A homo-FRET assay for patatin-specific proteolytic activity.

The potato protein patatin embeds bioactive peptides that require targeted hydrolysis to be released as promising food additives. This study presents a patatin-specific protease assay for assessing a wide range of protease activities in high-throughput format. Conjugating patatin to the amine reactive fluorogenic BODIPY FL dye provided a stable protease substrate with efficient homo-FRET quenching at a low degree (7-8) of labeling. Compared to commercial BODIPY-casein, BODIPY-patatin provided higher fluorescence enhancement (by de-quenching) at high protease concentrations, while the sensitivity was generally comparable for both highly specific (e.g. Trypsin) and industrial relevant proteases (e.g. Alcalase and Neutrase) at low doses. For Chymotrypsin, BODIPY-patatin provided a 39 % response improvement at 5 ng dose. A peptide-centric analysis of mass spectrometry-based bottom-up proteomics data identified several BODIPY-labeling sites with varying occupancies in patatin, indicating heterogenous labeling under the applied conjugation conditions. BODIPY-labeled patatin complements commercial BODIPY-labeled casein as a globular, plant-based alternative for screening of proteolytic activity.

Molecular characterization and biomarker discovery in gastric cancer progression through transcriptome meta-analysis.

Gastric cancer (GC) is a leading cause of cancer-related deaths globally. It is a multifactorial, molecularly heterogeneous disease whose carcinogenic patterns are not yet well established, requiring the development of new tools for better understanding and identifying gastric carcinogenesis. From this point of view, this study aims to compare transcriptome profiles from The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) and a human-merged dataset to identify potential biomarkers and therapeutic targets. Principal component analysis (PCA) revealed shared and distinct gene expression patterns between datasets. Differential expression analysis identified key genes with altered expression across non-malignant and malignant samples. Six genes, including SERPINE1 and CLDN9, were significantly associated with patient survival. The findings underscore the molecular diversity of GC and highlight novel biomarkers for early diagnosis and therapeutic strategies. Further validation in clinical specimens is necessary.

Colossal Dielectric Constant of Nanocrystalline/Amorphous Homo-Composite BaTiO3 Films Deposited via Pulsed Laser Deposition Technique.

We report the pulsed laser deposition (PLD) of nanocrystalline/amorphous homo-composite BaTiO3 (BTO) films exhibiting an unprecedented combination of a colossal dielectric constant (εr) and extremely low dielectric loss (tan δ). By varying the substrate deposition temperature (Td) over a wide range (300-800 °C), we identified Td = 550 °C as the optimal temperature for growing BTO films with an εr as high as ~3060 and a tan δ as low as 0.04 (at 20 kHz). High-resolution transmission electron microscopy revealed that the PLD-BTO films consist of BTO nanocrystals (~20-30 nm size) embedded within an otherwise amorphous BTO matrix. The impressive dielectric behavior is attributed to the combination of highly crystallized small BTO nanograins, which amplify interfacial polarization, and the surrounding amorphous matrix, which effectively isolates the nanograins from charge carrier transport. Our findings could facilitate the development of next-generation integrated dielectric devices.

The genetically predicted causal associations between circulating 3-hydroxybutyrate levels and malignant neoplasms: A pan-cancer Mendelian randomization study.

OBJECTIVE: The ketogenic diet or exogenous supplementation with 3-hydroxybutyrate (3HB) is progressively gaining recognition as a valuable therapeutic or health intervention strategy. However, the effects of 3HB on cancers have been inconsistent in previous studies. This study aimed to comprehensively investigate the causal effects of circulating 3HB levels on 120 cancer phenotypes, and explore the 3HB mediation effect between liver fat accumulation and cancers. METHODS: Univariate Mendelian randomization (UVMR) was used in this study to investigate the causal impact of circulating 3HB levels on cancers. We conducted meta-analyses for 3HB-cancer associations sourced from different exposure data. In multivariate MR(MVMR), the body mass index, alcohol frequency and diabetes were included as covariates to investigate the independent effect of 3HB on cancer risk. Additionally, utilizing mediation MR analysis, we checked the potential mediating role of 3HB in the association between liver fat and cancer. RESULTS: Integrating findings from UVMR and MVMR, we observed that elevated circulating 3HB levels were associated with reduced risk of developing diffuse large B-cell lymphoma(DLBCL) (OR[95%CI] = 0.28[0.14-0.57] p = 3.92e-04), biliary malignancies (OR[95%CI] = 0.30[0.15-0.60], p = 7.67e-04), hepatocellular carcinoma(HCC) (OR[95%CI] = 0.25[0.09-0.71], p = 9.33e-03), primary lymphoid and hematopoietic malignancies (OR[95%CI] = 0.76[0.58-0.99], p = 0.045). Further UVMR analysis revealed that an increase in the percent liver fat was associated with reduced 3HB levels (Beta[95%CI] = -0.073[-0.122∼-0.024], p = 0.0034) and enhanced susceptibility to HCC (OR[95%CI] = 13.9[9.76-19.79], p = 3.14e-48), biliary malignancies (OR[95%CI] = 4.04[3.22-5.07], p = 1.64e-33), nasopharyngeal cancer (OR[95%CI] = 3.26[1.10-9.67], p = 0.03), and primary lymphoid and hematopoietic malignancies (OR[95%CI] = 1.27[1.13-1.44], p = 1.04e-4). Furthermore, 3HB fully mediated the effect of liver fat on susceptibility to DLBCL (OR[95%CI] = 1.076[1.01-1.15], p = 0.034). CONCLUSIONS: Circulating 3HB is associated with a reduced susceptibility to developing DLBCL, HCC, biliary malignancies, and primary lymphoid and hematopoietic malignancies. The impaired ketogenesis induced by metabolic-dysfunction associated fatty liver disease (MAFLD) contributes to risk of DLBCL.

Quantum chemical treatment, electronic energy in various solvents, spectroscopic, molecular docking and dynamic simulation studies of 2-amino-N-(2-chloro-6-methylphenyl)thiazole-5-carboxamide: A core of anticancer drug.

The titled molecule 2-Amino-N-(2-chloro-6-methylphenyl)thiazole-5-carboxamide (ANMC) is a core of anticancer drug dasatinib (leukemia). Its derivatives exhibited bioactivity against breast cancer. Experimentally, the titled compound was described using NMR (1H NMR and 13C NMR), FTIR and UV-visible spectroscopy. The results were compared with the theoretical predictions, showing good agreement such as theoretical NH vibrations showed symmetric stretching and asymmetric stretching at 3429 and 3440 cm-1 respectively, λmax values appear at 305 nm for experimental and 307.75 nm for theoretical observations in acetone medium. Hirshfeld surface analysis well described the secondary internal and external interactions obtained like dnorm and di ranges -1.8551 to 1.4590 and 0.0918 to 2.6756 respectively. Comparing UV-visible spectra obtained in various solvents with the calculated TD-DFT results revealed minimal solvent effects. Molecular electrostatic potential (MEP) map and Fukui functions were employed, which indicated reactive sites of the molecule and the obtained order of nucleophilic reactivity was C16 > C2 > C8 > Cl1 > C22 > C21. The bioactivity profile probability of ANMC was theoretically explored by calculation of electrophilicity index and drug-likeness. Molecular docking of the ANMC molecule was performed with ten receptors to obtain the best ligand-protein interaction and the minimum binding energy obtained was -8.0 kcal/mol. Biomolecular stability of ANMC was investigated by Molecular Dynamic Simulation (MDS). And also the analysis of free energies showed strong interactions between the ligand and the protein.

The dentition of a new adult Neanderthal individual from Grotte Mandrin, France.

Grotte Mandrin is located in the middle Rhône River Valley, in Mediterranean France, and has yielded 11 Pleistocene archeological and paleoanthropological layers (ranging from the oldest layer J to the youngest layer B) dating from Marine Isotope Stage (MIS) 5 to MIS 3. We report here the nearly complete dentition of an adult Neanderthal individual, nicknamed 'Thorin,' associated to the last phase of the Post-Neronian II, in layer B2 (∼44.50-42.25 ka). A previous paleogenetic analysis revealed that Thorin is a male individual and that he shows a deep genetic divergence with other penecontemporaneous Neanderthals from western Europe that possibly occurred ∼105 ka. The 31 teeth of Thorin (including two distomolars) are described and analyzed using microcomputed tomography imaging and are compared with other Neanderthals and modern humans. Based on direct observation and measurements on the fossil remains, and using microtomographic imaging, tooth wear, nonmetric characters, crown dimensions, and dental tissue proportions were investigated, and the shape of the enamel-dentine junction of the M2, M2, and M3 was analyzed by geometric morphometrics. Our results indicate that Thorin's teeth show dental characteristics typical of MIS 5-3 Neanderthals. It is also the first time that the presence of two distomolars is reported in a Neanderthal individual, a trait that is rare among modern human populations. Combined with the genetic peculiarities of this individual, the results of the present study imply either a process of morphological convergence among the latest Neanderthal groups or an underestimation of the genetic variability of recent Neanderthal groups.

Is there a bias in the codon frequency corresponding to homo-repeats found in human proteins?

It is well known that there is a codon usage bias in genomes, that is, some codons are observed more often than others. Codons implicated in the homo-repeats regions in human proteins are no exception. In this work, we analyzed the codon usage bias for all amino acid residues in homo-repeats larger than 4 in 3753 human proteins from 20447 protein sequences from the canonically reviewed human proteome. We have discovered that almost all homo-repeats in the human proteome, most of which encode Ala, Glu, Gly, Leu, Pro, and Ser (∼80% of all homo-repeats), have a codon usage bias, i.e. are mainly encoded by one codon. Moreover, there is a strong shift in homo-repeats in favor of the content of GC rich codons. Homo-repeats with Ala, Glu, Gly, Leu, Pro, and Ser predominate in the PDB, which has both ordered and disordered status. Examining the distribution of splicing sites, we found that about 15% of homo-repeats either contain or are located within 10 nucleotides of the splicing site, and Glu and Leu predominate in these homo-repeats. Our data is important for future study of the functions of homo-repeats, protein-protein interactions, and evolutionary fitness.

Structural and electronic properties of AgNPs adsorbed by glucose molecules determined using DFT theory.

In order to build and design stable molecular structures of α-D-glucose molecules after adding to a cluster of silver atoms, an optimization process was precisely carried out for α-D glucose/Ag3 molecule at low energy. The correlation between glucose molecule and silver atoms is evaluated by investigating configurational and electronic features of the named molecules by adopting the Density functional theory DFT using the hybrid B3LYP functional and 6-311+G∗ as a basis set for C, O, and H atoms, while LANL2DZ set for silver (Ag) atoms. Frequencies of vibrational modes are essential analyses that have been instrumental in understanding the IR spectra of studied molecules. These analyses enable the detection of the active groups along the spectrum chart including C-O-C, C=O, C-O, O-H, C-C and C-H peaks confirming the previous experimental findings. Another important finding is the energy gap (E g ) obtained by the difference between the higher occupied molecular orbital (HOMO) and lower unoccupied molecular orbital (LUMO). Remarkably, E g was found to increase from 3.440 to 4.358 eV in a configuration consisting of two glucose molecules with one Ag atom (2α-D glucose/Ag-C12H24O12Ag) to another with one glucose molecule with three Ag atoms (α-D glucose/Ag3-C6H12O6Ag3) configuration. Additionally, the potential of the molecular electrostatic isosurface (MEP) in 3D diagram for two configurations is clarified by the colour-coded bar with the distributions of charge density distributions to examine the nucleophilicity and electrophilicity behaviour.

Synthesis, characterization, quantum mechanical calculations and biomedical docking studies on curcumin analogs: 2, 6-(Difurfurylidene) cyclohexanone and 2, 6 - Bis (2,6-Dichloro Benzylidene) Cyclohexanone.

The initiation of colorectal cancer is controlled by various factors, including random occurrences and genetic alterations affecting oncogenes and tumor suppressor genes.Curcumin, a significant compound extracted from turmeric, has attracted interest for its robust anticancer properties, particularly regarding its analogs, 2, 6-bisdifurfurylidene cyclohexanone (DFC) and 2, 6-bis (2, 6-dichlorobenzylidene) cyclohexanone (DCC), which were synthesized and assessed for their anticancer efficacy. A combination of spectroscopic techniques and molecular docking methods was utilized to comprehensively evaluate the interaction behaviors of DFC and DCC. The application of density functional theory (DFT) using the B3LYP/6-311G (d, p) basis set facilitated the prediction of spectroscopic properties. The molecular docking investigations conducted using the Glide docking program from Schrodinger Maestro elucidated the interactions of these drugs at the molecular level. In vitro investigations were performed to evaluate the cytotoxic efficacy of the synthesized curcumin analogs. The determined IC50 values revealed that DFC displayed an IC50 of approximately 82 µM, and DCC exhibited a significantly lower IC50 of around 10 µM. This notable disparity highlights the potential of DFC and DCC as a more efficacious cytotoxic agent and further research be conducted on the produced chemicals in the future.

Evolutionary Sequences and Structural Information-driven Reconstruction of New Insulin-like Growth Factor-I Peptide Variants.

BACKGROUND: Insulin-like growth factor-I (IGF-I) is crucial in controlling cell growth, proliferation, and apoptosis. Its strong link to the development of cancers such as breast, prostate, lung, thyroid, and colorectal has positioned the IGF-1 signalling pathway as a promising target for novel cancer therapies. When activated, the IGF-1 receptor (IGF-1R) binds to IGF-I, playing a central role in promoting tumour cell growth and survival. METHODS: In this study, we combined evolutionary sequences with structural and functional data of IGF-1 to reconstruct ancestral sequences and design novel IGF-1 peptide variants. RESULTS: The insulin-like growth factor system exhibits a vast sequence diversity, yet it shares a similar structural topology with conserved three pairs of disulfide linkages. Our study reveals that IGF-1 is associated with the IGF system of cell surface receptors through protein-protein interactions. Reconstructed IGF-1 variants show similar structure fold to reported viral IGF-1 competitive antagonists. CONCLUSION: This new insight guides the design of novel natural IGF-1 mimic peptides. It enhances our understanding of IGF-1's functionality and opens new avenues for the development of therapeutic peptides and small molecules as anticancer agents.

Early steps of protein disaggregation by Hsp70 chaperone and class B J-domain proteins are shaped by Hsp110.

Hsp70 is a key cellular system counteracting protein misfolding and aggregation, associated with stress, ageing, and disease. Hsp70 solubilises aggregates and aids protein refolding through substrate binding and release cycles regulated by co-chaperones: J-domain proteins (JDPs) and nucleotide exchange factors (NEFs). Here, we elucidate the collaborative impact of Hsp110 NEFs and different JDP classes throughout Hsp70-dependent aggregate processing. We show that Hsp110 plays a major role at initial stages of disaggregation, determining its final efficacy. The NEF catalyses the recruitment of thick Hsp70 assemblies onto aggregate surface, which modifies aggregates into smaller species more readily processed by chaperones. Hsp70 stimulation by Hsp110 is much stronger with class B than class A JDPs and requires the auxiliary interaction between class B JDP and the Hsp70 EEVD motif. Furthermore, we demonstrate for the first time that Hsp110 disrupts the JDP-Hsp70 interaction. Such destabilisation of chaperone complexes at the aggregate surface might improve disaggregation, but also lead to the inhibition above the sub-stoichiometric Hsp110 optimum. Thus, balanced interplay between the co-chaperones and Hsp70 is critical to unlock its disaggregating potential.

For proteins to accurately carry out their role in the cell, they must first be precisely folded into specific 3D shapes. Stress, aging or disease can interfere with this delicate process, leading to misfolded proteins clumping together and causing damage. In response, the cell can deploy 'chaperones' which disentangle these aggregates and ensure that proteins recover their proper structure. Chaperones from the Hsp70 protein family, for example, are crucial for cell survival, especially under biologically stressful conditions. Yet Hsp70 proteins cannot perform their role without the assistance of co-chaperones such as Hsp110; why this is the case, however, has remained unclear. To investigate this question, Sztangierska et al. used a variety of biochemical assays to test how purified human and yeast Hsp70, Hsp110 and other co-chaperones could bind aggregates and recover misfolded proteins. The role of each protein was examined at every stage of the disaggregation process ­ from the initial aggregate binding, through chaperone-driven changes in aggregate structure to the final protein folding. The experiments revealed that Hsp110 helps draw Hsp70 to the aggregate surface, breaking down the protein 'clump' into smaller pieces which are more easily processed by other chaperones. The results also showed that the various co-chaperones compete for Hsp70 binding; too much of one might interfere with another, emphasizing the need for balance between chaperones for optimal disaggregation. Overall, these results clarify the role of Hsp110 in the Hsp70 system and reveal several mechanistic details of the protein rescue process. Further experiments will be needed to fully understand these dynamics and identify how they may be relevant to conditions in which harmful protein aggregates are observed, such as Parkinson's or Alzheimer's disease.

Twinning and homo-epitaxy cooperation in the already rich growth morphology of CaCO3 polymorphs. II. Calcite.

The two most abundant CaCO3 polymorphs, calcite and aragonite, are universally recognized for the richness of their morphology to which different twins make relevant contributions. The epitaxial transformation calcite ↔ aragonite has long been debated. While the twinning has been thoroughly treated, the homo-epitaxy occurring within each of these minerals has, inexplicably, been overlooked to date, both experimentally and theoretically. Twinning can be deceptive to the point where it can be mistaken for homo-epitaxy, thus making the proposed growth mechanism in the crystal aggregate wrong. Within the present work, the first aim is a theoretical investigation of the homo-epitaxies among the three {10.4}-cleavage, {01.2}-steep and {01.8}-flat rhombohedra of calcite. Accordingly, the specific adhesion energies were calculated between facing crystal forms, unequivocally showing that the {01.2}/{01.8} homo-epitaxy competes with the generation of both {01.2} and {01.8} contact twins. Secondly, the calculation of the specific adhesion energy was extended to consider homo-epitaxy for the {10.4} rhombohedron. The two-dimensional geometric lattice coincidence has been tried for the {00.1} pinacoidal form as well.

A Quantum Mechanical MP2 Study of the Electronic Effect of Nonplanarity on the Carbon Pyramidalization of Fullerene C60.

Among C60's diverse functionalities, its potential application in CO2 sequestration has gained increasing interest. However, the processes involved are sensitive to the molecule's electronic structure, aspects of which remain debated and require greater precision. To address this, we performed structural optimization of fullerene C60 using the QM MP2/6-31G* method. The nonplanarity of the optimized icosahedron is characterized by two types of dihedral angles: 138° and 143°. The 120 dihedrals of 138° occur between two hexagons intersecting at C-C bonds of 1.42 Å, while the 60 dihedrals of 143° are observed between hexagons and pentagons at C-C bonds of 1.47 Å. NBO analysis reveals less pyramidal sp1.78 hybridization for carbons at the 1.42 Å bonds and more pyramidal sp2.13 hybridization for the 1.47 Å bonds. Electrostatic potential charges range from -0.04 a.u. to 0.04 a.u. on the carbon atoms. Second-order perturbation analysis indicates that delocalization interactions in the C-C bonds of 1.42 Å (143.70 kcal/mol) and 1.47 Å (34.98 kcal/mol) are 22% and 38% higher, respectively, than those in benzene. MP2/Def2SVP calculations yield a correlation energy of 13.49 kcal/mol per electron for C60, slightly higher than the 11.68 kcal/mol for benzene. However, the results from HOMO-LUMO calculations should be interpreted with caution. This study may assist in the rational design of fullerene C60 derivatives for CO2 reduction systems.

Molecular Engineering for UV-Vis to NIR Absorption/Emission Bands of Pyrazine-based A-π-D- π-A Switches to Design TiO2 Tuned Dyes: DFT Insights.

This study investigates the tuning of the UV-Vis/NIR absorption bands of pyrazine-based A-D-A switches for designing efficient UV retardancy over TiO2 surfaces. The electronic properties and optical characteristics of seven dyes (DP1-DP7) were analyzed using computational methods. The results indicate that the dyes possessed distinct UV-Vis/NIR absorption properties. Their absorption wavelengths ranged from 389 to 477 nm, with corresponding energies ranging from 2.59 to 3.19 eV. The major contributions to the absorption were found to be the HOMO-LUMO transitions, varying from 86 to 96%. The dyes exhibited different donor (D) and acceptor (A) groups, influencing their electronic properties and absorption characteristics. The tunable electronic and optical properties of these dyes make them promising candidates for applications requiring UV protection for TiO2-based materials. The results contribute to understand the structure-property relationships in the design of UV-Vis/NIR absorbers and provide a foundation for further experimental investigations in the field of UV retardancy.

Evolution of the thirst mechanism in Homo: The need and limitations of thirst and hydration.

There is a view that the perception of thirst and actual body fluid balance may affect cognitive and exercise performance. The evolutionary evidence suggests that our survival was dependent on our ability to sweat profusely when hunting during the heat of the day (persistence hunting), so if water deficits were not tolerated, consequently the thirst mechanism would limit our persistence hunting capability. This also means that hunting and searching for water was undertaken with some extent of water deficit, and in turn suggests that performance; physical and cognitive, was conducted with a degree of dehydration. Given the current views on the maintenance of body water for performance, there is a need to evaluate the evidence relating to tolerance limits for water deficits with respect to both physical and cognitive performance. This review considers the thirst mechanism and the conditions and selective pressures under which this might have evolved. Consideration will be given to how the thirst mechanism influences our physical and cognitive performance. The review suggests that Homo developed appropriate tolerances for water deficits and thirst perception, with a safety margin that prevented detrimental declines in physical and cognitive performance to the point of inhibiting corrective action. This would have offered a selective advantage, enabling the search for water and functioning adequately during periods of water scarcity.

Molecular, structural, and functional characterization of delta subunit of T-complex protein-1 from Leishmania donovani.

Chaperonins/Heat shock protein 60 are ubiquitous multimeric protein complexes that assist in the folding of partially and/or misfolded proteins using metabolic energy into their native stage. The eukaryotic group II chaperonin, also referred as T-complex protein-1 ring complex (TRiC)/T-complex protein-1 (TCP1)/chaperonin containing T-complex protein (CCT), contains 8-9 paralogous subunits, arranged in each of the two rings of hetero-oligomeric complex. In Leishmania, till date, only one subunit, LdTCP1γ, has been well studied. Here, we report the molecular, structural, and functional characterization of TCP1δ subunit of Leishmania donovani (LdTCP1δ), the causative agent of Indian kala-azar. LdTCP1δ gene exhibited only 27.9% identity with LdTCP1γ and clustered in a separate branch in the phylogenic tree of LdTCP1 subunits. The purified recombinant protein formed a high molecular weight complex (0.75 MDa), arranged into 16-mer assembly, and performed in vitro chaperonin activity as assayed by ATP-dependent luciferase folding. LdTCP1δ exhibits 1.8-fold upregulated expression in metabolically active, rapidly dividing log phase promastigotes. Over-expression of LdTCP1δ in promastigotes results in increased infectivity and rate of multiplication of intracellular amastigotes. The study thus establishes the existence of an individual functionally active homo-oligomeric complex of LdTCP1δ chaperonin with its role in parasite infectivity and multiplication.

Computational exploration of compounds in Xylocarpus granatum as a potential inhibitor of Plasmodium berghei using docking, molecular dynamics, and DFT studies.

Malaria remains a global health concern, with the emergence of resistance to the antimalarial drug atovaquone through cytochrome b (cyt b) being well-documented. This study was prompted by the presence of this mutation in cyt b to enable new drug candidates capable of overcoming drug resistance. Our objective was to identify potential drug candidates from compounds of Xylocarpus granatum by computationally assessing their interactions with Plasmodium berghei cyt b. Using computational methods, we modeled cyt b (GenBank: AF146076.1), identified the binding cavity, and analyzed the Ramachandran plot against cyt b. Additionally, we conducted drug-likeness and absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies, along with density functional theory (DFT) analysis of the compounds. Molecular docking and molecular dynamics simulation (MDS) were used to evaluate the binding energy and stability of the cyt b-ligand complex. Notably, our investigation highlighted kaempferol as a promising compound due to its high binding energy of 7.67 kcal/mol among all X. granatum compounds, coupled with favorable pharmacological properties (ADMET) and antiprotozoal properties at Pa 0.345 > Pi 0.009 (PASS value). DFT analysis showed that kaempferol has an energy gap of 4.514 eV. MDS indicated that all tested ligands caused changes in bonding and affected the structural conformation of cyt b, as observed before MDS (0 ns) and after MDS (100 ns). The most notable differences were observed in the types of hydrogen bonds between 0 and 100 ns. Nevertheles, MDS results from a 100 ns simulation revealed consistent behavior for kaempferol across various parameters including root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), solvent-accessible surface area (SASA), molecular mechanics-Poisson Boltzmann surface area (MM-PBSA), and hydrogen bonds. The cyt b-kaempferol complex demonstrated favorable energy stability, as supported by the internal energy distribution values observed in principal component analysis (PCA), which closely resembled those of the atovaquone control. Additionally, trajectory stability analysis indicated structural stability, with a cumulative eigenvalue of 24.7 %. Dynamic cross-correlation matrix (DCCM) analysis revealed a positive correlation among catalytic cytochrome residues within the amino acid residues range 119-268. The results of our research indicate that the structure of kaempferol holds promise as a potential candidate against Plasmodium.

An assessment of puberty status in adolescents from the European Upper Paleolithic.

Childhood and adolescence are two life-history stages that are either unique to humans, or significantly expanded in the human life course relative to other primates. While recent studies have deepened our knowledge of childhood in the Upper Paleolithic, adolescence in this period remains understudied. Here, we use bioarchaeological maturational markers to estimate puberty status of 13 Upper Paleolithic adolescents from sites in Russia, Czechia, and Italy to 1) evaluate the feasibility of the application of bioarchaeological puberty assessment methods to Upper Paleolithic (Homo sapiens) skeletal individuals, 2) estimate the timing and tempo of puberty in Upper Paleolithic adolescents compared to other archaeological populations analyzed using the same method, and 3) characterize adolescence in the Upper Paleolithic by contextualizing the results of this puberty assessment with data on individual and population-level health, morbidity and burial practices. Our results revealed that while puberty had begun by 13.5 years of age for the majority of individuals, there was a lot of variability, with the adolescents from Arene Candide (AC1 and AC16), both aged around 16 years when they died, taking several years longer to progress through puberty than their peers. Assessing the age of menarche was challenging due to the paucity of female adolescents, but based on the available evidence, it appears to have occurred between 16 and 17 years of age. For some, full adulthood had been achieved by 17-22 years, similar to the patterns seen in modern wealthy countries and in advance of historic populations living in urbanized environments. The bioarchaeological analysis of puberty among Upper Paleolithic adolescents has important implications for the study of the emergence of adolescence within human-life histories, as well as for understanding the developmental plasticity of sexual maturation across past and present human populations.

Effect of Ag2O nanoparticles on the excited state dipole moment of a novel BMNFC molecules through solvatochromic shift method.

We experimentally determined the ground and excited state dipole moments of BMNFC (5-bromo-N'-[(Z)-(4-methoxyphenyl)methylidene]naptho[2,1-b]furan-2-carbohydrazide) dye using the solvatochromic shift method and various solvatochromic correlations, including Lippert's, Bakhshiev's, Kawski-Chamma-Viallet's, and solvent polarity equations. We employed the B3LYP/6-311G (d) level of theory to calculate the HOMO, LUMO, and MESP. In this study, we synthesized Ag2O nanoparticles using a quick and cost-effective chemical reduction method. Then, we used carboxymethylcellulose (CMC) as a capping agent. We studied the size, shape, and composition of these nanoparticles using a variety of analytical techniques. Transmission electron microscopy (TEM) analysis revealed a spherical morphology with an average diameter of 17 nm. The results show that adding Ag2O nanoparticles to BMNFC molecules changes their symmetric charge distribution, which in turn enhances their dipole moment. Molecules of enhanced dipole moment have attractive features in biomedical applications. Each molecule's symmetry point group determines the extent to which nanoparticles affect the BMNFC molecule.

Diversity oriented total synthesis (DOTS) of pyridoquinazolinone alkaloids and their analogues.

A short diversity oriented total synthesis (DOTS) of substituted rutaecarpines, homo-luotonins, homo-vasicinone, homo-isaindigotones and homo-vasnetine has been achieved from the key tricyclic intermediate. The [6,6,6] tricyclic ketone, the mackinazolindione, was accessed from simple substrates i.e., quinazolinone diester obtained from the disubstituted anthranilamide which in turn was prepared from the coupling of amino acid ester and ethyl oxalyl chloride with isatoic anhydride and Dieckmann condensation chemistry.