Low Activity Research Articles

Pseudomonas aeruginosa LasR-deficient mutants have increased methylglyoxal and hydrogen peroxide sensitivity due to low intracellular glutathione.

Methylglyoxal is a highly reactive metabolite that is detected in various disease states, including those where Pseudomonas aeruginosa is present and MG resistance requires the glutathione-dependent glyoxalase enzyme GloA3 enzyme. This study reveals that P . aeruginosa strains with LasR mutations, which are commonly found in clinical isolates, are more sensitive to methylglyoxal (MG) and hydrogen peroxide due to lower intracellular glutathione levels and high activity of the CbrAB-Crc regulatory pathway. This could be significant for understanding the selective pressures that drive P. aeruginosa evolution in infection sites, as well as a better understanding of LasR-strain metabolism in infections such as those associated with cystic fibrosis.

HPV-driven heterogeneity in cervical cancer: study on the role of epithelial cells and myofibroblasts in the tumor progression based on single-cell RNA sequencing analysis.

Cervical cancer (CC) is a neoplasia with a high heterogeneity. We aimed to explore the characteristics of tumor microenvironment (TME) for CC treatment. HPV positive (+) and negative (-) samples from cervical cancer (CC) patients were sourced from the Gene Expression Omnibus (GEO) database. The single-cell RNA sequencing (scRNA-seq) data were processed and annotated for cell types utilizing the Seurat package. Following this, the expression levels and biological roles of the marker genes were analyzed applying real-time PCR (RT-PCR) and transwell assays. Furthermore, the enrichment of genes with significantly differential expressions and copy number variations was assessed by the ClusterProlifer and inferCNV software packages. Seven main cell clusters were classified based on a total of 12,431 cells. The HPV- CC samples exhibited a higher immune cell infiltration level, while epithelial cells and myofibroblasts had higher proportion in the HPV+ CC samples with extensive heterogeneity. Immune pathways including antigen treatment and presentation, immunoglobulin production and T cell mediated immunity were significantly activated in the HPV- CC group with lower cell cycle and proliferation activity. However, the anti-tumor immunity of these cells was inhibited in HPV+ CC group with higher cell proliferation activity. Moreover, the amplification and loss of CNVs also supported that these cells in HPV- CC samples were prone to anti-tumor activation. Further cell validation results showed that except GZMA, the levels of APOC1, CEACAM6, FOXP3, SFRP4 and TFF3 were all higher in CC cells Hela, and that silencing TFF3 could inhibit the migration and invasion of CC cells in-vitro. This study highlighted the critical role of HPV infection in CC progression, providing a novel molecular basis for optimizing the current preventive screening and personalized treatment for the cancer.

Phytochemical Profile and Antioxidant Activity of Medicinal Plant Extracts: Insights into Potential Therapeutic Applications .

This study evaluates the phytochemical composition and in-vitro antioxidant activities of various extracts such as Boswellia serrate (Bs), Zingiber officinale (Zs), Tribulus terrestris (Tt), Camellia sinensis (Cs), Withania somnifera (Ws), and Piper longum (Pl). Using soxhlet extraction, the plants were processed with various solvents, including n-hexane, dichloromethane, methanol, ethanol, and water. Phytochemical screening revealed a diverse range of compounds, such as alkaloids, flavonoids, and saponins, varying by extract. The antioxidant activities were assessed using superoxide, hydroxyl radical scavenging assays, and lipid peroxidation assays. The hydroalcoholic extract of C. sinensis exhibited the highest antioxidant activity, with significant superoxide and hydroxyl radical scavenging capabilities. T. terrestris and W. somnifera also demonstrated strong antioxidant properties, aligning with their traditional medicinal uses. Moderate activity was observed in P. longum, attributed to its bioactive compound, piperine. Meanwhile, B. serrata and Z. officinale showed lower antioxidant activities but are noted for their anti-inflammatory benefits. This research corroborates previous findings on the antioxidant potential of these plants, highlighting the importance of further investigations into their pharmacological applications. The study underscores the therapeutic potential of these extracts in oxidative stress-related conditions and supports their continued exploration in modern medicine.

Multiple Enzyme-Mimicking CuMOF-Driven Self-Cascading Antioxidant Reaction for Synergistic Electrochemiluminescence Modulation in Ultrasensitive Biosensing.

Developing nanozyme-based free radical scavenging is a promising signal modulation approach for ECL sensing. Nevertheless, the relatively low antioxidant activity and inherent pro-oxidant activity of numerous nanozymes have significantly hindered the development of this strategy. Here a biofunctional copper-based metal-organic framework (CuMOF) with multiple enzyme-mimicking activities was employed for the modulation of the ECL immunosensor, guided by the self-cascade antioxidant reaction. The inherent SOD, CAT, and the capacity to eliminate ·OH endow CuMOF with powerful synergistic antioxidant effects while little pro-oxidant activities were displayed, enabling efficient scavenging of the O2·- produced during the electrochemical oxidation of H2O2. Subsequently, the nanoconfinement effect of the layered double hydroxide was introduced to ensure a steady ECL signal. The suggested ECL immunosensor, using aflatoxin B1 as a proof-of-concept target, demonstrated a detection range spanning from 0.001 pg/mL to 10 ng/mL, with the detection limit calculated to be 0.18 fg/mL. This exceptional achievement greatly broadens the range of possible uses for nanozyme-based radical scavenging modulated ECL analysis.

Plasma adenosine deaminase-1 and -2 activities are lower at birth in Papua New Guinea than in The Gambia but converge over the first weeks of life.

Dynamic cellular and molecular adaptations in early life significantly impact health and disease. Upon birth, newborns are immediately challenged by their environment, placing urgent demands on the infant immune system. Adenosine deaminases (ADAs) are enzymatic immune modulators present in two isoforms - ADA-1 and ADA-2. Infants exhibit low ADA activity, resulting in high plasma adenosine concentrations and a consequent anti-inflammatory/anti-Th1 bias. While longitudinal studies of plasma ADA have been conducted in infants in The Gambia (GAM), little is known regarding ADA trajectories in other parts of the world. Herein, we characterized plasma ADA activity in an infant cohort in Papua New Guinea (PNG; n=83) and compared to ontogeny of ADA activity in a larger cohort in GAM (n=646). Heparinized peripheral blood samples were collected at day of life (DOL) 0, DOL7, DOL30, and DOL128. Plasma ADA-1, ADA-2, and total ADA activities were measured by chromogenic assay. Compared to GAM infants, PNG infants had significantly lower ADA-1 (0.9-fold), ADA-2 (0.42-fold), and total ADA (0.84-fold) activities at birth which converged by DOL30. Overall, discovery of a distinct baseline and a consistent pattern of increasing plasma ADA activity in early life in two genetically and geographically distinct populations validates and extends previous findings on the robustness of early life immune ontogeny.

A Novel Ce─Mn Heterojunction‐Based Multi‐Enzymatic Nanozyme with Cancer‐Specific Enzymatic Activity and Photothermal Capacity for Efficient Tumor Combination Therapy

AbstractCatalytic medicine, using enzymes or nanozymes, is an emerging method for cancer treatment. However, its applicability is limited by the low catalytic activity in the tumor microenvironment (TME). In this work, a versatile and synthesis‐friendly nanozyme, CeO2Mn1.08Ox nanoclusters, is prepared. This novel Ce─Mn heterojunction is formed by oxidation of CeO2 nanoparticles through H2SO4/KMnO4. CeO2Mn1.08Ox exhibits high multi‐enzymatic catalytic activities and acts as a catalase (CAT), peroxidase (POD), and oxidase (OXD) mimics under acidic conditions. It can regulate the TME by relieving hypoxia and consuming endogenous glutathione (GSH). Glucose oxidase (GOx) is then incorporated into CeO2Mn1.08Ox and linked with poly(ethylene glycol) (PEG) to obtain the cascade enzyme system (Ce─Mn)‐PEI/GOx‐PEG. CeO2Mn1.08Ox exhibits CAT‐like properties, which sensitize GOx‐based starvation therapy, and POD‐ and OXD‐like properties, which generate highly cytotoxic reactive oxygen species (ROS) in cancer cells. The glucose catabolic product, H2O2, is also used to generate O2 and ROS. In addition, the heterojunction structure provides CeO2Mn1.08Ox with near‐infrared (NIR) photothermal capability, making it suitable for photothermal therapy (PTT). Density functional theory (DFT) calculations provide possible reasons for the high catalytic activity and photothermal capability of CeO2Mn1.08Ox. When combining mild PTT with catalytic therapy, the cascade enzyme system (Ce─Mn)‐PEI/GOx‐PEG can efficiently ablate tumors.

Analysis of Magnitude–Frequency Distribution of Earthquakes in the Sichuan Basin, Southwest China

Abstract The Sichuan basin is characterized by underdeveloped active geological structures and low seismic activities. In recent years, an increase in seismicity has been observed in the southern Sichuan basin, which includes small earthquakes induced by water injection during shale gas exploitation and M ≥ 5.0 earthquakes, causing unexpected damage and casualties. This necessitates a comprehensive analysis of the magnitude–frequency distribution of the current seismicity. In this study, we examined the current seismicity using instrumental earthquake records at different periods and estimated the temporal and spatial variations in b-value. We found that the b-values widely vary in the Sichuan basin and analyzed the spatial differences in b-value in seven different earthquake clusters. The results show that the intense fault movement on the western boundary of the Sichuan basin might be the main controlling factor of the increased seismicity in the southern basin instead of being induced by water injection. Furthermore, earthquakes in the Sichuan basin follow the same size distribution as the events on the boundary faults and the Sichuan–Yunnan rhombus active block. Thus, it is appropriate to consider the magnitude–frequency distribution of earthquakes for the Sichuan basin and the Sichuan–Yunnan rhombus block together rather than separately. These results may help improve the recurrence models in probabilistic seismic hazard assessment of the region.

Heterologous expression of bacterial tyrosinase and its applications in biological hair dyeing and DOPA modification of hydrolyzed silk fibroin

Tyrosinase is a copper-containing polyphenol oxidase widely applied in the food, cosmetics, pharmaceutical, and other industries. Currently, the production of commercial tyrosinase primarily relies on extraction from fungi, which has high costs, low purity, low specific activity, and poor stability. The objective of this study is to obtain highly expressed bacterial tyrosinase with potential for industrial applications. The bacterial tyrosinases from five different sources were heterologously expressed in Escherichia coli BL21(DE3), and the tyrosinases TyrBm and TyrVs derived from Bacillus megaterium and Verrucomicrobium spinosum were obtained with the enzyme activities of (16.1±0.2) U/mL and (48.6±0.9) U/mL, respectively. After protein purification, we compared the enzymatic properties of TyrBm and TyrVs, which revealed that TyrVs exhibited better thermal stability and higher substrate specificity than TyrBm. On the basis of characterizing TyrVs with high catalytic performance, we established a biological hair dyeing system based on TyrVs catalysis to achieve in-situ catalytic hair dyeing. The color washing fastness test measured the ∆E value less than 7.38±0.64 after simulated 14-day cleaning. To facilitate the rapid separation of catalytic products and enzymes, we successfully constructed an immobilized enzyme TyrVs-CipA dependent on self-assembly label CipA and applied this enzyme in the DOPA modification of hydrolyzed silk fibroin (HSF). The immobilized enzyme continuously catalyzed HSF for more than seven cycles, resulting in a single DOPA modification degree exceeding 70.00%. Further investigations demonstrated that DOPA modification enhances the scavenging activity of HSF towards DPPH and O2- radicals by 507.80% and 78.23%, respectively. This study provides a technical foundation for the development of environmentally friendly biological hair dye based on tyrosinase and biomaterials for tissue engineering.

Characterisation Analysis of Sulphur and Phosphorous Doped and Co-doped Graphitic Carbon Nitride (g-C3N4) Materials

Graphitic carbon nitride (g-C3N4) is tailored with doping of different non-metals (Sulphur and Phosphorus). For synthesis through thermal condensation method, the mixtures of urea and dopant with diverse concentrations have been added for preparation of materials. The basic effect of doping and its concentration on the structural morphology and absorption spectra of the samples is investigated in detail. Pure g-C3N4 suffers from high recombination rate of photogenerated electron-hole pairs resulting in low photocatalytic activity. Different techniques like X-ray diffraction (XRD), Scanning electron microscopy (SEM), Fourier transforms infrared (FTIR) spectroscopy, and Photoluminescence spectroscopy (PL) have been used for the characterization. X-ray diffraction studies confirm the formation of the g-C3N4 structure and SEM images reveal crumpled sheets and irregular plate like shapes of the doped graphitic nitride samples. FTIR analysis identify the presence of surface amino (N-H) and water (O-H) groups, cyano terminal group (C≡N), (C≡C), C–N) and (C=N) bonds and breathing mode of the tri-s-triazine units in the samples. PL spectra shows that the sulphur and phosphorus co-doped PSGCN (8 wt.%) sample is better for photocatalytic activity.

The independent and joint association between physical activity, sleep duration and daily sitting time with bone mineral density: A real world study from NHANES 2007–2018.

PurposeTo assess the independent and joint effect of physical activity, sleep duration, and daily sitting time on bone mineral density (BMD), based on National Health and Nutrition Examination Survey (NHANES) 2007–2018. DesignCross-sectional design. MethodsThe primary outcome was risk of low BMD. All associations between lifestyle factors and the prevalence of low BMD were based on logistic regression, and dose-response relationships were further explored by restricted cubic spline (RCS). Finally, multiplicative and additive interaction was examined by P interaction and relative excess risk due to interaction (RERI). Results10,346 individuals (N normal BMD = 6353; N Low BMD = 3993) were analyzed. Multivariate logistic regression indicated low intensity physical activity (odds ratio [OR] 0.84; 95 % confidence interval [95%CI] 0.78–0.90) and high intensity physical activity (0.67, 0.56–0.78) had protective impact on risk of low BMD, whereas short sleep (1.41, 1.20–1.64), long sleep (1.36, 1.03–1.79) and prolonged daily sitting (1.58, 1.32–1.88) had harmful effect. RCS revealed dose-response associations between physical activity (J-shaped), sleep duration (U-shaped), daily sitting time (positive-associated) and risk of low BMD. Multiplicative interaction between sleep duration and physical activity was observed (P interaction = 0.003), while not between daily sitting time and physical activity (P interaction = 0.600). Notably, negative additive interactions indicated that physical activity mitigated the increased risk of low BMD associated with irregular sleep patterns and prolonged sedentary behavior. ConclusionIncreasing physical activity was presented as a modulating factor, potentially altering the relationship between independent variables that have deleterious effects on BMD like sleep duration and sedentary behavior. The study underscores the importance of lifestyle modifications in the prevention of early onset low BMD.

Optimized periphery-core interface increases fitness of the Bacillus subtilisglmS ribozyme.

Like other functional RNAs, ribozymes encode a conserved catalytic center supported by peripheral domains that vary among ribozyme sub-families. To understand how core-periphery interactions contribute to ribozyme fitness, we compared the cleavage kinetics of all single base substitutions at 152 sites across the Bacillus subtilis glmS ribozyme by high-throughput sequencing (k-seq). The in vitro activity map mirrored phylogenetic sequence conservation in glmS ribozymes, indicating that biological fitness reports all biochemically important positions. The k-seq results and folding assays showed that most deleterious mutations lower activity by impairing ribozyme self-assembly. All-atom molecular dynamics simulations of the complete ribozyme revealed how individual mutations in the core or the IL4 peripheral loop introduce a non-native tertiary interface that rewires the catalytic center, eliminating activity. We conclude that the need to avoid non-native helix packing powerfully constrains the evolution of tertiary structure motifs in RNA.

Antioxidant and Whitening Effects of Dahlia based on Variety, Flowering Form, Harvest Time, and Plant Part

Purpose: This study evaluated the antioxidant activity of dahlias based on variety, flowering form, harvest time, and plant parts, analyzed the content of bioactive compounds, and assessed the whitening effect of different plant parts to explore potential applications in the food, pharmaceutical, and cosmetic industries.Methods: Antioxidant activity was assessed using DPPH radical scavenging assays, whereas bioactive compounds were quantified through total polyphenol content (TPC) and total flavonoid content (TFC) measurements. The whitening effect was evaluated based on tyrosinase inhibition rates.Results: Among the six dahlia varieties examined, <i>D. diva</i> demonstrated the highest antioxidant activity, with purple and deep red varieties, showing particularly high levels of activity and polyphenol content. Analysis of flowering forms indicated that flowers in the early half-blooming stage exhibited the highest antioxidant activity. Regarding harvest time, dahlias harvested during the third period in the fall, showed the greatest antioxidant activity. Examination of different plant parts revealed that petals had the highest antioxidant activity, whereas leaves and tubers had comparatively lower activity. Additionally, petals exhibited the highest tyrosinase inhibition rate among the plant parts, although the overall whitening effect was minimal.Conclusion: The study identified the optimal dahlia variety, flowering form, harvest time, and plant parts for maximizing antioxidant effects. These findings provide valuable insights for potential applications of dahlias in various industries.

Promotion of Intellectual Activity Results of Scientific Organizations. Value Estimation

We consider approaches to assessing the value of intellectual activity results (IAR) from the points of view of the seller and the buyer. The analysis was carried out on the basis of a comparison of the total costs of implementing IAR in which the purchase of a license may be only a part of the costs. The analysis takes into account the risks associated with the implementation of IAR. They can potentially lead to reducing the economic performance in the realization of IAR. The authors examine choices of buyers and sellers in relation to the purchase and sale of IAR, taking into account the scale of the markets available to them. Some considerations explaining the low activity on the IAR market in Russia by the scale of business and the size of manufacturing companies are presented. We define the reasons for the low interest of scientific organizations in promoting IAR for sale. They are a consequence of the small volume of markets and can also be explained by the fact that using budgetary funds, research institutions can cover the costs of creating IAR more substantially than they can by selling IAR on the market. We have formulated proposals that make it possible to increase the efficiency of the work of scientific organizations with IAR. In particular, a reasonable economic policy focuses on sales of IAR through R&D (including with the assistance of extra-budgetary funds). With regard to the reserves being created, it is advisable to use protection options that do not disclose the essence of the IAR and uphold the protection period with significant time spent on searching. This, for instance, may be an option to set up a trade secret regime with subsequent patenting within the framework of R&D for the benefit of a particular buyer. This approach reduces the risks not only for the seller, but also for the buyer. For government agencies, it can be recommended to increase the importance of license sales while assessing efficiency in comparison with simple registration of IAR. It is advisable to finance applied R&D involving the creation of IAR if there is a guarantee for the implementation of the corresponding IAR by developers or industrial partners.

Screening and engineering of a protocatechuic acid decarboxylase for efficient biosynthesis of catechol

Catechol (CA) is an important chemical and pharmaceutical intermediate with wide applications. At present, CA is produced by phenol hydroxylation with non-renewable petrochemical resources, which causes serious environmental pollution. Hence, the biosynthesis of CA attracts much attention recently. However, due to the low activities of protocatechuic acid (PCA) decarboxylases, the production efficiency of biosynthetic catechol is too low to meet the requirements of large-scale industrial production. To improve the yield of CA, we screened 21 PCA decarboxylases from different species. RbAroY originated from Rikenellaceae had the best catalytic performance. The whole-cell biocatalyst ER11 with RbAroY was able to produce CA at a titer of 13.54 g/L. Then, the online tool HotSpot Wizard was employed to measure the enzyme stability, which revealed 10 potential mutation sites causing significant decreases in Gibbs free energy. The whole-cell biocatalyst ERT01 with the mutated RbAroYG99A could produce CA at a titer of 15.16 g/L, which increased by 12% compared with that of the wild-type whole-cell biocatalyst. After optimization of the biocatalytic conditions, the whole-cell biocatalyst ERT01 was able to produce CA at a titer of 25.70 g/L with PCA as the substrate. Finally, with the fermentation broth of 3-dehydroshikimate as the substrate, the whole-cell biocatalyst DER03 expressing both 3-dehydroshikimate dehydratase and PCA decarboxylase realized the production CA at a titer of 29.55 g/L, which is currently the highest biosynthetic titer reported. This study provides a reference for the industrial production of CA by biosynthesis.

Use of KASP technologies for the identification of alleles of polyphenoloxidase genes of common wheat (Triticum aestivum L.)

Aim. Characterization of recombinant inbred lines F7 Luzanivka odeska/Odeska chervonokolosa by polyphenol oxidase (PPO) genes using KASP technologies and detection of the associations of allelic differences in Ppo genes with agronomically important traits of common wheat. Methods. Competitive allele-specific PCR (KASP). Phenological observations, elements of yield structure. Results. The polymorphism of the parental genotypes and the population of recombinant inbred lines for Ppo-A1 and Ppo-D1 genes was evaluated. A polymorphism between parental forms on the Ppo-D1 gene was detected. A comparison of the data of KASP-analysis of lines with the results of evaluation of lines by eight agronomic traits of wheat was carried out. Conclusions. Differences in the alleles of the Ppo-D1 gene did not affect the traits duration of a period prior to heading, plant height, productive tillering, grain number per spike, thousand-grain weight, productive tiller number per unit area and grain yield. An increase in the grain weight per spike was observed in lines with a favorable Ppo-D1a allele. The selection of genotypes with the Ppo-D1a allele, which corresponds to the low activity of the PPO enzyme, does not have a negative effect on the agronomically important characteristics of wheat.

Impact of Ligand Design on an Iron NHC Epoxidation Catalyst.

An open-chain iron pyridine-NHC framework is expanded utilizing a benzimidazole moiety to deepen the understanding of the impact of electronic variations on iron NHC epoxidation catalysts, especially regarding the stability. The thereby newly obtained iron(II) NHC complex is characterized and employed in olefin epoxidation. It is remarkably temperature tolerant and achieves a TOF of ca. 10 000 h-1 and TON of ca. 700 at 60 °C in the presence of the Lewis acid Sc(OTf)3, displaying equal stability, but lower activity than the unmodified iron pyridine-NHC (pre-)catalyst. In addition, a synthetic approach towards another ligand containing 2-imidazoline units is described but formylation as well as hydrolysis hamper its successful synthesis.

The seasonal variation of the inhibitory effect of bioactive extracts of a marine algae (Corallina officinalis) collected from the Algerian west coast

Algae are increasingly becoming the center for interest due to researchers for their composition of various important bioactive molecules. The objective of this study is to investigate the seasonal variations in the concentrations of flavonoids, polyphenols, chlorophyll a, chlorophyll b, and carotenoids, as well as the antimicrobial activity of methanolic extracts from the red alga Corallina officinalis collected from western Algeria. The results of the biochemical assays show that the best polyphenol contents are recorded by the summer extract with a concentration of 33.29 μgEqAG/mg. The recorded flavonoid contents are 967.33; 869; 239.66 and 156 µgEQ/mg for summer, autumn, spring and winter respectively. For chlorophyll a and b the winter extract recorded the highest values. The best results of antibacterial tests were noted for the summer season with diameters of 14.33 mm against the two-bacteria E. coli and Staphylococcus aureus resistant to methicillin (SARM). The autumn extract gave low activity against E. coli, Pseudomonas, SARM and Klebsiella. For the winter extract we noted resistance against B. cereus, Pseudomonas and B. subtilis while E. coli, SARM, Klebsiella and the yeast Candida albicans recorded low activity. For the spring extract, resistance was observed against all the bacteria tested except for the E. coli and Klebsiella strains. The extracts obtained can be used as an antibacterial due to their rich content of bioactive molecules. The best results of antibacterial tests are noted for the summer season.

Assessment of Essential Trace Elements Cu, Zn, Mn, and Ni in Mediterranean Mussels (Mytilus galloprovincialis) from the Algerian Coast.

The aim of this study was to determine the levels of essential trace elements copper, zinc, manganese, and nickel in two size groups of mussels, Mytilus galloprovincialis, sampled from three sites along the Algerian coast with different levels of pollution. The results of this work are very interesting for determining the effect of mussel size on the variation of contaminant levels in environmental monitoring studies. Thirty individuals from 2 size groups, less than 4-cm and more than 4-cm shell length, were collected over 4 seasons at each site studied. The samples were dissected, and copper, zinc, manganese, and nickel were measured in the whole soft tissues by inductively coupled plasma mass spectrometry (ICP-MS). The maximum concentrations of copper, zinc, manganese, and nickel expressed in mg/kg dry weight at the three sites were 54.01, 146.25, 20.69, and 8.85, respectively. A clear distribution pattern of the studied elements was observed in the two size classes. In fact, significantly higher concentrations (P < 0.05) were found in individuals with a shell length of less than 4 cm. Significantly, higher concentrations (P < 0.05) were found in individuals with a shell length of less than 4 cm due to their high filtration and low excretion activities compared to long individuals. In addition, metal pollution index (MPI) values were higher in small bivalve individuals. The trace element contents found in the mussel samples of the present study showed large spatial and temporal variations among the different sites studied, highlighting the typical exposure of marine sites to different marine pollutants. Notably, elevated concentrations of copper were observed in the port of Zemmouri, likely due to port activities. Conversely, the highest levels of manganese and nickel were recorded at Boudouaou El Bahri, potentially attributable to the use of fertilisers by agricultural activities. Some shellfish samples had exceeded the permissible concentration levels of copper and manganese, thereby posing a danger to bivalve consumers.

Characterization of Mycobacterium smegmatis Glutaminase-Free Asparaginase (MSMEG_3173).

l-asparaginase is an enzyme catalyzing the hydrolysis of l-asparagine into l-aspartate and ammonia, which is of great therapeutic importance in tumor treatment. However, commercially available enzymes are associated with adverse effects, and searching for a new l-asparaginase with better pharmaceutical properties was the aim of this work. The coding sequence for Mycobacterium smegmatisl-asparaginase (MsA) was cloned and expressed. The recombinant protein showed high activity toward l-asparagine, whereas none was detected for l-glutamine. The enzymatic properties (K m = 1.403 ± 0.24 mM and k cat = 708.1 ± 25.05 s-1) indicate that the enzyme would be functional within the expected blood l-asparagine concentration, with good activity, as shown by k cat. The pH and temperature profiles suggest its use as a biopharmaceutical in humans. Molecular dynamics analysis of the MsA model reveals the formation of a hydrogen bond network involving catalytic residues with l-asparagine. However, the same is not observed with l-glutamine, mainly due to steric hindrance. Additionally, the structural feature of residue 119 being a serine rather than a proline has significant implications. These findings help explain the low glutaminase activity observed in MsA, like what is described for the Wolinella succinogenes enzyme. This establishes mycobacterial asparaginases as key scaffolds to develop biopharmaceuticals against acute lymphocytic leukemia.

In silico design and ADMET evaluation of new inhibitors for PIM1 kinase using QSAR studies, molecular docking, and molecular dynamic simulation

The proviral Integration site of Moloney (PIM) kinase is highly expressed in various diseases, including cancer, making the development of selective inhibitors for this protein important. A series of PIM1 inhibitors, triazolo [4, 3-b] pyridazin-3-yl-quinoline derivatives, have been studied to design new inhibitors. The activity and structural features of these derivatives were investigated to understand their interactions with PIM1 using molecular docking, molecular dynamic simulation, and QSAR techniques.In a study of 30 compounds using the structure-activity technique and the MLR method, a linear model with R2train = 0.91 and R2test = 0.96 was obtained. The model utilized descriptors such as RDF080v, RDF105v, RDF135v, Mor03v, and H046 to express the structural characteristics of the inhibitors. To enhance the model, the SVR non-linear method with the RBF function was also used, resulting in an improved model with R2train = 0.98 and R2test = 0.98.Furthermore, the molecular docking technique was employed to investigate the interaction of compounds with high (compound 25) and low (compound 13) inhibitory activity. It was observed that the rings with nitrogen atoms interacted with the protein. The molecular binding results indicate that groups such as OMe and rings with Nitrogen can enhance the inhibitory activity of the compounds. Additionally, oxygen and nitrogen atoms contribute to an increased number of hydrogen bonds, thereby increasing the inhibitory activity of the compounds.Additionally, the stability and bonding modes of active and inactive compounds were studied using molecular dynamic simulation. Based on the results, four new inhibitors were designed, demonstrating better inhibition efficiency with the PIM1 kinase compared to the reference compounds. Moreover, the designed compounds underwent evaluation for ADMET, yielding promising results.