ATM, SLC22A1, SLC47A1, and SLC2A2 genes with metformin response in 299 patients with T2DM. Likewise, the distribution of allele and genotype frequencies of the studied gene variants was analyzed in an extended group of patients with T2DM (n = 464) and a population group (n = 129). According to our results, one variant, rs12208357 in the SLC22A1 gene, had a significant impact on response to metformin in T2DM patients. Carriers of TT genotype and T allele had a lower response to metformin compared to carriers of CC/CT genotypes and C allele . To identify the parameters that had the greatest importance for the prediction of the therapy response to metformin, we next built a set of machine learning models, based on the various combinations of genetic and phenotypic characteristics. The model based on a set of four parameters, including gender, rs12208357 genotype, familial T2DM background, and waist–hip ratio (WHR) showed the highest prediction accuracy for the response to metformin therapy in patients with T2DM . Further pharmacogenetic studies may aid in the discovery of the fundamental mechanisms of type 2 diabetes, the identification of new drug targets, and finally, it could advance the development of personalized treatment.Metformin is an oral hypoglycemic agent widely used in clinical practice for treatment of patients with type 2 diabetes mellitus (T2DM). The wide interindividual variability of response to metformin therapy was shown, and recently the impact of several genetic variants was reported. To assess the independent and combined effect of the genetic polymorphism on glycemic response to metformin, we performed an association analysis of the variants in  Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by insulin resistance and progressive pancreatic Beta cell dysfunction. The etiology of the disorder is known to have a significant genetic component that is confirmed by family- and twin-based studies . MetformATM, SLC22A1, SLC47A1, and SLC2A2 genes and therapeutic responses to metformin. A protein encoded by the ATM gene belongs to the phosphatidylinositol 3-kinase family of proteins involved in the processes of DNA repair and/or cell cycle control. Mutations in this gene play a causative role in ataxia telangiectasia, an autosomal recessive disorder. The variant rs11212617 near the ATM gene was demonstrated to be associated with the response to metformin therapy in a GWA study in a GoDART (Genetics of Diabetes Audit and Research in Tayside) cohort of European ancestry, and in some other studies [SLC22A1, SLC47A1, and SLC2A2 genes encode the transmembrane transporters OCT1, MATE1, and MATE2, respectively, which are known to be involved in the pharmacokinetics of a variety of environmental toxins and drugs, including metformin. Recent findings indicate that several polymorphic variants of these genes can make a significant contribution to the modulation of the glycemic response [Over the past few years, several studies showed the association between the variants in the response ,14,15. Tresponse , very feATM, SLC22A1, SLC47A1, and SLC2A2 genes influenced the glycemic response to metformin in a cohort of patients with T2DM in Russia and, furthermore, to reveal the integrated contribution of the genetic factors and phenotypic features to therapeutic response, using the machine learning approach.In this study, we aimed to analyze whether the genetic variants in the A total of 464 unrelated patients with type 2 diabetes and 129 healthy volunteers were recruited. This study was performed using large-scale research facilities #3076082 “Human Reproductive Health”. Written informed consent for the research was obtained from all of the patients and healthy donors. T2DM was diagnosed based on the World Health Organization criteria. Patients with newly diagnosed diabetes mellitus (less than 1 year), type 1 diabetes, gestational diabetes, acute and/or decompensated liver and kidney disease, autoimmune disorders, malignancies, and under 30 years of age were excluded from the study. The level of HbA1c was determined in a fasting blood sample, body height and body weight were measured, and the body mass index (BMI) and waist–hip ratio (WHR) were calculated for all of the patients. The clinical parameters of the participants are shown in The peripheral blood samples from patients were collected in tubes with EDTA. The genomic DNA was extracted from peripheral blood leukocytes, using the protocol for salt/chloroform DNA extraction with modifications . The SNPThe SNPs were genotyped via polymerase chain reaction, followed by the restriction fragment length polymorphism (PCR-RFLP) method. Amplification was performed as follows: denaturation at 95 °C for 4 min; followed by 37 cycles of denaturation at 95 °C for 30 s; primer annealing at 60 °C for 30 s; and elongation at 72 °C for 30 s; and final extension at 72 °C for 5 min. The primers were designed by means of Oligo 6.0 software and NCBI BLAST tool. The sequences of the primers used and restriction enzymes for each analyzed SNP are given in ATM, SLC22A1, SLC2A2, and SLC47A1 genes affects the therapy response, the genotype/allele frequencies were analyzed in four groups of metformin-treated patients: (i) metformin monotherapy and no response to treatment; (ii) metformin monotherapy/combination therapy and no response to treatment; (iii) metformin monotherapy/combination therapy and positive response to treatment; (iv) metformin monotherapy and positive response to treatment. To exclude possible biases in the results of the association analysis caused by ethnic differences, a comparative analysis of the frequencies of the genotypes/alleles of the ATM, SLC22A1, SLC2A2, and SLC47A1 genes in the population cohort and the group of patients was carried out. Additionally, we compared the MAFs in the Russian population with reported data in European populations. For the comparison, we used the data presented in the resources 1000 Genomes Project and GnomAD (Genome and Exome sequence data) [p-value ≤ 0.05 was considered to be statistically significant. All of the data were analyzed by using SPSS  software. The odds ratios were estimated with 95% confidence intervals.To determine whether the polymorphism of the ce data) ,29. To aATM; rs628031 and rs12208357 in SLC22A1; rs2289669 in SLC47A1; and rs8192675 in SLC2A2. Prior to model fitting, the SNP genotypes were transformed to numeric variables indicating the number of minor alleles at each locus. Next, Pearson’s correlation between the variables was assessed to test for predictor collinearity. No significant correlation between predictor variables was found, except for two LD-linked variants in SLC22A1 , and creatinine levels in plasma; age and sex of the patient; BMI; WHR; familial T2DM background; and genotypes at five studied variant sites: rs11212617 in  SLC22A1 .The model training was performed using the caret package for R . The patDue to the low sample size and a heavy class imbalance in the data, model training and validation were performed, using a custom permutation-based approach. At each step of the algorithm, a random set of 44 cases was drawn and then combined with 44 controls to construct a training set of 88 samples. Such a strategy allows us to train models with equal sizes of “positive’ and “negative” samples, which is known to increase the accuracy of model fitting. The obtained set of 88 samples at each step was used to train each type of model. For the model validation, two different metrics were then computed. First, the area under the receiver-operator curve (ROC/AUC) was evaluated, using a four-fold cross-validation (CV). While this value can be considered as the most unbiased measure of classifier performance, the splitting of the training data during CV might negatively affect the accuracy of the model fitting on smaller samples, decreasing the final estimate of model performance. Hence, we also used an alternative method of model evaluation. To do so, an independent non-overlapping set of 44 cases was drawn from the initial dataset and combined with the same 44 control individuals. The ROC/AUC value was then computed for such a ‘validation’ set (this approach is further referred to as “case-shuffling”).Prior to further analysis, we evaluated the accuracy of the predictive model performance estimate by CV and case-shuffling methods. To this end, we attempted to classify random noise variables . Expectedly, the mean AUC estimate in four-fold CV was close to 0.5 and did not depend on the number of predictors; at the same time, the AUC estimated using the training dataset was higher and increased substantially by adding random variables to the model . Most imt-statistic values were computed, using the varImp function from the caret package. The data visualization was performed using the ggplot2 package [To evaluate the importance of the predictor variables in the final models, scaled  package .ATM, SLC22A1, SLC47A1, and SLC2A2 genes in patients with T2DM and healthy controls are shown in p-value > 0.05). According to our results, the MAF of rs12208357 in the SLC22A1 gene was found to be slightly statistically higher, and the rs2289669 in SLC47A1 gene and rs8192675 in SLC2A2 gene significantly lower than those in the European cohorts . The MAFs of the rs628031 and rs2289669 variants in the Russian patient groups were commensurate with those of other European populations   .ATM), rs628031 (SLC22A1), rs2289669 (SLC47A1), and rs8192675 (SLC2A2) variants in the responders and non-responders, we did not find any statistical differences. According to our results, the frequency of the T allele of the rs12208357 variant in the SLC22A1 gene was increased in the group of non-responders in comparison with both the group of patients with a positive response to monotherapy/combination therapy with metformin , and the group with a positive response to monotherapy with metformin . Additionally, the association analysis of the rs12208357 variant with response to metformin showed that the TT genotype was statistically more common , and the CC genotype was significantly less common  in the non-responders, in comparison with the group with monotherapy/combination therapy.The distribution of the genotype and allele frequencies for genetic variants in the four groups of T2DM patients with different responses to metformin therapy is shown in SLC22A1), rs2289669 (SLC47A1), and rs8192675 (SLC2A2) variants in male and female responders and non-responders, we did not find any significant differences. For the variant rs11212617 in ATM gene, we found a statistically significant increase in the frequency of the CC genotype and C allele in the female T2DM patients with glycemic response compared to the female non-responders . Significant differences in the allele frequencies of the variant rs12208357 in SLC22A1 gene were also found between the groups of male and female non-responders. The rare T allele was statistically more frequent in the male non-responders in comparison with the female non-responders .To assess the influence of gene polymorphism on the glycemic response to metformin depending on the gender of the T2DM patients, we performed an analysis of the genotype and allele frequencies of studied variants in the groups of metformin responders and non-responders with different sex  . When coSLC22A1 (the only variant that showed an association in the single variant tests); (ii) the genotypes at all of the tested variant sites; and (iii) the genotypes at all of the variant sites, as well as additional parameters, such as sex, age, BMI, WHR, plasma creatinine levels, and familial T2DM background. We also built a model that included fasting glucose and HbA1c levels as a positive control, as these variables should allow for a nearly complete discrimination between the cases and controls  the patient’s genotype at the rs12208357 variant in controls . To evalSLC22A1 gene allowed the prediction of the response to metformin with a median AUC = 0.572 . A model that included all of the variant genotypes showed a slight performance gain over a single-variant model; at the same time, a model based on all of the genotypes and additional phenotypic features had a remarkably good performance (AUC = 0.772). As expected, a positive control model based on all of the 13 traits, including glycemic ones, showed nearly absolute predictive power (median AUC = 0.982).All of the predictive models demonstrated a certain level of power to predict the response to metformin treatment . The genWe next went on to identify a set of parameters that had the greatest importance for the prediction of the response to metformin therapy. To do so, we decided to apply a regularization (Lasso) approach to construct a logistic regression model with the minimum necessary set of parameters. Similar to previous experiments, the Lasso fitting was performed in 1000 permutations to estimate the performance of the model and the importance of the model parameters. The Lasso approach successfully reduced the minimum necessary number of variables  while maintaining the general prediction accuracy. The analysis of the scaled parameter importance clearly identified a set of four features that had the highest impact on predictive power b: sex; rATM, SLC22A1, SLC2A2, and SLC47A1 genes associated with the therapeutic response to metformin demonstrated their potential involvement in the metformin action mechanisms. However, these findings were not replicated in some cohorts, while a number of studies even received controversial results [The glucose-lowering effect of metformin was previously shown to have a wide interindividual variability, due to numerous causes including genetic factors . The rec results ,26,27,34 results .ATM (rs11212617), SLC22A1 (rs628031), SLC47A1 (rs2289669), and SLC2A2 (rs8192675) genes and the therapeutic response to metformin in the Russian patients with T2DM. The same results were obtained in the previous studies: for the rs11212617 variant in a set of studies in different European and Asian populations [ATM (rs11212617), SLC22A1 (rs628031), SLC47A1 (rs2289669), and SLC2A2 (rs8192675) genes between the different populations could be assumed. Our results showed the statistically significant differences in the MAFs of rs12208357 (SLC22A1), rs2289669 (SLC47A1), and rs8192675 (SLC2A2) between the Russian population and the European cohorts, which also is supposed to be an argument in favor of the point about the possible interethnic differences in the distribution of these gene alleles.Firstly, to explore whether the variants rs11212617, rs628031, rs12208357, rs2289669, and rs8192675 could be involved in the genetic susceptibility to T2DM in the Russian population, we performed a comparative analysis for the allele and genotype frequencies for all of the studied variants between the group of patients with T2DM and the sample of healthy controls in the cohort with Russian ethnicity. The results of this study found no association of the variants with T2DM development in Russia. Secondly, we analyzed the independent association of each of the studied variants with the metformin response for the patients categorized into four groups: (i) all responders vs. non-responders; (ii) metformin-responding patients (taking monotherapy only) vs. non-responders; (iii) all responders vs. non-responders (taking monotherapy only); and (iv) metformin-responding patients (taking monotherapy only) vs. non-responders (taking monotherapy only). According to the results of our study, no association was found between the variants in the ulations ,37,38; fulations ,39; for ulations ,41 and Iulations ,43; for SLC22A1, is known to encode for a polyspecific organic cation transporter 1 (OCT1), a member of the solute carrier 22 family of transporter proteins which are involved in the absorption, distribution, metabolism, and excretion of several organic cations. OCT1 is predominantly expressed in the liver, but it is also found in other tissues [TT genotype and T allele of rs12208357 (SLC22A1 gene) had a lower response to metformin therapy compared to the carriers of the CC/CT genotypes and C allele . Our data are consistent with the previously obtained results which determine this variant as affecting the treatment response, including that through the hepatic exposure of metformin [SLC22A1 gene was previously shown to possibly influence the functioning of the OCT1 protein and, therefore, to modulate the pharmacokinetics and therapeutic response to metformin. The rs12208357 in the SLC22A1 gene is a nonsynonymous missense variant located in exon 1 of the gene, which results in the loss of the OCT1 protein function and causes the reduced uptake of metformin and 1-methyl-4-phenylpyridinium (MPP(+)) [SLC22A1 gene might independently impact the glucose-lowering effect of metformin in the Russian population.One of the studied genes,  tissues ,45. It w tissues . OCT1 waetformin . The gen(MPP(+)) ,49. TherTT genotype of the variant rs12208357 (SLC22A1), familial T2DM background, and increased WHR were found to be associated with the reduced metformin response in our population.In the present study, we next questioned whether the combinations of the genotyped variants and other affecting factors  were associated with the metformin response, and whether the patient’s genotype could be used to predict the response to the metformin therapy. To answer these questions, we applied a machine learning-based approach and constructed a series of classification models to predict the response to metformin treatment, either alone (monotherapy vs. non-responding patients) or combined with other therapeutics . A model based on the data of all of the studied gene variants and phenotypic parameters had the best performance, whereas the predictive power of the model including only SNPs did not differ from the model based on a single variant rs12208357. This may be caused by both the possibly large contribution of environmental factors or the small influence of each specific genetic variant in the metformin response; additionally, the population characteristics of the Russian cohort and insufficient sample size can be the logical explanation for these results. Finally, we were able to construct an optimal model demonstrating that a set of four parameters taken together  had the greatest importance for the prediction of the response to metformin therapy in Russian patients. According to the data obtained, male gender, CC genotype of rs11212617 (ATM) and TT of rs12208357 (SLC22A1). Some evidence was found for the potential effect of metformin on blood glucose levels in a sex-dependent manner. Li and colleagues suggested a better glycemic response during treatment in females compared with that of males in Chinese patients. Moreover, an increase in the insulin secretion was determined in the same study in the female patients, whereas the males displayed no significant change [Interestingly, the study also showed a gender-specific difference in response to metformin treatment for the carriers of the t change . Howevert change . In a Cht change . Thus, gThereby, our results demonstrate the utility of genotypic and phenotypic information for predicting the response to metformin therapy, which could undoubtedly contribute to the improvement of the treatment strategy of T2DM patients. Further studies of the aforementioned factors and the other genotypic and phenotypic parameters in different, large and ethnically homogeneous cohorts may be useful to confirm the findings and to improve the predictive power of the model constructed.


The effect of three process parameters, cutting speed, tool feed and cutting depth, is being studied on the matching responses. Orthogonal design of experiment (Taguchi L9) has been adopted to execute the process parameters in each level. To validate the process output parameters, the Grey Relational Analysis (GRA) optimization approach was applied. The percentage contribution of machining parameters to the parameter of response performance was interpreted through variance analysis (ANOVA). Through the GRA process, the emphasis was on the fact that for TI6Al4V metal matrix composite among all machining parameters, tool feed serves as the highest contribution to the output responses accompanied by the cutting depth with the cutting speed in addition. From optimal testing, it is found that for minimization of machining forces, maximization of MRR and minimization of Ra, the best combinations of input parameters are the 2nd stage of cutting speed (175 m/min), the 3rd stage of feed (0.25 mm/edge) as well as the 2nd stage of cutting depth (1.2 mm). It is also found that hardness of Ti6Al4V MMC is 59.4 HRA and composition of that material remain the same after milling operation.This paper shows the novel approach of Taguchi-Based Grey Relational Analysis of Ti6Al4V Machining parameter. Ti6Al4V metal matrix composite has been fabricated using the powder metallurgy route. Here, all the components of TI6Al4V machining forces, including longitudinal force (F A metal matrix composite system is generally designed by the metal alloy with the combination of the matrix and the material type, volume fraction, and form of the reinforcement. It is proved that pure titanium can be strengthened by adding aluminum for α-phase and vanadium for β-phase. The presence of α + β phase in the Ti-6Al-4V alloy increases its mechanical strength ,2,3,4. ISahu et al.  have stup < 0.05) whereas veneering material had no statistically significant effect on the fit of the titanium frameworks (p > 0.05). The influence of electrical discharge machining (EDM) parameters such as pulse-on time (TON), pulse-off time (TOFF), voltage (V) and current (I) on material removal rate (MRR) in 304 stainless steel was explored by Rajmohan et al. , MRR and Surface Roughness are calculated as output parameters [MRR is calculated by using Equation (1). The cubic millimeter volume of material removed in one minute is known as MRR. It can be calculated per the following formula and is presented in Taguchi L9 Orthogonal Array is used for Design of Experiment because it provides fewer runs for the experiment ,28,29,30rameters . Nine exfM = Initial mass of the sample before millingiM = Final mass of the sample after millingρ = Density of Ti alloy materialt = Milling time for the sampleThe surface roughness, Ra is calculated using diamond tip stylus equipment. Five experiments are conducted for one sample to get better accuracy. The average of the five experimented values will give the Ra for each machined sample. Before calculating the Ra, the surfaces of the machined specimens are cleaned to remove dust. Tip of the equipment is placed on the test specimen, allow moving on it. The data are stored in the memory and are analyzed by TALUSURF software ,33,34,35ijQ) for jth signal with respect to ith output  for various types of response parameters are provided below Equation (2) to Equation (7) along with The main goal of the manufacturing company is to maximize productivity by minimizing cost and improving quality. For attaining such goal, the best technique to apply in the manufacturing process is optimization. It is the method of determining the best outputs or responses by feeding input parameters. This maximizes the required outputs by minimizing input parameters ,38,39,40 is best ,42. The For smaller is the best,For larger is the best,For nominal is the best,ijkZ is the calculated values of jth output in ith inputs at kth replication, and ijQ is the degraded performance loss for jth output in ith inputs. The S/N value  Sij (ijQ (jth output in the ith inputs by using Equation (5).In the above Equation ‘n’ denotes the number of replication experimentations, tio) Sij  is achieSij  result is being used as the Process Performance Index (PPI). The rate of achievement of the PPI is as quantified. The value of signal to noise ratio (se ratio  for the Gaining the S/N ratio (jth output in the ith input is determined by using Equation (7),|, min {max {ε = distinguishing coefficient . Using of the distinguishing coefficient (ε) is to increase or decrease the distribution of the grey relational cofficient and is often taken as 0.5 [iGRG) that communicates to the Grey Relationship Grade corresponding to the input as shown below.jth input and Grey Relational coefficient  and is shown in This study shows the development of Ti6Al4V metal matrix composite by the powder metallurgy technique and the effect of input machining parameters  on machining forces, MRR, surface roughness during milling. The optimization of GRA accompanied by Taguchi design of experiment is implemented for getting the optimal value of input parameters. Surface morphology and phase analysis are conducted to investigate the presence of voids and phases of the material. It is concluded from the response plot that tool feed has the highest rate contribution toward the producing responses ensued by the depth of cut and cutting velocity. From the optimal test, it is found that for minimization of machining forces, maximization of MRR and minimization of Ra, the best combinations of input parameters are the 2nd stage of cutting speed (175 m/min), the 3rd stage of feed (0.25 mm/edge) as well as the 2nd stage of cutting depth (1.2 mm). It is also found that the hardness of Ti6Al4V MMC is 59.4 HRA and the composition of the material remains thesame after milling operation.


Analysis of the effectiveness of in-hospital transfer care based on the STABLE  technique in critically ill neonates.  Retrospective analysis of the case data of 180 critically ill neonates transferred to the NICU  via the delivery room (operating room) in our hospital from April 2020 to December 2021. Of which, 88 newborns from April 2020 to February 2021 were resuscitated by conventional resuscitation and then transferred to the NICU by the nurses in the delivery room (operating room) through the green channel, and they were recorded as the control group; and 92 newborns from March to December 2021 were transferred to the NICU by the NICU transfer nurses who arrived at the delivery room (operating room) earlier and used the in-hospital transfer care based on STABLE technology, and they were recorded as the intervention group. The indicators to be assessed were the execution pass rate in the simulated assessment of the transfer emergency procedure for both groups of transporters, execution times of the various subprocesses during the transfer procedure for both groups of transporters, accidents in transit, and blood glucose, blood pressure, body temperature, respiration, blood gas indicators, and family satisfaction of children in both groups after transfer. P < 0.05). The execution times of the various subprocesses during the transfer procedure of transporters were shorter in the intervention group than in the control group (P < 0.05). The incidence of accidents in transit was lower in the intervention group than in the control group (P < 0.05). After transfer, the blood glucose, blood pressure, body temperature, respiratory, and blood gas indicators of the children in the intervention group were all more stable than those in the control group (P < 0.05). The satisfaction of the families of the children in the intervention group was higher than that of the control group (P < 0.05).  The total execution pass rate for transporters was higher in the intervention group than in the control group ( The implementation of transfer care based on STABLE technology for newborns in urgent need of in-hospital transfer can effectively improve the comprehensive quality and emergency response ability of transfer nurses and shorten the in-hospital transfer time, and the incidence of adverse reactions during the transfer of children is less, the vital signs are stable, and the satisfaction of family members is high, which is of promotion value. About 20 million newborns are born in China every year, and 10%∼20% of them are high-risk newborns  and thatNeonatal transport (NT) is an important part of the work of the newborn care centre (NCC). The purpose is to safely transfer high-risk newborns to the neonatal intensive care unit (NICU) of NCC for treatment and give full play to the role of high-quality health resources . HoweverP > 0.05).This study includes a retrospective analysis of the case data of 180 critically ill neonates transferred to the NICU via the delivery room (operating room) in our hospital from April 2020 to December 2021. Of which, 88 newborns from April 2020 to February 2021 were resuscitated by conventional resuscitation and then transferred to the NICU by the nurses in the delivery room (operating room) through the green channel and were recorded as the control group; and 92 newborns from March to December 2021 were transferred to the NICU by the NICU transfer nurses who arrived at the delivery room (operating room) earlier and used the in-hospital transfer care based on STABLE technology, and they were recorded as the intervention group. The comparison of baseline data in Two transfer nurses from the NICU joined the neonatal in-hospital safe transfer care team, which also included 9 neonatologists, 8 midwives, and 10 obstetricians, making a total of 29 people.(1) Birth weight <1500 g or gestational week <32 weeks; (2) severe birth asphyxia, which remains in a critical condition after resuscitation; (3) severe respiratory distress, frequent apnoea requiring assisted ventilation; (4) cyanosis after birth that does not improve with oxygen therapy, shock, or congenital heart disease; (5) congenital anomalies requiring immediate surgical treatment; and (6) severe infection, abnormal neurobehaviour, frequent convulsions, severe jaundice requiring blood exchange, acute anaemia, frequent vomiting, diarrhoea, dehydration, etc.(1) Meeting the diagnostic criteria for high-risk neonates; (2) complete maternal data; and (3) informed consent of the child's family.(1) Those who could not be treated in our NICU and needed to be transferred to an outside hospital; (2) those who were stabilised and transferred directly to an obstetric ward; and (3) those who had died or abandoned treatment.(1) Control group: resuscitated by conventional resuscitation and then transferred to the NICU from the green channel by the nurses in the delivery room (operating room). The routine transfer care process for critically ill newborns is detailed in 2, and PaCO2 of the children in both groups after the transfer. (6) Comparison of family satisfaction after transfer of children in both groups. A questionnaire was administered to the families of the children being transferred through a self-designed satisfaction assessment form. The questionnaire consisted of 3 aspects of transfer process (40 points), transfer technique (30 points), and service attitude (30 points) with 5 levels: very satisfied (100–90 points), satisfied (89–80 points), basically satisfied (79–60 points), dissatisfied (59–50 points), and very dissatisfied (49–0 points).(1) Comparison of execution pass rate in the simulated assessment of the transfer emergency procedure for both groups of transporters. The assessment consisted of four parts: item preparation (10 scores), operational processes (50 scores), operational techniques (20 scores), and effectiveness evaluation (20 scores). The total score was 100, with 80 being a pass. Trainees with a score of 95 or more could be officially admitted to the transit team shifts. (2) Comparison of execution times of the various subprocesses during the transfer procedure for both groups of transporters, including nurse arrival time (day/night), time to establish airway, time to oxygen inhalation, time to establish intravenous access, time to keep warm and shockproof, time to cardiac monitoring, and time to establish medical records. (3) Record the occurrence of accidents in transit for both groups of children. (4) Record the blood glucose, blood pressure, body temperature, and respiration of the children in both groups after the transfer. (5) Record the blood gas indicators including pH, PaOs, and ANOVA was used for comparison between groups; the count data were described by frequency and percentage, and the χ2 test was used between groups; and differences were considered statistically significant at P < 0.05.The SPSS 21.0 statistical package was used for data analysis. The measurement data were described by P < 0.05)  .P < 0.05) (The execution times of the various subprocesses during the transfer procedure of transporters were shorter in the intervention group than in the control group ( < 0.05) .P < 0.05) (The incidence of accidents in transit was lower in the intervention group than in the control group ( < 0.05) .P < 0.05)  .2, and PaCO2 of the children in the intervention group were all more stable than those in the control group (P < 0.05)  .P < 0.05)  .Critical neonatal transport is not just a simple transport process, it is a complete emergency and monitoring system that can largely reduce neonatal morbidity and mortality and is a breakthrough in neonatal emergency technology . In a stImproving the comprehensive quality of emergency care for transporters during transport is an important prerequisite for ensuring the quality of care for critically ill neonates , 16. TheThe transfer care based on the STABLE technique enhances the awareness and skills of the transfer staff and improves their overall coordination and resilience. The crippled physiological system leaves the child without the ability to adapt to life outside the womb. Any fluctuation in blood glucose, blood pressure, or body temperature can pose a great threat to the life of the newborn, making the success of the transfer much lower or even fatal, so it is important to provide safe care for the child at all times and in all places to ensure the stability of the child's physiological system and behaviour , 21. In The results also show that in-hospital transfer care based on STABLE technology increases the satisfaction of the child's family. During the transfer of a critically ill neonate, the speed and quality of the transfer are crucial to the life and prognosis of the child. The implementation of the STABLE technique for in-hospital transfer care has transformed the previous “master-slave” relationship into a “side-by-side and complementary” partnership. As a result, team spirit has increased significantly and all members involved in the transfer process are able to perform the treatment with skill and confidence. This, together with the emotional support and assistance provided by the transport staff to the family and the encouragement of the family to face the crisis in a positive manner, resulted in a significant increase in the satisfaction of the family with the transport process.To sum up, the implementation of transfer care based on STABLE technology for newborns in urgent need of in-hospital transfer can effectively improve the comprehensive quality and emergency response ability of transfer nurses and shorten the in-hospital transfer time, and the incidence of adverse reactions during the transfer of children is less, the vital signs are stable, and the satisfaction of family members is high, which is of promotion value.


The influence of processing intumescent bio-based poly(lactic acid) (PLA) composites by injection and fused filament fabrication (FFF) was evaluated. A raw (ANa) and two acidic-activated (AH2 and AH5) montmorillonites were added to the intumescent formulation, composed by lignin and ammonium polyphosphate, in order to evaluate the influence of the strength and the nature (Brønsted or Lewis) of their acidic sites on the fire behavior of the composites. The thermal stability and the volatile thermal degradation products of the composites were assessed. The injected and 3D-printed composites were submitted to cone calorimeter (CC), limit oxygen index (LOI), and UL-94 flammability tests. A similar tendency was observed for the injected and 3D-printed samples. The high density of strong Lewis sites in AH2 showed to be detrimental to the fire-retarding properties. For the CC test, the addition of the intumescent composite reduced the peak of heat released (pHRR) in approximately 49% when compared to neat PLA, while the composites containing ANa and AH5 presented a reduction of at least 54%. However, the addition of AH2 caused a pHRR reduction of around 47%, close to the one of the composite without clay (49%). In the LOI tests, the composites containing ANa and AH5 achieved the best results: 39% and 35%, respectively, for the injected samples, and 35 and 38% for the 3D-printed samples. For the composite containing AH2 the LOI values were 34% and 32% for injected and 3D-printed samples, respectively. Overall, the best performance in the flammability tests was achieved by the composites containing clays with only weak and moderate strength acidic sites (ANa and AH5). Z axis) and a new layer is added  < 50s for the five specimens, a condition required for V-0 classification). However, all the samples promoted the ignition of the underneath cotton due to flammable dripping, denoting a V-2 classification. As the UL-94 test configuration consists on a specimen hanged up vertically, heated by a flame on its bottom surface, the dripping observed during the tests can be associated to the increase of the melt flow rate (MFR) caused by the addition of APP/Lig and clays , the lowest LOI value is achieved for the composite containing AH2, the only clay with strong acidic sites, with a high excess of Lewis sites relative to the Brønsted ones. On the other hand, the highest LOI values are obtained for the composites with the ANa and AH5 clays, which do not contain strong acidic sites, but a more homogeneous distribution of Brønsted and Lewis with moderate strength.A previous work  using thThe main parameters extracted from the stress versus strain curves a–e are rThere are no significant differences for the other parameters among the composites. The 3D-printed composites present stress versus strain curve profiles similar to those of the injected samples a–e and nA comparison between the tensile strengths and the Young modulus for the injected and 3D-printed samples is shown in For the Young’s modulus b, all thThis work studied the influence of Brønsted and Lewis acidity of acidic-activated montmorillonites on the flame-retardancy and mechanical properties of intumescent PLA composites produced by both injection molding and FFF techniques. The intumescent formulations were composed of ammonium polyphosphate, lignin, raw and acidic-activated montmorillonites.In general, compared to the neat PLA, the addition of the intumescent formulation and clays increased the ductility and the rigidity of the composites, both for the injected and the 3D-printed samples. The injected samples present higher Young modulus than those of the 3D-printed ones. The tensile strength values are also higher for the injected composites when compared to the 3D-printed ones, except for the PLA/APP/Lig one, which showed similar values for both the injected and the 3D-printed samples. It can be suggested that the lack of adhesion and void formation is favored by the presence of clays.Neat PLA did not classify in UL-94 test, while all the injected and 3D-printed composites achieved a V-2 classification. For both processing methods (injection and FFF), the LOI tests indicate a significant enhancement of the fire behavior with the addition of the intumescent formulation APP/Lig. An even better performance was reached by the composites containing clay, the highest LOI values being achieved by the PLA/APP/Lig/ANa and PLA/APP/Lig/AH5 composites.The thermogravimetry and flammability results evidence that the strong acidic sites composed mostly by the Lewis type are detrimental for the thermal stability and the fire-retarding properties. Conversely, the absence of these sites and the presence of moderate strength ones enhance the fire behavior. A similar behavior was observed both in cone calorimeter and LOI tests for the clay-containing samples submitted to injection and FFF, showing that the influence of the montmorillonite acidity is independent of the processing technique. The samples containing AH2, with strong Lewis sites, presented the worst performance, while the ones with ANa and AH5  achieved the best results. The strong sites present in AH2, mostly of the Lewis type, can compromise the esterification kinetics and, consequently, impair the cyclization reactions, as evidenced by the presence of a remarkable narrow band at 1401 cm-1 (CH2 bending absorption) in the FTIR spectrum of the cone calorimeter residue.Overall, this work brings out a new insight on the influence of montmorillonite on a novel bio-based intumescent composite, promoting a deeper comprehension on how the chemistry of the acidic sites of the montmorillonite can help to tune the flammability properties of intumescence composites leading to the development of more efficient flame-retarding materials.


It was shown that the addition of polysaccharide significantly affects the rheological properties and microstructure of ZnO NPs gels. We found that the optimal polysaccharide for the synthesis of ZnO NPs gels is hydroxyethyl cellulose. It is shown that the microstructure of a gel of ZnO NPs stabilized with hydroxyethyl cellulose is represented by irregularly shaped particles that are assembled into aggregates, with sizes ranging from 150 to 1400 nm. A significant hysteresis region is observed in a gel of ZnO NPs stabilized with hydroxyethyl cellulose. The process of interaction of ZnO NPs with polysaccharides was investigated. It was shown that the interaction of ZnO NPs with polysaccharides occurs through a charged hydroxyl group. In the experiment, a sample of a gel of ZnO NPs modified with hydroxyethyl cellulose was tested. It was shown that the gel of ZnO NPs modified with hydroxyethyl cellulose has a pronounced regenerative effect on burn wounds, which is significantly higher than that of the control group and the group treated with a gel of ZnO microparticles (MPs) and hydroxyethyl cellulose. It is also shown that the rate of healing of burn wounds in animals treated with gel of ZnO nanoparticles with hydroxyethyl cellulose (group 3) is 16.23% higher than in animals treated with gel of ZnO microparticles with hydroxyethyl cellulose (group 2), and 24.33% higher than in the control group treated with hydroxyethyl cellulose. The average rate of healing of burn wounds for the entire experimental period in experimental animals of group 3 is 1.26 and 1.54 times higher than in animals of group 2 and control group, respectively. An experimental study of a gel of ZnO NPs modified with hydroxyethyl cellulose has shown the effectiveness of its use in modeling the healing of skin wounds through primary tension.A method for the synthesis of ZnO nanoparticles (ZnO NPs) gels was developed. ZnO NPs were obtained through a sol–gel method with zinc acetate usage as a precursor. Optimization of the method of synthesis of ZnO NPs gel has been carried out. It was observed that the most stable ZnO NPs gels are formed at room temperature, pH = 8 and molar concentration of zinc C(Zn The history of the use of zinc as a biologically active mineral goes back to ancient times. Zinc ointment was used for skin diseases and to accelerate wound healing in ancient Egypt 5000 years ago. However, a serious study of the role of this mineral in biological processes began only in the middle of the twentieth century, after it was accidentally discovered that wounds began to heal much faster when a little zinc was added to the of diet rats that received burns .Zinc is an important element for the functioning of a wide range of physiological functions of living organisms . Zinc paCurrently, an ongoing task for materials science is the development and research of gels based on ZnO. ZnO has a number of useful physical and chemical properties, which include high photosensitivity, the ability to effectively absorb UV radiation, antibacterial properties and protection from UV radiation. ZnO is widely used in modern science and technology. For example, the introduction of ZnO into cosmetic creams and gels increases their sunscreen and antibacterial properties . The effTo date, many hydrogels with special functional inclusions from various biological substances have been studied. Essentially, polysaccharides demonstrate great potential for application in the field of nanomaterials due to the fact that they have high biocompatibility and non-toxicity ,20,21,22The aim of this work was to synthesize ZnO NPs stabilized with various polysaccharides and to study their wound-healing properties.The results of the effect of synthesis parameters on the dynamic viscosity of ZnO NPs gels are presented in As a result of the mathematical processing of experimental data, the dependences of the viscosity of ZnO gels on various synthesis parameters were obtained.v (dynamic viscosity of ZnO gels) depending on the concentration of zinc acetate and the temperature of the reaction medium under other optimal conditions.2+) and an increase in t. Moreover, during the experiment, it was observed that at temperatures above 40 ℃, the structure of ZnO gels was destroyed with the formation of a flake-like amorphous precipitate. This fact allows us to conclude that ZnO gels are thermally unstable (thermolabile), which correlates with results of Mocioiu et al. (2021) 2− [This graphical dependence confirms the previously presented response surfaces and shows the influence of another factor on the synthesis of ZnO gel–pH. Analysis of (OH)4]2− ,26.2+) = 0.05 ÷ 0.2 M.Based on the analysis of the data obtained, it can be concluded that the most stable complex ZnO gels are formed at room temperature, pH = 8 and molar concentration of zinc C22+) and zinc hydroxocomplexes ([Zn(OH)4]2−) 2−) ,28. As aThe chemical processes that occur during the synthesis of ZnO gels are schematically presented in At the next stage, the effect of the addition of polysaccharides  on the structure and rheological properties of nanoscale ZnO gels was investigated. The microstructure of nanoscale ZnO gels was studied using scanning electron microscopy (SEM). The resulting SEM micrographs are shown in Analysis of SEM micrographs of nanoscale ZnO showed that the samples of ZnO NPs gels consist of irregularly shaped aggregates. In the agar–agar stabilized sample, the aggregates have a lamellar shape. In turn, the surface of ZnO NPs stabilized with methylcellulose and hydroxyethylcellulose is represented by irregularly shaped particles that are assembled into aggregates with sizes ranging from 150 to 1400 nm. In addition, the microstructure of samples with maltodextrin and amylopectin is represented by spherical particles, the diameter of which ranged from 30 to 70 nm.At the next stage, the rheological properties of ZnO NPs gels were investigated. The obtained dependences of the shear rate on the shear stress are shown in The analysis of the obtained dependences showed that the addition of polysaccharides to the samples of ZnO gels significantly affects their rheological properties. It was also found that the nature of the polysaccharide significantly affects the type of dependence of the shear rate on the shear stress. A slight hysteresis loop is observed in a sample of ZnO gel without polysaccharides. A similar dependence is observed in all samples of ZnO NPs gels except for the sample containing hydroxyethyl cellulose. A significant hysteresis region is present in the sample modified with hydroxyethyl cellulose, which is explained by the preservation of residual deformation after a strong weakening of the structure under the influence of previously applied stress . The preAnalysis of the data obtained showed that the optimal polysaccharide for the synthesis of ZnO NPs gels is hydroxyethyl cellulose, which forms a gel with an ordered structure. In the case of using other polysaccharides, the formation of a disordered gel structure is observed, which is confirmed by the data of the rheological properties study .At the next stage, the process of polysaccharide interaction with the surface of nanoscale ZnO was investigated using computer quantum chemical modeling in the QChem program using the IQmol molecular editor. The data of quantum chemical calculations of molecular complexes “ZnO-polysaccharide” are presented in As a result of the simulation, the value of the absolute chemical hardness ɳ is calculated. This value characterizes the stability of the system, preventing its change.The analysis of the obtained data showed that the most stable system is the molecular system “ZnO-hydroxyethyl cellulose”, for which the value of absolute chemical hardness (ɳ) was 0.193 eV .At the next stage, the presence of fluctuations in the bonds of functional groups was studied in samples of gels of ZnO NPs modified with polysaccharides. The study was carried out using the infrared spectroscopy method on the FSM-1201 device. The results are presented in −1, there is a significant drop in the intensity of the bands characterizing the deformation vibrations of the ionized charged group–OH. Thus, it was established that the interaction of ZnO NPs occurs through the charged hydroxyl group of the polysaccharide [As a result of the analysis of IR spectra, it was found that in the spectra of all polysaccharides in the range from 1350 to 1450 cmccharide ,31,32. TAs a result of modeling a burn wound, burns of the III B degree were formed, which had a rounded shape; the bottom of the wounds was bright red, with a brown tinge in places. The edges of the wound were slightly overhanging pieces of red–brown soft tissue. There was a hyperemia zone 0.5–0.8 cm wide around the wound.On the third day, in animals of all experimental groups, a scab began to be rejected at the edges of the wound surface with varying intensity, and weak epithelization of the wound edges was observed. The demarcation lines around the wounds in Group 3 (gel of ZnO NPs modified with hydroxyethyl cellulose) were in the range of 2–3 mm. The weakest regeneration processes were observed in Group 2 (gel of ZnO MPs and hydroxyethyl cellulose). The demarcation line in Group 2 reached 8 mm. There was a reduction in the area of burn wounds and gradual rejection of the scab, marking marginal epithelization of the burn wound.In Group 1 (hydroxyethylcellulose gel) and Group 3, deep wounds were formed in all animals in place of scabby crusts, along the edges of which epithelization was slowly going on, and an increasing hyperemia zone was noted around the wound. In Group 2, where the animals were applied with zinc ointment, extensive edema zones were noted around the wounds, reaching a diameter of 25 mm, irregular shape and fuzzy edges. By the 6th day, the burn scab rejection occurred in the animals of Group 3. The scab in the experimental groups was dry, thin. Regeneration processes were actively going on under it. There was an increased marginal epithelization without the development of concentric contraction of wounds.On the 10th day of the experiment, a scab was removed from the burn surfaces  . A cleanAt the next stage, the degree of healing of burn wounds on the 21st day of the experiment was evaluated. The data obtained are presented in Analysis of The results of calculations of the healing rate of burn wounds in experimental animals are shown in 2/day, which is 1.34 and 6.14 times higher than in animals of Group 2 and 1, respectively. On the 3rd–5th day, in animals of Group 3, the value of the healing rate of burn wounds was 0.31 cm2/day, which is 6.2 and 7.75 times higher than in animals of Group 2 and Group 1, respectively. On the 5th–10th day, in experimental animals, to whose wound surfaces gel of ZnO NPs modified with hydroxyethyl cellulose was applied, the value of the healing rate of burn wounds was 0.18 cm2/day, which is 1.8 and 1.29 times higher than in animals of Group 2 and Group 1, respectively. From all of the above, it follows that the rate of healing of burn wounds in experimental animals of Group 3 gradually decreases by the end of the experiment. The decrease in the average rate of healing of experimental wounds in Group 3 by the 10th–14th days is due to the fact that 60–70% of animals in this group had almost complete healing of burn wounds by this time.Analysis of the obtained data presented in The following The analysis of Thus, the analysis of changes in the area of wounds in dynamics in experimental animals showed that the gel of ZnO NPs modified with hydroxyethyl cellulose has a pronounced regenerative effect of burn wounds, which is significantly higher than in the Group 1 and Group 2. The use of ZnO NPs with a large specific surface area in the composition of the gel makes it possible to enrich the cells and tissues of the damaged wound surface with zinc ions in the right amount. Due to the normalization of the level of zinc intake into the cells of the damaged wound surface, the normalization of thymidine kinase, the rate of the limiting enzyme of DNA synthesis and cell replication, also occurs, which was confirmed and described in other works ,34,35.At the next stage, histological studies were performed. In animals of the experimental group, during the same period, a large fragmented scab covered the wound partially, and was sometimes separated from the underlying tissues throughout. Mature granulation tissue containing various hematogenic and tissue cellular elements was located in the center of the wound, and single macrophages, fibroblasts and collagen fibers appeared from the edges of the wound. The growth of the newly formed epithelium was observed, and the length of the regenerate was 574.5 ± 12.46 µm in the experimental group versus 589.01 ± 14.58 µm in the control group. Hypertrophy was detected at the border with the intact epidermis in both groups.p < 0.05). Under the epithelium, the wound defect was filled with mature granulation tissue with pronounced vascularization and a characteristic horizontal arrangement of fibroblasts around the vessels.Five days after the beginning of healing, the remains of a fragmented scab remained in the center of the injury in the animals of the control group. A small area of granulation tissue containing round-cell elements was localized under the scab. At the border with the intact skin, the epithelium was sharply hypertrophied, and the regenerate was distinguished by the formation of small outgrowths of the basement membrane into the underlying tissue. Formed granulation tissue with leukocyte infiltrate in the area of wound defect of the dermis occurred in the control group a. In aniAfter seven days, the differences we noted earlier presented especially clearly. In the animals of the control group, complete epithelization of experimental lesions was observed. The newly formed epithelial layer, consisting of several rows of cells, covered the entire area of the defect for 634 ± 22. Its basement membrane had an uneven configuration, but no outgrowths were observed in the underlying tissue and the formation of hair follicles and sebaceous glands did not occur. Under the epithelium there was connective tissue with typical cellular structures, shown in In animals of the experimental group, the wound process ended with the formation of an organ-specific regenerant. This was evidenced by the complete epithelialization of wounds, pronounced contraction of the lesion area, expressed in a significantly shorter length of the regenerate  and neoplasm of hair follicles and sebaceous glands .Thus, an experimental study of gel of ZnO NPs modified with hydroxyethyl cellulose has shown the effectiveness of its use in modeling the healing of skin wounds through primary tension. The inclusion of ZnO NPs in the composition leads to a less pronounced and rapidly relieving process of inflammation, which is a morphological substrate for the formation of granulation tissue in the area of injury. Active angiogenesis and proliferation of fibroblasts accompanying the formation of granulations, their subsequent transformation into connective tissue, and an increase in the rate of epithelialization of the injury zone are essentially a reflection of the transition of the wound healing process from the phase of inflammation to the phase of proliferation.2+) = 0.05–0.2 M. It was shown that the addition of polysaccharide significantly affects the rheological properties and microstructure of ZnO NPs gels. It was shown that the optimal polysaccharide for the synthesis of ZnO NPs gels is hydroxyethyl cellulose. It was shown that the microstructure of gel of ZnO NPs stabilized with hydroxyethyl cellulose is represented by irregularly shaped particles that are assembled into aggregates with sizes from 150 to 1400 nm. The process of interaction of ZnO NPs with polysaccharides was investigated. It was determined that the interaction of ZnO NPs with polysaccharides occurs through a charged hydroxyl group.For the experiment, a method was developed for the synthesis of ZnO NPs gels. It was found that the most stable gels of ZnO NPs are formed at room temperature, pH = 8 and a molar concentration of zinc C is 16.23% higher than in animals treated with gel of ZnO microparticles with hydroxyethyl cellulose (group 2), and 24.33% higher than in the control group treated with hydroxyethyl cellulose. The average rate of healing of burn wounds for the entire experimental period in experimental animals of group 3 is 1.26 and 1.54 times higher than in animals of group 2 and control group, respectively. An experimental study of a gel of ZnO NPs modified with hydroxyethyl cellulose has shown the effectiveness of its use in modeling the healing of skin wounds through primary tension.Zinc acetate II , 25% ammonia solution , maltodextrin , agar–agar , methylcellulose , hydroxyethicellulose of the B30K brand , amylopectin , and 0.9% sodium chloride solution  were obtained.3COO)2·2H2O) was weighed on analytical scales. Then, the suspension was quantitatively transferred to a beaker and 200 mL of distilled water was added. A 12.5% ammonia solution was added to the resulting solution to obtain pH = 8. The resulting mixture was left to stir for 30 min until the gel was formed. The resulting ZnO NPs gel was centrifuged at 2500 rpm for 5 min and washed 3 times with distilled water. The resulting ZnO precipitate was dried at a temperature of 80 ℃.Synthesis of ZnO NPs gels was carried out using the sol–gel method. At the first stage, 8.76 g of zinc acetate 2-aqueous (Zn(CH3COO)2·2H2O) and 0.5 g of polysaccharide were weighed on analytical scales. Maltodextrin, agar–agar, methylcellulose, hydroxyethylcellulose, amylopectin were used as polysaccharides. The suspension was then quantitatively transferred to a beaker and 200 mL of distilled water was added. A 12.5% ammonia solution was added to the resulting solution to obtain pH = 8. The resulting mixture was left to stir for 30 min until the gel was formed. The resulting ZnO NPs gel was centrifuged at 2500 rpm for 5 min and washed 3 times with distilled water. The resulting ZnO precipitate was dried at a temperature of 80 ℃  with Fourier-transform was used. Research parameters:Samples of ZnO NPs were examined using scanning electron microscopy on a MIRA-LMH scanning electron microscope with the AZtecEnergy Standard/X-max 20 (standard) elemental composition determination system .Quantum chemical modeling was carried out in the Q-Chem software using the IQmol molecular editor . Simulation parameters: Calculation–Energy, method–M06, Basis–6-31G*, Convergence–4, Force field–Chemical. To simplify calculations, free bonds were hydrogenated.The study of rheological properties and measurement of the dynamic viscosity of ZnO NPs gels was carried out on the IKA ROTAVISC me-vi advanced rotary viscometer .Molar concentration of zinc acetate, M;Active acidity of the reaction medium (pH);Duration of synthesis, minutes;Temperature of the reaction medium, ℃.Preliminary experiments and analysis of the literature data revealed the factors (variable parameters) that have the greatest impact on the synthesis of ZnO gels ,37,38,39The variable parameters during the experiments took the values indicated in v, MPa·s. The planning matrix was obtained with the method of Greek-Latin squares and is presented in An experiment-planning matrix was created for the synthesis of ZnO gels with different parameters. The output parameter was the dynamic viscosity of ZnO gels–YThe experimental data were processed using the Statistica 10.0 software package . The obtained results were processed using the Statistica Neural Networks v.4.0e application software package. The multilayer perceptron is shown in An experiment to study the effect of an ointment composition based on ZnO NPs gels on the healing process of burn wounds was carried out on mongrel white rats aged 6 months and weighing up to 250 g. To test the ointment composition, clinically healthy laboratory animals were used, which were kept in the same vivarium conditions on a standard food regime. For the research, three groups with ten rats in each were formed:Group 1–hydroxyethyl cellulose gel;Group 2–gel containing ZnO MPs and hydroxyethyl cellulose;Group 3–gel of ZnO NPs modified with hydroxyethyl cellulose;The duration of the experiment was 21 days, during 7 of which the animals were kept in quarantine. A day before the simulation of thermal burn on the side surface of the rat’s body, 4 × 4 cm skin areas were shaved with a safety razor. Having previously injected 5–10 mL of 0.9% NaCl solution under the skin for the convenience of shaving, the skin was stretched and no damage occurred during shaving.2) and a length of 15 cm was filled with hot water, placed vertically in boiling water at 2/3 of the height, heated for 1 min, filled over the edge at 2/3 of the height and, in a vertical position, brought into close contact with the exposed skin of the animal for 10 s. Its area is about 8–9% of the entire body surface. To calculate its values in a rat, the Meeh Formula (1) was used [Thermal burn modeling was carried out in accordance with generally accepted methods ,38,39,40bS is the surface of the body, cm2;W is the body weight of the animal, kg;k is the Meeh constant (9.46).2. A saline solution was used as a control substance. On the next day after the simulation of the burn, the objects were monitored.Twice a day, the experimental animals were examined, the wound surface was treated and the healing indicators were recorded. During the entire experimental period, we monitored the burn surface on the 1st, 3rd, 5th, 10th and 14th days. The tested substances were used at a dose of 10 mg/cmFor the purpose of a more detailed analysis of the dynamics of regeneration of burn wounds in experimental animals of all experimental groups, the following parameters were calculated:The rate of wound healing was determined using the Markaryan and Sarkisyan Formula (2) :(2)U=S−SU is the healing rate of the wound area per day, cm2/day;S is the area of the wound at the previous measurement, cm2;nS is the area of the wound at this measurement, cm2;n is the number of days, day.The average rate of healing of burn wounds for the entire experimental period was determined according to the Formula (3):av is the average healing rate of the wound area for the entire experimental period, cm2/day;U1 is the area of the wound at the initial moment of the experiment, cm2;S2 is the area of the wound at the final moment of the experiment, cm2;SHistological sections with a thickness of 5–6 μm were carried out on a sledge microtome MS-2 . Finished sections were stained with hematoxylin and eosin, followed by histopathological analysis. Histological micropreparation was evaluated using a laboratory microscope of the Axio Imager 2 (A2) research class  at magnifications of ×200 and ×400 with image fixation using a specialized AxioCam MRc5 camera (Carl Zeiss Microscopy) and Zen V.2 software (Carl Zeiss Microscopy) according to protocol from our previous work .(1)A group treated with a gel of ZnO MPs and hydroxyethyl cellulose (control group);(2)A group treated with a gel of ZnO NPs modified with hydroxyethyl cellulose .The experiment was carried out for two groups:


The ecotoxicity of composite surfaces was determined in model systems using methods which are standard in eco-microbiology. The microorganism was identified by studying morphological, cultural, biochemical, and antigenic properties. Studies of the structure and the microrelief of the surfaces of composite materials were conducted using scanning electron microscopy (SEM) and X-ray energy dispersive spectroscopy. Based on comprehensive research, it was established that the composition of oxytetracycline with content of q = 1.5 wt% and nanosilver with a content of q = 0.075 wt% per 100 wt% of the DER-331 oligomer and 10 parts by the mass of the TETA hardener ensures the formation of a porous nano-heterogeneous structure of the coating, which leads to the acceleration of the release of silver ions from the surface of the polymer. The rational content of the complex additives of biocides ensures adhesion to the cell wall of bacteria with subsequent penetration into it and subsequent change to the cell membrane, its death, and, therefore, the suppression of the fouling process of metal structures.The impact of fillers in the epoxy oligomer on the test culture of the marine ecosystem was investigated. The content of additive—biocides—was selected based on the complex research using STAT-GRAPHICS The search for ways to improve the performance of mechanisms and parts of maritime transport corresponds to the general concept of sustainable development, which involves the conservation and rational usage of marine resources and the implementation of mindful consumption and production, which contributes to better socio-natural well-being ,2. The pAt the same time, the practical use of any chemical intensifies the issues of their environmental toxicity and impact on ecosystems in the long run. Numerous studies on the bioaccumulation of anthropogenic chemical pollutants indicate that biocides have a long half-life and can accumulate in the environment ,25,26,27It is a well-known fact that microorganisms are critical for modeling and studying the F and T (Fate and Transport) and the effects of engineering nanomaterials entering aquatic biocenosis. The creation of model systems for predicting the realistic fate and action of nanomaterials using microorganisms is based on existing data about the toxic effect of some nanoparticles on microscopic objects in marine systems ,33.Modeling the impact of nanoparticles released from composites on microorganisms allows the minimizing of their potential toxic impact on the environment during further practical implementations of antifouling coatings. The creation of composites to protect surfaces from fouling in an aquatic environment is based on the known facts of the antibacterial effect of some nanoparticles, for example, nanosilver (NS) . The proThe lack of a precise algorithm for modeling the toxic effects of chemical “intervention” on the ecosystem as a whole is effectively compensated for by studies of the initial stage of interaction between the factor and the biocenosis, which is considered a trigger for possible future negative changes in ecosystems. The study of changes in the microbiota of the aquatic environment and living organisms can serve as a source of information for predicting the biological effects of chemicals on aquatic organisms.Pseudoaltermonas tunicata, Pseudomonas sp. SS304, Cyanobium sp. LEGE 10375, Roseobacter, and others [To study the formation of biofilms on polymer coatings with antifouling properties, the microorganism characteristics of aquatic systems are used, such as d others ,36. TheyFrom the viewpoint of the authors of most studies, these microscopic organisms determine the biofilm’s structure and functions on artificial and natural surfaces in the aquatic environment and create conditions for attaching larger organisms. The creation and study of antifouling coatings involve the study of primary biofilms in test systems that simulate similar processes in natural conditions. Usually, under experimental conditions, monocultures of the indicated microorganisms are used. Strictly for certain species of microorganisms, unequivocal conclusions regarding the formation of biofilms can be made during the study of the action of nanoparticles of antifouling materials on the microbiota of the hydrogen environment. As is known, in natural conditions, multispecies biofilms are formed.The main studies focus on the behavior of individual representatives of microbiota on the effect of nanoparticles. The study of the formation of multispecies biofilms has technical and theoretical issues for interpreting the results .One of the promising components for forming an anti-adhesive coating is silver nanoparticles that have antibacterial properties ,39.Studies of biofilms are used to assess the effectiveness and toxicity of similar biocides in creating new composites. It is known that coatings with nanoparticles of silver, copper, and other metals prevent the formation of adhesive structures of microorganisms.Simultaneously, there have not been many studies on biofilms in the natural environment and the role of microorganisms in the biodegradation of nanoparticles, and this area requires further research in the context of the growing number of new materials. Microbial biofilms on surfaces are fundamental to aquatic ecosystems and play a key role in macrofouling. On an industrial scale, they are of interest because of their adverse impact on artificial surfaces in the aquatic environment, which leads to the surface strain of hulls, microbial blistering, and the corrosion of metal surfaces. Scientists suggest that, in the future, biofilms can be used to counteract or control these processes, as well as for bioremediation of environmental pollution .The study of the process of biofilm formation on modified surfaces can be helpful, both in terms of assessing the dynamics of biofouling and in terms of studying the toxic effects of new materials on the aquatic environment ,42.This study aimed to assess the toxicity and inhibition of biofouling using new composite polymeric material based on epoxy oligomer DER-331 with additive–biocides by studying the process of multispecies biofilm formation and analysis of antibacterial properties in model test systems of microorganisms.q) of the hardener was q = 10 wt%, indicated per 100 parts by weight of epoxy resin DER-331 .Epoxy oligomer DER-331 (CAS No. 25085-99-8), manufactured by Dow Chemical Comp , was used to form epoxy-composite materials. Triethylenetetramine TETA hardener  was used to crosslink the epoxy composition. The content (in the weigh fraction Nanosilver (NS) and (OT) oxytetracycline  were used as biocide fillers. NS belongs to the group of metals of intermediate thermodynamic stability. Silver nanoparticles have a positive standard electrode potential, which does not exceed the electrode potential value associated with the oxidizing action of oxygen in a neutral environment. Therefore, the filler is resistant to any acidic and neutral environments without oxygen. This biocide provides high antibacterial activity against microorganisms. The dispersion of NS was 10–100 nm .22H24N2O9. The structural formula is shown in A tetracycline antibiotic, oxytetracycline, was also used. It had a dispersion of 5–10 microns. This compound has various biocidal properties and can be used against many bacterial organisms. OT is, by nature, a lipophilic substance and can easily penetrate the cell membrane of bacterial microorganisms, which inhibits the development of their population. Therefore, it is advisable to use it as an antibacterial ingredient in the formation of the epoxy composition, which will prevent fouling of the hull by microorganisms. The molecular formula of this filler is Cthe preliminary preparation and dosing of ingredientsT = (373 ± 2) K and exposure for a specified time τ = (20 ± 0.1) minthe heating of epoxy resin DER-331 to a temperature of τ = (1.5 ± 0.1) minthe mechanical mixing of ingredients during τ = (1.5 ± 0.1) min;the ultrasonic treatment (UST) of the composition during T = (273 ± 2) K, during τ = (60 ± 5) minthe cooling of the composition to room temperature τ = (5 ± 0.1) minthe adding the hardener TETA and mixing the composition for a time the application of the composition by mechanical or pneumatic spraying.the solidification of materials according to the experimentally established regimet = (12.0 ± 0.1) h at a temperature T = (293 ± 2) Kthe formation of samples and their keeping during υ = 3 K/min to a temperature of T = (393 ± 2) Kheating at a rate of t = (120 ± 5) minthe keeping of the samples at a given temperature for a time T = (293 ± 2) K.slow cooling to a temperature of The change in the temperature regimes was not implemented as it would lead to a change in the results of the research unit filled with nanosilver and oxytetracycline.t = 24 h in the air at a temperature T = (293 ± 2) K. Then, they were coated with the epoxy resin DER-331 composite filled with nanosilver (at q = 0.5–1.5 wt%) and/or oxytetracycline (at q = 0.5–1.5 wt%). Pneumatic spraying was used for covering metal surfaces with composite materials.For the stabilization of the structural processes in the matrix, the samples were kept for l = (120 ± 2) mm, width b = (15 ± 0.5) mm, and height h = (10 ± 0.5) mm. Studies of the structure and microrelief of surfaces were conducted using scanning electron microscopy (SEM) , Sumy, Ukraine) and X-ray energy dispersive spectroscopy .The ultimate tensile strength and flexural modulus were determined according to ASTM D 790-03. The sample parameters were length Lactobacillus acidophilus derived from the probiotic preparation Acidophilus Plus-Solgar ; the Bifidobacterium bifidum strain, isolated from the probiotic preparation “Bifidumbacterinum-Biopharma” ; and the Escherichia coli strain isolated from the aquatic environment in vitro. The identification of the microorganism was performed by studying the morphological, cultural, biochemical, and antigenic properties in the microbiological laboratory of Sumy State University (the certificate № RU-0213/19 from 15 March 2019).The ecotoxicity of composite surfaces on metal test plates was determined using methods standard in eco-microbiology ,47,48,49Escherichia coli, Klebsiella pneumonia, isolated from an aquatic environment. Based on scientific data on the composition of marine microflora [Escherichia coli, Klebsiella pneumoniae, isolated from an aquatic environment. During the second series of the experiment, a three-component biofilm was formed: test cultures of Escherichia coli, Klebsiella pneumoniae isolated from the aquatic environment and museum culture of Aspergillus niger. Each series of experiments was carried out five times with two-component and three-component biofilms. The reason for the design features of the second series of experiments is the fact that, in the natural marine environment, along with bacterial organisms, there are yeasts and microscopic fungi, which can also participate in biofilm formation and are microorganisms–bio-destructors.The standard method of Denisov, D. B. et al.  was usedcroflora , 18 h teλ = 595 nm, NanoDrop 2000®, Thermo Fischer Scientific, Waltham, MA, US). The reduction factor of the microbial biomass was calculated as the ratio of the optical density of the sample to the optical density of the control in percentage equivalent.The process of biofilm formation and the influence of the coating components of  metal teThe biofilm-formation process on test samples was also studied using a scanning electron microscope: SEO-SEM Inspect S50-B with pre-spraying silver. Biofilm fixation was carried out using 2% glutaraldehyde solution. The dehydration of samples was performed in a series of ethanol concentrations . The final dehydration of the samples was carried out in alcohol of maximum concentration (100%) for 15 min.The statistical processing of the obtained results was performed using the software package for statistical data processing: Graph Pud Prism 8 , with the definition of the Student’s criterion.q = 0.5 wt% (specified per 100 parts by weight of epoxy resin DER-331); 2. Oxytetracycline at q = 1.0 wt%; 3. Oxytetracycline at q = 1.5 wt%; 4. Nanosilver at q = 0.050 wt%; and 5. Nanosilver at q = 0.075 wt%; 6. Nanosilver at q = 0.100 wt%. It should be noted that we observed an improvement in the physical and mechanical parameters with the above-mentioned amounts of fillers in the epoxy oligomer. However, the thermophysical properties of the composite, which correspond to the values of the epoxy matrix, remain unchanged.What is significant in the use of coatings to protect hulls is the ability to maintain adhesive and cohesive strength under the influence of environmental factors and to prevent the penetration of aggressive agents through the polymer to the base and the coatings’ ability to counteract fouling. Therefore, in the preliminary stages of research, the influence of fillers, namely nanosilver and oxytetracycline, on the physical–mechanical and thermophysical properties of the epoxy matrix relative to the content of each component was determined. By analyzing the obtained results, it can be asserted that composites containing the following ingredients  are char® Centurion XVI application package. Orthogonal central compositional planning was used to optimize the content of fillers of different nature to form the protective coating [Additionally, two fillers in the complex (nanosilver and oxytetracycline) were used to improve the properties of the protective coatings, the optimal content of which was determined by the method of the mathematical planning of the experiment using the STATGRAPHICS coating ,51. The N = 9), each of which was repeated three times (p = 3) to rule out system errors , was formed as a regression (see Equation (2)) with regression coefficients ib (2). The obtained coefficients of the regression equation are shown in A mathematical model, As a result of the analysis of the destructive stresses of CM, we observe the following regression Equation (3).i-th combination of factor levels for m = 3; m is the number of parallel experiments; and For the statistical processing of the obtained experimental results, the reproducibility of experiments was tested by Cochran’s test (4).y obtained in parallel experiments.The dispersion of adequacy was determined using Reproduction variances were determined using (6) and (7):The specific calculated values are:From the viewpoint of the above-mentioned facts, the value of Cochran’s test at 5% equal significance can be represented by (9).α = 0.05, verification of the results of experimental studies according to Cochran’s test [i-th combination of factor levels is calcG = 0.174. The tabular value of Cochran’s test is tableG = 0.478. Comparing the obtained values, we fulfil the following conditions:Thus, for a fixed probability of n’s test  confirmeThe next step was to analyze the results according to the experimental design, determining the significance of the coefficients of the regression equation .Subsequently, the variances of the regression coefficients were determined  accordint-test [mt) and calculated (pt) t-tests were determined  = 9 (3 – 1) = 18, the tabular value of the t-test was determined, which is Tt = 2.1.Depending on the degrees of freedom: t-test (pt) and the significance of the coefficients were determined: tp0, tp1, tp2, tp11, tp22, tp12 > Tt.The calculated values of the This is represented in (12):t-tests tp0, tp1, tp2, tp12, tp11, tp22 are higher than Tt, we consider that all coefficients of the regression equation b0, b1, b2, b12, b11, b22 are significant. Therefore, the regression equation has its original form (13).Since the calculated values of the Student’s yS2 = 0.026 is the variance of reproducibility.According to Fisher’s test, the adequacy of the obtained model was checked (14) .(14)Fp=adequacy  (15).(1pF = 1.565. f1 = N − (k + 1) = 9 − (6 + 1) = 2, f2 = N (n − 1) = 9 (3 − 1) = 18). This is represented by Ft) = 3.55 ,53.Comparing the calculated value of Fisher’s test with the tabular, we see the fulfilment of condition (13). It can be assumed that the equation reliably describes the composition. As a rule, the process of the interpretation of the resulting mathematical model is not limited to determining the influence of factors. A simple comparison of the absolute value of linear coefficients does not determine the relative degree of influence of factors, since there are also quadratic terms and pairwise interactions. In a detailed analysis of the obtained adequate model, it should be considered that, for the quadratic model, the degree of influence of the factor on the change of the initial value is not constant.iq represents the value of the i-th experiment factor, i0q represents the value of zero level, and Δiq represents the interval of variation [Consider the following dependencies that connect the normalized and natural values of the variables .(16)xi=ariation .According to (16), replacing these values in the regression equation, and then converting them, we obtained a regression equation with a natural value of variable parameters (17).bmR = 92.4 Mpa).With natural values, this equation allows you to predict only the value of the original value for any point that is within the range of factors. Despite the above, it can be used to plot the dependence of the initial value (yield strength during bending) on any factor (or two factors). The geometric interpretation of the obtained values is shown in the form of the response surface . During According to the previous calculations, the components of the composition were optimized according to the modulus of elasticity in bending. According to As a result of the regression, the equation is as follows (18).According to the Cochran test (4), the reproducibility of experiments was checked for the statistical processing of the obtained experimental results.The values of the variances determined by (6) and (7) are shown in ψ = 0.05 confirmed the reproducibility of the experiments. The dispersion characterizing the scattering of the experimental results on the i-th combination of factor levels is The calculated value of the Cochran test was found by (8) and then compared with tabular data. The verification of the results of the experiment by the Cochran test for a fixed probability Gpo3p = 0.295. Accordingly, the tabular value of the Cochran test is tableG = 0.478. That is, the condition is fulfilled, so Gpo3p = 0.295 ≤ tableG = 0.48.The calculated value of the Cochran test is Tt = 2.1. Subsequently, the dispersion of the regression coefficients (9) and the calculated values of the Student’s t-test (10) were determined .According to the Student’s F(t) = 2.93 and is higher than the calculated value (pF = 2.657) under which condition (12) is satisfied. As mentioned above, the regression equation adequately describes the composition. When converting the elements of the regression equation according to (14), we obtained the following equation using the natural value of the variable parameters (20).Using Fisher’s test, we tested the adequacy of the obtained model (13), (14). In the process of work, its tabular and calculated values were determined. According to Fisher’s test, the tabular value at the 5% significance level is During experimental research, the value of both factors was determined. We emphasize that according to the analysis of the Pareto map, it can be argued that the effect of nanosilver on these indicators of the modulus of elasticity is more pronounced than the influence of oxytetracycline .E = 3.3 GPa). The change in the ratio of the content of the filler deteriorates the modulus of elasticity during bending. Therefore, on the basis of complex research and the mathematical planning of the experiment, variants of coatings were established, which were studied for ecotoxicity and biofilm formation  and nanosilver (q = 0.075 wt%) allowed us to identify significant differences in surface morphology (The study results of the structure and microrelief of surfaces (scanning electron microscopy) of composite materials are shown in rphology b. The narphology . Coatingrphology c,d are cq = 1.5 wt% and nanosilver at q = 0.075 wt%) using X-ray energy dispersive spectroscopy are shown in The study results of the sample . The results of the in vitro tests used to assess the safety of nanomaterials in these model systems are shown in Given all the above, we conducted an ecotoxicity in vitro analysis of samples using laboratory and analytical studies generally accepted in microbiology  in modelq = 1.5 wt%) and nanosilver (q = 0.075 wt%) inhibits probiotic strains of L. acidophilus, E. coli, as there is a significant reduction in CFU/mL test strains in media with the tested nanomaterial and in media without it by at least one logarithmic order in the in vitro model. A toxic effect on this probiotic test culture was recorded for this sample. For all other samples of test plates with nanosilver and/or oxytetracycline of different concentrations, no toxic effect was recorded on the model system of typical intestinal microflora.When comparing the results of in vitro tests to assess the safety of test specimens coated with nanosilver and/or oxytetracycline, the time of the physiological stages of propagation of pure test cultures in a liquid medium with an uncoated metal test plate was considered. We found that a metal test plate with a coating containing oxytetracycline (p ≤ 0.05) a number of bacterial cells in 1 mL of nutrient medium compared to the controlled growth of test cultures in the thioglycolic medium for 72 h of cultivation is noteworthy. It can indirectly indicate the leaching of the coating fillers (oxytetracycline or nanosilver) of the metal test plates and the bacteriostatic effect of the formed medium on the test cultures.The fact that test cultures of the model system of typical intestinal microflora in the presence of tested coated metal plates have a significantly lower , it was found that the original strains of these test cultures had high adhesive power (IAM ≥ 7 bact. Cells/erythrocyte). After 72 h of cultivation with samples of tested metal plates, the level of adhesion significantly (p ≤ 0.05) decreased. Thus, Lactobacillus acidophilus, which showed a high level of adhesion, had a medium degree of adhesion after 72 h (IAM 3.5 bact.cells/erythrocyte); Bifidobacterium bifidum had a low degree of adhesion (IAM 1.95 bact.cells/erythrocyte); and Escherichia coli test culture, which had the highest level of adhesion at the beginning of the experiment (IAM 8.3 bact.cells/erythrocyte), reduced the adhesive potential to a low level (IAM 2.0 bact.cells/erythrocyte). The obtained data indicate that, after the prolonged contact of the test culture with the coating of metal plates or due to the leaching of the components of this coating, planktonic microflora change their adhesive properties to reduce the adhesive potential. These results indicate the suppression of the initial stage of development of biofilms, namely the attachment of bacteria to the biotic or abiotic surface, inhibiting the transition to a biofilm lifestyle.By analyzing the study results of the adhesive properties of the test cultures used in in vitro tests for the ecotoxicity of the fillers of the coating of metal plates  showed that, in the early incubation period (72 h) and on the surface of samples with oxytetracycline  in the long term. The forming and components of the biofilm are influenced by various factors. Adding nanoparticles to coatings changes the physicochemical properties of active substances, which in turn changes the behavior of microorganisms in forming these “communities”. The direction of change is difficult to predict, as nanoparticles and nanomaterials are characterized by properties such as emergence.The obtained result can indicate that the long-term incubation of these test metal plates containing the antibiotic filler stimulates the growth of fungal microbiota, namely the fungus-biodestructor—s fungus . On the Escherichia coli and Klebsiella pneumonia (compared to 120 h of the experiment) on metal test plates. Microorganisms were found in the typical vegetative form without signs of active division  generation. Changing the functioning of cell biostructures leads to the inhibition of the last stage of the formation of mature biofilms with the construction of a massive exocellular matrix. Additionally, research reports have demonstrated that the Ag+ ions firmly connect with the thiol (-SH) links of crucial compounds and disable them [q = 0.075 wt% ; the Bifidobacterium bifidum strain, isolated from the probiotic preparation “Bifidobacterium-Biopharma” ; and the Escherichia coli strain isolated from the aquatic environment in vitro. The microorganism was identified by studying morphological, cultural, biochemical, and antigenic properties in the microbiological laboratory of Sumy State University (certificate No. RU-0213/19 dated 15 March 2019).Three test cultures of probiotic bacterial strains were used to study the ecotoxicity of the tested samples (reported in the manuscript of the article): the probiotic strains of Three test cultures were also used in the study of biofilm formation as the main process of biodegradation (reported in the manuscript of the article). Each series of experiments was performed five times with two- and three-component biofilms.Escherichia coli, Klebsiella pneumonia, isolated from an aqueous environment. Based on scientific data about the composition of marine microflora [Escherichia coli, Klebsiella pneumoniae, isolated from an aquatic environment.The first series of experiments aimed to create a two-component biofilm: heterophilic croflora , 18 h teEscherichia coli, Klebsiella pneumoniae, isolated from an aqueous environment and a museum culture of Aspergillus niger. The reason for the design features of the second series of experiments is that in the natural marine environment, along with bacterial organisms; there are yeasts and microscopic fungi that can also participate in biofilm formation and are classified as “microorganism-biodestructors”.The second series of experiments produced a ternary biofilm: test cultures of q = 1.5 wt% and nanosilver at q = 0.075 wt% per 100 parts by weight oligomer DER-331 and 10 wt% of the TETA hardener provided the formation of a material with the following properties: flexural strength—bmR = 87.7 MPa, flexural modulus—E = 3.3 GPa. The increase in mechanical characteristics is associated with the change of the polymer structure because of the compaction of the spatial network of the polymer, which ensures the moderate mobility of the segments and side groups of the composite macromolecules.The content of different additive–biocides, which differ by physicochemical properties and the dispersion in the epoxy matrix DER-331, was optimized by the method of the mathematical planning of the experiment to obtain functional coatings. The optimal content of basic (oxytetracycline) and additional (nanosilver) fillers for forming composites with high-cohesion characteristics has been established. It was proved that the introduction of oxytetracycline at Escherichia coli and probiotic strain Lactobacillus acidophilus only for samples with oxytetracycline at q = 1.5 wt% and with nanosilver at q = 0.075 wt%. All other samples of metal test plates with different concentrations of nanosilver and/or oxytetracycline in the composite coating do not have a toxic effect on the typical intestinal microflora.The analysis of the results of the in vitro testing of surfaces formed using a composite material based on epoxy oligomer DER-331 with additive–biocides (nanosilver and/or oxytetracycline) showed toxic effects on After prolonged contact with the coatings of the metal test samples, the planktonic microflora change their adhesive properties. The decreased adhesive potential inhibits the initial stage of biofilm development (the attachment of bacteria to the biotic or abiotic surface) and represses the transition to a biofilm lifestyle. The dynamics of the processes in the initial stages of biofilm formation indicate that silver nanoparticles (in concentrations that inhibit the growth and reproduction of microbiota), as part of composite coatings based on epoxy oligomer DER-331, can be a factor of decreasing in biofouling. In perspective, these properties of the new composite material based on epoxy oligomer DER-331 allow us to recommend the designed coatings to protect the bodies of water transport vessels from fouling and destruction by microorganisms.Seawater is a specific habitat for microorganisms associated with the characteristic salt composition of water, low temperatures, high pressure, low concentrations of organic matter, and more. Additionally, the waters of some seas contain significant concentrations of hydrogen sulfide. Thus, in the Black Sea, there is a hydrogen sulfide zone, in which the amount of hydrogen sulfide increases with depth. Hydrogen sulfide in water is formed solely by the activity of microorganisms because of two processes—ammonification (decomposition) of proteins by anaerobic putrefactive microorganisms, and desulfation—i.e., the reduction of salts of sulfuric and sulfurous acids with the formation of hydrogen sulfide in the presence of organic matter. Both processes are equally active. 2 is emitted into the atmosphere and then dissolved in seawater to form H2CO3, increasing its acidity. Its slightly alkaline nature is increasingly approaching neutral pH values, with a number of serious consequences for marine organisms [Toxic effects on the environment and marine life are currently manifested by an accelerated reduction in ocean pH, mainly due to the excessive burning of fossil fuels. More than a third of excess COrganisms .All these factors have a long-term impact, which causes the biological fouling of ships/structures, significantly impairs the efficiency of use of these facilities, and increases the economic costs associated with their maintenance and operation. Based on the above, the prospects for further research are to study the structural changes of nanomaterial-based coatings in modeling systems for biofilm formation in the long term (3–4 months), taking into account the chemical composition of seawater and the inclusion of algae in the model test system.The results of the microbiological studies of the biofilm formation could not be compared with data from other studies because the present experiment used information on protective polymer coatings with a combination of nanosilver and oxytetracycline not found in previously available scientific publications.