Current Issue

Advancements in Life Sciences, volume 11, issue 4 – November 2024Cover; Volume 11, Issue 4
ISSN 2310-5380

IN THIS ISSUE

This 4th issue of the 11th volume has featured 31 multidisciplinary articles including 3 reviews articles and 28 research papers of authors from 13 countries covering aspects from different stems of life science. Enjoy reading!

 

 

 Review Articles


Neimann-Pick Diseases: Beyond Lipid Accumulation – Genetic, Diagnostics, and Therapeutic Strategies
Hind M Naffadi, pages 703-713
Read Abstract
 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. 

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Advancing Frontiers and Novel Insights in Colorectal Cancer
Amer Al Ali, pages 714-725
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 Colorectal cancer, a known form of cancer poses a global health threat. Ongoing studies are actively investigating perspectives and evolving treatments. This review explores the developments in cancer research covering topics such as profiling, microbiome interactions, immunotherapy, precision medicine, tumor environment analysis, liquid biopsies, metabolic changes, artificial intelligence applications and patient centric care. Molecular subtyping advancements have greatly improved our understanding of the nature of cancer and how different individuals respond to therapies. The significant link between gut microbiome composition, inflammation levels and immune responses underscores the importance of interventions targeting the microbiome and innovative immunotherapy strategies. Precision medicine initiatives are leveraging biomarkers and molecular signals to inform treatment decisions and optimize outcomes. This thorough examination highlights the impact of evolving trends in cancer research and treatment strategies while offering insights into directions for improving patient care and results. 

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Mavorixafor: A spotlight on the clinical aspects and prospects of the first USFDA-approved treatment for the primary immunodeficiency WHIM syndrome
Mohd Imran, Abdulaziz Khalaf Alshammari, Khalid Ramadan Alhamad, Majd Ahmed Alghamdi, Maryam Adnan Alghareeb, Renad Adnan Alghareeb, Omar Ibrahim Aldhafiri, Jumanah Basem Al-Humud, Syed Mohammed Basheeruddin Asdaq, Abida, pages 726-732

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 WHIM syndrome (WHIMS) is an extremely rare, severe, and potentially fatal genetic condition that affects the immune system, leading to warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM). Effective therapy for WHIMS requires regular monitoring, medical intervention, and a collaborative approach to treatment. Due to the limited therapeutic options, addressing WHIMS is an unmet medical need. The United States Food and Drug Administration (USFDA) recently granted approval for mavorixafor as the first treatment for WHIMS. This review focuses on the pharmacological characteristics, clinical investigations, associated inventions, and prospects of mavorixafor. The literature for this article was searched on PubMed, reputable websites (USFDA and X4 Pharmaceuticals) and free patent databases like Espacenet. WHIMS is distinguished by severe neutropenia and hypogammaglobulinemia, which increases the risk of developing cancer. Mavorixafor enhances the movement of neutrophils and lymphocytes from the bone marrow (BM) to the bloodstream. Hence, it could be beneficial for managing medical illnesses characterized by a decrease in the quantity of neutrophils and lymphocytes in the bloodstream. X4 Pharmaceuticals has submitted patent applications for the utilization of mavorixafor in the treatment of diverse cancer types, inflammatory ailments, B-cell dysfunction, Waldenstrom's macroglobulinemia, and primary immunodeficiency disorders. This suggests that mavorixafor can effectively treat various disorders either alone or when used in conjunction with other medications. It will be intriguing to observe the future approvals of mavorixafor for various disorders. 

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Full Length Research Articles


Risk factors for Beta-lactam and carbapenem-resistant bacteria causing post-burn infections
Muhammad Hayat Haider, Amina Akram, Maira Nasir, Rehan Ahmad Khan Sherwani, Muhammad Umair Shareef, Muhammad Nauman Ali, Saba Riaz, pages 733 -740

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 Background: Burn patients are predisposed to infection because of the loss of skin barrier protection and low immunity. This study aims to evaluate the  risk factors of post-burn infections due to beta-lactam and carbapenem-resistant bacteria (CR) isolated from a major burn unit.

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. 

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Identification of BlaTEM Gene Encode Extended Spectrum Beta Lactamase (ESBL) Producing Escherichia coli Isolated from Fresh Beef
Lailatul Maghfiroh, Mustofa Helmi Effendi, Wiwiek Tyasningsih, Adiana Mutamsari Witaningrum, Agumah Nnabuife Bernard, pages 741-747

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 Background: The community needs fresh beef of good quality. Dirty sanitation causes Escherichia coli to easily contaminate fresh meat and E. coli is one of the bacteria that can produce ESBL enzymes that impact human health. This study aimed to isolate Escherichia coli from fresh meat at the Surabaya Traditional Markets to identify the presence of the ESBL-encoding blaTEM gene.

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. 

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Comparative Efficiency of Polyethylene Glycol, Ammonium Sulphate, Methanol Precipitation, and Ultrafiltration Techniques for the Down Streaming of Viral Antigen
Faisal Ayub, Afifa Shahzad, Saad Bin Shabbir, Tayyaba Kaleem, Mahnoor Rao, Umair Aqeel, Imran Altaf, Zeshan Khursheed, Aemin Rasheed, Muhammad Shahzad, Hafiz Muhammad Moavia Atique, Abdul Razak, Muhammad Arshad Durrani, pages 748-755

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 Background: Foot and mouth disease (FMD) is ubiquitous  worldwide but endemic in many countries of Africa, Asia, South America, and the Middle East. Many reasons contribute to the incidence of viral diseases even in vaccinated animals. These reasons include low antigenic payload, low PD50, improper formulation, unstable vaccine containing antigen, and genetically different from field strain. Among these, the most important one is the low antigenic load per dose of the vaccine. Vaccine failure is mainly due to the direct use of  virus suspension in the vaccine without the concentration of viral antigen. Another reason to concentrate the antigen is small volume storage in the vaccine bank. These issues are mostly concerned with developing countries like Pakistan which lack antigen concentration technology. The concentration of the virus is a major milestone to be achieved for the production of an effective vaccine as well as for the diagnostic tool.

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. 

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Altered placental expression of genes related to Vitamin D Metabolism and their correlation with spiral artery remodeling in Preeclamptic Women
Pushpa Goswami, Samreen Memon, Ikram Din Ujjan, Fahmida Gul, pages 756-760

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 Background: Several studies reveals the correlation of preeclampsia (PE) with low vitamin D (VD) level due to disturbed trophoblast invasion and failure of spiral artery remodeling. The metabolism of VD is regularized by it signaling molecules expressed by the placenta during pregnancy. Therefore, this study was designed to assess and compare the levels of VD and it signaling molecules in placentae from normotensive and preeclamptic pregnancies and their correlation with spiral artery remodeling.

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. 

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Bioremediation of hydrocarbon pollutants by Pseudomonas putida under optimal conditions
Fatima Kareem Shandookh, Melad Khalaf Mohammed, Ahmed Darweesh Jabbar, pages 761-766

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 Background: The extreme toxicity of petroleum products to human and environmental health, particularly when linked to large-scale unintentional spills, has made them one of the most serious and current environmental pollution issue. Petroleum products are a complex mixture of hydrocarbons.

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. 

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Impact of varying sorbitol concentrations on hematological and biochemical blood parameters in Wistar rats (Rattus norvegicus)
Zahraa H. K. Al-Mousawi, Mozhir K. K. Almahdawi, Abdulsatar S. S. Al-Bayati, pages 767-772

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 Background: Sorbitol is an artificial sweetener that is very similar to natural sugar, but it is sweeter than natural sugar and lower in calories. Sorbitol is used as an alternative to natural sugar, and it is extracted from regular glucose. It does not have any negative effects on the animals’ health, and it is  characterized in safe use in many scientific experiments for the diet of humans and animals.

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. 

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Beneficial impacts of natural antioxidants on molecular structure and parameters of human sperm
Rafed Abbas Kadhum, Aqdas Mohammed Sfaieh , Asmaa Musaed Salih, pages 773-778

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 Background: Sexual dysfunctions are often associated with oxidative stress, DNA damage, and reduced levels of sex hormones.

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 IraqSurgically 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. 

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Identification and control of toxin-producing fungus in wheat grain stores using environment friendly factors
Ali Faraj Jubair, Zina Jawad Abdulhussein, Saad Manee Enad Al-Jabry, Musaab Abdulrasool Abdulzahra Alabid, pages 779-784

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 Background: The problem of mycotoxins in wheat crops can lead to health issues for humans and animals. It is very important to find safe and efficient methods to prevent the growth of toxin-producing fungi or reduce and remove them from food to prevent their risks to humans, animals, and agricultural crops. The paper focuses on finding environmentally friendly materials to protect wheat grains from toxin-secreting fungi, particularly Aspergillus niger,  reducing the production of aflatoxin B1.

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.  

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The Relationship of CXCL12 with Sperm Agglutination and Anti-Sperm Antibody Among Infertile Men
Fahad Dhamin Oleiwi, Mousa J. Mohammed, Chatin I. Ali, pages 785-790

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 Background: It is known that structural elements like the ‘blood-testis barrier’ (BTB) and local & systemic tolerance mechanisms help to maintain testicular homeostasis, which shields germ cells and mature sperms from immune attack. Any damage to this barrier could result in immune attack and may cause infertility.

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.  

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Characterization of garlic virus A, garlic virus D, and onion yellow dwarf virus infecting onion
Mahmoud A. Amer, Muhammad Amir, Khadim Hussain, Ibrahim M Al-Shahwan, Mohammed A. Al-Saleh, pages 791-796

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 Background: Allium cepa is one of the major vegetable crops cultivated in Saudi Arabia. This economically important crop faces several biotic stresses which adversely affect the quality and quantity of its production. Several virus groups (potyviruses, carlaviruses, tospoviruses, and allexiviruses) have been reported infecting Allium crops.

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. 

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Evaluation of the effectiveness of Azolla fern in removing the toxicity of lead and cadmium in water
Wurood Hamzah Muttaleb, Huda Jasim Altameme, pages 797-802

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 Background: Heavy metals are harmful to living organisms and are emitted into the environment from many different sources. Compared to alternative remediation technologies that are either too expensive or impractical, phytoremediation, in which plants are used to remove hazardous toxins from water and soil, is a viable option for use at extremely large field sites. Heavy metals may be removed from the environment by a wide variety of plants. Azolla, a kind of aquatic fern, is one example.

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. 

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Photosynthesis microbial desalination cell: Analysis and kinetic study of microbial community contribute to biofilm formation, system performance and bioenergy recovery
Ahmed Mustafa Sadeq, Zainab Ziad Ismail, pages 803-809
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 Background: Detection of bacterial species using 16S rRNA is a popular approach in microbiology. This method focuses on 16S rRNA gene which includes both conserved regions shared among bacterial species and variable regions unique to each species. This study aimed for the first time to apply this technique for identifying and classifying the bacterial species which contribute to the formation of anodic biofilm in a tubular photosynthetic microbial desalination cell (PMDC).

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. 

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Effects of seed coating with (titanium dioxide and selenium) nanoparticles on fenugreek (Trigonella foenum graecum L.) plant growth and antioxidant activity
Wasan H. Mazeil Al-Shammeryi, pages 810-814
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 Background: The fenugreek plant is a kind of herbaceous plant that resembles a clover. It is extensively used as a spice and condiment, as well as a medicinal plant. Studying the effect of seed coating on fenugreek is an important step to learn about the effects it imprints on plant growth and its antioxidant activity when its seeds are coated by nanoparticles of titanium and selenium. 

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. 

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Influence of diverse pH and temperatures on the gene expression of toxin-antitoxin systems in Klebsiella pneumoniae
Fatima J. Hassan, Mohammed F. Al-Marjani, Intesar N. Khelkal, pages 815-821
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 Background: The type II toxin-antitoxin system consists of tightly linked genetic units that produce  a toxin and its specific antitoxin. Under typical circumstances, the antitoxin  neutralizes the toxic effects caused by the toxin. However, the toxin-antitoxin systems during stress regulate bacterial growth and persistence by affecting translation or DNA replication. This study aimed to assess how variations in temperature and pH stress influence the regulation of type II toxin-antitoxin gene expression  within Klebsiella pneumoniae isolates.

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. 

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Exploring Natural Compounds Targeting the Bacterial SHV Protein to Combat Antibiotic Resistance: A Biocomputational Study
Farah Anjum, Hamsa Jameel Banjer, Nahed Hawsawi, Fouzeyyah Ali Alsaeedi, Ahad Amer Alsaiari, Afaf Alharthi, Abdulraheem Ali Almalki, Maram Jameel Hulbah, Norah Alharthi, Alaa Shafie, Maha Bakhuraysah, pages 822-826
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 Background: Antibiotic-resistant (AR) bacteria are rapidly spreading worldwide, posing a serious threat to antibiotic efficacy. Bacterial infections have emerged as a persistent threat following decades of antibiotic use. Sulfhydryl variable (SHV) is a well-known bacterial enzyme linked to AR. SHV has a high degree of genetic diversity, resulting in the existence of numerous distinct variants. 

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. 

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Computational assessment of targeting angiotensin-converting enzyme for hypertension management: A structure-based virtual screening approach
Ahmad Salah Alkathiri, pages 827-832
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 Background: Hypertension is a growing public health concern globally. The angiotensin-converting enzyme (ACE) is an enzyme that cleaves the carboxy-terminal His-Leu dipeptide from angiotensin I, yielding the potent vasopressor octapeptide, angiotensin II. ACE inhibitors are a primary treatment option for hypertension, heart failure, and myocardial infarction. However, the use of synthetic ACE inhibitors has been linked to a number of side effects. Therefore, the development of novel and safe ACE inhibitors is a need of time.

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. 

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Chemical Profiling and Pharmaceutical and Biological Activities of Methanolic Extract of Citrullus colocynthis L. Seeds Collected from the Arid Zone of Qassim, Saudi Arabia against Aphis craccivora
Emad M. Abdallah, Ahmed M. H. Ali, Hanaa Fadl Hashem, Adil A. Mujawah, Eman R. Elsharkawy, pages 833-842
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 Background: Citrullus colocynthis L. (C. colocynthis) is a medicinal plant with a long history of traditional usage in Saudi Arabia, particularly for the treatment of digestive issues such as indigestion and stomach pain.

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.  

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Bioinformatic Analysis of Oxygen Sensitivity in Arcobacter bivalviorum's Pyruvate:Ferredoxin Oxidoreductase (PFOR)
Abdulmajeed Alqurashi, pages 843-848
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 Background: Arcobacter bivalviorum is an emerging foodborne pathogen particularly found in shellfish and other bivalves. This bacterium's metabolic versatility is highlighted by its possession of both the Pyruvate Dehydrogenase Complex (PDC) and Pyruvate:Ferredoxin Oxidoreductase (PFOR). The PFOR enzyme is crucial for linking glycolysis to the citric acid cycle. Previous studies of PFOR enzyme reveal its susceptibility to oxygen damage due to its reliance on Fe-S clusters for electron transfer.

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. africanusM. 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. 

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Association of Celiac Disease and H. pylori Infection with ATG5 Polymorphism and Interleukin-33
Omar Atrooz, Sura Mumtaz, Ahmed Abood, Ansam Atrooz, pages 849-855
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 Background: Celiac disease (CD) is an inflammatory small intestine autoimmune disease.  The study aims to investigate the association and the detection of ATG5 polymorphism between celiac disease (CD) and  H. pylori infection, and the association with Interleukin-33 (IL-33).

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. 

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A Virtual Insight into Bioactive Compounds of Ginger as Potential Inhibitors of NEK7 for Cancer Management
Akram Ahmed Aloqbi, pages 856-861
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 Background: NIMA-related kinase 7 (NEK7) is a serine/threonine kinase that is required for cell cycle progression, particularly mitotic spindle formation and cytokinesis, and has been linked to various cancers. Furthermore, NEK7 modulates the NLRP3 inflammasome, which activates Caspase-1 and causes cell pyroptosis. A growing body of studies indicates that ginger has the ability to prevent and treat a variety of health issues.

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. 

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Evaluating the Antioxidant Capacity, Phenolic Contents, and Anticancer Potential of Caralluma europaea Extracts
Omar M. Atrooz, Makarem Al-Awaida, Wajdy Al-Awaida, Hamzeh J. Al-Ameer, Hamdi Uysal, pages 862-870
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 Background: Caralluma europaea (C. europaea) is a genus of shrubs in the Apocynaceae family, endemic to the Mediterranean region. Assessing the anticancer properties, total phenolic and flavonoid content, and antioxidant activity of different C. europaea extracts were the aim of this study.

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. 

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In Vitro Synergistic Activity of Ceftazidime-Avibactam and Aztreonam against New Delhi Metallo-β-Lactamase-Producing Clinical Enterobacterales Isolates
Naif Fahd AlAnazi, Mohammad Marie, Ali Mohammad Somily, Khalifa Binkhamis, Muhammad Arshad, Akram A. Alfuraydi, Muhammad Absar, pages 871-877
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 Background: Carbapenemase-producing-Enterobacterales (CPE) infections are on the rise and associated with increased morbidity and mortality, due to a limited number of therapeutic options. The goal of this study was to assess the synergistic activity of ceftazidime-avibactam (CZA) and aztreonam (ATM) combination against phenotypically and genetically characterized blaMBL-producing Enterobacterales.

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 blaMBL-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. 

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In-Silico Perspectives on the Potential Therapeutic Aids of Hesperetin Derivatives for Lung Cancer
Abdulaziz Asiri, pages 878-886
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 Background: Lung carcinoma has become one of the most noteworthy and dangerous health problems discovered today. The disease is mainly caused by smoking and becomes among the leading causes of death spread by growing the cancerous cells into the lining of the lungs and nearby lobes. The FDA has given clearance to numerous drugs and chemotherapy agents; nevertheless, they can be exceedingly costly as well as frequently fall short of entirely addressing the ailment. In the medical management of lung cancer, new medicines or active leads with high efficacy and minimal toxicity are required in this era.

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. 

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Role of heavy metals pollution on emergence of antibiotic co-resistance in E. coli isolates
Aseel AbdulRazaq Kadhim, Melad Khalaf Mohammed, Ahmed Darweesh Jabbar, pages 887-892
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 Background: Heavy metal pollution in water is one of the most serious environmental problems. These findings have prompted the idea that metal-exposed bacteria may have altered resistance to antibiotics. This study was performed to investigate the presence of heavy metal resistance genes (HMRGs) in Escherichia coli.

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. 

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Veterinary and sanitary assessment of milk quality in black-and-white cows fed with extruded compound feeds in North Kazakhstan
R.A. Zhaxalykov, K.N. Bayazitova, A.I. Polyak, L.N. Kassymbekova, R. Mustafina, M.V. Zabolotnykh, pages 893-898
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 Background: Today, one of the most effective ways to increase the digestibility of nutrients is extrusion processing. Raw materials are exposed to high temperatures and pressure, which leads to qualitative and nutritional transformations. The study aims to identify the effect of extruded compound feeds on cow productivity and the qualitative composition of milk.

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%. 

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Method for disrupting the reproductive pheromone bond of the cotton bollworm on sunflower crops
V. Ismailov, A. Komantsev, V. Borodin, pages 899-903
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 Background: Synthetic analogs of sexual pheromones provide an effective method of biorational control of the number of phytophagous insects based on the directed disruption of reproductive functions in populations of the target pest on the protected crop without affecting the integrity of the agrocenosis. The work aims to determine the biological effectiveness of methods of mass trapping and disorientation of the cotton bollworm (Helicoverpa armigera) to protect sunflower (Helianthus annuus) crops.

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. 

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Cultivar Mixtures as Part of Integrated Protection of Winter Barley from Leaf Diseases and Abiotic Stresses
Yana Yakhnik, Galina Volkova, Anastasia Danilova, Kirill Kutumov, pages 904-911
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 Background: Currently, cultivar mixtures are being extensively used in agriculture worldwide. The current research study aimed to identify the optimal proportion of cultivars with different resistance to pathogens to reduce the severity of leaf diseases in mixed cultivars against net blotch and leaf rust of barley.

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. 

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In-vitro and in-silico studies based discovery of 2-aryl-N-(4-morpholinophenyl)thiazol-4-amines as promising DNA gyrase inhibitors
Mohd. Imran, Abdulaziz Khalaf Alshammari, Khattab Fahed Alfarh­­­­, Rakan Khalid Alanazi, Samr Fahed Alfrah, Osama Muqbil Alshammri, Reem Saleh Alanazi, Sumaih Saeed Alsaeed, Feras Salah Albasha, Hanan Furayj Alhulayfi, Syed Mohammed Basheeruddin Asdaq, Abida, pages 912-917
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 Background: DNA gyrase is an important enzyme for the survival of bacteria. Many DNA gyrase inhibitors are in clinical practice. However, these inhibitors also encompass certain toxic and drug/food interactions. This warrants the development of a new template as DNA gyrase inhibitors. Therefore, this study aimed to deliver morpholine-based thiazoles (5a-5l) as safer DNA gyrase inhibitors.

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. 

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