The synthesis, anticancer and antioxidant activity of a series of indole-derived hybrid chalcones are reported here. First, using well known Claisen-Schmidt condensation method a set of 29 chalcones has been designed, synthesized, and consequently characterized. Subsequently, screening for the antiproliferative activity of the synthesized hybrid chalcones was performed on the on five cancer (HCT116, HeLa, Jurkat, MDA-MB-231 and MCF7) and two non-cancer (MCF-10A and Bj-5ta) cell lines. Chalcone 18c bearing 1-methoxyindole and catechol structural features, exhibited selective activity against cancer cell lines with IC50 values of 8.0 ± 1.4 µM (Jurkat) and 18.2 ± 2.9 µM (HCT116) and showed no toxicity to non-cancer cells. Furthermore, antioxidant activity was evaluated using tree different methods. The in vitro studies of radical scavenging activity utilizing DPPH radicals, as well as FRAP method, demonstrated the strong activity of catechol derivatives 18a-c. According to the ABTS radical scavenging assay, the 3-methoxy-4-hydroxy substituted chalcones 19a–c were slightly more favorable. In general, a series of 3,4-dihydroxychalcone derivatives showed properties as a lead compound for both antioxidant and anticancer activity.

Treatment of the non-purified mixture of dinitro isomers obtained from the nitration of 1,4-dimethoxybenzene with piperidine, led to the isolation of novel but minor adduct, 1-(2,5-dimethoxy-4-nitrophenyl)piperidine (2b) in 15% yield. Yields of nucleophilic aromatic substitution adducts are high when using purified 1,4-dimethoxy-2,5-dinitrobenzene (1b) with piperidine and pyrrolidine to give 2b and 1-(2,5-dimethoxy-4-nitrophenyl)pyrrolidine (3b) in 76% and 82%, respectively.

Nucleophilic aromatic substitution (SNAr) reactions can provide metal-free access to synthesize mono-substituted aromatic compounds. We have developed efficient SNAr conditions for p-selective substitution of polyfluoroarenes with phenothiazine in the presence of a mild base to afford the corresponding 10-phenylphenothiazine (PTH) derivatives. The resulting polyfluoroarene-bearing PTH derivatives were subjected to a second SNAr reaction to generate highly functionalized PTH derivatives with potential applicability as photocatalysts for the reduction of carbon–halogen bonds.

A new form of coronavirus called severe acute respiratory disease coronavirus type 2 (SARS-CoV-2) is currently causing a pandemic. A six-month evolutionary history of SARS-CoV-2 is witnessed by characterising the total genome of 821 samples using comparative phylogenomic approaches. Our analyses produced striking inclusive results that may guide scientists/professionals for the past/future of pandemic. Phylogenetic and time estimation analyses suggest the proximate origin of pandemic strain as Guangdong and the origin time as first half of September 2019, not Wuhan and December 2019, respectively. The viral genome experienced a substitution rate similar to other RNA viruses, but it is particularly high in some of the peptides encoding sequences such as leader protein, E gene, orf8, orf10, nsp10, N gene, S gene and M gene and nsp4, while low in nsp11, orf7a, 3C-like proteinase, nsp9, nsp8 and endoRNase. Most strikingly, the divergence rate of amino acid sequences is high proportional to nucleotide divergence. Additionally, specific non-synonymous mutations in nsp3 and nsp6 evolved under positive selection. The exponential growth rate (r), doubling time (Td) and R₀ were estimated to be 47.43 per year, 5.39 days and 2.72, respectively. Comparison of synapomorphies distinguishing the SARS-CoV-2 and the candidate ancestor bat coronavirus indicates that mutation pattern in nsp3 and S gene enabled the new strain to invade human and become a pandemic strain. We arrive at the following main conclusions: (i) six months evolution of viral genome is nearly neutral, (ii) origin of pandemic is not Wuhan and predates formal reports, (iii) although viral population is ongoing an exponential growth, the doubling time is evolving towards shortening, and (iv) divergence rate of total genome is similar to other RNA viruses, but it is prominently high in some genes while low in some others and evolution in these genes should be closely monitored as their protein products intervening to pathogenicity, virulence and immune response.

Palmer amaranth (Amaranthus palmeri) is a problematic common weed species, especially in cotton (Gossypium hirsutum). With the wide use of chemical herbicide and herbicide-tolerant transgenic cotton lines, Palmer amaranth populations have developed tolerance to commonly used herbicides. It is imperative to develop alternative weed control methods to slow the evolution of herbicide-resistant weed populations and provide new sources for weed management. Eleven chromosome substitution (CS) cotton lines CS-B26lo, CS-T17, CS-B16-15, CS-B17-11, CS-B12, CS-T05sh, CS-T26lo, CS-T11sh, CS-M11sh, CS-B22sh, and CS-B22lo were screened for weed-suppressing abilities in this study. The cotton lines were tested using the established stair-step structure methodology, which provided scope to study the effect of individual CS lines on the growth and development of Palmer amaranth weed without any interference of other external factors in the greenhouse. Height (cm) and chlorophyll concentration (cci) were measured for each plant in the system. The data were analyzed as a randomized complete block design using LSD mean comparisons of the genotypes at the P≤ .05 level. The 14th day after establishment resulted in the most significant variation in Palmer amaranth height reduction among the CS lines. Results indicated that CS-B22sh had the highest effect in reducing Palmer amaranth height and chlorophyll concentration with the most heightened susceptibility for Palmer amaranth. The cluster analysis revealed that Enlist® cotton, CS-CS-B22sh, and CS-T26lo were clustered in one group suggesting similar genetic potential with reference to Palmer amaranth growth and development. CS-B22sh showed novel genetic potential to control the growth and development of Palmer amaranth, a major weed in cotton fields. In the future, it will be interesting to investigate if CS-B22sh exudates from its root contain allelochemicals able to impede the growth and development of Palmer amaranth.

This paper provides estimates of the elasticity of substitution between operational and managerial jobs in the US economy covering a period of almost five decades, derived from an aggregate CES production function. Estimating the long-term relationship between (the log of) the aggregate employment/self-employment ratio and (the log of) the returns from paid-employment relative to self-employment and testing for structural breaks, we report different estimates of the elasticity of substitution in each of the two regimes identified. Our results help to understand and interpret one of the most intriguing aspects in the evolution of self-employment rates in developed countries: the reversal of the trend in self-employment rates. Our estimates show that a higher level of development is associated with a greater number of entrepreneurs and smaller firms. Some rationales for understanding the growth of the elasticity between paid-employment and self-employment, including the recent trends in the digital economy—are also suggested.

When asked to estimate the carbon footprint of a bundle of relatively low carbon footprint items and relatively high carbon footprint items, people typically report a lower value compared to estimating the high carbon footprint items alone. This finding is called the negative footprint illusion and suggests people report the average rather than sum of the combined items’ carbon footprint. In a recent paper by Gorissen et al. (2024), the authors claimed that people are immune to this illusion if the question is framed differently. Specifically, they found that estimates of the environmental friendliness of a set comprising a burger (high carbon footprint) and an organic apple (low carbon footprint) was higher than for a set comprising the burger alone, whereas no difference was found between the two sets when participants were asked to estimate how environmentally damaging they were. Using larger item categories wherein the degree of the items’ environmental impact is clearly communicated, here we show it does not matter whether participants are required to estimate how friendly or damaging the items are. The roles of attribute substitution, dependent variables, and independent variables (stimulus characteristics) in modulating the negative footprint illusion is discussed.

Acid promoted amination of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine with anilines have been studied using hydrochloric acid. Four alcoholic solvents and water were evaluated as reaction medium, and the highest rate was observed in water. Although the initial rate increased by using higher concentration of acid, this leads to more solvolysis of the pyrrolopyrimidine, reducing the potential yield. The substrate scope of the amination of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine in water using 0.1 equivalent of hydrochloric acid was evaluated using 20 aniline derivatives with variance in basicity and steric bulk. Preparative useful reactions were seen for 14 of the 20 derivatives. Unsuited anilines are ortho substituted anilines with a pKa below 1. Aliphatic and benzylic amines react poorly under these conditions, but such aminations can proceed well in water without acid. Pyrrolopyrimidines with a low water solubility, also reacted slowly in water, however they could easily be aminated in 2-propanol.

To avoid the endless accumulation of QTL effects during pyramiding breeding, QTL epistasis plays a role of homeostasis. Four single-segment substitution lines with heading date QTLs were utilized to construct pyramiding materials with dual QTLs and triple QTLs, allowing for the estimation of QTL epistatic effects on heading date in rice. The epistatic components of dual QTL and triple QTL interactions were analyzed using data from three seasons of two years. All four QTLs can be considered as dominant loci, demonstrating superdominance. 75% of dual QTL interactions and 81.25% of triple QTL interactions obtained statistically significant results, reaffirming the prevalence of epistasis. Interactions of four QTLs with three positive effects and one negative effect generated 62.5% negative dual QTL epistatic effects and 57.7% positive triple QTL epistatic effects, forming the balance relationship “positive-negative-positive”. In fact, QTL effects were consistently partially neutralized by mixed QTL epistatic effects so as to control the infinite accumulation of QTL effects. QTL epistasis plays a role of homeostasis on heading date in rice. However, there were two exceptions. The directions of OsMADS50 and Hd3a-2 effects were consistently aligned with those of their mixed epistases, suggesting that the QTL or gene could be employed in pyramiding breeding with different objectives. This study elucidated the mechanism of epistatic interactions among four QTLs and provided valuable genetic resources for improving heading date in rice.

Several methods of processing wood into strong, durable products for the construction industry provide transformative opportunities to substitute for less sustainable building materials. Carbon storage is a further advantage, with the added possibility of combustion for bioenergy at end of life. Intense research activity in this area is expected to open up new markets for wood fiber during the lifetime of trees now being planted. Here, wood-derived materials are classified according to the particle size, from metres to nanometres, into which the wood is fragmented before reconstitution. Materials made by densifying or chemically modifying solid wood with no fragmentation are already in production for exterior doors, window frames and cladding, with improved uniformity and stability compared with unmodified wood. Pre-commercial developments promise further gains in durability and strength. Emerging developments extend these process technologies to wood that has been chipped or stranded or pulped, retaining the above advantages over raw timber for weather-facing applications and adding processability by moulding or extrusion. Crucially, the raw material does not then need to be sawn timber but can be bioenergy-grade wood biomass. This will facilitate afforestation strategies that combine the aims of carbon sequestration and biodiversity.

Core-shell structured magnetic nanoparticles combine hard and a soft phases to improve energy efficiency. The mutual interaction of the two phases can lead to the exchange spring effect leading to higher magnetic energy. In this regard, synthesis of Nd2Fe14B based core-shell structured powders have proven to be elusive due to the relatively reactive nature of this phase. In this study, a process has been established for successfully coating the surface of Nd2Fe14B powders with FeCo layer using galvanic displacement method. Initially, a binary phase magnetic powder was synthesized containing Nd2Fe14B and Nd2Fe17 phase. Subsequently, the powders were coated using a Co precursor at 303 K. During coating the metastable Nd2Fe17 phase was dissolved and the Fe ions were released into the solution. Subsequently, the Fe ions deposited together with the Co ions on the surface of Nd2Fe14B powder to form a FeCo shell. The deposited layer thickness and composition was confirmed using TEM analysis.

Background:Peripheral neuropathy (PN) can result in either partial or complete loss of distal sensation resulting in an increased fall risk. Walkasins^® uses a shoe insert to detect the magnitude and direction of sway and sends signals to a leg unit that provides sensory balance cues. The objective of this case report is to describe the long-term influence of the Walkasins^® lower limb sensory neuroprosthesis on balance and gait for an individual with diabetic PN.Case Description:A fifty-one-year-old male with a 3-year history of PN and a 10-year history of type II diabetes mellitus was fitted with Walkasins^® and utilized the shoe inserts 8-10 hours/day for more than 1 year. Although, vibration and tactile thresholds were severely impaired at his 1^st metatarsophalangeal joint and the lateral malleolus bilaterally he could perceive tactile stimuli from the Walkasins^® above the ankles.Outcomes:Following Walkasins^® use, his Activities-specific Balance Confidence Scale (ABC) scores improved from 33% to 80%. His mean Vestibular Activities of Daily Living (VADL) scores decreased from 3.54 to 1. His Functional Gait Assessment (FGA) scores increased from 13/30 to 28/30 and his miniBESTest scores improved from 15/28 to 26/28. Gait speed increased from 0.23 m/sec to 1.5 m/sec. The patient described a decrease in pain and cramping throughout his lower extremities and an increase in function.Discussion:Gait and balance improved with the use of the Walkasins^® and participation in the Neuro Wellness Program. This improvement suggests that the use of sensory substitution devices, such as the Walkasins^®, may replace sensory deficits related to gait and balance dysfunction experienced by patients with PN. Further research is needed to determine if other patients will have a similar response and what the necessary threshold of sensory function is to benefit from use of the Walkasins^®.

Sodium substitution Li1-xNaxMn2O4 cathodes were synthesized by a solid-state reaction method. The morphologies and crystal structures of Li1-xNaxMn2O4 were characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD), respectively. All Li1-xNaxMn2O4 samples exhibited a single phase LiMn2O4 spinel structure with good crystallinity. The effect of Na+ ions on the electrochemical performance of Li1-xNaxMn2O4 was investigated by galvanostatic charge-discharge test. The results showed that lithium substituted by sodium deteriorated its capacity retention but enhance its discharge capacity when it worked at large current densities. The initial discharge capacity was 114.2 mAh/g for Li0.94Na0.06Mn2O4, and 93.1 mAh/g remained after 300 cycles at a current density of 2220 mA/g in the voltage range 3.0–4.3 V at room temperature.

In the past few decades, the transmission of data over an unsecure channel resulted in an increased rate of hacking. Therefore, the requirement to make multimedia data more secure is increasing day by day. Numerous algorithms are developed to improve efficiency and robustness. In this article, a novel and secure image encryption algorithm is presented. It is based on a modified chaotic logistic map (CLM) that provides the advantage of having less computational time to encrypt an input image. The encryption algorithm is based on Shannon’s idea of using substitution-permutation and one-time-pad network to achieve ideal secrecy. The CLM is used for substitution and permutation to improve randomness and increase dependency on the encryption key. Various statistical tests are conducted, such as Key Space Analysis, Complexity Analysis, Sensitivity Analysis, Strict Avalanche Criteria (SAC), Histogram Analysis, Entropy Analysis, Mean of Absolute Deviation (MAD) Analysis, Correlation Analysis, Contrast Analysis, and Homogeneity to give a comparative analysis of the proposed algorithm and verify its security. As a result of various statistical tests, it is evident that the proposed algorithm is more efficient and robust as compared to previous ones.

We consider a classial case of irrational integrals containing a square root of a quadratic polynomial. It is well known that they can be expressed in terms of elementary functions by one of three Euler’s substitutions. It is less known that the Euler substittutions have a beautiful geometric interpretation. In the framework of this interpretation one can see that the number 3 is not the most suitable. We show that it is natural to introduce the fourth Euler substitution. By the way, it is not clear who was the first to attribute these three substitutions to Euler. In his original treatise Leonhard Euler uses two substitutions which are sufficient to cover all cases.

Nizatidine is a gastroprotective drug with a short biological half-life and narrow absorption window. This study aimed at developing floating tablets of nizatidine using various HPMC viscosity grades, namely K4M, E4M, K15 and K200M. Directly compressed tablets revealed an excellent uniformity in hardness, thickness and weight and nizatidine was evenly distributed within the matrix floating tablets. Buoyancy study revealed floating lag time as low as 18–38 s, and tablets remain buoyant for upto 24 h. However, the later depended upon viscosity grade of HPMC and that the higher the viscosity, the less was the total floating time. In vitro dissolution indicated viscosity dependent nizatidine release from the floating tablets. HPMC K4M and E4M based floating tablets released almost 100% drug in 12 h, whilst higher viscosity polymers such as K15 and K200M only released 81.88% and 75.81% drug, respectively. The drug release followed non-Fickian diffusion from tablets formulated with K4M, K15 and K200M, whilst super case II transport was observed with E4M based tablets. More interestingly, K4M and E4M polymers have similar viscosity yet exhibited different drug release mechanism. This was attributed to the difference in degree of substitution of methoxyl- and hydroxypropoxyl- groups on polymer backbone.

Genus Clematis is one of the largest within Ranunculaceae. Here we report the chloroplast genome of two Clematis species, C. brachyura and C. trichotoma endemic to Korea. The chloroplast genome lengths of C. brachyura and C. trichotoma are 159,532 bp and 159,170 bp, respectively. Gene contents in the complete chloroplast genomes of these two Clematis species are identical to that of most Ranunculaceae and other angiosperms. However, our data results demonstrated that genus Clematis has inversion and rearrangement events concerning gene rps4 gene, rps16 to trnH region, and trnL to ndhC region, and IR regions expansion. Comparison of IR regions among Ranunculaceae species revealed that Clematis species contained six protein coding genes (infA, rps8, rpl14, rpl16, rps3, and rpl22) usually found in the long single copy (LSC) region of other species. Phylogenetic analysis demonstrated that genus Clematis is closely related to genus Ranunculus. Differences in repeat structure, substitution rates, and IR expansion in genera Clematis and Ranunculus, explained their relationship. Clematis species showed slightly higher tandem repeats content than Ranunculus species. The six protein-coding genes showed lower synonymous substitution rates in the IR of Clematis species than in the LSC of Ranunculus species. Overall, the chloroplast genomes and results presented here provide important information on the evolution of Ranunculaceae.

Magnesium, as one of the most abundant cation in the human body, plays an important role in both physiological and pathological processes. In this study, it was shown that a promising biomedical material Mg-substituted hydroxyapatite (Mg-HA) can be synthesized via fast mechanochemical method. For this method, the nature of magnesium-contained carriers was shown to be important. When using magnesium oxide as a source of magnesium, the partial insertion of magnesium cations into the apatite structure occurs. In contrast, when magnesium hydroxide or monomagnesium phosphate is used, a single-phase Mg-HA is formed. Both experimental and theoretical investigations showed that an increase in the Mg content leads to a decrease in the lattice parameters and unit cell volume of Mg-HA. Density functional theory calculations showed the high sensitivity of the lattice parameters towards the crystallographic position of the calcium site substituted by magnesium. It was shown experimentally that insertion of magnesium cations decreases the thermal stability of the hydroxyapatite. The thermal decomposition of Mg-HA leads to the formation of a mixture of stoichiometric HA, magnesium oxide and Mg-substituted tricalcium phosphate phases.

CuO/ZnO/Al2O3 catalyst is a commonly used catalyst for rea methanol steam reforming reaction. Oxalic acid was as precipitant in preparing oxalate precursor of CuO/ZnO/Al2O3 catalyst by co-precipitation, deionized water and ethanol were as solvents, microwave irradiation and water bath were as aging heating manner respectively. It indicated that ethanol selected crystal phase composition of oxalate precursors and restricted their growth. Microwave irradiation prompted the isomorphous substitution between Cu2+ of CuC2O4 and Zn2+ of ZnC2O4 in mother liquid, forming the master phase (Cu,Zn)C2O4 in precursor, the solid solution Cu-O-Zn formed after calcination, which exhibited nano-fibriform morphology. It possessed small CuO grains, large surface area and strong synergy between CuO and ZnO, which is beneficial to improve the catalytic performance of methanol steam reforming, the STY of H2 reached 516.7 mL·g-1·h-1, and the selectivity of CO was only 0.29%.

The effect of defatted Hermetia illucens meal (HIM) dietary inclusion on growth performance, stress indicators and gut histological traits of Sparus aurata was studied. For 131 days, 312 fish were fed with one basal diet, containing fish meal as animal protein source, and three diets containing 25%, 35% and 50% HIM as a partial replacement for fishmeal. On all fish (26 fish per tank, 3 replicate tanks per diet, 78 fish per diet) the growth performance were calculated. At the end of the trial, on a subsample of 72 specimens (6 fish per tank, 3 replicate tanks per diet, 18 fish per diet), stress parameters were determined on blood samples and gut histological tract investigated. Insect meal inclusion did not affect (p > 0.05) growth performance, blood parameters, length and width of villi and goblet cell count of the posterior gut tract while, those of the anterior gut tract while increased (p < 0.05). The histological examination of the intestinal sections showed in fish fed the HIM25 and HIM50 diets, more frequent and evident morphological changes; instead, there were no substantial differences between HIM0 and HIM35 groups. In conclusion, the HIM35 was the most tolerated formulation by fish.

In spite of unique structural, spectroscopic and redox properties, the synthetic variants of the planar, antiaromatic hexaphyrin (1.0.1.0.1.0) derivatives 2, has been limited due to the low yields and difficulty in access to the starting material. A chemical modification of the meso-substituents could be good alternative overcoming the synthetic barrier. Herein, we report a regio-selective nucleophilic aromatic substitution (SNAr) of meso-pentafluorophenyl group in rosarrin 2 with catechol. The reaction afforded benzodioxane fused rosarrin 3 as single product with high yield. The intrinsic antiaromatic character of the starting rosarrin 2 retained throughout the reactions. Clean, two electron reduction was achieved by treatment of 3 with SnCl2•2H2O affording 26pi-electron aromatic rosarrin 4. The synthesized compounds exhibited noticeable changes in photophysical and redox properties compared with starting rosarrin 2. .

We consider Pisot family substitution tilings in $\R^d$ whose dynamical spectrum is pure point. There are two cut-and-project schemes(CPS) which arise naturally: one from the Pisot family property and the other from the pure point spectrum respectively. The first CPS has an internal space $\R^m$ for some integer $m \in \N$ defined from the Pisot family property, and the second CPS has an internal space $H$ which is an abstract space defined from the property of the pure point spectrum. However it is not known how these two CPS's are related. Here we provide a sufficient condition to make a connection between the two CPS's. In the case of Pisot unimodular substitution tiling in $\R$, the two CPS's turn out to be same due to [5, Remark 18.5].

Conventional fertilization practices can lead to many ecological problems, such as nutrient imbalance, soil acidity, and reduced soil fertility in natural rubber plantations. To address these challenges, a field investigation was strategically carried out to substitute inorganic fertilizer with organic fertilizers consisted of six treatments, i.e., no fertilization (CK), inorganic fertilizer (NPK), 25 % replacement of inorganic through organic (25%M), 50 % replacement of inorganic through organic (50%M), 75 % replacement of inorganic through organic (75%M), and 100% organic fertilizer (100%M). The soil physicochemical properties (SOC, TN, AN, C:N, pH, NH4+-N, and NO3--N) and carbon and nitrogen converting enzymes (BG, NAG, and LAP) were all determined. The partial substitution of inorganic fertilizers with organic fertilizers (i.e., 75%M at surface soil layer) showed higher SOC (14.52 g.kg-1), TN (1.06 g.kg-1), AN (20.07 mg.kg-1), C:N (14.63), NH4+-N (10.63 mgkg-1), and NO3--N(11.06 mg.kg-1) than NPK and CK. Such increase in physicochemical properties in partial replacement of inorganic with organic fertilizers plots resulted from higher carbon and nitrogen enzymes activities (BG (143.17 nmol.g-1.h-1), NAG (153.96 nmol.g-1.h-1), and LAP (153.48 nmol.g-1.h-1)) compared to NPK and CK, and further the person correlation and RDA analysis confirmed a significant positive correlation between SOC, AN, and soil enzymes. This study presents a new strategy for assessing the impact of partially replacing inorganic fertilizers with organic fertilizers in rubber plantations, mainly by modifying the soil nutrient composition in tropical regions.

SARS-CoV-2 is mutating and creating divergent variants across the world. An in-depth investigation of the amino acid substitution in the genomic signature of SARS-CoV-2 proteins is highly essential for understanding its host adaptation and infection biology. A total of 9587 SARS-CoV-2 structural protein sequences collected from 49 different countries are used to characterize protein-wise variants, substitution pattern (type and location), and major substitution changes. The majority of the substitutions are distinct, occurred mostly in a particular location, and leads to a change in amino acid's biochemical properties. In terms of mutational changes, Envelope (E) and Membrane (M) proteins are relatively stable than Nucleocapsid (N) and Spike (S) proteins. Several co-occurrence substitutions are observed, particularly in S and N proteins. Substitution specific to active sub-domains reveals that Heptapeptide Repeat, Fusion peptides, Transmembrane in S protein, and N-terminal and C-terminal domains in N protein are remarkably mutated, and also found few deleterious mutations in these domains.

In December 2019, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in the province of Wuhan, China. Since then, it has spread worldwide with new mutations being reported. We performed genomic analysis to identify the changes in genetic diversity of SARS-CoV-2 between December 2019 and November 2020, and through molecular surveillance, we monitored the mutations that could be involved in viral fitness. We analyzed 2,213 complete genomes from 6 geographical regions worldwide, which were downloaded from GenBank and GISAID databases. Although SARS-CoV-2 presented low genetic diversity, there has been an increase over time, with the presence of several hotspot mutations throughout its genome. We identified 7 frequent mutations that resulted in non-synonymous substitutions (dN). Two of them, C14408T>P323L and A23403G>D614G, located in the nsp12 and Spike protein, respectively, emerged early in the pandemic and showed a considerable increase in frequency over time. Two other mutations, A1163T>I120F in nsp2 and G22992A>S477N in the Spike protein emerged recently and have spread in Oceania and Europe. Continuous molecular surveillance of SARS-CoV-2 will be necessary to detect and describe the transmission dynamics of new variants of the virus with clinical relevance. This information is important to improve programs to control the virus.

Exploring the biological significance of mutations in SARS-CoV-2 coronavirus, causing the COVID–19 pandemic, has recently become an area of paramount interest for many researchers, who are pouring their tremendous efforts, in cracking the COVID–19 pandemic code. One of many such mutations that have occurred in the viral genome is V483A mutation, which is a part of the receptor-binding motif (RBM), present in the S1 domain of the spike protein. V483A mutant virus is becoming popular in North America with 36 cases so far, due to its frequent occurrences in recent days. In this review, we have assembled all information, currently available on V483A mutation, and have made a critical analysis based on the perspectives of many researchers all around the world. Comparison is made between the wild type and the V483A mutants to analyze certain factors like the type of interaction between the virus and host cell interface, binding affinity, stability, partition energy, hydrophobicity, occurrence rate, and transmissibility. Insilico dynamic analysis shows minimal alteration in the receptor-binding domain (RBD) of V483A mutant protein in free-state and no significant change of mutant tertiary structure of RBM upon binding to the ACE2 receptor. Comprehensive details about infectivity and evasion of the immune system by the virus are discussed. This information can in turn be of monumental importance in the field of vaccine and drug development because the mutants are becoming resistant to the vaccines and monoclonal antibodies.

Tuberculosis (TB) caused by Mycobacterium tuberculosis remains a predominant cause of mortality, especially in low- and middle-income nations. Recently antimicrobial peptides were discovered that at low concentrations could stimulate the growth of M. tuberculosis (hormetic response). In this study, such a peptide was used to investigate the effects on the time to positivity (TTP). A systematic substitution analysis of peptide 14D was synthesized using Spot synthesis technology, resulting in 171 novel peptides. Our findings revealed a spectrum of interactions, with some peptides accelerating M. tuberculosis growth, potentially aiding in faster diagnostics, while others exhibited inhibitory effects. Notably, peptide NH2-wkivfiwrr-CONH2 significantly reduced the TTP by 25 hours compared to the wild-type peptide 14D, highlighting its potential in improving TB diagnostics by culture. Several peptides demonstrated potent antimycobacterial activity, with a minimum inhibitory concentration (MIC) of 20 µg/mL against H37Rv and a multidrug-resistant M. tuberculosis strain. Additionally, a reduction in the formation of cord-like structures was observed, which is indicative of reduced virulence and transmission potential. This study underscores the multifaceted roles of antimicrobial peptides in TB management, from enhancing diagnostic efficiency to offering therapeutic avenues against M. tuberculosis.

The reaction of mercaptoacetic acid esters with pentachloro-2-nitro-1,3-butadiene provides appropriate precursors for the synthesis of 2,3,4-trisubstituted benzo[h]quinolines. These heterocycles are easily accessible via a single-step reaction with 1-naphthyl- or 1-anthracenylamine, respectively. Due to steric bulk and high electron density ring closure to benzo[h]quinolines takes place, exclusively. Such highly substituted annelated pyridine systems can be modified in subsequent, selective reactions to build up new N-heterocycles with promising microbiological properties. Antibacterial and antiproliferative assays against four cell mammalian cell lines demonstrate that some of the sulfur-substituted benzo[h]quinolines analogs display potent phenotypic bioactivities in the single-digit micromolar range.

A series of cysteine-based perfluoroaromatic (hexafluorobenzene (I) and decafluorobiphenyl (II) were synthesized and established as a chemoselective and available core to simple or more complex systems since small molecules to biomolecules with interesting properties. As proof of concept of the potential application of perfluorinated derivatives as non-cleavable linkers, some antibody-perfluorinated conjugates were prepared via thiol, demonstrating that the bioconjugation process doesn’t affect to the macromolecular entity. Besides, some molecular properties of synthesized compounds are evaluated using a combination of spectroscopic characterization (FT-IR and 19F-NMR chemical shifts) and theoretical calculations. Moreover, molecular Docking was also developed to predict cysteine-based hexafluorobenzene and decafluorobiphenyl derivatives’ affinity against topoisomerase Il and cyclooxygenase 2 (COX-2). The results suggested that mainly cysteine-based decafluorobiphenyl derivatives could be potential topoisomerase II α and COX-2 inhibitors, becoming potential anticancer agents and candidates for anti-inflammatory treatment.

Upland cotton is sensitive to 2,4-dichlorophenoxyacetic acid (2,4-D), and the identification of potentially 2,4-D tolerant cotton chromosome substitution (CS) lines and understanding tolerance mechanisms provide a significant step into the development and genetic improvement of upland cotton to reduce yield loss caused by 2,4-D herbicide effects including the drifts. Experiments were conducted to understand the possible mechanism of herbicide tolerance in CS-T04-15, CS-T07, and CS-B15sh, 2,4-D herbicide-tolerant cotton CS lines compared with TM-1, the 2,4-D herbicide susceptible recurrent parent of the CS line as control, using [14C]2,4-D. Percent absorption rate and translocation patterns of the 14C-labeled herbicide application at 5.17 kBq at 6 to 48 hours after treatment (HAT) were determined. The tolerant cotton CS lines showed 15-19% [14C]2,4-D uptake while TM-1 exhibited a reduced uptake of only 1.4% [14C]2,4-D at 24 HAT. Distribution of the absorbed [14C]2,4-D showed that 2-5% was translocated outside the treated leaf. In TM-1, 77% of the herbicide was translocated above and below the treated leaf, contrasting with the reduced translocation of 14C-labeled herbicide observed in the tolerant CS lines. Interestingly, CS-T04-15 showed a restricted movement of 14C below the treated leaf at 6 to 48 HAT, suggesting a novel mechanism of herbicide tolerance. This finding is the first report on upland cotton demonstrating a complex differential uptake and translocation associated with herbicide tolerance for [14C]2,4-D in cotton CS lines.

The factors that determine the relative rates of amino acid substitution during protein evolution are complex and they are known to vary among taxa. We estimated relative exchangeabilities for pairs of amino acids from clades spread across the tree of life and assessed the historical signal in the distances among these clade-specific models. We trained these models separately on collections of arbitrarily selected protein alignments and on ribosomal protein alignments. In both cases we found a clear separation between the models trained using multiple sequence alignments from bacterial clades and the models trained on archaeal and eukaryotic data. We assessed the predictive power of our novel clade-specific models of sequence evolution by asking whether fit to the models could be used to identify the source of multiple sequence alignments. Model fit was generally able to classify protein alignments correctly at the level of domain (bacterial versus archaeal), but the accuracy of classification at finer scales was much lower. The only exceptions to this were the relatively high classification accuracy for two archaeal lineages: Halobacteriaceae and Thermoprotei. Genomic GC content had a modest impact on relative exchangeabilities despite having a large impact on amino acid frequencies. Relative exchangeabilities involving aromatic residues exhibited the largest differences among models. There were a small number of exchangeabilities that exhibited large differences in comparisons among major clades and between generalized models and ribosomal protein models. Taken as a whole, these results reveal that a small number of relative exchangeabilities are responsible for much of the structure of the “model space” for protein sequence evolution. If we look beyond the information that these clade-specific models reveal about protein evolution the models themselves are likely to be useful tools for phylogenomic inference across the tree of life.

：An effective technology for predicting the end-point phosphorous content of basic oxygen furnace (BOF) can provide theoretical instruction to improve the quality of steel via controlling the hardness and toughness. Given the slightly inadequate prediction accuracy in the existing prediction model, a novel hybrid method was suggested to more accurately predict the end-point phosphorus content by integrating an enhanced sparrow search algorithm (ESSA) and a multi-strategy with a deep extreme learning machine (DELM) as ESSA-DELM in this study. To begin with, the input weights and hidden biases of DELM were randomly selected, resulting in that DELM inevitably had a set of non-optimal or unnecessary weights and biases. Therefore, the ESSA was used to optimize the DELM in this work. For the ESSA, the Trigonometric substitution mechanism and Cauchy mutation were introduced to avoid trapping in local optima and improve the global exploration capacity in SSA. Finally, to evaluate the prediction efficiency of ESSSA-DELM, the proposed model was tested on process data of the converter from the Baogang steel plant. The efficacy of ESSA-DELM was more superior to that of other DELM-based hybrid prediction models and conventional models. The result demonstrated that the hit rate of end-point phosphorus content within ±0.003%, ±0.002%, and ±0.001% was 91.67%, 83.33%, and 63.55%, respectively. The proposed ESSA-DELM model could possess better prediction accuracy compared with other models, which could guide field operations.

The expression of the Fasciola hepatica Carboxylesterase type B (CestB) gene is induced in response to the anthelmintic triclabendazole (TCBZ), resulting in a significant increase in enzymatic specific activity. Furthermore, the amino acid sequence of CestB exhibits variations that could lead to substantial amino acid substitutions at the ligand-binding site. These substitutions have the potential to affect the interaction between the ligand and the protein, as well as the catalytic properties of the enzyme. The objective of this study was to identify new CestB polymorphisms in TCBZ-resistant parasites using 3D modeling against the metabolically oxidized form of the anthelmintic TCBZSOX. Our aim was to observe the formation of TCBZSOX-specific binding pockets that could potentially explain the resistance to anthelmintic agents. We identified a CestB polymorphism in a TCBZ-resistant strain of parasites exhibiting three radical amino acid substitutions at positions 147, 215, and 243, resulting in the formation of a TCBZSOX-affinity pocket capable of binding the anthelmintic drug. Additionally, our 3D modeling analysis revealed that these amino acid substitutions also had an impact on the configuration of the CestB catalytic site, affecting the enzyme's interaction with chromogenic carboxylic ester substrates and altering its catalytic properties; however, the identified TCBZSOX-binding pocket was located far from the enzyme's catalytic site, making the enzymatic hydrolysis of TCBZSOX theoretically impossible. Nonetheless, the increased affinity for the anthelmintic may explain a drug-sequestration type of anthelmintic resistance and lays the foundation for the development of a molecular diagnostic tool for identifying anthelmintic resistance in F. hepatica.

The emergence of the COVID-19 pandemic has propelled the use of alcohol-based hand sanitizers to the fore as a SARS-CoV-2 control measure. To be effective these products must comply with relevant quality parameters such as alcohol concentration, methanol limits and purity. The current study was designed to determine the quality of alcohol-based hand sanitizer products in the Nairobi metropolitan area. For this purpose, 74 commercially marketed samples were collected and subjected to analysis by gas chromatography. Only three samples (4.1%) complied with the regulatory specifications for alcohol content, methanol limits and pH. Five samples (6.8%) complied with the specification for alcohol content but did not meet methanol or pH limits. A total of 44 (59.5%) samples had methanol levels that exceeded threshold limits. Eleven samples (14.9%) were found with methanol substitution (i.e., methanol, instead of ethanol or isopropanol, was the main alcohol component). The results show that users of alcohol-based hand sanitizers are being exposed to substandard and falsified products which in addition to being non-efficacious pose harm due to unacceptable levels of toxic impurities. Regular, routine post-market surveillance is needed to prevent such products from reaching the market.

Hydroxyapatite (HAP) is the main mineral component of bones and teeth. It is widely used in medicine as a bone filler and coating for implants to promote new bone growth. Ion substitutions into the HAP structure highly affect its properties. One of the important substituents is manganese. This paper presents the new results obtained by high-precision density functional theory calculations using hybrid functionals, for studies of the Mn/Ca substitutions in HAP in a wide manganese concentration range within 2x2x2 supercell model. The experimental data on the mechanochemical synthesis of HAP-Mn samples with different Mn concentrations are also presented. The comparison between experiment and theory showed good agreement: the HAP-Mg unit cell parameters and volume decrease with increasing degree of Mn/Ca substitution. It is shown that electronic energy levels appear inside the band gap Eg of HAP, which depend on the concentration of Mn and change the photo-excitation energy of HAP, making its effective value Eg* less than the band gap Eg, and generally changing the photoelectronic properties of HAP. It was established that the energies of formation of the substitutions Mn/Ca depend on the position of the Ca atom (Ca1 or Ca2) and on the concentration of manganese. It has been shown that the replacement of calcium cations with manganese occurs predominantly at the Ca2 position.

The reduction of Ce cations in CeO2 can be enhanced by its partial substitution by Fe cations. The enhanced reduction of Ce cations results in a considerable increase in the reaction rates for thermal water splitting reaction when compared to CeO2 alone. This mixed oxide has a smaller crystallite size when compared to CeO2 in addition to a smaller lattice size. In this work, two Fe-substituted Ce oxides are studied (Ce0.95Fe0.05O2 and Ce0.75Fe0.25O2) by core and valence level spectroscopy in their as-prepared and Ar-ions sputtered states. Ar-ions sputtering substantially increases Ce4f lines at about 1.5 eV below the Fermi level. In addition, it is found that the XPS Ce5p/O2s ratio is sensitive to the degree of reduction, most likely due to a higher charge transfer from the oxygen to Ce ions upon reduction. Quantitatively it is also found that XPS Ce3d of the fraction of Ce3+ (uo, u’ and vo, v’) formed upon Ar-ions sputtering and the ratio Ce5p/O2s lines are higher for reduced Ce0.95Fe0.05O2 than for reduced Ce0.75Fe0.25O2. XPS Fe2p showed however no preferential increase for Fe3+ reduction to Fe0 with increasing time for both oxides. Since water splitting was higher on Ce0.95Fe0.05O2 when compared to Ce0.75Fe0.25O2, it is inferred that the reaction centers for the thermal water splitting to hydrogen are the reduced Ce cations and not the reduced Fe cations. These reduced Ce cations can be tracked by their XPS Ce5p/O2s ratio in addition to the common XPS Ce3d lines.

This study reports the synthesis and characterization of novel per-fluorinated organic polymers with azo- and azomethine-based linkers using nucleophilic aromatic substitution. The polymers reveal variations in the fluorine content via the incorporation of decafluorobiphenyl and hexafluorobenzene linkers, which enhanced their hydrophobic nature. The rich fluorine polymers were slightly soluble in THF and have shown molecular weights between 4886 to 11948 g/mol. All polymers exhibit thermal stability in the range of 350-500°C, with varying thermal stability depending on the fluorine and nitrogen content. Conjugation of the polymers was confirmed through changes in the UV-Vis spectra, with a hypsochromic shift observed in all cases, more pronounced in azo-based fluorinated chains due to H-bonding on the nitrogen sites, chain conformations, and planarity. The optical band gap (Eg) of the polymers was determined from the UV-Vis data, with the Eg values of the azo-based fluorinated polymers being 1 eV higher than those of their corresponding linkers. The cross-linking formation was characterized by porosity measurements, with the azo-based polymer exhibiting the highest surface area of 770 m²/g with a pore volume of 0.35 cm³/g, while the open-chain azomethine-based polymer exhibited the lowest surface area of 285 m²/g with a pore volume of 0.0872 cm³/g. Porous structures with varied hydrophobicities were investigated as adsorbents for separating water-benzene and water-phenol mixtures and selectively binding methane/carbon dioxide gases from the air. The most hydrophobic polymers containing the decafluorbiphenyl linker were suitable for benzene separation, while the best methane uptake values were 6.14 and 3.46 mg/g for DAB-Z-1O and DAB-A-1O, respectively. DAB-Z-1h, with the highest surface area and rich in nitrogen sites, exhibited the highest CO₂ uptake at 298 K (17.25).

Chlorotoxin (CTX) is a 36–amino acid peptide with 8 Cys residues that forms four Cys-Cys bonds. It has high affinity for the glioma-specific chloride channel and matrix metalloprotease-2. Structural and binding properties of CTX analogs with various Cys residue substitutions with L-a-aminobutyric acid (Abu) have been previously reported. Using 4.2 ìs molecular dynamics, we compared the conformational and essential space sampling of CTX and analogs [Abu/Ser^2,19]CTX, [Abu/Ser^5,28]CTX, [Abu/Ser^16,33]CTX, [Abu/Ser^20,35]CTX, and [Abu/Ser^{2,5,16,19,20,28,33,35}]CTX. The native and substituted peptides maintained a high degree of a-helix propensity from residues 8 through 21, with the exception of [Ser^5,28]CTX and [Abu^16,33]CTX. In agreement with previous circular dichroism spectropolarimetry results, the C-terminal b-sheet content varied less from residues 25 through 29 and 32 through 36 and was well conserved in all analogs, except: [Abu^16,33]CTX, [Ser^20,35]CTX, [Abu^{2,5,16,19,20,28,33,35}]CTX, and [Ser^{2,5,16,19,20,28,33,35}]CTX. The Cys¹⁶-Cys³³ and Cys²⁰-Cys³⁵ Cys-Cys bonds appear to be required to maintain the ab-motif of CTX. Their selective substitution with Ser^16,33 however, may mitigate the destabilizing effect of Cys¹⁶-Cys³³ substitution by the formation of an inter residue H-bond from OgH of Ser¹⁶ to OgH of Ser³³ bridged by a water molecule. All peptides shared considerable sampled conformational space, which explains the retained receptor binding of the nonnative analogs.

SiO2-SO3H, with a surface area of 115 m2/g, pore volume of 0.38 cm3g-1 and 1.32 mmol H+/g, was used as a 20% w/w catalyst for the preparation of methyl salicylate (Wintergreen oil or MS) from acetylsalicylic acid (ASA). A 94% conversion was achieved in a microwave reactor during 40.0 minutes at 120 oC in MeOH. The resulting crude product was purified by flash chromatography. The catalyst could be re-used three times.

Phylogenomic analyses have revolutionized the study of biodiversity, but they have revealed that estimated tree topologies can depend, at least in part, on the subset of the genome that is analyzed. For example, estimates of trees for avian orders differ if protein coding or non-coding data are analyzed. The bird tree is a good study system because the historical signal for relationships among orders is very weak, which should permit subtle non-historical signals to be identified, while monophyly of orders is strongly corroborated, allowing identification of strong non-historical signals. Hydrophobic amino acids in mitochondrially-encoded proteins, which are expected to be found in transmembrane helices, have been hypothesized to be associated with non-historical signals. We tested this hypothesis by comparing the evolution of transmembrane helices and extramembrane segments of mitochondrial proteins from 420 bird species, sampled from most avian orders. We estimated amino acids exchangeabilities for both structural environments and assessed the performance of phylogenetic analysis using each data type. We compared those relative exchangeabilities with values calculated using a substitution dataset for transmembrane helices from a variety of sampled set of nuclear- and mitochondrially-encoded proteins, allowing us to compare the bird-specific mitochondrial models with a general model of transmembrane protein evolution. To complement our amino acid analyses, we examined the impact of protein structure on patterns of nucleotide evolution. Models of transmembrane and extramembrane sequence evolution for amino acids and nucleotides exhibited striking differences, but there was no evidence for strong topological data type effects. However, incorporating protein structure into analyses of mitochondrially-encoded proteins improved model fit. Thus, we believe that considering protein structure will improve analyses of mitogenomic data, both in birds and in other taxa.

Nineteen million Americans have significant vision loss. Over 70% of these are not employed full-time, and more than a quarter live below the poverty line. Globally, there are 36 million blind people, but less than half use white canes or more costly commercial sensory substitutions. The quality of life for visually impaired people is hampered by the resultant lack of independence. To help alleviate these challenges this study reports on the development of a low-cost (<$24), open-source navigational support system to allow people with the lost vision to navigate, orient themselves in their surroundings and avoid obstacles when moving. The system can be largely made with digitally distributed manufacturing using low-cost 3-D printing/milling. It conveys point-distance information by utilizing the natural active sensing approach and modulates measurements into haptic feedback with various vibration patterns within the distance range of 3 m. The developed system allows people with lost vision to solve the primary tasks of navigation, orientation, and obstacle detection (>20 cm stationary, moving up to 0.5 m/s) to ensure their safety and mobility. Sighted blindfolded participants successfully demonstrated the device for eight primary everyday navigation and guidance tasks including indoor and outdoor navigation and avoiding collisions with other pedestrians.

A new method for the synthesis of azido-propargyloxy derivatives of 1,3,5-triazine has been developed. The antibacterial activity against E. coli bacteria of propargyloxy substituted 1,3,5-triazines - 2,4,6-trispropargyloxy-1,3,5-triazine, 2-azido-4,6-bispropargyloxy-1,3,5-triazine and 2,4-diazido-6-propargyloxy-1,3,5-triazine and their hyperbranched polymers. It has been shown that the presence of an azide group in the compound directly affects the antibacterial activity. The cytotoxicity of these compounds against the M-HeLa, FetMSC and Vero cell lines was studied. The IC50 value was determined for low molecular weight compounds. It has been shown that hyperbranched polymers without azide groups don’t exhibit pronounced cytotoxicity and can be used in biomedical applications.

Dietary recommendations to decrease the risk of cardiovascular disease (CVD) have focused on reducing intake of saturated fatty acids (SFA) for more than 50 years. While the 2015-2020 Dietary Guidelines for Americans advise substituting both monounsaturated and polyunsaturated fatty acids for SFA, evidence supports other nutrient substitutions that will also reduce CVD risk. For example, replacing SFA with whole grains, but not refined carbohydrates, reduces CVD risk. Replacing SFA with protein, especially plant protein may also reduce CVD risk. While dairy fat (milk, cheese) is associated with a slightly lower CVD risk compared to meat, dairy fat results in a significantly greater CVD risk relative to unsaturated fatty acids. As research continues, we will refine our understanding of dietary patterns associated with lower CVD risk.

A four-step synthesis of bifunctional, noncovalent organocatalysts based on the chiral (1R,2R)-cyclohexane-1,2-diamine scaffold containing a 1,2-benzenediamine H-bond donor was developed. Nucleophilic aromatic substitution of the 2-fluoronitrobenzene derivative with the commercial (1R,2R)-cyclohexane-1,2-diamine was followed by selective alkylation of the primary amino group, reduction of the aromatic nitro group and final derivatization of the primary aromatic amino group, i.e. acylation, sulfonation, reductive alkylation and arylation, leading to the four subtypes of organocatalysts. All new compounds were fully characterized. The prepared organocatalysts (32 examples) were tested in the Michael addition of acetylacetone to trans-β-nitrostyrene, yielding the addition product with incomplete conversions (up to 93%) and enantioselectivities of up to 41% ee.

In order to counter the impending shortage of skilled professionals in the aging societies of our time in many western countries such as Germany, solutions for business and society are urgently needed. Here, artificial intelligence (AI) can play an important role in mitigating the problem with the help of diverse applications. At the same time, it is important to consider both the needs of the respective employee1 and the company to ensure that the use of AI has a positive impact on the organization and finds social acceptance. In this article, we describe the newly developed OSQE model (Optimize, Secure, Qualify, Expand), which for the first time outlines an AI cycle against the shortage of skilled professionals in a holistic approach that focuses equally on people and companies. This can serve organizations as a guide for strategy development, decision-making for and implementation of AI-supported measures in an entire cycle of an employee's affiliation with a company. The model takes three driving forces into account: companies, professionals, and AI applications. In the model, the measures to be implemented are prioritized with ascending numbering based on what would be most urgent for a company to implement. All measures relate to areas of action that place people at the center and can be assigned to the classic cycle of belonging of an employee in the company. In this regard, the opportunities that AI offers to professionals and companies are highlighted.