novel rotor design model, the leakage coefficient of the excitation winding decreases, and the air gap magnetic flux increases, which will save on a superconductor material. Research limitations/implications For the purposes of this investigation, a finite element study of flux distribution in the cross section of a superconducting synchronous generator with a 10 MW rating at 10 rpm was conducted, and the magnetic fluxes and air gap flux densities were obtained for different modes. For direct-drive superconducting synchronous generators with distributed winding and different pole numbers, the calculations of magnetic fluxes were carried out by calculating the magnetic conductivities. Originality/value A new method of the cryostat arrangement in the magnetic system of a rotor has been classified as an invention and was protected by a patent. This paper is directly applicable to the field of superconducting synchronous generators.

Detailed description of methodology and reagents

Статья рассматривает влияние системы образования на общество. Автором описываются различные аспекты влияния, такие как социальная мобильность, экономическое развитие, культурное развитие и формирование национальной идентичности, а также подчеркивается, что система образования может иметь как положительное, так и отрицательное влияние на общество, и важно постоянно совершенствовать ее для максимального использования ее потенциала.

Next generation sequencing copy number plots for Case #2

Summary of EGFR inhibitor resistant patient-derived xenografts.

Antibodies used in the study

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) are the standard-of-care treatment for EGFR-mutant non–small cell lung cancers (NSCLC). However, most patients develop acquired drug resistance to EGFR TKIs. HER3 is a unique pseudokinase member of the ERBB family that functions by dimerizing with other ERBB family members (EGFR and HER2) and is frequently overexpressed in EGFR-mutant NSCLC. Although EGFR TKI resistance mechanisms do not lead to alterations in HER3, we hypothesized that targeting HER3 might improve efficacy of EGFR TKI. HER3–DXd is an antibody–drug conjugate (ADC) comprised of HER3-targeting antibody linked to a topoisomerase I inhibitor currently in clinical development. In this study, we evaluated the efficacy of HER3–DXd across a series of EGFR inhibitor–resistant, patient-derived xenografts and observed it to be broadly effective in HER3-expressing cancers. We further developed a preclinical strategy to enhance the efficacy of HER3–DXd through osimertinib pretreatment, which increased membrane expression of HER3 and led to enhanced internalization and efficacy of HER3–DXd. The combination of osimertinib and HER3–DXd may be an effective treatment approach and should be evaluated in future clinical trials in EGFR-mutant NSCLC patients.Significance:EGFR inhibition leads to increased HER3 membrane expression and promotes HER3–DXd ADC internalization and efficacy, supporting the clinical development of the EGFR inhibitor/HER3–DXd combination in EGFR-mutant lung cancer.See related commentary by Lim et al., p. 18

Allelic Frequencies in PC-9 vs PC-9 T790M/C797S cells.

Purpose:The RET proto-oncogene encodes a receptor tyrosine kinase that is activated by gene fusion in 1%–2% of non–small cell lung cancers (NSCLC) and rarely in other cancer types. Selpercatinib is a highly selective RET kinase inhibitor that has recently been approved by the FDA in lung and thyroid cancers with activating RET gene fusions and mutations. Molecular mechanisms of acquired resistance to selpercatinib are poorly understood.Patients and Methods:We studied patients treated on the first-in-human clinical trial of selpercatinib (NCT03157129) who were found to have MET amplification associated with resistance to selpercatinib. We validated MET activation as a targetable mediator of resistance to RET-directed therapy, and combined selpercatinib with the MET/ALK/ROS1 inhibitor crizotinib in a series of single patient protocols (SPP).Results:MET amplification was identified in posttreatment biopsies in 4 patients with RET fusion–positive NSCLC treated with selpercatinib. In at least one case, MET amplification was clearly evident prior to therapy with selpercatinib. We demonstrate that increased MET expression in RET fusion–positive tumor cells causes resistance to selpercatinib, and this can be overcome by combining selpercatinib with crizotinib. Using SPPs, selpercatinib with crizotinib were given together generating anecdotal evidence of clinical activity and tolerability, with one response lasting 10 months.Conclusions:Through the use of SPPs, we were able to offer combination therapy targeting MET-amplified resistance identified on the first-in-human study of selpercatinib. These data suggest that MET dependence is a recurring and potentially targetable mechanism of resistance to selective RET inhibition in advanced NSCLC.

Antibodies, compounds, oligonucleotides, and other reagents used in the study

Supplementary Methods

Supplemental Figure 2

В статье рассматриваются социальные процессы в контексте глобализации. Глобализация оказывает существенное влияние на многие аспекты общественной жизни, включая межкультурные отношения, трудовые рынки, культурные стандарты и социальные институты. С одной стороны, глобализация может создавать новые возможности для бизнеса и культурного обмена. С другой стороны, она может вызывать социальное неравенство и угрожать культурной идентичности народов. Важно, чтобы общество умело адаптироваться к глобализации и использовать ее потенциал для достижения более благоприятного социального развития.

Supplementary Figures and legends

В статье рассмотрены современные методики обучения образовательным компетенциям, такие как коллаборативное обучение, проектное обучение, обучение на основе задач, онлайн-обучение, обратная связь и оценка, а также индивидуальный подход. Описаны основные принципы каждой из этих методик и их преимущества для учеников и учителей. Рассмотрение этих методик позволяет участникам образовательного процесса разнообразить формат обучения и достичь более эффективного усвоения знаний и навыков.

В статье рассматривается вопрос о том, как использование информационных технологий может помочь в обучении экономической тематике учеников. Автор отмечает, что информационные технологии могут помочь ученикам получить знания и навыки, повысить их мотивацию к изучению этой темы и обеспечить более интерактивное обучение. Однако важно учитывать, что информационные технологии не являются единственным решением для всех проблем в обучении экономике. В статье также подчеркивается необходимость правильного использования информационных технологий в обучении, а также индивидуального подхода к ученикам.

Статья рассматривает перспективы развития педагогической компетенции в современном образовании. Автором подробно описываются факторы, которые способствуют развитию педагогической компетенции, такие как профессиональное обучение, исследования, сотрудничество с коллегами, использование инновационных методов обучения и другие, а также рассматривается важность интеграции международного опыта и межкультурного обмена в образовательный процесс. В целом статья показывает, что постоянное обновление знаний и умений, сотрудничество с коллегами и использование новейших методов обучения являются ключевыми факторами для эффективного преподавания и обеспечения качественного образования для всех учащихся.

В статье рассматриваются основные тенденции и инновации в сфере образования, направленные на улучшение качества учебного процесса и повышение эффективности обучения. Подчеркивается важность перехода от традиционных методов обучения к новым технологиям и методикам, таким как обучение на основе данных, дистанционное обучение и обучение с использованием мобильных приложений. Рассмотрены преимущества и недостатки каждого из подходов, а также возможности их применения в современном образовании. В целом, статья показывает, каким образом современные подходы в обучении могут существенно повысить качество образования и подготовить учеников к решению реальных проблем в современном мире.

A unique controlled laser head with an adaptive module was developed to stabilize the trajectory of movement. The scientific and practical problem of developing a technology for restoring the inner surface of a small diameter up to ∅44 mm was solved by the introduction of a laser head. Adhesion was achieved by moving the laser along the vectors, forming a regular pyramid with opening angles at the top. High physical and mechanical properties of the restored pump surface were achieved by the laser technology when spraying powder composition 15Cr17Ni12V3F35ZrO2. The optimal values of the microhardness of the coating of 5000 MPa were achieved due to the optimal transition melting zone of 0.8 ÷ 1.45 mm; the laser radiation power density of 3 × 105 W/cm2; and the diameter of the focus spot of the laser beam of up to 1.3 mm. High corrosion resistance and tribology were achieved by an optimally matched distance of 10 ÷ 15 mm and a surfacing speed of 15 mm/s. Homogeneous spheroidized particles of the material were observed in the martensitic phase of the structure. The stable compression stresses in the phase structure during the laser deposition of zirconium dioxide were fixed at the level of 1.0 ÷ 1.5 N/m2, and the compression stresses were at the level of 0.2 ÷ 0.4 N/m2. A multifactorial experiment established the dependence of the coating hardness on the distance to the focal plane and the energy characteristics of the laser source, providing optimal laser parameters (area, pulse power, and duration).

Nowadays, magnetoelectric nanomaterials are on their way to finding wide applications in biomedicine for various cancer and neurological disease treatment, which is mainly restricted by their relatively high toxicity and complex synthesis. This study for the first time reports novel magnetoelectric nanocomposites of CoxFe3−xO4-BaTiO3 series with tuned magnetic phase structures, which were synthesized via a two-step chemical approach in polyol media. The magnetic CoxFe3−xO4 phases with x = 0.0, 0.5, and 1.0 were obtained by thermal decomposition in triethylene glycol media. The magnetoelectric nanocomposites were synthesized by the decomposition of barium titanate precursors in the presence of a magnetic phase under solvothermal conditions and subsequent annealing at 700 °C. X-ray diffraction revealed the presence of both spinel and perovskite phases after annealing with average crystallite sizes in the range of 9.0–14.5 nm. Transmission electron microscopy data showed two-phase composite nanostructures consisting of ferrites and barium titanate. The presence of interfacial connections between magnetic and ferroelectric phases was confirmed by high-resolution transmission electron microscopy. Magnetization data showed expected ferrimagnetic behavior and σs decrease after the nanocomposite formation. Magnetoelectric coefficient measurements after the annealing showed non-linear change with a maximum of 89 mV/cm*Oe with x = 0.5, 74 mV/cm*Oe with x = 0, and a minimum of 50 mV/cm*Oe with x = 0.0 core composition, that corresponds with the coercive force of the nanocomposites: 240 Oe, 89 Oe and 36 Oe, respectively. The obtained nanocomposites show low toxicity in the whole studied concentration range of 25–400 μg/mL on CT-26 cancer cells. The synthesized nanocomposites show low cytotoxicity and high magnetoelectric effects, therefore they can find wide applications in biomedicine.

Background Assessment of ‘physiological stress levels’ and ‘nutritional status’ before surgery is important for predicting complications and indirect interventions on the pancreas. The aim of this study was to determine neutrophil-lymphocyte ratio (NLR) and nutritional risk index (NRI) indicators before surgery to predict 90-day complications and mortality in a cohort of patients with complicated chronic pancreatitis and cancer of the head of the pancreas. Methods We evaluated preoperative levels of NLR and NRI among 225 subjects treated at different centres located in three countries. Short-term outcomes included length of hospital stay, postoperative complications, and mortality at 90 days and were appreciated based on NLR and NRI. The level of physiological stress was divided according by the formulas: neutrophil-lymphocyte ratio (NLR) = (neutrophil count, %)/(lymphocyte count, %). The nutritional state of the patients was divided according to the INR: NRI = (1.519 x serum albumin, g/L) + (41.7 x present weight, kg / usual weight, kg)] Results All patients were operated. An analysis of the operations performed in three institutions demonstrated mortality in chronic pancreatitis and pancreatic pseudocysts in 1.4 %, in chronic pancreatitis and the presence of an inflammatory mass mainly in the pancreatic head in 1.2 %, and in cancer of the pancreatic head in 5.9 %. The mean preoperative NLR was normal in 33.8% of the patients, the mild physiologic stress level was 54.7%, and the moderate was 11.5% before surgery. 10.2% of patients had a normal nutritional status, 20% had mild, 19.6% had moderate, and 50.2% had severe malnutrition. In a univariate analysis, at the cutoff of NLR³9.5 (AUC=0.803) and the cutoff of NRI≤98.5 (AUC=0.801), increasing the risk of complications was observed (hazard ratio, 2.01; 95% CI, 1.247-3.250, p=0.006), but at the cutoff of NRI≤83.55 (AUC=0.81), we observed a survival difference in operated patients (hazard ratio, 2.15; 95% CI, 1.334-3.477, p=0.0025). Conclusions Our study demonstrated that NLR and NRI were predictors of postoperative complications, but only NRI was a predictor of 90-day mortality in patients after surgery.

Activation of c-Jun N-terminal kinases (JNKs) is involved in myocardial injury, left ventricular remodeling (LV), and heart failure (HF) after myocardial infarction (MI). The aim of this research was to evaluate the effects of a selective JNK inhibitor, 11H-indeno [1,2-b]quinoxalin-11-one oxime (IQ-1), on myocardial injury and acute myocardial ischemia/reperfusion (I/R) in adult male Wistar rats. Intraperitoneal administration of IQ-1 (25 mg/kg daily for 5 days) resulted in a significant decrease in myocardial infarct size on day 5 after MI. On day 60 after MI, a significant (2.6-fold) decrease in LV scar size, a 2.2-fold decrease in the size of the LV cavity, a 2.9-fold decrease in the area of mature connective tissue, and a 1.7-fold decrease in connective tissue in the interventricular septum were observed compared with the control group. The improved contractile function of the heart resulted in a significant (33%) increase in stroke size, a 40% increase in cardiac output, a 12% increase in LV systolic pressure, a 28% increase in the LV maximum rate of pressure rise, a 45% increase in the LV maximum rate of pressure drop, a 29% increase in the contractility index, a 14% increase in aortic pressure, a 2.7-fold decrease in LV end-diastolic pressure, and a 4.2-fold decrease in LV minimum pressure. We conclude that IQ-1 has cardioprotective activity and reduces the severity of HF after MI.

This pilot study aimed at comparing zinc (Zn) and nickel (Ni) effects on the fatty acid (FA) profiles, oxidative stress and desaturase activity in the Zn hyperaccumulator Arabidopsis halleri and the excluder Arabidopsis lyrata to allow a better picture of the physiological mechanisms which may contribute to metal tolerance or acclimation. The most significant changes in the FA composition were observed in the shoots of the hyperaccumulator and in the roots of the excluder, and were not only metal-dependent, but also species-specific, since the most significant changes in the shoots of A. halleri were observed under Ni treatment, though Ni, in contrast to Zn, was accumulated mainly in its roots. Several FAs appeared in the roots and shoots of A. lyrata only upon metal exposure, whereas they were already found in control A. halleri. In both species, there was an increase in oleic acid under Ni treatment in both organs, whereas in Zn-treated plants the increase was shown only for the shoots. A rare conjugated α-parinaric acid was identified only in the shoots of metal-treated A. halleri. In the shoots of the hyperaccumulator, there was an increase in the content of saturated FAs and a decrease in the content of unsaturated FAs, while in the roots of the excluder, the opposite pattern was observed. These metal-induced changes in FA composition in the shoots of A. halleri can lead to a decrease in the fluidity of membranes, which could diminish the penetration of ROS into the membrane and thus maintain its stability.

Intermediate uveitis is among most severe forms of endogenous uveitis which is more common in young people, being characterized by minimal clinical manifestations at early stages of the disorder. A significant and, sometimes, irreversible decrease in visual acuity is associated with development of long-term complications of chronic cintermediate uveitis (CIU), i.e., complicating cataracts (in up to 57% of the cases), cystic maular edema developing at a frequency of up to 31%), as well as ophthalmic hypertension and glaucoma (up to 16% of the patients). The incidence rate of CIU is 1.5 per 100,000 per year. The eye, despite its high immune privilege, is susceptible to infectious and inflammatory diseases. Clinical and histopathological data suggest autoimmune origin of CIU associated with possible response to some endogenous antigen of unknown origin. The main effectors of inflammation in peripheral chorioretinal structures are CD4+T lymphocytes, which are found in paravasal infiltrates and vitreoretinal exudates in CIU. An important role in CIU pathogenesis is attributed to IL-6 and IL-8, TNFá, vascular endothelial growth factor (VEGF), and micro-RNAs, which show increased expression in most CIU patients. Impaired state of intestinal bacterial microbiome is a potential trigger of intraocular inflammation. Genetic predisposition for CIU was also revealed, due to polymorphisms of human leukocyte antigens and some other genes. It is necessary to expand and deepen our knowledge on the disease pathogenesis, in order to develop effective pharmacological treatment of CIU. The article is review of literature discussing the modern scientific ideas concerning etiology and mechanisms of the CIU development.

Introduction. The results of numerous studies indicating the relationship between the development of reactive arthritis (ReA) and the disturbance of the intestinal microbiocenosis give rise to interest in commensal microorganisms that make up the intestinal microbiota as potential initiators of immune-dependent inflammatory diseases of the joints. In this regard, the question of the expediency of using probiotic preparations for the correction of ReA patients intestinal microflora is of practical interest.The purpose of the study was to evaluate the effectiveness of Lactobacillus rhamnosus LGG (LGG) in the preventive treatment of children with ReA to prevent the development of relapses.Materials and methods. Clinical and microbiological study included 60 patients with ReA from 3 to 17 years old, who were divided into two groups, 30 children each. Patients of the group 1 received courses of treatment with LGG in the inactive phase of the disease. Patients of the group 2 (comparison group) were not treated with probiotic. The criteria for the effectiveness of treatment were the number of relapses of ReA during follow-up observation for 1 year; dynamics of intestinal microbiocenosis condition according to the following parameters: indicator of microbial contamination (IMC) of intestinal microsymbionts; ability to biofilm formation (BF); levels of lactoferrin and lysozyme in coprofiltrates.Results. In patients treated with LGG, relapses of arthritis were significantly less frequent during 12 months of prospective observation relative to the comparison group. Patients of the group 1 showed positive dynamics of the state of intestinal microbiocenosis: a decrease in the severity of dysbiosis, a decrease of lactoferrin and lysozyme level in coprofiltrates, IMC and BF of opportunistic microorganisms against the increase IMC and BF in bifidobacteria and lactobacilli.Conclusions. The use of LGG in the treatment of children with ReA in the inactive phase of the disease contributes to the correction of intestinal microbiocenosis disorders and reduces the number of arthritis relapses.

The aim of the study was to study the effectiveness of the method of photodynamic therapy of purulent wounds in conditions of experimental diabetes mellitus. Materials and methods. Experimental studies were carried out on 30 mature male Wistar rats, which were injected with diabetogenic cytotoxin streptozotocin to induce type 2 diabetes mellitus, and also simulated a purulent wound. Various combinations of topical treatments have been used for treatment. A comparative analysis of the use of various methods of treating purulent wounds was carried out using the following methods: clinical, bacteriological, planimetric, histological, and statistical data processing. Results and discussion. In the course of clinical observation, it was found that a day after the modeling of infected wounds, the general condition of the animals could be assessed as moderate: the animals were lethargic, inactive, some of them had sanious discharge from the nose. Wounds in all animals had signs of suppuration: accumulation of liquid fibrinous-hemorrhagic exudate was noted in the cavity of the ring, in some animals there was no exudate. in two experimental groups (B and C), PDT sessions were performed according to the plan; in the control group (A), the wounds were treated with chlorhexidine solution. During the experiment, it was shown that the proposed method for the treatment of purulent wounds against the background of diabetes mellitus makes it possible to optimize the wound process, reduce the time for the appearance of granulations and the filling of mature granulation wounds. The use of photodynamic therapy contributed to the rapid cleansing of wounds, the appearance and marginal epithelization. Microbiological examination testified to the rapid decontamination of wounds. Сonclusions. The use of the photosensitizer 5-ALA in the complex of wound treatment under conditions of photoactivation enhances the antibacterial, anti-inflammatory and pro-regenerative effects; This opens up the possibility of a promising use of this complex for antibacterial photodynamic therapy as a new method for the treatment of infectious and inflammatory diseases of the skin and soft tissues in diabetes mellitus.

FUS1/TUSC2 (FUSion1/TUmor Suppressor Candidate 2) is a tumor suppressor gene (TSG) originally described as a member of the TSG cluster from human 3p21.3 chromosomal region frequently deleted in lung cancer. Its role as a TSG in lung, breast, bone, and other cancers was demonstrated by several groups, but molecular mechanisms of its activities are starting to unveil lately. They suggest that Fus1-dependent mechanisms are relevant in etiologies of diseases beyond cancer, such as chronic inflammation, bacterial and viral infections, premature aging, and geriatric diseases. Here, we revisit the discovery of FUS1 gene in the context of tumor initiation and progression, and review 20 years of research into FUS1 functions and its molecular, structural, and biological aspects that have led to its use in clinical trials and gene therapy. We present a data-driven view on how interactions of Fus1 with the mitochondrial Ca2+ (mitoCa2+) transport machinery maintain cellular Ca2+ homeostasis and control cell apoptosis and senescence. This Fus1-mediated cellular homeostasis is at the crux of tumor suppressor, anti-inflammatory and anti-aging activities.

Forests cover one-third of the planet’s land surface. Forests are essential for maintaining a clean environment, food security and biodiversity. Forests are also a source of food for animals. In the processing of forest resources, the forest industry accumulates various forest biomass wastes containing valuable and nutritious biologically active substances. The article provides an overview of the current state of the art in applying forest industry waste to feed farm animals and poultry. The authors presented the characteristics of biological properties of plant forestry raw materials and described the mechanism of their action on the animal organism. The authors analysed the results of studies of domestic and foreign scientists on feeding animals and poultry with feed additives containing pine needles and pine nutshells. The authors also characterised the possible advantages and disadvantages of using feed additives. The analysis of Russian and foreign scientific literature in the area under study has shown that forest industry waste in feed production and animal feeding is relevant as the available fodder base does not always allow to satisfy the need of animals for nutrients and biologically active substances. It has been noted that pine needles are used worldwide as a feed additive, but in the countries with the most significant areas of forests and developed forest industry, their use is the most common and effective. The use of cedar nut shells in the feeding of farm animals and poultry is most produced in Russia, while this area is underdeveloped in the world. The literature review has confirmed that using forest industry wastes such as pine nut needles and shells in animal feed production is promising livestock production.

An efficient approach to the gram-scale synthesis of 3(5)-substituted, 1,3- and 1,5-disubstituted 1,2,4-triazole-derived building blocks is described. The key synthetic precursors - 1,2,4-triazole-3(5)-carboxylates (20 examples, 35-89% yield) were prepared from readily available acyl hydrazides and ethyl 2-ethoxy-2-iminoacetate hydrochloride. Further transformations were performed following the convergent synthetic strategy and allowed the preparation of 1,3- and 1,5-disubstituted 1,2,4-triazole-derived esters (16 examples, 25-75% yield), 3(5)-substituted, 1,3- and 1,5-disubstituted carboxylate salts (18 examples, 78-93% yield), amides (5 examples, 82-93% yield), nitriles (5 examples, 30-85% yield), hydrazides (6 examples, 84-89% yield), and hydroxamic acids (3 examples, 73-78% yield). Considering wide applications of the 1,2,4-triazole motif in medicinal chemistry, these compounds are valuable building blocks for lead-oriented synthesis; they have also great potential for coordination chemistry.The online version contains supplementary material available at 10.1007/s10593-022-03064-z.