Neimann-Pick Diseases: Beyond Lipid Accumulation – Genetic, Diagnostics, and Therapeutic Strategies
Hind M Naffadi, pages 703-713
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 Rare genetic disorders are the group of disorders/diseases that occur in such a low count that they are not considered much active market for therapeutics unless encouraged by appropriate incentives and support. They are too rare to be fully investigated and managed by health professionals. Genetic disorders are caused by change in genes and are often serious and complex. Around the world, most affected individuals are found to be children. They can be progressive and might get worse as children grow older. Niemann-Pick diseases (NPD) is one such group of rare genetic diseases that are characterized by unwanted and abnormal accumulation of lipids within the cells. In this review, we discuss the history, genetic basis, clinical manifestations and diagnostic approaches for NPD. We further discuss the pathophysiology of accumulation of lipids and their impact on cellular functions and organ systems and various management strategies. 

Methods: The descriptive study was conducted at Jinnah Hospital Lahore’s Burn and Reconstructive Surgery Centre (JB & RSC) and the Institute of Microbiology and Molecular Genetics (MMG), University of the Punjab, Lahore. The clinical specimens of wound swabs, including the age, gender, socio-economic status, residence, occupation, hospital stay, wards, burn degree, total burnt surface area (TBSA%), etiology of burn, and other factors were recorded. Antimicrobial susceptibility testing (AST), ESBL and CR screening (Beta- lactam and carbapenem resistant bacteria) were performed using CLSI guidelines 2017.

Results: The most dominant strain was Pseudomonas spp. 26.5% (n=106), followed by 15% (n=60) Klebsiella spp., and 7.5% (n=30) Acinetobacter spp. with ESBL-producing strains. Compared to nosocomial infections, community-acquired infections were observed in 314 (78.5%) patients with more ESBL production. There was a significant relation between burnt people having an age of ≤ 29 years with ESBL (p=0.985) and carbapenemases (p=0.694) infections. None of the other factors, like low socioeconomic status and more hospital stays had a significant correlation (p > 0.05).

Concluded: It has been concluded that MDR gram-negative strains play a serious role in burn infections and demand suitable methods to decrease their number. Pseudomonas spp. was the most common post-burn infection causing bacteria. Unfortunately, a high frequency of burn infections was observed in the patients at a young age. 

Methods: One hundred fifty fresh beef samples were collected from six traditional markets located in Surabaya city. Then, a polymerase chain reaction (PCR) test was performed to detect the blaTEM gene which codes for ESBL in isolates that unveiled positive results for MDR (resistant to three antibiotics) and suspected beta-lactamase enzyme (resistant to ampicillin).

Results: The research showed that from 150 samples of fresh beef at the Surabaya Traditional Market, 68 Escherichia coli isolates were found (45.3%). Escherichia coli isolates were shown to be susceptible to the antibiotic’s ampicillin (73.5%), gentamicin (95%), tetracycline (7.5%), aztreonam (100%), and ciprofloxacin (95%). The highest percentage of resistance of Escherichia coli isolates to the antibiotic ampicillin (19.1%). PCR analysis of ampicillin-resistant isolates showed that the blaTEM gene encoding ESBL was present in 7 (53.8%) of the 13 Escherichia coli isolates.

Conclusion: The research results show that there is a risk of ESBL transmission to the community through Escherichia coli which was identified in fresh beef at the Surabaya Traditional Market. Therefore, it is hoped that public awareness can increase regarding food safety issues which can have an impact on public health. 

Methods: Different techniques including precipitation with polyethylene glycol, ammonium sulfate, methanol, and filtration through an ultra-filter membrane were used for the concentration of viral suspension. Antigen quantification in terms of µg/ml was determined through size exclusion chromatography by using Sephacryl S-300 as a stationary phase.

Results: Percentage recovery of FMDV calculated through analysis of chromatograms found 77.80%, 59.75%, 32.50%, and 13.83% for polyethylene glycol, ammonium sulfate, ultra-filtration, and methanol treated samples respectively.

Conclusion: Classical polyethylene glycol precipitation showed a maximum percentage recovery of foot and mouth disease virus as compared to other concentration methods. 

Methods: This study was carried out at Department of Anatomy at Liaquat University of Medical & Health Sciences, Jamshoro after ethical approval on placentae of 122 parturients; 61 from normal and 61 from preeclampsia, data was collected on predesigned proforma and was analyzed on SPSS 23.

Results: The mean and standard deviation of maternal age, gestational age, and parity was 32.73±5.9 years, 37.3±3.6 weeks and 3±1 respectively. The wall thickness of SA and VD when compared in two groups found statically significant. Vitamin D signaling molecules were determined by immunostaining compared in two groups by applying Mann Whitney U test and Pearson’s correlation which reveals significant differences in preeclamptic versus controls.

Conclusions: Despite extensive research indicating a link between low levels of VD and its signaling molecules in the context of inadequate spiral artery remodeling, there is still a need for further investigation to fully understand the mechanisms underlying this association in preeclampsia. 

Methods: Oil-contaminated soil samples were gathered and utilized to isolate hydrocarbon-degrading bacterial isolates. The bacterial isolates possessing bioremediation capabilities were identified using phenotypic determination and biochemical properties. The Optimal conditions including incubation period, temperature, different pH values and different carbon sources were studied for bioremediation of crude oil by bacterial isolates.

Result: In Wasit province of Iraq, Pseudomonas putida, P. fluorescens, and P. aeruginosa isolated from soil samples tainted with petroleum hydrocarbons. Pseudomonas putida have more ability for bioremediation of crude oil (68%) compared to P. aeruginosa and P. fluorescens (47%, 58%) respectively. The results of optical density (600nm), biomass and (E24%) index for Pseudomonas putida were (1.080, 1.98 and 60%) respectively. The Optimal conditions (incubation period, temperature, different pH values and different carbon sources) were studied for bioremediation of crude oil by Pseudomonas putida by using liquid BHM supplemented with 1% crude oil. The result of this study showed that the incubation period of 9 days was the optimum for  bioremediation of hydrocarbons which was 88.33%. The optimum temperature and pH were 35 °C and 7 respectively. The carbon source (glucose and fructose) was optimal for hydrocarbon bioremediation.

Conclusion: This bacterial isolate Pseudomonas putida can be use in petroleum hydrocarbon bioremediation process. 

Methods: This study was conducted  in the animal house, College of Veterinary Medicine, Al-Qasim Green University for a period of 90 days. Forty rats of the Wistar strain (Rattus norvegicus) were randomly distributed into 4 groups, namely the first group (control group) while the second, third and fourth groups were treated with 100, 200 and 300 μg of sorbitol/kg of body weight .The rats were iso in live weight and age at the beginning of the experiment. Blood samples were drawn at the end of the experimental period.  

Results: Increase in level dose of sorbitol resulted significant improvement in accounts of red blood cells, white blood cells, and a significant increase in level of hemoglobin, lymphocytes, and monocytes for second, third, and fourth groups compared to the control group. Moreover, the significant improvement in most of the blood parameters was reflected to significant increase in clotting and bleeding time in the second, third and fourth groups of rats compared to the control group. Also, the results showed a significant increase in the levels of FSH, LH, testosterone, Inhibin and MAD hormones for the second, third and fourth groups  compared to the control group.

Conclusions: The results of the current study revealed that sorbitol has many benefits in the diet of humans and animals and has an effect on blood indicators, some sex hormones and antioxidants in the body. It is recommended not to consume excessive sorbitol in the diet. 

Methods: In this study, a combination of polyfloral honey, royal jelly (RJ), Korean ginseng, and palm pollen were tested to reduce oxidative DNA damage in semen. The study involved 25 male patients aged 22-45 years who were participating in a fertility clinic in Wasit, South-East Iraq. Surgically resolvable problems were excluded, as well as subjects who smoked.

Results:  Semen analysis and serum total oxidant status were used to assess the fertility potential in males, and pregnancy occurrence served as evidence of sperm ability for fertilization. Our findings indicate that consuming honey with Korean ginseng and palm pollen improved sperm count by reducing caspase-3 activity and protecting against oxidative DNA damage. In addition, forward progressive motility and morphology of the sperm were significantly improved by the treatment and also had a direct effect on mitochondrial enzymes.

Conclusion: Therefore, the use of honey combined with specific herbals appears to be a promising treatment option for the improvement of sperm parameters to treat male infertility. 

Methods: Eight fungal genera were isolated from wheat grain samples, and the most frequent fungus was A. niger. Plant extracts were used to reduce the growth of A. niger, and the culture media was used to test the ability of A. niger fungus isolates to produce aflatoxin toxins. The media was also used to sow wheat grains for the purpose of isolating the fungi associated with them, growing the fungi, and purifying it. The culture media was poured into sterile petri dishes with a diameter of 9 cm, with three replicates for each concentration, and the comparison treatment in which an untreated food media was used.  

Results: The paper found that A. niger was the frequent fungus among the isolated fungal genera in wheat grain samples. The plant extracts, particularly citrullus extract, showed a clear effect in inhibiting the growth of A. niger and reduced the AFB1 toxin that it produces. The paper recommends continuous examination of stored wheat grains to determine the amount of fungal contamination and to ensure good storage conditions before receiving the grains in grain stores.

Conclusion: The paper aimed to detect fungi associated with local and imported wheat grains stored in the stores of Al-Muthanna Governorate and the possibility of reducing them by using some plant extracts.  

Methods: The most important goal of this study was to find the vital connection between male infertility and immunological factors (CXCL12 and anti-sperm antibody). During the months of October 2021 and July 2022, a total of 144 samples were taken from patients who sought to have infertility tested. Semen and blood samples were taken from the subjects to assess seminal plasma CXCL12 levels and the prevalence of anti-sperm antibody (ASA) in their serum. Alternatively, research on sperm function parameters, sperm agglutination risk, and its relationship to ASA and CXCL12.

Result: statistically there was no ‘significant’ difference in CXCL12 levels across study groups in this investigation. The prevalence of sperm agglutination was 23.61% across all patients under study, the majority of whom had asthenozoospermia. In contrast, 60% of the samples from ASA-positive patients were agglutinated. The results revealed a relatively weak positive link that may call for additional research even if there was no significant statistical correlation in the relationship between CXCL12 and sperm functions and ASA.

Conclusion: The findings of this study suggest that ASA affects seminal fluid parameters, which in turn affects male fertility, and that a weak, non-significant association between CXCL12 and sperm function could impair sperm function by reducing sperm motility. Sperm agglutination could be a sign of immunological infertility.  ASA can impact male fertility in a number of ways. Others had to do with sperm agglutination.  

Methods: During the growing season of 2021-2022, a total of 81 onion samples exhibiting virus-like symptoms were collected from two different geographical regions in Saudi Arabia. The serological technique (ELISA) was used to detect the important allexiviruses and potyviruses. RT-PCR amplification of partial genome sequence was done using degenerate primers for allexiviruses and potyviruses and the phylogenetic trees were constructed using different bioinformatic tools.

Results: The results obtained from ELISA tests showed that 26% and 32% of onion samples were positive with both Garlic Virus A (GarV-A) and Onion yellow dwarf virus (OYDV) respectively. RT-PCR amplification and sequencing results showed that two allexiviruses, GarV-A, garlic virus D (GarV-D), and one Potyvirus (OYDV) were detected in both regions. Sequence data were deposited in the GenBank database with accession numbers, OQ397545, OQ397546 for GarV-A, OQ397547 for GarV-D, and OQ397548, OQ397549 for OYDV, sequentially. Phylogenetic tree analysis of these virus isolates showed making clades with closely related isolates of their respective viruses. Pairwise nucleotide sequence identity showed their similarity with GarV-A, GarV-D, and OYDV isolates reported earlier in the GenBank.

Conclusion: To the best of our knowledge, these two distinct allexiviruses (GarV-A, GarV-D) and one Potyvirus (OYDV) were isolated for the first time from an onion crop in Saudi Arabia. 

Methods: Different concentrations of heavy elements (5,10, and 25mg/ L) were prepared and treated with the plant in different masses (0.2,0.4, and 0.8 grams)and over time periods of one and two weeks. The concentration of each element was measured before and after the treatment periods using an atomic absorption device.

Results: As evidenced that spring Azolla (green type) was more effective at removing cadmium and lead elements than autumn Azolla (red type), where the spring Azolla recorded higher removal efficiency for Cd , where it was 1.80% under biomass 0.8g, contact time 10 days, and at metal concentration 10mg\L ,while the highest percentage removal for Pb , was 40.02% under biomass 0.4g, contact time 15 day and at metal concentration 5mg\L . Azolla has great potential for removing heavy metals from water resources and can be used in heavy metal phytoremediation initiatives in environmental improvement projects.

Conclusion: This research suggests using the aquatic macrophyte Azolla, especially spring fern, to treat sewage and household wastewater containing Cadmium and Lead. 

Methods: A tubular photosynthesis microbial desalination cell was designed and set up for simultaneous wastewater biotreatment and desalination of seawater associated with clean power generation.16S rRNA sequencing was used for characterization of the dominant microbial strains in the anodic biofilm. The materials involve DNA extracting from bacteria and PCR amplifying for 16S rRNA gene. The kinetic of the bacterial growth in relation to the substrate utilization was studied.

Results: The results revealed the identification of 19 new dominant microbial strains; 13 in the initial shallow biofilm and 6 in the developed biofilm. Results of evaluating the PMDC performance demonstrated that maximum removal efficiency of organic content from sewage was 93±3% associated with power generation of 24.3±2.5 mW/m³ and 70±4% desalination efficiency of saline water. Results of the kinetic study of biomass growth demonstrated that among the 5 examined models, Monod and Blackman models significantly fitted the experimental data with determination coefficients (R²) of 0.951 and 0.907, respectively.

Conclusion: This study adds to our knowledge of the anode biofilm's involvement in PMDC performance by identifying dominant microbial strains using 16S rRNA sequencing. The findings emphasize microbial contributions to simultaneous treatment of wastewater, desalination of sea water, and electricity generation. This experimental and theoretical investigation paves the way for future breakthroughs in microbial desalination technology, addressing crucial water scarcity issues. 

Methods: To study the effects of seed coating with Nanoparticles of Titanium dioxide at concentrations of (0, 100, 200, 300, and 400) ppm and  selenium at concentrations of (0, 20, 40, 60, and 80) ppm on shoot length, number of leaves per plant, carbohydrate %, protein %, and antioxidant activity peroxidase %, single and two way interaction on fenugreek’s growth is taken into account. Treatments are designed as a properly randomized factorial experiment (5×5×3), with three replicates in a totally randomized design.

Results: It was revealed that a single application of the previously mentioned ingredients had a significant impact on fenugreek growth and antioxidant activity, especially at high concentrations.

Conclusions: Plant physiological properties were favorably influenced by seed coating with (Titanium dioxide and Selenium) nanoparticles. Based on the results of TiO₂ NPs’ effect on seed germination and early seedling growth, it is possible that NPs aided in seed water absorption, increased seed ability to absorb and utilize efficiently, and activated and promoted hydrolytic enzymes in the seed antioxidant system. 

Methods: Sixty-five Klebsiella pneumoniae isolates were identified by the VITEK®2 compact system and confirmed identity by Polymerase Chain Reaction assay by amplified rpoB gene (Housekeeping gene). The isolates were subjected to Reverse Transcriptase-polymerase chain Reaction assay to determine the transcriptional variations of the type II toxin-antitoxin system genes at diverse temperature and pH values.

Results: The results of the current study demonstrated higher expression levels of the antitoxin hipB gene at (37℃, 30℃, 44℃, pH 7, pH 9), mqsR toxin gene at (37℃, 30℃, pH 7, pH 5, pH 11) and relE toxin gene at (pH 5, pH 11).

Conclusion: These findings suggest the possible influence of pH and temperature on toxin-antitoxin systems, which might enhance bacterial antibiotic tolerance and persistence. 

Methods: The PyRx AutoDock VINA was used to conduct in-silico screening of a natural compound library to assess their interaction with the SHV-1 protein. SwissADME web tools were used to predict the physicochemical, drug-likeness, and ADMET properties of the selected compounds.

Result: The compounds PSCdb00708, PSCdb00149, PSCdb00698, and PSCdb00175 bind strongly to the SHV-1 protein and interact strongly with the SHV-1 active site residues, as well as having several amino acid residue interactions in common with avibactam. These compounds exhibited higher binding affinity values than avibactam. Furthermore, these compounds demonstrated no violation of drug-likeness.

Conclusion: The compounds PSCdb00708, PSCdb00149, PSCdb00698, and PSCdb00175 can be employed as SHV-1 inhibitors in the management of AR. However, experimental validation is required to optimize them as SHV-1 inhibitors. 

Methods: This study used a computational screening of a library of known compounds with anti-inflammatory activities against the active site of ACE using the PyRx-Python 0.8 tool to find more potent ACE inhibitors with less or no side effects. The physicochemical properties of the anti-inflammatory compounds were obtained from the Life Chemicals website.

Result: The five hits, specifically F3398-2114, F0193-0245, F0163-0089, F0193-0237, and F0302-0060, exhibited notable interactions within the ACE binding pocket and demonstrated greater binding energy compared to the control compound, Lisinopril. All of these compounds displayed favorable physicochemical characteristics and aligned to Lipinski's rule.

Conclusion: The compounds F3398-2114, F0193-0245, F0163-0089, F0193-0237, and F0302-0060 have the potential to be used as ACE inhibitors; however, further experimental validation is required to optimize them as ACE inhibitors. 

Methods: C. colocynthis seeds were examined using qualitative and quantitative phytochemical methods. Antioxidant testing was conducted using DPPH assay and the reducing power test. Antibacterial properties were evaluated using the well-diffusion test, minimum inhibitory concentration (MIC) test, and minimum bactericidal concentration (MBC) test. The effectiveness of the extract against Aphis craccivora (A. craccivora) was assessed using a leaf-dip bioassay, measuring generation time (GT), net reproduction rate (R₀), intrinsic rate of increase (rm), doubling time (DT), and finite rate of growth (λ).

Results: The methanolic extract of C. colocynthis seeds included diverse bioactive compounds, a good quantity of phenolic content (60.45 mg GAE/g) and flavonoid content (46.66 mg/g). The antibacterial tests showed that the extract was effective only against Staphylococcus aureus and Proteus mirabilis. The extract recorded inhibition zones of 14.5 ± 0.7 mm and 10.5 ± 0.5 mm for Staphylococcus aureus and Proteus mirabilis, respectively. Staphylococcus aureus showed the greatest sensitivity, with MIC of 6.25 mg/mL and MBC of 25.0 mg/mL. The extract was found to have a fatal concentration (LC₅₀) of 9.02% and a lethal concentration (LC₉₅) of 20.50% against A. craccivora aphid.

Conclusions: The current vitro study on C. colocynthis reported that the seeds are effective as antioxidants, antibacterial agents (only against Gram-positive bacteria), and aphicidal agents against aphids. More investigations are recommended to examine the possible toxicity and biochemical interactions in vivo.  

Methods: The current study employs bioinformatic approaches to explore the oxygen sensitivity of A. bivalviorum's PFOR, comparing it with Desulfovibrio africanus and Moorella thermoacetica. The UniProt database was used to obtain the sequences of PFOR from D. africanus (CAA70873), A. bivalviorum (AXH11209), and M. thermoacetica (Q2RMD6). This comparative analysis sheds light on the structural similarities and differences between the enzymes, providing a deeper understanding of their functional mechanisms.

Result: PFOR enzyme is a heterodimer, with its functional subunits containing three [4Fe-4S]²⁺ clusters. Its exposed Fe-S clusters are vulnerable to oxygen and ROS, leading to enzyme inactivation. A comparison of PFOR sequences from D. africanus, M. thermoacetica, and A. bivalviorum reveals a crucial difference: the final 43 residues at the C-terminal of D. africanus are missing in the other two enzymes, depriving the M. thermoacetica and A. bivalviorum enzymes of a self-protective mechanism.

Conclusion: Pyruvate:ferredoxin oxidoreductase (PFOR) in A. bivalviorum lacks protection from oxidative damage due to the absence of the final 43 amino acids at the C-terminal. 

Methods: The study groups included patients from Iraq, ages 4 to 35. Two primary patient groups were created: sixteen had positive H. pylori and celiac disease, and thirty had positive CD and negative H. pylori disease. The levels of tissue transglutaminase IgA (TTG IgA), H. pylori IgG, and IL-33 were measured using the ELISA method. The primers were amplified using PCR.

Results: With celiac disease, the patient group's TTG IgA levels increased dramatically. The test also showed significant variations (P=0.054) in the H. pylori IgG levels between the patient and control groups. The H. pylori seropositivity test showed a statistically significant difference (p ≤0.033) between seropositive and seronegative individuals, while the patient group's IL-33 levels did not significantly differ (P ≤0.299) from the control group.

Conclusions: Our results showed that CD is more common in women and occurs in the age range of 24-35 years. It also showed that the mutant variant of ATG5 is associated with CD, and the significance of H. pylori IgG serum levels in the patient group may indicate that the bacteria involved in CD. Furthermore, H. pylori infection is more strongly linked to serum IL-33 levels than CD. 

Methods: In this study, 383 distinct bioactive compounds were extracted from the LOTUS database from Zingiber officinale and were screened against NEK7 protein using the PyRx 0.8 software. The top six hits' physicochemical characteristics, molecular descriptors, and natural product-likeness ratings were assessed using the LOTUS database.

Results: The compounds LTS0101379, LTS0022317, TS0094590, LTS0231343, LTS0085481, and LTS0110340 showed high affinity for NEK7, forming interactions with critical amino acid residues. Notably, these compounds had multiple interactions with amino acid residues similar to those of the control compound Dabrafenib. Furthermore, the molecular properties and descriptors of these compounds indicated favorable drug-like properties.

Conclusion: These findings highlight the potential of these compounds as NEK7 inhibitors for cancer management, though additional experimental validation is required. 

Methods: To determine antioxidant activity, we used three free radical scavenging assays: DPPH (2,2-Diphenyl-1-picrylhydrazyl), hydrogen peroxide (H₂O₂), and nitric oxide (NO) assays. Total phenolic and flavonoid contents were measured using colorimetric methods. The anti-important activity was evaluated by MTT assay.

Results: Our findings showed that the efficacy of the extract in MCF7 cells decreased in the system containing chloroform, methanol, ethyl acetate, and water. The strength of the extract for U87 cells decreased according to methanolic, chloroform and water, where ethyl acetate was the strongest. The highest total phenolic and flavonoid content was found in methanol extract. All extracts showed a high scavenging activity of DPPH. Methanol extract showed the highest antioxidant activity in the NO assay of the solution, followed by ethyl acetate, chloroform, and aqueous extract. In the H₂O₂-based antioxidant activity assay, the methanol extract again showed the highest activity, followed by ethyl acetate, chloroform, and aqueous extracts.

Conclusions: Extracts of C. europaea have  shown great potential as natural antioxidants and anticancer agents in this study, suggesting that they deserve further investigation into the food and pharmaceutical fields. 

Methods: In this study, forty (n=40) non-repeat, CPE clinical isolates, including: n=35 Klebsiella pneumoniae, n=2 each of Escherichia coli and Klebsiella oxytoca, and n=1 Enterobacter cloacae isolates were identified and susceptibilities were assessed using the Vitek-II compact (bioMérieux, Inc., France) and Microscan Walkaway (Beckman Coulter) systems. Genotypic analysis of clinically relevant carbapenemases was performed by using Xpert-Carba-R assay on GeneXpert (Cepheid, USA). The minimum inhibitory concentrations (MICs) and synergy testing of CZA and ATM, were tested by the Etest fixed ratio method (bioMérieux, Inc., France). The fractional inhibitory concentration index (FICI) was calculated for each antibiotic.

Results: Our results showed that 97.5% of bla_MBL-producing Enterobacterales isolates were susceptible to an in-vitro CZA + ATM combination regimen. The fractional inhibitory concentration index (FICI) ranged from 0.001 to 1.001. Among the tested CPE isolates, Synergy was observed in 36/40 (90%), an additive effect was observed in 5% (n=2)’ while two (5%) isolates showed indifference. There was no antagonism observed in our study.

Conclusion: Our study exhibited a potent activity of CZA and ATM combination synergy against clinical CPE metallo- β-lactamase producers. More extensive studies involving a variety of Gram-negative pathogens with different resistance mechanisms are required to determine the efficacy of this combination regimen. 

Methods: The study has been conducted with the intent to uncover a prospective approach to treating lung cancer through structural modification of Hesperetin by creating its analogs to enhance its efficacy compared to its parent compound with the computational drug design. The analysis has been conducted with various approaches followed by PASS prediction, ADME, toxicity profile, molecular docking, data filtration, and anticancer activity.

Results: All the compounds showed satisfactory criteria in each parameter that was assessed. The data mining was done carefully by pointing out the compounds that had the greatest value among all the compounds in each investigation, which resulted in a total of 3 compounds out of 50. 

Conclusions: Finally, the selected compounds were further analyzed for MD simulation studies. Afterward, PCA analysis was also conducted in order to get the lead compound with this additional investigation. 

Methods: HMRGs and antibiotic resistance of 100 E. coli from sewage and fresh water were detected by PCR. Minimum inhibitory concentrations (MICs) of heavy metals were determined by the broth micro dilution method. Antibiotic discs used to detect multidrug resistance, was recovered and assembled using third-generation sequencing.

Results: The frequency of different HMRGs in E. coli ranged from 1–67%., while prevalence of ESBL genes ranged 5-17% in freshwater isolates, and 54- 96% in swage isolates. MICs of heavy metals for E. coli ranged widely from ≤8.0-800 mg/L. Moreover, HMRGs (PbRT, cadD arsB, PcoA, czrc, and chrA) were found to be significantly associated with one or more ARGs ( tetA,  blaTEM, blaSHV and blaCTX) (P < 0.05).

Conclusion: In conclusion, HMRGs were widely present in E. coli isolated Dujla river and sewage water were significantly associated with DRGs . It is remarkable that the coexistence of HMRGs, DRGs and ARGs confer co-resistance to heavy metals, and antibiotics. 

Methods: Based on the chemical analysis of milk, the following indicators were studied: fat mass fraction, protein mass fraction, casein, lactose, dry matter, skimmed milk residue, urea, density, titrated acidity, active acidity, and somatic cells. An organoleptic evaluation of milk was carried out according to the following indicators: color, smell, taste, appearance, and consistency. Once a month, a control milking was carried out to account for productivity.

Results: The EG's raw milk had higher casein and lactose content compared to the CG, with EG II showing the highest levels. Additionally, milk from the EG contained more solids, indicating better nutritional and technological properties, with solid content being 3.8-5.7% higher than in the CG.

Conclusion: Based on the obtained results, it was found that milk productivity had increased by 10-20%, the fat mass fraction by 7-10%, the protein mass fraction by 5.1-6.5%, the amount of dry matter by 3.8-5.7%, and lactose by 1.1-4.3%. 

Methods: The experiments were carried out in 2022-2023 in the Central Zone of the Krasnodar Territory, Russia in the stationary scientific crop rotation at the Federal Research Center for Biological Plant Protection, Krasnodar (2.5 ha) and the Kononenko farm, Novovelichkovskaya village, Dinsky district (10 ha). The biological effectiveness of elimination and disorientation methods was judged by the degree of damage to plants and buds. The disorientation effect was calculated by the number of males captured at the disorientation sites compared to the control sites.

Result: The decrease in males’ search activity (disorientation effect) reached 85.3%. The damage to buds by the pest in this variant was 2.0% compared to 10.8% in the control group. In the mass trapping variant, it equaled 1.5-3.0 and 7.5%, respectively, indicating the prospects of including these techniques in the H. armigera biorational control system.

Conclusion: Our findings could aid future research on insect chemical communication to develop effective biological control methods. 

Methods: Leaf rust severity was assessed using a modified Cobb scale, and net blotch severity with the E. E. Geshele scale. Disease severity was averaged from triplicate measurements on 25–30 plants. After harvest, 1000 seeds per plot were weighed. Differences were evaluated using the Fisher test (α = 0.05), and correlations via the Chaddock scale in Statistica 13.3.

Results: A high degree of inverse correlation was established between the proportion of resistant cultivars and the severity by both diseases r= – 0.93/– 0.99. The optimal mixture combination of a resistant and susceptible cultivar against net blotch was recorded as 1S:4R, and leaf rust as 1S:3R and 1S:4R.

Conclusion: In mixed barley crops, a strong inverse correlation was found between the proportion of resistant cultivars and disease severity (r = –0.93/–0.99). Disease severity correlated directly with humidity and temperature in spring, with an inverse correlation for net blotch in June. Using mixed cultivars enhances crop resistance to abiotic and biotic stresses, making it suitable for eco-friendly farming. 

Methods: The 5a-5l were prepared by reacting compound 3 with various aryl thioamides. The structures of 5a-5l were ascertained by their spectral records. The 5a-5l were subjected to their antibacterial activity potential (serial plate dilution method), DNA gyrase inhibiting activity, and toxicity analysis (MTT assay) against HepG2 & Vero cell lines. The in-silico studies (pharmacokinetic parameters and molecular docking) of 5a-5l were likewise performed.

Results: It was surprisingly observed that the MIC values of 5a-5l were equal to the MIC values of ciprofloxacin (12.5 µg/ml) against the tested bacteria, whereas the DNA gyrase inhibitory activity (IC₅₀ in µg/ml) of 5h (3.52), 5g (3.76), 5f (3.88), 5e (4.08), 5l (4.11), 5b (4.28), 5k (4.28), 5i (4.30), and 5d (4.32) was equal/better than ciprofloxacin (4.32). The MTT assay also implied the non-cytotoxic nature of 5a-5l against HepG2 & Vero cell lines up to 200 µg/ml concentration. The docking outcomes indicated a similar binding pattern of 5a-5l and ciprofloxacin at the active site of DNA gyrase, wherein 5a-5l displayed a better binding affinity for the active site. The in-silico toxicity data employing the ProTox-II web server indicated no hepatotoxicity, carcinogenicity, immunotoxicity, mutagenicity, or cytotoxic effect of 5a-5l. Also, the SwissADME software supported the drug-likeliness properties and high gastrointestinal absorption of 5a-5l.

Conclusion: Compounds 5h, 5g, 5f, 5e, 5l, 5b, 5k, 5i, and 5d are potent DNA gyrase inhibitors with promising safety profiles.