Design and Implementation of Brief Interventions to Address Noncommunicable Diseases in Uzbekistan.

In Uzbekistan, NCDs, including cardiovascular diseases, cancer, and diabetes, accounted for over 80% of mortality in 2019. In 2021, national stakeholders, in conjunction with the World Health Organization, identified brief interventions (BIs) to implement in primary health care settings to change unhealthy behaviors and reduce the burden of NCDs in the country. BIs consist of a validated set of questions to identify and measure NCD behavioral risk factors and a short conversation with patients/clients about their behavior, as well as the provision of a referral opportunity for further in-depth counseling or treatment if needed. We used a multimethod approach of document review, participatory workshops, and key informant interviews to describe how BIs were designed and implemented in Uzbekistan and generated a theory of change for its large-scale implementation. BIs in Uzbekistan targeted 4 risk factors (alcohol use, tobacco use, unhealthy diet, and physical inactivity) and entailed training clinicians on how to conduct behavioral change counseling using the 5As and 5Rs toolkit, conducting supportive supervision, and using feedback to improve service delivery. The program was collaboratively designed by multiple stakeholders across sectors, including the Ministries of Health, Higher Education, Science, and Innovations, with buy-in from key political leaders. The potential impact of the program (i.e., reducing the incidence of NCDs) was mediated by several intermediate and implementation outcomes at the individual, primary care, and community levels operating along multiple pathways. Significant health system challenges remain to the program, such as limited human resources, lack of incentives for clinicians, outdated systems and data collection processes for performance monitoring, and coordination among different relevant sectors. These and other challenges will need to be addressed to ensure the effective large-scale implementation of BIs in Uzbekistan and similar LMICs.

Implementation of School Nutrition Policies to Address Noncommunicable Diseases in Uzbekistan and Kyrgyzstan.

Noncommunicable diseases (NCDs), including cardiovascular diseases, cancer, and diabetes, account for over 80% of mortality in Uzbekistan and Kyrgyzstan in 2019, and unhealthy dietary behaviors are a major risk factor for NCDs in both countries. In 2021, national stakeholders, in consultation with the World Health Organization, identified school nutrition policies (SNPs) as a major approach to reducing the burden of NCDs in both countries. The SNPs included interventions implemented through a multistakeholder and multisectoral arrangement that aimed to improve the health and nutrition status of children and young people by providing healthy food/beverages and restricting unhealthy foods or beverages in schools. We used a multimethod approach of document review, participatory workshops, and key informant interviews to generate theories of change for the large-scale implementation of SNPs and describe the implementation processes to date, including key implementation and health system challenges, salient implementation strategies, and implementation outcomes in both countries. Multiple pathways for enacting and implementing SNPs successfully were identified. However, significant health system challenges, such as the lack of accountability for contracting and tender processes and coordination among different sectors, continue to hamper the large-scale implementation of these policies in both countries. The pathways, theories, and implementation outcomes identified will facilitate the development of implementation strategies and systematic learning and evaluation around SNPs for NCD prevention and control programs in the Central Asian region and other low- and middle-income countries more broadly.

Synthesis, cytotoxicity and antioxidant activity of new conjugates of N-acetyl-d-glucosamine with α-aminophosphonates.

A series of the first conjugates of N-acetyl-d-glucosamine with α-aminophosphonates was synthesized using the Kabachnik-Fields reaction, the Pudovik reaction, a copper(I)-catalyzed azide-alkyne cycloaddition reaction (CuAAC) and evaluated for the in vitro cytotoxicity against human cancer cell lines M - HeLa, HuTu-80, A549, PANC-1, MCF-7, T98G and normal lung fibroblast cells WI-38. The tested conjugates, with exception of compound 21b, considered as a lead compound, were either inactive against the used cancer cells or showed moderate cytotoxicity in the range of IC50 values 33-80 µM. The lead compound 21b, being non cytotoxic against normal human cells WI-38 (IC50 = 90 µM), demonstrated good activity (IC50 = 17 µM) against breast adenocarcinoma cells (MCF-7) which to be 1.5 times higher than the activity of the used reference anticancer drug tamoxifen (IC50 = 25.0 µM). A flexible receptor molecular docking simulation showed that the cytotoxicity of the synthesized conjugates of N-acetyl-d-glucosamine with α-aminophosphonates against breast adenocarcinoma MCF-7 cell line is due to their ability to inhibit EGFR kinase domain. In addition, it was found that conjugates 22a and 22b demonstrated antioxidant activity that was not typical for α-aminophosphonates.

Assessing and Forecasting Fatigue Strength of Metals and Alloys under Cyclic Loads.

Within the scope of this research, patterns of changes in the fatigue life and limit of metals under cyclic stress were identified and the most informative parameters were determined as the basis for developing a method for the universal transformation of experimental data on the fatigue of metals and alloys for their subsequent generalization. Experimental data on metal fatigue, obtained by a large number of authors for a wide range of grades of steels and alloys, under the influence of various combinations of factors, were systematized. A generalized dependence of the recalculated parameters of fatigue life and limit was obtained, its characteristics were assessed, and a sensitivity analysis was performed, confirming the universal nature of the obtained dependence. A system of parameters has been proposed making it possible to consider and forecast high-cycle fatigue processes for a wide range of metals and alloys, under the conditions of various combinations of operating factors, from unified positions and a more general point of view.

Irreversible inhibition of estrogen receptor α signaling and the emergence of hormonal resistance in MCF7 breast cancer cells induced by DNA damage agents.

Combining chemotherapy and hormone therapy is a prevalent approach in breast cancer treatment. While the cytotoxic impact of numerous chemotherapy drugs stems from DNA damage, the exact role of these DNA alterations in modulating estrogen receptor α (ERα) machinery remains elusive. The present study aimed to analyze the impact of DNA damage agents on ERα signaling in breast cancer cells and assess the signaling pathways mediating the influence of DNA damage drugs on the ERα machinery. Cell viability was assessed using the MTT method, while the expression of signaling proteins was analyzed by immunoblotting. ERα activity in the cells treated with various drugs (17ß-estradiol, tamoxifen, 5-fluorouracil) was assessed through reporter gene assays. In vitro experiments were conducted on MCF7 breast cancer cells subjected to varying durations of 5-fluorouracil (5-FU) treatment. Two distinct cell responses to 5-FU were identified based on the duration of the treatment. A singular dose of 5-FU induces pronounced DNA fragmentation, temporally suppressing ERα signaling while concurrently activating AKT phosphorylation. This suppression reverses upon 5-FU withdrawal, restoring normalcy within ten days. However, chronic 5-FU treatment led to the emergence of 5-FU-resistant cells with irreversible alterations in ERα signaling, resulting in partial hormonal resistance. These changes mirror those observed in cells subjected to UV-induced DNA damage, underscoring the pivotal role of DNA damage in shaping estrogen signaling alterations in breast cancer cells. In summary, the results of the present study suggested that the administration of DNA damage agents to cancer cells can trigger irreversible suppression of estrogen signaling, fostering the development of partial hormonal resistance. This outcome may ultimately impede the efficacy of combined or subsequent chemo- and hormone therapy strategies.

Exosomes are involved in the intercellular transfer of rapamycin resistance in the breast cancer cells.

Introduction: Resistance to chemotherapy and/or irradiation remains one of the key features of malignant tumors, which largely limits the efficiency of antitumor therapy. In this work, we studied the progression mechanism of breast cancer cell resistance to target drugs, including mTOR blockers, and in particular, we studied the exosome function in intercellular resistance transfer. Methods: The cell viability was assessed by the MTT assay, exosomes were purified by successive centrifugations, immunoblotting was used to evaluate protein expression, AP-1 activity was analyzed using reporter assay. Results: In experiments on the MCF-7 cell line (breast cancer) and the MCF-7/Rap subline that is resistant to rapamycin, the capability of resistant cell exosomes to trigger a similar rapamycin resistance in the parent MCF-7 cells was demonstrated. Exosome-induced resistance reproduces the changes revealed in MCF-7/Rap resistant cells, including the activation of ERK/AP-1 signaling, and it remains for a long time, for at least several months, after exosome withdrawal. We have shown that both the MCF-7 subline resistant to rapamycin and cells having exosome-triggered resistance demonstrate a stable decrease in the expression of DNMT3A, the key enzyme responsible for DNA methylation. Knockdown of DNMT3A in MCF-7 cells by siRNA leads to partial cell resistance to rapamycin; thus, the DNMT3A suppression is regarded as one of the necessary elements for the development of acquired rapamycin resistance. Conclusion: We propose that DNA demethylation followed by increased expression of key genes may be one of the factors responsible for the progression and maintenance of the resistant cell phenotype that includes exosome-induced resistance.

Application of the Concept of Land Degradation Neutrality for Remote Monitoring of Agricultural Sustainability of Irrigated Areas in Uzbekistan.

A scientific approach to the assessment of trends in land changes based on the novel concept of Land Degradation Neutrality (LDN) was applied to monitor the sustainability of irrigated farmlands in test areas in Uzbekistan (the Andijan, Namangan, Fergana, and Syrdarya regions). The tool "Trends.Earth", which was recommended by the UN Convention to Combat Desertification and developed as a special plugin for the Quantum GIS platform, was used to describe the dynamics of land degradation in the period 2001-2020. This study demonstrates the results of monitoring land productivity dynamics that reflect the investments in irrigation improvement during the last 10-15 years. A comparison between changes in land productivity measured via Normalized Difference Vegetation Index and its average value for the entire observation period is more informative than comparison with the initial 5-year period. More details could be noted through application of the "moving average" calculation method. The described trends demonstrate that the use of sustainable land management practices in the last decade led to a decreasing proportion of degraded lands compared to the average figure for the period 2001-2020 (from 25-40% to 10-20%). This trend is confirmed by reviewing state statistics and indicates the success of national policies and approaches to adaptation. However, the dynamics of land productivity in the study areas is diverse and includes "dry" and "humid" extremes, depending on climate fluctuations. Despite the generally positive trends identified across regions, the high dynamics of degraded hotspots and improved lands within certain areas confirm the instability of ongoing changes.

Laser-Induced Chirality of Plasmonic Nanoparticles Embedded in Porous Matrix.

Chiral plasmonic nanostructures have emerged as promising objects for numerous applications in nanophotonics, optoelectronics, biosensing, chemistry, and pharmacy. Here, we propose a novel method to induce strong chirality in achiral ensembles of gold nanoparticles via irradiation with circularly-polarized light of a picosecond Nd:YAG laser. Embedding of gold nanoparticles into a nanoporous silicate matrix leads to the formation of a racemic mixture of metal nanoparticles of different chirality that is enhanced by highly asymmetric dielectric environment of the nanoporous matrix. Then, illumination with intense circularly-polarized light selectively modifies the particles with the chirality defined by the handedness of the laser light, while their "enantiomers" survive the laser action almost unaffected. This novel modification of the spectral hole burning technique leads to the formation of an ensemble of plasmonic metal nanoparticles that demonstrates circular dichroism up to 100 mdeg. An unforeseen peculiarity of the chiral nanostructures obtained in this way is that 2D and 3D nanostructures contribute almost equally to the observed circular dichroism signals. Thus, the circular dichroism is neither even nor odd under reversal of direction of light propagation. These findings will help guide the development of a passive optical modulator and nanoplatform for enhanced chiral sensing and catalysis.

Characterizing Fall Circumstances in Community-Dwelling Older Adults: A Mixed Methods Approach.

BACKGROUND: Understanding fall circumstances can help researchers better identify causes of falls and develop effective and tailored fall prevention programs. This study aims to describe fall circumstances among older adults from quantitative data using conventional statistical approaches and qualitative analyses using a machine learning approach. METHODS: The MOBILIZE Boston Study enrolled 765 community-dwelling adults aged 70 years and older in Boston, MA. Occurrence and circumstances of falls (ie, locations, activities, and self-reported causes of falls) were recorded using monthly fall calendar postcards and fall follow-up interviews with open- and close-ended questions during a 4-year period. Descriptive analyses were used to summarize circumstances of falls. Natural language processing was used to analyze narrative responses from open-ended questions. RESULTS: During the 4-year follow-up, 490 participants (64%) had at least 1 fall. Among 1 829 falls, 965 falls occurred indoors and 804 falls occurred outdoors. Commonly reported activities when the fall occurred were walking (915, 50.0%), standing (175, 9.6%), and going down stairs (125, 6.8%). The most commonly reported causes of falls were slip or trip (943, 51.6%) and inappropriate footwear (444, 24.3%). Using qualitative data, we extracted more detailed information on locations and activities, and additional information on obstacles related to falls and commonly reported scenarios such as "lost my balance and fell." CONCLUSIONS: Self-reported fall circumstances provide important information on both intrinsic and extrinsic factors contributing to falls. Future studies are warranted to replicate our findings and optimize approaches to analyzing narrative data on fall circumstances in older adults.

Discovery of highly potent proapoptotic antiestrogens in a series of androst-5,16-dienes D-modified with imidazole-annulated pendants.

Heterocyclic derivatives of steroid hormones are potent anticancer agents, which are used in the chemotherapy of breast and prostate cancers. Here, we describe a novel series of androstenes, D-modified with imidazole-annulated pendants, with significant anticancer activity. Novel C17-linked imidazole-annulated heterocyclic derivatives of dehydropregnenolone acetate were synthesized by the cyclocondensation with amidines using 3ß-acetoxy-21-bromopregna-5,16-dien-20-one as the substrate. The antiproliferative potency of all the synthesized compounds was evaluated against human prostate (22Rv1) and human breast (MCF7) cancer cell lines and cytochromes P450. The lead compound, imidazo[1,2-a]pyridine derivative 3h, was revealed to be a promising candidate for future anticancer drug design, particularly against ERα-positive breast cancer. Lead compound 3h was found to be selective against MCF7 cells with IC50 of 0.1 µM and to act as both a potent selective agent blocking estrogen receptor α, which is involved in the stimulation of breast cancer growth, and an effective apoptosis inducer. The potential ability of compound 3h to bind to ERα was studded using molecular docking and molecular dynamics simulation. The selectivity analysis showed that lead steroid 3h produces no effects on cytochromes P450 CYP17A1, CYP7A1, and CYP21A2.

Novel pentacyclic derivatives and benzylidenes of the progesterone series cause anti-estrogenic and antiproliferative effects and induce apoptosis in breast cancer cells.

The promising antitumor effects of progesterone derivatives have been identified in many studies. However, the specific mechanism of action of this class of compounds has not been fully described. Therefore, in this study, we investigated the antiproliferative and (anti)estrogenic activities of novel pentacyclic derivatives and benzylidenes of the progesterone series. The antiproliferative effects of the compounds were evaluated on hormone-dependent MCF7 breast cancer cells using the MTT test. Estrogen receptor α (ERα) activity was assessed by a luciferase-based reporter assay. Immunoblotting was used to evaluate the expression of signaling proteins. All benzylidenes demonstrated inhibitory effects with IC50 values below 10 µM, whereas pentacyclic derivatives were less active. These patterns may be associated with the lability of the geometry of benzylidene molecules, which contributes to an increase in the affinity of interaction with the receptor. The selected compounds showed significant anti-estrogenic potency. Benzylidene 1d ((8 S,9 S,10R,13 S,14 S,17 S)-17-[(2E)-3-(4-fluorophenyl)prop-2-enoyl]-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15-decahydrocyclopenta[a]phenanthren-3-one) was the most active in antiproliferative and anti-estrogenic assays. Apoptosis induced by compound 1d was accompanied by decreases in CDK4, ERα, and Cyclin D1 expression. Compounds 1d and 3d were characterized by high inhibitory potency against resistant breast cancer cells. Apoptosis induced by the leader compounds was confirmed by PARP cleavage and flow cytometry analysis. Compound 3d caused cell arrest in the G2/M phase. Further analysis of novel derivatives of the progesterone series is of great importance for medicinal chemistry, drug design, and oncology.

Secosteroid-quinoline hybrids as new anticancer agents.

An elegant approach to unknown secosteroid-quinoline hybrids is disclosed. A series of 13,17-secoestra-1,3,5(10)-trien-17-oic acid [N'-(iso)quinolylmethylene]hydrazides was prepared and these novel type of secosteroids was screened for antiproliferative activity against estrogen-responsive human breast cancer cell line MCF-7. Most of the synthesized compounds showed a cytotoxic effect superior to that of reference drug cisplatin; the lead compound exhibits the highest activity with the IC50 value of about 0.8 µM and is 7 times more active than cisplatin. A high selectivity index was observed for the hit 13,17-secoestra-1,3,5(10)-trien-17-oic acid [N'-quinolylmethylene]hydrazides 2a and 2c. Compounds 2a and 2c evaluated in luciferase reporter assays exhibited high antiestrogenic potency which was superior to that of tamoxifen. These hit compounds were characterized by high activity against MCF-7 cells that retained towards multidrug-resistant NCI/ADR-RES cells.

Detection of A and B Influenza Viruses by Surface-Enhanced Raman Scattering Spectroscopy and Machine Learning.

We demonstrate the possibility of applying surface-enhanced Raman spectroscopy (SERS) combined with machine learning technology to detect and differentiate influenza type A and B viruses in a buffer environment. The SERS spectra of the influenza viruses do not possess specific peaks that allow for their straight classification and detection. Machine learning technologies (particularly, the support vector machine method) enabled the differentiation of samples containing influenza A and B viruses using SERS with an accuracy of 93% at a concentration of 200 µg/mL. The minimum detectable concentration of the virus in the sample using the proposed approach was ~0.05 µg/mL of protein (according to the Lowry protein assay), and the detection accuracy of a sample with this pathogen concentration was 84%.

Synthesis and biological activity of 21,22-cyclosteroids and their derivatives.

Synthesis of 21,22-cyclosteroids has been achieved starting from pregnenolone acetate. The key transformation was the Kulinkovich reaction of 17-vinyl steroids with esters. The resulting cyclopropanols were further subjected to three-membered ring-opening under various conditions including to base-, palladium or visible light-promoted isomerization and cross-coupling reaction. A number of steroidal Δ2-6-ketones and 3ß-hydroxy-Δ5-enes with functional groups at C-21 - C-23 have been synthesized via the 21,22-cyclosteroids. The antiproliferative and antihormonal activity of the obtained compounds on the cell lines of prostate (22Rv1) and breast (MCF-7) cancer was studied. The androgen receptor activity was assessed by reporter assay when the expression of signalling proteins was evaluated by immunoblotting. (20S,22R)-22-Acetoxy-21,22-cyclo-5α-cholest-5-ene with the moderate antiandrogenic potency revealed IC50 values of 18.4 ± 1.2 and 14.6 ± 1.4 µM against MCF-7 and 22Rv1 cells, respectively, and its effects on the expression of AR-V7, cyclin D1 and BCL2 were explored.

The First 5'-Phosphorylated 1,2,3-Triazolyl Nucleoside Analogues with Uracil and Quinazoline-2,4-Dione Moieties: A Synthesis and Antiviral Evaluation.

A series of 5'-phosphorylated (dialkyl phosphates, diaryl phosphates, phosphoramidates, H-phosphonates, phosphates) 1,2,3-triazolyl nucleoside analogues in which the 1,2,3-triazole-4-yl-ß-D-ribofuranose fragment is attached via a methylene group or a butylene chain to the N-1 atom of the heterocycle moiety (uracil or quinazoline-2,4-dione) was synthesized. All compounds were evaluated for antiviral activity against influenza virus A/PR/8/34/(H1N1). Antiviral assays revealed three compounds, 13b, 14b, and 17a, which showed moderate activity against influenza virus A (H1N1) with IC50 values of 17.9 µM, 51 µM, and 25 µM, respectively. In the first two compounds, the quinazoline-2,4-dione moiety is attached via a methylene or a butylene linker, respectively, to the 1,2,3-triazole-4-yl-ß-D-ribofuranosyl fragment possessing a 5'-diphenyl phosphate substituent. In compound 17a, the uracil moiety is attached via the methylene unit to the 1,2,3-triazole-4-yl-ß-D-ribofuranosyl fragment possessing a 5'-(phenyl methoxy-L-alaninyl)phosphate substituent. The remaining compounds appeared to be inactive against influenza virus A/PR/8/34/(H1N1). The results of molecular docking simulations indirectly confirmed the literature data that the inhibition of viral replication is carried out not by nucleoside analogues themselves, but by their 5'-triphosphate derivatives.

Using co-production to implement patient reported outcome measures in third sector organisations: a mixed methods study.

BACKGROUND: Third sector organisations such as charities and community groups are using Patient Reported Outcome Measures (PROMs) at an aggregated service level to demonstrate their impact to commissioners to generate or retain funding. Despite this motivation, organisations can struggle with implementing PROMs. Previous studies have identified facilitators including organisations using an appropriate measure, co-producing the PROMs process with staff, and investing resources to support the use of measures. However, to date no studies have applied this learning to third sector organisations to evaluate whether taking an evidence-informed implementation approach improves the use of PROMs. METHODS: A Community-Based Participatory Research approach was used which involved university-based researchers supporting two third sector organisations to implement PROMs. The researchers provided evidence-informed advice and training. The organisations were responsible for implementing PROMs. The researchers evaluated implementation through a mixed methods approach including five key informant interviews, four evaluation groups and analysis of collected PROMs data (n = 313). RESULTS: Both third sector organisations faced considerable constraints in incorporating known facilitators and addressing barriers. The organisations involved staff in choosing an acceptable measure. However, competing priorities including external pressures to use specific PROMs, busy workloads and staff opinions created challenges to using measures. Investment of time and energy into developing an outcomes-based organisational culture was key to enable the prioritisation of PROMs. For example, discussing PROMs in supervision so that they were viewed as part of people's job roles. Organisations found that implementation took several years and was disrupted by other pressures. CONCLUSIONS: Whilst organisations were motivated to implement PROMs to obtain or retain funding, they faced considerable practical and ideological challenges. Consequently, some stakeholders felt that alternative methods to measuring impact could potentially be more feasible than PROMs.

Fall risk assessment through a synergistic multi-source DNN learning model.

Falls are a complex problem and play a leading role in the development of disabilities in the older population. While fall detection systems are important, it is also essential to work on fall preventive strategies, which will have the most significant impact in reducing disability in the elderly. In this work, we explore a prospective cohort study, specifically designed for examining novel risk factors for falls in community-living older adults. Various types of data were acquired that are common for real-world applications. Learning from multiple data sources often leads to more valuable findings than any of the data sources can provide alone. However, simply merging features from disparate datasets usually will not produce a synergy effect. Hence, it becomes crucial to properly manage the synergy, complementarity, and conflicts that arise in multi-source learning. In this work, we propose a multi-source learning approach called the Synergy LSTM model, which exploits complementarity among textual fall descriptions together with people's physical characteristics. We further use the learned complementarities to evaluate fall risk factors present in the data. Experiment results show that our Synergy LSTM model can significantly improve classification performance and capture meaningful relations between data from multiple sources.

Towards Unravelling the Role of ERα-Targeting miRNAs in the Exosome-Mediated Transferring of the Hormone Resistance.

Hormone therapy is one of the most effective breast cancer treatments, however, its application is limited by the progression of hormonal resistance, both primary or acquired. The development of hormonal resistance is caused either by an irreversible block of hormonal signalling (suppression of the activity or synthesis of hormone receptors), or by activation of oestrogen-independent signalling pathways. Recently the effect of exosome-mediated intercellular transfer of hormonal resistance was revealed, however, the molecular mechanism of this effect is still unknown. Here, the role of exosomal miRNAs (microRNAs) in the transferring of hormonal resistance in breast cancer cells has been studied. The methods used in the work include extraction, purification and RNAseq of miRNAs, transfection of miRNA mimetics, immunoblotting, reporter analysis and the MTT test. Using MCF7 breast cancer cells and MCF7/T tamoxifen-resistant sub-line, we have found that some miRNAs, suppressors of oestrogen receptor signalling, are overexpressed in the exosomes of the resistant breast cancer cells. The multiple (but not single) transfection of one of the identified miRNA, miR-181a-2, into oestrogen-dependent MCF7 cells induced the irreversible tamoxifen resistance associated with the continuous block of the oestrogen receptor signalling and the activation of PI3K/Akt pathway. We suppose that the miRNAs-ERα suppressors may act as trigger agents inducing the block of oestrogen receptor signalling and breast cancer cell transition to an aggressive oestrogen-independent state.

Synthesis, antimicrobial activity and cytotoxicity of triphenylphosphonium (TPP) conjugates of 1,2,3-triazolyl nucleoside analogues.

Four new triphenylphosphonium (TPP) conjugates of 1,2,3-triazolyl nucleoside analogues were synthesized by coupling with 8-bromoctyl- or 10- bromdecyltriphenylphosphonium bromide and evaluated for the in vitro antibacterial activity against S. aureus, B. cereus, E. faecalis, two MRSA strains isolated from patients and resistant to fluoroquinolone antibiotic ciprofloxacin and ß-lactam antibiotic amoxicillin, E. coli, antifungal activity against T. mentagrophytes C. albicans and cytotoxicity against human cancer cell lines M-HeLa, MCF-7, A549, HuTu-80, PC3, PANC-1 and normal cell line Wi-38. In these compounds a TPP cation was attached via an octyl or a decyl linker to the N 3 atom of the heterocycle moiety (thymine, 6-methyluracil, quinazoline-2,4-dione) which was bonded with 2',3',5'-tri- O - acetyl-greek beta-d-ribofuranose residue by the (1,2,3-triazol-4-il)methyl bridge. All synthesized compounds showed high antibacterial activity against S. aureus within the range of MIC values 1.2-4.3 greek muM, and three of them appeared to be bactericidal with respect to tis bacterium at MBC values 4.1-4.3 greek muM. Two lead compounds showed both high antibacterial activity against the MRSA strains resistant to Ciprofloxacin and Amoxicillin within the range of MIC values 1.0-4.3 greek muM and high cytotoxicity against human cancer cell lines HuTu-80 and MCF-7 within the range of IC50 values 6.4-10.2 greek muM. This is one of the few examples when phosphonium salts exhibited both antibacterial activity and cytotoxicity against human cancer cell lines. According to the results obtained the bactericidal effect of the lead compounds, unlike classical surfactants, was not caused by a violation of the integrity of the cytoplasmic membrane of bacteria and their cytotoxic activity is most likely associated both with the induction of apoptosis along the mitochondrial pathway and the arrest of the cell cycle in the G0/G1 phase.