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Purpose: This study aims to enhance the targeting of erlotinib by grafting saccharides—galactose, pectin, and chitosan via oxalyl chloride-mediated processes. The objective is to evaluate the potential of these saccharide derivatives as ligands for targeted drug delivery, particularly to improve therapeutic efficacy in cancer treatments. Methods: Saccharides (galactose, pectin, and chitosan) were chemically grafted onto erlotinib, forming conjugates. Characterization was conducted using 1H NMR, differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy (FTIR). The conjugates’ drug delivery efficiency was tested using A549 cell lines to assess their efficacy in targeting cancer cells. Results: Characterization confirmed the successful grafting of saccharides onto erlotinib, as evidenced by 1H NMR, DSC, and FTIR. The in vitro drug release study demonstrated enhanced targeting efficiency of the saccharide-erlotinib conjugates, with improved cell-specific distribution and potential therapeutic benefits. Conclusions: Grafting saccharides onto erlotinib offers a promising approach to enhance drug absorption, reduce degradation, and minimize side effects in cancer therapy. This targeted drug delivery strategy represents a significant advancement in biomedical engineering for optimizing cancer treatment efficacy. [ABSTRACT FROM AUTHOR]

Mating assays are common laboratory experiments for measuring the conjugation frequency, i.e. efficiency at which a plasmid transfers from a population of donor cells to a population of recipient cells. Selective plating remains a widely used quantification method to enumerate transconjugants at the end of such assays. However, conjugation frequencies may be inaccurately estimated because plasmid transfer can occur on transconjugant-selective plates rather than only during the intended mating duration. We investigated the influence of cell density on this phenomenon. We conducted mating experiments with IncPα plasmid RP4 harbored in Escherichia coli at a fixed cell density and mating conditions, inoculated a serial dilution of the mating mixture on transconjugant-selective plates or in transconjugant-selective broth, and compared the results to a model of cell-to-cell distance distribution. Our findings suggest that irrespective of the mating mode (liquid vs solid), the enumeration of transconjugants becomes significantly biased if the plated cell density exceeds 28 Colony Forming Unit (CFU)/mm2 (or 1.68•105 CFU/standard 9 cm Petri dish). This threshold is determined with a 95% confidence interval of ± 4 CFU/mm2 (± 2.46•104 CFU/standard 9 cm Petri dish). Liquid mating assays were more sensitive to this bias because the conjugation frequency of RP4 is several orders of magnitude lower in suspension compared to surface mating. Therefore, if selective plating is used, we recommend to plate at this density threshold and that negative controls are performed where donors and recipients are briefly mixed before plating at the same dilutions as for the actual mating assay. As an alternative, a liquid enumeration method can be utilized to increase the signal-to-noise ratio and allow for more accurate enumeration of transconjugants. [ABSTRACT FROM AUTHOR]

An operator T ∈ L (H) is said to be C-normal if there exists a conjugation C on H such that the commutator [ (C T) # , C T ] equals zero, where [ R , S ] : = R S - S R and R # is a Hermitian adjont operator of R as in (1). If there exists a conjugation C with respect to which T ∈ L (H) is C-normal, then T is called a conjugation-normal operator. In this paper, we study properties of conjugation-normal operator matrices. In particular, we focus on the conjugation-normality of the component operators of operator matrices which are conjugation-normal. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of low concentration of Wenyang Tonglin Decoction (WTD) on the binding conditions of R45 plasmid conjugative transfer under liquid phase conjugation and its mechanism. Methods: Escherichia coli CP9 (R45) and Staphylococcus aureus RN450RF were cultured in medium containing WTD, and their minimum inhibitory concentration (MIC) values were obtained. Using promoter fusion technology, E. coli CP9 (R45) containing a promoter fusion was obtained. β-Galactosidase activity of TrfAp and TrbBp was tested, and the mRNA expression of regulatory factors (TrbA, KorA, and KorB) was detected by real-time fluorescent quantitative polymerase chain reaction. Results: The MIC of E. coli CP9 (R45) was 400 g/L and that of S. aureus RN450RF was 200 g/L. When the drug concentration in the culture medium was 200 g/L, the highest number of conjugants was (3.47 ±0.20) × 107 CFU/mL At 90 h of conjugation, the maximum number of conjugants was (1.15 ±0.06) × 108 CFU/mL When the initial bacterial concentration was 108 CFU/mL, the maximum number of conjugants was (3.47 ± 0.20) × 107 CFU/mL. When the drug concentration was 200 g/L, the β-galactosidase activity of TrfAp and TrbBp significantly increased; the relative quantification of TrbA, KorA and KorB were significantly inhibited. Conclusion: Low concentration of WTD promoted the development of bacterial resistance by affecting promoters and inhibiting the expression of regulatory factors. [ABSTRACT FROM AUTHOR]

We introduce the C-decomposition property for reducible bounded linear operators on a Hilbert space, and prove that an arbitrary idempotent operator has the C-decomposition property with respect to a particular space decomposition, which is related to Halmos’ two projections theory. Using this, we obtain a general explicit description for all the conjugations C such that a given idempotent operator is a C-projection. We also present a characterization of the ranges of C-projections for any conjugation C. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) is a major public health threat, exacerbated by the ability of bacteria to rapidly disseminate antimicrobial resistance genes (ARG). Since conjugative plasmids of the incompatibility group P (IncP) are ubiquitous mobile genetic elements that often carry ARG and are broad-host-range, they are important targets to prevent the dissemination of AMR. Plasmid-dependent phages infect plasmid-carrying bacteria by recognizing components of the conjugative secretion system as receptors. We sought to isolate plasmid-dependent phages from wastewater using an avirulent strain of Salmonella enterica carrying the conjugative IncP plasmid pKJK5. Irrespective of the site, we only obtained bacteriophages belonging to the genus Alphatectivirus. Eleven isolates were sequenced, their genomes analyzed, and their host range established using S. enterica, Escherichia coli, and Pseudomonas putida carrying diverse conjugative plasmids. We confirmed that Alphatectivirus are abundant in domestic and hospital wastewater using culture-dependent and culture-independent approaches. However, these results are not consistent with their low or undetectable occurrence in metagenomes. Therefore, overall, our results emphasize the importance of performing phage isolation to uncover diversity, especially considering the potential of plasmid-dependent phages to reduce the spread of ARG carried by conjugative plasmids, and to help combat the AMR crisis. [ABSTRACT FROM AUTHOR]

Can order markets lead participants towards price-taking equilibrium? Viewing market sessions as steps of iterative algorithms, this paper indicates positive prospects for convergence. Mathematical arguments turn on convolution, efficiency and generalized gradients. Economic arguments revolve around reservation costs, derived from indifference or threshold payments for quantities supplied or demanded. [ABSTRACT FROM AUTHOR]

Based on the properties of the conjugated p-electron system in cyclic polyenes, possible steric and electronic structures of transition states in thermal isomerizations of pyridine and phosphinine in an oxygen-free atmosphere have been determined by DFT calculations using B3LYP functional and 6-31G* basis set. The degree of stabilization of the transition states depends on the level of p-electron conjugation. Schemes of the thermal isomerizations of pyridine and phosphinine have been constructed, and potential barriers to these transformations have been calculated. The study of the reactivities of pyridine and phosphinine in the thermal isomerization processes has revealed lower aromaticity of phosphinine compared to pyridine. [ABSTRACT FROM AUTHOR]

Amanita phalloides is the primary species responsible for fatal mushroom poisoning, as its main toxin, α-amanitin, irreversibly and potently inhibits eukaryotic RNA polymerase II (RNAP II), leading to cell death. There is no specific antidote for α-amanitin, which hinders its clinical application. However, with the advancement of precision medicine in oncology, including the development of antibody–drug conjugates (ADCs), the potential value of various toxic small molecules has been explored. These ADCs ingeniously combine the targeting precision of antibodies with the cytotoxicity of small-molecule payloads to precisely kill tumor cells. We searched PubMed for studies in this area using these MeSH terms "Amanitins, Alpha-Amanitin, Therapeutic use, Immunotherapy, Immunoconjugates, Antibodies" and did not limit the time interval. Recent studies have conducted preclinical experiments on ADCs based on α-amanitin, showing promising therapeutic effects and good tolerance in primates. The current challenges include the not fully understood toxicological mechanism of α-amanitin and the lack of clinical studies to evaluate the therapeutic efficacy of ADCs developed based on α-amanitin. In this article, we will discuss the role and therapeutic efficacy of α-amanitin as an effective payload in ADCs for the treatment of various cancers, providing background information for the research and application strategies of current and future drugs. [ABSTRACT FROM AUTHOR]

The search for better energy storage systems that are less expensive, resource-abundant, and safer has sparked intense research into zinc ion batteries (ZIBs). Organic materials, especially quinones-based ZIBs, improved the rate performances by providing structural flexibility for the movement of zinc ions. In this work, a highly conjugated quinone molecule, tetrakis-lawsone (TLS), with multiple active sites, was used to enhance the capacity of the ZIBs. The non-planar geometry of TLS due to the different orientations of all four lawsone units of TLS provided a sufficient void for the Zn2+ movement, making it a suitable host cathode material for the ZIBs. TLS molecule consists of four LS units, which are aligned differently, thus, creating many empty void spaces in its matrix. Hence, it facilitates the Zn2+ ion movement within its lattice and thereby maximizes the utilization of TLS for energy storage. [ABSTRACT FROM AUTHOR]

ctive: In light of their diverse molecular features and wide range of biological activities, compounds with coumarin-based chemical structures have drawn significant scientific interest. On the other hand, despite the massive development of anti-aerobic bacterial agents, those that fight anaerobic bacteria are less advanced. Methods: In this work, 3-halomequinol derivatives were condensed via a Pechmann coupling reaction with 3-oxopentanedioic acid, affording precursors named 7-halo-6-methoxycoumarin-4-acetic acids and coded (P1–P4). These were esterified with metronidazole by thionyl chloride to give the four new coumarin-metronidazole composites coded (COU–MTZ1–COU–MTZ4). The structural conformation of these composites and their corresponding precursors was determined by analyzing the spectra acquired from FT-IR, 1H NMR, and 13C NMR spectrophotometers. The anti-anaerobic bacterial activity was assessed by determining the composites' inhibitory impact against four strains of pathogenic bacteria using broth dilution as a methodology. The biocompatibility profiles of the synthesized composites were spotlighted by in vitro inspection as well as by following their effects on the cellular growth of two normal-type bacterial strains and three healthy-type cell lines. Finally, the possibility of the composites being drug candidates was checked in silico by calculating their pharmacokinetic and drug-like attributes. Results: The results indicated that the new composites are biocompatible and demonstrated improved activity relative to the reference, with a golden effect attributed to the flouro-based composite. Discussion: This work reports the success in the synthesis and characterization of four (COU–MTZ) composites and their precursors. The synthetic composites showed more promising anti-anaerobic bacterial activity than the parent drug, with better theoretical aqueous solubility, intestinal absorption, and association with plasma proteins. Concerning the biocompatibility study, the synthetic composites did not demonstrate any obvious negative impact on the cellular growth of two normal-type bacterial strains and three healthy-type cell lines. Conclusions: It is concluded that the conjugation of metronidazole with the synthesized coumarins can improve its lipophilicity and consequently the candidate's penetration into the test anaerobic pathogens, affording a promising synthon template for advanced research. [ABSTRACT FROM AUTHOR]

Influenced by PT operators (parity and time reversal operators) the general conjugations acting in the L 2 space on the real line with the Lebesgue measure are studied. The behaviour of conjugations with respect to multiplication operators and translations is investigated. We consider conjugations defined as the convolution of the Fourier transform of a given unimodular (even) function and test functions. We characterize all conjugations commuting (intertwining) with all translation operators on the real line. The conjugations leaving kernels of Toeplitz operators (a generalization of model spaces) on H 2 space on the upper half plane invariant are also characterized. Analogous results are obtained for conjugations and kernels of Wiener–Hopf operators. [ABSTRACT FROM AUTHOR]

Reactive dyes exhibit suitable opto-electronic properties, making them promising for dye-sensitized solar cell (DSSC) applications. The present study uses reactive orange 16 dye to design an efficient dye sensitizer for DSSC application using a donor–π–acceptor concept. The sensitizer structures and their electronic and optical properties were investigated using density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations. The molecular electrostatic potential maps, HOMO–LUMO distributions, and density of states plots were obtained for the optimized geometry. The analysis showed that the electronic properties of reactive orange 16 are enhanced due to the π-linkage, responsible for extending the conjugation length of the system. The TD-DFT calculations showed a bathochromic shift in the absorption spectra due to the introduction of the π-linker. The shift confirmed the conjugation's role in enhancing the sensitizers' electronic properties. The transitions were π → π* and n → π*, and the transition with maximum oscillator strength was assigned to the H → L excitation. The study showed that donor–π–acceptor concept-based sensitizers derived from reactive dyes favor DSSC applications. Hence, this study's findings could be used to design and develop more efficient dye sensitizers based on reactive dyes. [ABSTRACT FROM AUTHOR]

Chemical modification of the enzymes with biospecific macromolecules is used in various fields of biotechnology to impart new functions or improve their properties and is a fast and convenient way to get the final products. The preparation of highly active, stable, and functionally active conjugates of the thermostable luciferase through the NH2-groups or free SH-groups of the enzyme with target molecules of different molecular weight (albumin, avidin from chicken eggs, antibodies, and progesterone) is described. The obtained conjugates were successfully tested as a reporter in bioluminescent immunoassay for the detection of the molecules and pathogens. Thus, the luc-albumin (Luc-Alb) and luc-insulin (Luc-Ins) conjugates were used in competitive ELISA for the detection of an analyte (albumin or insulin) in the samples. Luc-progesterone (Luc-Pg) was used in the rapid homogeneous immunoassay of progesterone by the BRET technique with the detection limit of 0.5 ng/ml. Luciferase conjugates with avidin (Luc-Avi) and secondary and primary antibodies (Luc-RAM and Luc-Sal) were used for enzyme immunoassay detection of Salmonella paratyphi A cells with the cell detection limit of 5 × 104 CFU/ml. To reduce the detection limit of Salmonella cells, we developed a pseudo-homogeneous bioluminescent enzyme immunoassay of cells using a new matrix for the analyte capture—polystyrene microparticles coated with Pluronic F108, covalently labeled with Sal antibodies. This allowed to achieve efficient trapping of cells from solution, significantly reduced nonspecific sorption and decreased the cell detection limit to 2.7 × 103 CFU/ml without prior concentration of the sample. The methodology that was developed in this study can be applied for the development of novel bioanalytical systems based on firefly luciferases. [ABSTRACT FROM AUTHOR]

Context: Chronic inflammation is a risk factor for diabetes, but it can also be a complication of diabetes, leading to severe diabetes and causing many other clinical manifestations. Inflammation is a major emerging complication in both type I and type II diabetes, which causes increasing interest in targeting inflammation to improve and control diabetes. Diabetes with insulin resistance and impaired glucose utilization in humans and their underlying mechanism is not fully understood. But a growing understanding of the intricacy of the insulin signaling cascade in diabetic inflammatory cells reveals potential target genes and their proteins responsible for severe insulin resistance. With this baseline concept, the current project explores the binding affinities of the hyaluronic acid anti-diabetic compounds conjugates to such target proteins in diabetic inflammatory cells and their molecular geometries. A range of 48 anti-diabetic compounds was screened against aldose reductase binding pocket 3 protein target through in silico molecular docking, and results revealed that three compounds viz, metformin (CID:4091), phenformin (CID:8249), sitagliptin (CID:4,369,359), possess significant binding affinity out of 48 chosen drugs. Further, these three anti-diabetic compounds were conjugated with hyaluronic acid (HA), and their binding affinity and their molecular geometrics towards aldose reductase enzyme were screened compared with the free form of the drug. The molecular geometries of three shortlisted drugs (metformin, phenformin, sitagliptin) and their HA conjugates were also explored through density functional theory studies, and it proves their good molecular geometry towards pocket 3 of aldose reductase target. Further, MD simulation trajectories affirm that HA conjugates possess good binding affinity and simulation trajectories with protein target aldose reductase than a free form of the drug. Our current study unravels the new mechanism of drug targeting for diabetes through HA conjugation for inflammatory diabetes. HA conjugates act as novel drug candidates for treating inflammatory diabetes; however, it needs further human clinical trials. Methods: For ligand structure, PubChem, ACD chem sketch, and online structure file generator platform are utilized for ligand preparation. Target protein aldose reductase obtained from protein database (PDB). For molecular docking analysis, AutoDock Vina (Version 4) was utilized. pKCSM online server used to predict ADMET properties of the above three shortlisted drugs from the docking study. Using mol-inspiration software (version 2011.06), three shortlisted compounds' bioactivity scores were predicted. DFT analysis for three shortlisted anti-diabetic drugs and their hyaluronic acid conjugates were calculated using a functional B3LYP set of Gaussian 09 software. Molecular dynamics simulation calculations for six chosen protein–ligand complexes were done through YASARA dynamics software and AMBER14 force field. [ABSTRACT FROM AUTHOR]

This study was conducted to evidence the dissemination potential of antibiotic resistance genetic elements in E. coli isolates of Costa Rican domestic wastewater treatment plants (WWTPs). Few studies have addressed this phenomenon in WWTPs in Central America. Phenotypical resistance profiles to β-lactams, quinolones, aminoglycosides, phenicols, tetracyclines, and folate pathway inhibitors of 133 Escherichia coli isolates from the influent and effluent of two urban WWTPs located in the Greater Metropolitan Area of Costa Rica were described. Thirty multidrug-resistant profiles were identified and grouped into 15 genetic clones by ERIC-PCR; 6 of 15 genetic clones were from effluents. Six of the seven examined genes (sulI, sulII, intI1, intI2, blaTEM, and tetA) were found in multidrug-resistant isolates, whereas blaOXA was absent. The horizontal gene conjugation test confirmed the gene transfer capacity of all tested isolates n = 8. Multidrug-resistant isolates in effluents with horizontal gene transfer capacity suggest that Costa Rican WWTPs represent spots related to antibiotic resistance spread to the environment. In domestic WWTPs, we found that nearly 22% of E. coli isolates presented a multidrug-resistant phenotype capable of transferring their resistance determinants by conjugation processes. [ABSTRACT FROM AUTHOR]

Analysis of the results of nonempirical simulations of Met+(H2O)n clusters with Met = Li, Na, and K, and n = 20–55 carried out at the density functional level with B3LYP exchange-correlation functional and extended double-zeta basis sets revealed the prevailing structure motifs of the aqua complexes of alkali metal ions and their fingerprints in the infrared absorption spectra in the range of 2000–4000 cm–1. The hydration structures of the ions are found to be predetermined by the balance between the conjugated H-bonded rings and extended ordered H-bonded sequences. The extension of the latter is shown to decrease with an increase in the effective radius of the ion, which is reflected in the stronger localization of the coupling of OH oscillators within the homodromic structural rings and the respective shift in the characteristic frequencies within the OH stretching domain. [ABSTRACT FROM AUTHOR]

Abstract Plasmid fitness is directed by two orthogonal processes—vertical transfer through cell division and horizontal transfer through conjugation. When considered individually, improvements in either mode of transfer can promote how well a plasmid spreads and persists. Together, however, the metabolic cost of conjugation could create a tradeoff that constrains plasmid evolution. Here, we present evidence for the presence, consequences, and molecular basis of a conjugation‐growth tradeoff across 40 plasmids derived from clinical Escherichia coli pathogens. We discover that most plasmids operate below a conjugation efficiency threshold for major growth effects, indicating strong natural selection for vertical transfer. Below this threshold, E. coli demonstrates a remarkable growth tolerance to over four orders of magnitude change in conjugation efficiency. This tolerance fades as nutrients become scarce and horizontal transfer attracts a greater share of host resources. Our results provide insight into evolutionary constraints directing plasmid fitness and strategies to combat the spread of antibiotic resistance.

In this article, we study the C-normal weighted composition operator W ψ , φ with respect to the weighted composition conjugation on the Fock space F 2 (C n) , n ≥ 2 . We also discuss the instance, where C-normality of W ψ , φ coincides with normality. [ABSTRACT FROM AUTHOR]

It has been proven by Schupp and Bergman that the inner automorphisms of groups can be characterized purely categorically as those group automorphisms that can be coherently extended along any outgoing homomorphism. One is thus motivated to define a notion of (categorical) inner automorphism in an arbitrary category, as an automorphism that can be coherently extended along any outgoing morphism, and the theory of such automorphisms forms part of the theory of covariant isotropy. In this paper, we prove that the categorical inner automorphisms in any category Group J of presheaves of groups can be characterized in terms of conjugation-theoretic inner automorphisms of the component groups, together with a natural automorphism of the identity functor on the index category J . In fact, we deduce such a characterization from a much more general result characterizing the categorical inner automorphisms in any category T mod J of presheaves of T -models for a suitable first-order theory T . [ABSTRACT FROM AUTHOR]

Japanese has a rich verbal conjugation system. For example, the lemma miru may be realized as the non-past indicative form miru, the past indicative form mita, or the imperative form miro. A verb is conjugated depending on a variety of factors such as aspect and mood. That is, a speaker has to choose an appropriate conjugated form in speech production. The aim of this study is to explore whether the production of a verb is influenced by the probability of choosing a conjugated form given the verbal lemma. Our corpus-based research demonstrates that, if a verb has been produced as a non-past indicative form frequently, the verb is produced with shorter duration when produced as the non-past indicative form. This result can be neatly captured by positing that a speaker stores both episodic memories and abstract categories (i.e., lemma and conjugation form), and that the ease in production target creation is a function of the resting activation level of an abstract category. [ABSTRACT FROM AUTHOR]

We study conjugations in L 2 (T) and their relation with kernels of Toeplitz operators on H 2 (T) space. Such kernels are a generalization of model spaces. We investigate properties of an inequality relation between two unimodular functions defined on the unit circle. This allows us to significantly strengthen previous theorems characterizing all M z -commuting and M z -conjugations leaving invariant model spaces to the Toeplitz kernels setting. [ABSTRACT FROM AUTHOR]

This work proposed synthesis of chitosan NPs and silica NPs, conjugation of deltamethrin with chitosan NPs and silica NPs to produce chitosan loaded with deltamethrin and silica loaded with deltamethrin to be used against disease vectors, such as mosquito, and assessment of the acute toxicity in male albino rats. First, dynamic light scattering technique verified the hydrodynamic size of chitosan loaded with deltamethrin and silica loaded with deltamethrin (568.3 ± 15.36 and 284.6 ± 11.23 nm, respectively) and the negative zeta potential value (− 12.5 and − 20.8 mV, respectively). Deltamethrin encapsulation efficiency was found to be 87.031% in chitosan loaded with deltamethrin and 93.739% in silica loaded with deltamethrin. Second, chitosan loaded with deltamethrin and silica loaded with deltamethrin were exposed to mosquito (Culex pipiens larvae) for a 24-h bioassay, and the results were compared with the bulk deltamethrin. The LC50 of chitosan loaded with deltamethrin, silica loaded with deltamethrin, and deltamethrin was found to be 0.5718, 0.0186, and 0.3388 mg/L, respectively. Third, the median lethal dose of deltamethrin, chitosan loaded with deltamethrin, and silica loaded with deltamethrin was calculated using Dixon's up-and-down method (38.55, 304.438, and 87.95 mg/kg, respectively). The acute toxicity was evaluated at 14 d after oral administration of deltamethrin at 25.35, 32.95 and 42.84 mg/kg, chitosan loaded with deltamethrin at 217.20, 282.36 and 367.06 mg/kg and silica loaded with deltamethrin at 57.8, 75.13 and 97.68 mg/kg. It was concluded that silica loaded with deltamethrin and chitosan loaded with deltamethrin can be used as an effectual larvicide at low concentrations and a safe alternative to deltamethrin with minimal environmental impacts. [ABSTRACT FROM AUTHOR]

We present a simple and efficient algorithm for finding the lexicographically minimal representative in a given conjugacy class of the action of the symmetric group on endofunctions. [ABSTRACT FROM AUTHOR]

Piperine (PIP) is a neuroprotective phytomedicine that has profound acetylcholine esterase and reactive oxygen species inhibition effect in Alzheimer's disease (AD) model. However, the oral delivery of PIP is limited by poor aqueous solubility and low bioavailability in systemic circulation. To improve the PIP bioavailability, the polyamidoamine (PAMAM) G4 dendrimer is grafted with tocopheryl polyethylene glycol succinate-1000 (TPGS) through carbodiimide chemistry to form TPGS-PAMAM conjugate. The TPGS-PAMAM coupling was confirmed through proton NMR and FTIR techniques. PIP was encapsulated in the TPGS-PAMAM through solvent diffusion method to form PIP-TPGS-PAMAM. The particle size for PIP-TPGS-PAMAM found the less than 50 nm, whereas entrapment efficiency found to 87 ± 3.5% and 10.6 ± 2.9% drug loading. The powder differential scanning calorimetry and powder X-ray diffraction characterization were employed to evaluate the amorphous encapsulation of the PIP in TPGS-PAMAM. The PIP-TPGS-PAMAM stability was studied in the gastric fluids which showed no drastic difference in particle size and encapsulation efficiency compared to PIP-PAMAM. The in vitro release analysis revealed 37 ± 4.1% PIP release from the PIP-TPGS-PAMAM matrix, and 71 ± 4.9% PIP release from the PIP-PAMAM dendrimer was observed in 48 h. The single-dose oral gavage to Wistar rats of PIP-TPGS-PAMAM showed the AUC0-∞ 14.38 µg/mL.h, Cmax 7.77 ± 1.65 µg/mL, Tmax, 1.6 ± 0.18 h, and half-life 3.47 ± 0.64 h for PIP in systemic circulation. PIP-PAMAM and free PIP showed significantly poor AUC0-∞ compared to PIP-TPGS-PAMAM. The brain uptake studies revealed PIP-TPGS-PAMAM treated group showed 2.2 ± 0.37 µg/g PIP content compared to free PIP administered group which was 0.4 ± 0.10 µg/g. Therefore, PIP-TPGS-PAMAM can offer excellent prospect for the delivery hydrophobic drugs to brain in AD. [ABSTRACT FROM AUTHOR]

We study conjugations on L 2 (T N) and their behaviour with respect to multiplication operators. Full characterizations of conjugations commuting or intertwining with multiplication operators are obtained. We also characterize conjugations leaving invariant subspaces being invariant for multiplication by independent variables. The subspaces not being the multiplication of the Hardy space H 2 (D N) by inner function are also considered. [ABSTRACT FROM AUTHOR]

The conjugation system of the pBS72 plasmid, which is widespread among the extrachromosomal genetic elements of environmental Bacillus strains, is unique and may be assigned to a new family. The new systematic group, designated MpfS, while exhibiting similarity to the conjugation system of the well-studied pLS20 plasmid of B. subtillis strain nato, was characterized by specific features of molecular genetic organization and functional activity. In particular, the key conjugation proteins VirB4, VirB6, VirB11, VirD4, and Adg of the plasmids pLS20 and pBS72, despite certain similarity of their functional domain regions, were significantly different and belonged to separate phylogenetic groups. The genes encoding the conjugation regulation proteins (rco, rap, and phr) in pLS20 had different localization in pBS72, and the level of amino acid sequence similarity did not exceed 40.21% for the Rco protein and 24.41% for the Rap protein, and it was zero for the Phr protein. Unlike the behavior of pLS20, the conjugation transfer frequency of pBS72 and of the mobilized plasmid pBC16 did not depend on the growth phase or on donor cell concentration but depended on the medium composition and genetic properties of recipient bacteria. These results will serve as a basis for investigation of the mechanisms of propagation of pBS72-like plasmids in natural environments and for development of a system of genetic analysis for biotechnologically important members of the genus Bacillus. [ABSTRACT FROM AUTHOR]

Only two plasmid-mediated carbapenemases (KPC-2 and VIM-1) are reported in Klebsiella grimontii. Here, we report two blaKPC-3-positive isolates that were identified as K. oxytoca and E. coli by MALDI-TOF MS in the same rectal swab. Whole-genome sequencing indicated that K. oxytoca was actually K. grimontii of ST391, whereas E. coli was of ST10. In both, blaKPC-3 was carried by a pQil conjugative plasmid. The core-genome analysis identified additional blaKPC-positive K. grimontii strains from public databases, most of which were misidentified as K. oxytoca. Since K. grimontii represents an emerging reservoir of resistance traits, routine tools should improve their ability to detect this species. [ABSTRACT FROM AUTHOR]

The possibility of obtaining polymer–drug conjugates as prolonged-action antibacterial systems by mechanochemical synthesis using the copolymer of maleic anhydride with vinyl acetate or oxidized potato starch as polymer matrices and sulfanilamide as the antimicrobial drug was studied. It is established that drug conjugation with the polymer results from covalent bonding, the degree of sulfanilamide conversion depends on the magnitude of active force and the time of the solid-phase reaction, and the product continues to accumulate after the load is removed. The conjugate with the polysaccharide matrix, from which the drug release due to cleavage of an azomethine bond was slower than its removal from the body if the initial dosage form was used, was most promising. [ABSTRACT FROM AUTHOR]

The molecular approach has been suggested as an effective surface engineering method to improve the optoelectronic performance of the halide perovskite materials. In this manuscript, we employ the data mining method to find appropriate conjugated organic molecules bearing amine terminal groups from the organic crystal database for adsorption onto low-dimensional halide perovskite materials, with the conjugation quantified by the bond length alternation (BLA), which has been widely adopted in crystallography to quantify the molecular conjugation. The proposed candidates with the acceptable conjugation and amine groups are thoroughly investigated via first-principles calculations to understand the detailed interactions between the molecules and the Cs2PbBr4-based perovskite substrate and their impacts on the optoelectronic properties and stability. The present study highlights the quantitative bond length analysis of molecular adsorbates and serves as a theoretical platform of data mining chemical species for perovskite solar cells. [ABSTRACT FROM AUTHOR]

Abstract Plasmid conjugation is a major mechanism responsible for the spread of antibiotic resistance. Plasmid fitness costs are known to impact long‐term growth dynamics of microbial populations by providing plasmid‐carrying cells a relative (dis)advantage compared to plasmid‐free counterparts. Separately, plasmid acquisition introduces an immediate, but transient, metabolic perturbation. However, the impact of these short‐term effects on subsequent growth dynamics has not previously been established. Here, we observed that de novo transconjugants grew significantly slower and/or with overall prolonged lag times, compared to lineages that had been replicating for several generations, indicating the presence of a plasmid acquisition cost. These effects were general to diverse incompatibility groups, well‐characterized and clinically captured plasmids, Gram‐negative recipient strains and species, and experimental conditions. Modeling revealed that both fitness and acquisition costs modulate overall conjugation dynamics, validated with previously published data. These results suggest that the hours immediately following conjugation may play a critical role in both short‐ and long‐term plasmid prevalence. This time frame is particularly relevant to microbiomes with high plasmid/strain diversity considered to be hot spots for conjugation.

Multi-drug resistance (MDR) in bacteria is regarded as an emerging pollutant in different food production avenues including aquaculture. One hundred and sixty out of 2304 bacterial isolates from shrimp farm samples (n = 192) of Andhra Pradesh, India, were MDR. Based on biochemical identification and 16S rRNA sequencing, they were grouped into 35 bacterial species with the predominance of Vibrio parahaemolyticus (12.5%). The MDR isolates showed highest resistance toward oxytetracycline (89%) with more than 0.2 MAR (multiple antibiotic resistance), demonstrates a high-risk source. The most prevalent antibiotic-resistance gene (ARG) and mobile genetic element (MGE) detected were tetA (47.5%) and int1 (46.2%), respectively. In conjugation experiments, overall transfer frequency was found to be in the range of 1.1 × 10−9 to 1.8 × 10−3 with the transconjugants harbouring ARGs and MGEs. This study exposed the wide distribution of MDR bacteria in shrimp and its environment, which can further aggravate the already raised concerns of antibiotic residues in the absence of proper mitigation measures. [ABSTRACT FROM AUTHOR]

This study aimed to determine the β-lactam antibiotics (ampicillin, amoxicillin, penicillin G, oxacillin, and carbenicillin) using conjugated antibody along with gold nanorods (AuNRs). For this purpose, XRD, ATR-FTIR spectroscopy, transmission electron microscopy, and dynamic light scattering were utilized to detect the crystallinity, to identify functional groups involved in the synthesis of AuNRs, and to measure the size of the AuNRs, respectively. In this regard, pH of 9 and a concentration of 9.6 μg of antibody at 1 mL poly(4-styrenesulfonic acid (PSS))-modified AuNRs solution were selected as the best levels of pH and concentration of antibody for the conjugation of antibody with PSS-modified AuNRs. Thereafter, the maximum wavelength rates of the PSS-modified AuNRs, conjugation of antibody with PSS-modified AuNRs, and detection of antibiotics (from 1 nM to 1 mM) with PSS-modified AuNRs–PAb were recorded using a microvolume spectrophotometer system. The results indicate that the LSPR absorption wavelength of PSS-modified AuNRs is red-shifted by increasing the concentration of β-lactam antibiotics. By increasing the concentrations of ampicillin, penicillin G, and carbenicillin, the maximum wavelength changed, and after the saturation of the antibiotic concentration, the curve reached a plateau. Correspondingly, this indicated that the antibody had a similar behavior in the detection of these antibiotics. However, regarding amoxicillin, the saturation concentration is much higher, which indicate that the antibody is more specific for its detection. In contrast, for oxacillin, saturation occurred immediately, demonstrating that the antibody had an extremely low detection capability for this antibiotic. Finally, the findings showed that the antibody was sensitive to 1 nM of five studied β-lactam antibiotics. [ABSTRACT FROM AUTHOR]

All possible transition state structures that could mediate thermally induced skeletal transformations of cyclooctatetraene in an oxygen-free atmosphere have been identified on the basis of the properties of the π-conjugated system in cyclic polyenes. DFT study of the potential energy surface and the nature of localized stationary points using the B3LYP functional and 6-31G* basis set confirmed the existence of 30 transition states. A scheme for the thermal isomerization of cyclooctatetraene, which includes 47 forward and reverse reactions, was constructed by the Gonzalez–Schlegel method for the determination of potential barriers. The obtained results were consistent with the available experimental data. [ABSTRACT FROM AUTHOR]

The purpose of this paper is to present explicitly the solution curve for commutative affine control systems on Lie groups under the assumption that the automorphisms associated with the linear vector fields commutes. If we assume that the derivations associated with the linear vector fields of the system are inner, we obtain a simpler solution and we show some results of controllability. To finish, we work with conjugation by homomorphism of Lie groups between affine systems. [ABSTRACT FROM AUTHOR]

Mougeotia spp. collected from field samples were investigated for their conjugation morphology by light-, fluorescence-, scanning- and transmission electron microscopy. During a scalarifom conjugation, the extragametangial zygospores were initially surrounded by a thin cell wall that developed into a multi-layered zygospore wall. Maturing zygospores turned dark brown and were filled with storage compounds such as lipids and starch. While M. parvula had a smooth surface, M. disjuncta had a punctated surface structure and a prominent suture. The zygospore wall consisted of a polysaccharide rich endospore, followed by a thin layer with a lipid-like appaerance, a massive electron dense mesospore and a very thin exospore composed of polysaccharides. Glycan microarray analysis of zygospores of different developmental stages revealed the occurrence of pectins and hemicelluloses, mostly composed of homogalacturonan (HG), xyloglucans, xylans, arabino-galactan proteins and extensins. In situ localization by the probe OG7-13AF 488 labelled HG in young zygospore walls, vegetative filaments and most prominently in conjugation tubes and cross walls. Raman imaging showed the distribution of proteins, lipids, carbohydrates and aromatic components of the mature zygospore with a spatial resolution of ~ 250 nm. The carbohydrate nature of the endo- and exospore was confirmed and in-between an enrichment of lipids and aromatic components, probably algaenan or a sporopollenin-like material. Taken together, these results indicate that during zygospore formation, reorganizations of the cell walls occurred, leading to a resistant and protective structure. [ABSTRACT FROM AUTHOR]

Anthropogenic contamination of coastal-marine water is responsible for introducing multidrug-resistant bacteria such as the pNDM-harbouring Escherichia coli into the seafood chain. This study was conducted to understand the survivability of a multidrug-resistant, the New Delhi Metallo-β-lactamase-producing E. coli (AS-EC121) in tropical seawater at room temperature (28–32 °C) compared to E. coli K12 strain. The experimental and control strains were inoculated at 6 log CFU/ml level into seawater. After an initial sharp decline in counts, AS-EC121 and K12 strains showed a gradual loss of viability after week-1 of inoculation. AS-EC121 was undetectable after day-56, while K12 colonies disappeared a week later, from day-63. The conjugation experiment revealed that pNDM was transferable to a recipient E. coli strain in seawater. This study suggests that the multidrug-resistant, pNDM-harbouring E. coli is able to survive in seawater for over 2 months stably maintaining the resistance plasmid. The resistance genotypes do not seem to compromise the survivability of MDR E. coli and the stability of plasmid provides ample opportunities for dissemination of plasmids among co-inhabiting bacteria in the coastal–marine environments. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a potentially fatal contagious disease and is a second leading infectious cause of death in the world. Osteoarticular TB is treated using standard regimen of 1st and 2nd line anti-tubercular drugs (ATDs) for extensive period of 8–20 months. These drugs are commonly administered in high doses by oral route or by intravenous route, because of their compromised bioavailability. The common drawbacks associated with conventional therapy are poor patient compliance due to long treatment period, frequent and high dosing, and toxicity. This aspect marks for the need of formulations to eliminate these drawbacks. MTB is an intracellular pathogen of mononuclear phagocyte. This attribute makes nanotherapeutics an ideal approach for MTB treatment as macrophages capture nano forms. Polymeric nanoparticles are removed from the body by opsonization and phagocytosis, which forms an ideal strategy to target macrophage containing mycobacteria. To further improve targetability, the nanoparticles are conjugated with ligand, which serves as an easy substrate for the receptors present on the macrophage surface. The purpose of present work was to develop intra-articular injectable in situ gelling system containing polymeric nanoparticles, which would have promising advantages over conventional method of treatment. The rationale behind formulating nanoparticle incorporated in situ gel-based system was to ensure localization of the formulation in intra-articular cavity along with sustained release and conjugation of nanoparticles with mannose as ligand to improve uptake by macrophages. Rifampicin standard ATD was formulated into chitosan nanoparticles. Chitosan with 85% degree of deacetylation (DDA) and sodium tripolyphosphate (TPP) as the crosslinking agent was used for preparing nanoparticles. The percent entrapment was found to be about 71%. The prepared nanoparticles were conjugated with mannose. Conjugation of ligand was ascertained by performing Fourier transformed infrared spectroscopy. The particle size was found to be in the range of 130–140 nm and zeta potential of 38.5 mV. Additionally, we performed scanning electron microscopy to characterize the surface morphology of ligand-conjugated nanoparticles. The conjugated chitosan nanoparticles were incorporated into in situ gelling system comprising Poloxamer 407 and HPMC K4M. The gelling system was evaluated for viscosity, gelling characteristics, and syringeability. The drug release from conjugated nanoparticles incorporated in in situ gel was found to be about 70.3% at the end of 40 h in simulated synovial fluid following zero-order release kinetics. Based on the initial encouraging results obtained, the nanoparticles are being envisaged for ex vivo cellular uptake study using TB-infected macrophages [ABSTRACT FROM AUTHOR]

Chum salmon myofibrillar protein (Mf) digested by pepsin-trypsin (dMf) was conjugated to alginate oligosaccharide (AO) through the Maillard reaction between the lysine residues in the dMf and the reducing end-groups of AO. The dMf-AO conjugate strongly suppressed the production of inflammatory cytokines, particularly tumor necrosis factor-α and interleukin-6, in lipopolysaccharide-stimulated murine macrophages. The anti-inflammatory effect was enhanced with increasing amounts of AO bound to dMf through the Maillard reaction, and the subsequent process of the Maillard reaction was involved in the enhancement of the anti-inflammatory activity. AO-conjugated peptides, the major anti-inflammatory components contained in the dMf-AO conjugate, were successfully recovered using isoelectric focusing without the use of carrier ampholytes (autofocusing); they were effectively concentrated in acidic peptide fractions, with the negative charge of the carboxyl groups of AO contributing to this separation. In conclusion, the combined use of AO conjugation and autofocusing is a useful method for producing novel anti-inflammatory peptides from fish Mf. [ABSTRACT FROM AUTHOR]

Rare actinomycetes are likely treasure troves for bioactive natural products, and it is therefore important that we enrich our understanding of biosynthetic potential of these relatively understudied bacteria. Dactylosporangium are a genus of such rare Actinobacteria that are known to produce a number of important antibacterial compounds, but for which there are still no fully assembled reference genomes, and where the extent of encoded biosynthetic capacity is not defined. Dactylosporangium vinaceum (NRRL B-16297) is known to readily produce a deep wine red-coloured diffusible pigment of unknown origin, and it was decided to define the chemical identity of this natural product pigment, and in parallel use whole genome sequencing and transcriptional analysis to lay a foundation for understanding the biosynthetic capacity of these bacteria. Results show that the produced pigment is made of various rubrolone conjugates, the spontaneous product of the reactive pre-rubrolone, produced by the bacterium. Genome and transcriptome analysis identified the highly expressed biosynthetic gene cluster (BGC) for pre-rubrolone. Further analysis of the fully assembled genome found it to carry 24 additional BGCs, of which the majority were poorly transcribed, confirming the encoded capacity of this bacterium to produce natural products but also illustrating the main bottleneck to exploiting this capacity. Finally, analysis of the potential environmental role of pre-rubrolone found it to react with a number of amine containing antibiotics, antimicrobial peptides and siderophores pointing to its potential role as a "minesweeper" of xenobiotic molecules in the bacterial environment. Key points: • D. vinaceum encodes many BGC, but the majority are transcriptionally silent. • Chemical screening identifies molecules that modulate rubrolone production. • Pre-rubrolone is efficient at binding and inactivating many natural antibiotics. [ABSTRACT FROM AUTHOR]

Purpose: Glioblastoma (GBM) is a malignant brain tumor with a poor long-term prognosis due to recurrence from highly resistant GBM cancer stem cells (CSCs), for which the current standard of treatment with temozolomide (TMZ) alone will unlikely produce a viable cure. In addition, CSCs regenerate rapidly and overexpress methyl transferase which overrides the DNA-alkylating mechanism of TMZ, leading to resistance. The objective of this research was to apply the concepts of nanotechnology to develop a multi-drug therapy, TMZ and idasanutlin (RG7388, a potent mouse double minute 2 (MDM2) antagonist), loaded in functionalized nanoparticles (NPs) that target the GBM CSC subpopulation, reduce the cell viability and provide possibility of in vivo preclinical imaging. Methods: Polymer-micellar NPs composed of poly(styrene-b-ethylene oxide) (PS-b-PEO) and poly(lactic-co-glycolic) acid (PLGA) were developed by a double emulsion technique loading TMZ and/or RG7388. The NPs were covalently bound to a 15-nucleotide base-pair CD133 aptamer to target the CD133 antigen expressed on the surfaces of GBM CSCs. For diagnostic functionality, the NPs were labelled with radiotracer Zirconium-89 (89Zr). Results: NPs maintained size range less than 100 nm, a low negative charge and exhibited the ability to target and kill the CSC subpopulation when TMZ and RG7388 were used in combination. The targeting function of CD133 aptamer promoted killing in GBM CSCs providing impetus for further development of targeted nanosystems for localized therapy in future in vivo models. Conclusions: This work has provided a potential clinical application for targeting GBM CSCs with simultaneous diagnostic imaging. [ABSTRACT FROM AUTHOR]

The renin–angiotensin system (RAS) has a central role in renal and cardiovascular homeostasis. Angiotensin-(1–7) (Ang1–7), one of the RAS active peptides, exerts beneficial effects through different mechanisms. These biological actions suggest that Ang1–7 is an effective therapeutic agent for treating various diseases associated with activated RAS. However, its short half-life and poor pharmacokinetics restrict its therapeutic utility. Our laboratory has successfully synthesized and characterized an Ang1–7 conjugate (Ang Conj.) with a prolonged half-life and improved pharmacokinetics profile. The Ang Conj. has been prepared by PEGylation of Ang1–7 and conjugation with a bisphosphonate using solid-phase peptide synthesis and characterized by HPLC and mass spectrometer. The compound's stability has been tested in different storage conditions. The bone binding capacity was evaluated using a hydroxyapatite assay. Pharmacokinetic and tissue distribution studies were performed using iodinated peptides in rats. Ang Conj. was synthesized with > 90% purity. Bone mineral affinity testing showed Ang Conj. exhibited significantly higher bone mineral affinity than Ang1–7. The Ang Conj. remained stable for more than a month using all tested storage conditions. The Ang Conj. demonstrated higher affinity to bone, a longer half-life, and better bioavailability when compared with the native peptide. These results support that conjugation of Ang1–7 with bisphosphonate enables it to utilize bone as a reservoir for the sustained delivery of Ang1–7 to maintain therapeutic plasma levels. High chemical stability and about five to tenfold prolongation of Ang Conj. plasma half-life after administrations into rats proves the effectiveness of our approach. [ABSTRACT FROM AUTHOR]

This study presents a light microscopy observation of the life cycle of the hypotrich ciliate, Paraurostyla weissei. The main aim of this study was to find out the primary reaction of the species P. weissei through the changing environmental conditions. First, the reaction to favorable conditions – asexual binary cell division was observed. The asexual division was a response to the persisting original conditions, which resulted in an overgrowth of cultures. Subsequently, the changes in culture conditions in two groups of watch glasses were tested. The first group of watch glasses was characterised by gradual dehydration, loss of living space and lack of food. Here, the unexpected total conjugation process was identified, and this rare process was characterised as a priority response of the Paraurostyla species to the unfavorable conditions. This is the first reference not to the course of the conjugation process, but to the fact that not only the formation of resting cysts, but also total conjugation can be an important adaptation strategy of the ciliates. Secondly, a gradual decrease in temperature associated with slower drying was tested. The observation result was almost an unchanged state in cultures. Just before the samples completely dried, the cells reacted by cell death. The finding of the inability to stimulate the encystation process of a relatively common hypotrich species was unexpected. Finally, the total conjugation process in the first group of tested cultures was a priority response to altered conditions. The aim was also to point out the plasticity of adaptation mechanisms within the life cycle of P. weissei. [ABSTRACT FROM AUTHOR]

Due to the broad-spectrum of antibiotic resistance, herein we investigated the possibility of using imipenem-conjugated silver nanoparticles (IMP-AgNPs) against multidrug-resistant isolates of Pseudomonas aeruginosa. For this purpose, 200 clinical isolates were tested against different antibiotics to determine the antimicrobial susceptibility. To identify blaVIM and blaIMP resistance genes, PCR was used. The synthesized AgNPs and conjugants were characterized using UV-vis spectroscopy, XRD, SEM, TEM, DLS, and FTIR. The stability, drug release kinetics, cytotoxicity, hemolytic and apoptotic effects of NPs were also investigated. MIC of the imipenem, AgNPs, and conjugants were evaluated versus P. aeruginosa isolates. Finally, the effects of the IMP-AgNPs to heal burn wounds in rats was evaluated. According to the results, about 68% of isolates showed resistance to imipenem (MIC ≥ 64 μg/ml to ≥ 512 μg/ml). Analytical results verified the synthesis of AgNPs and IMP-AgNPs. A Dose-dependent decrease happened in terms of the MIC values of IMP-AgNPs were also affected by the existence of resistant genes. Low cytotoxic was observed regarding AgNPs which lead to apoptosis. The histopathological results showed a considerable epithelization in treated groups with IMP-AgNPs. Accordingly, IMP-AgNPs can be considered as a powerful antibacterial agent to treat the infections caused by multidrug-resistant P. aeruginosa. [ABSTRACT FROM AUTHOR]

This study aims to detect β-lactam antibiotics using a conjugated antibody with gold nanoparticles (GNPs). For this purpose, the gold nanoparticles synthesized from Chinese lettuce leaf extract (as reductant) were used for the colorimetric detection of β-lactam antibiotics (such as ampicillin, amoxicillin, penicillin G, oxacillin, and carbenicillin). XRD, FTIR spectroscopy, TEM, and dynamic light scattering were utilized to detect the crystallinity, to identify functional groups involved in the synthesis of GNPs, and to measure the size of the GNPs; pH 8 and a concentration of 8.4 μg of antibody at 1 mL GNPs solution were selected as the best pH and concentration of antibody for the conjugation of antibody with GNPs. The maximum wavelengths of the colloidal GNPs, conjugation of antibody with GNPs, and detection of antibiotics (from 1 nM to 1 mM) with GNPs–PAb were recorded using a micro-volume spectrophotometer system. The results indicated that the localized surface plasmon resonance spectrometer absorption wavelength of GNPs red-shifted with increasing concentration of β-lactam antibiotics. With increasing concentration of ampicillin, penicillin G, and carbenicillin, the wavelength of maximum changed, and after saturation of antibiotics concentration, the curve reaches a plateau. This indicated that the antibody showed similar behavior in the detection of these antibiotics. But regarding amoxicillin, the saturation concentration is much higher, indicating that the antibody was more specific for its detection. In contrast, for oxacillin, saturation occurred very soon, which demonstrated that the antibody had an extremely low detection capability for this antibiotic. Finally, the results showed that the antibody was sensitive to 1 nM of the five β-lactam antibiotics studied. [ABSTRACT FROM AUTHOR]

In this paper, we mainly investigate the conjugation of the sylowizer that was introduced by Gaschütz (Math Z 122(4):319–320, 1971) and study the p-supersolvability of finite groups by analyzing the intersection between O p (G) and sylowizers of p-subgroups. As a continuation of research (Lei and Li in Arch Math (Basel) 114:367–376, 2020), we also give some characterizations on p-nilpotent groups by using the permutability of a sylowizer of a p-subgroup. [ABSTRACT FROM AUTHOR]

Based on the properties of a conjugate p-electron system, a method is proposed for predicting possible spatial structures of aromatic hydrocarbons during their skeletal carbon transformation. The existence of predicted spatial structures is explained by the stabilizing effect of π-electron conjugation. The proposed method for predicting possible spatial structures was verified by DFT B3LYP/6-31G* and RHF/6-31G calculations including electron correlation at the MR4-SDTQ level on the example of benzene and hexafluorobenzene molecules. The proposed method gives stable results regardless of the methods used for calculating the electronic structure of molecules. It is found that of all the predicted spatial structures, one corresponds to the ground state, and the others correspond to transition states. The schemes of thermal isomerization of benzene and hexafluorobenzene, constructed with the potential barriers calculated by the Gonzales–Schlegel method, are consistent with the experimental data. [ABSTRACT FROM AUTHOR]

Main conclusion: Excited state lifetime-based separation of fluorophore-tagged antibiotic conjugate emission from the spectrally broad plant autofluorescence enables in planta tracking of the translocation of systemic cargo such as antibiotics via fluorescence lifetime imaging. The efficacy of antibiotic treatments in citrus crops is uncertain due to mixed results from in-field experiments and a lack of study on their systemic movement. As of yet there has been an inability to track treatments using traditional fluorescence microscopy due to treatments having little fluorescence characteristics, and signal convolution due to plant autofluorescence. In this study, we used streptomycin sulfate, a commercially available antibiotic, and conjugated it to a modified tris(bipyridine) ruthenium (II) chloride, a dye with an excited state lifetime magnitudes higher than other commonly used organic fluorescent probes. The resultant is a fluorescence lifetime imaging (FLIM) trackable antibiotic conjugate, covalently attached via an amide linkage that is uniquely distinguishable from plant autofluorescence. Characterization of the fluorescent antibiotic conjugate showed no mitigation of excited state lifetime, and a distinct IR peak not found in any synthetic components. Subsequent tracking using FLIM in citrus tissue was achieved, with identification of movement through citrus plant vasculature via tissue localization in xylem and phloem. Results indicated upwards systemic movement of the conjugate in both xylem and phloem after 48 h of incubation. However, the conjugate failed to move down towards the root system of the plant by 168 h. Mechanistically, it is likely that xylem contributes heavily in the translocation of the conjugate upwards; however, phloem led flow due to growth changes could act as a contributor. This proof-of-concept sets groundwork for subsequent studies regarding antibiotic localization and movement in citrus. [ABSTRACT FROM AUTHOR]

This review summarizes the experience in laboratory- and industrial-scale syntheses of glycoconjugate vaccines used for prevention of infectious diseases caused by Haemophilus influenzae type b bacteria based on the linear capsular polysaccharide poly-3-β-D-ribosyl-(1→1)-D-ribitol-5-phosphate (PRP) or related synthetic oligosaccharide ligands. The methods for preparation of related oligosaccharide derivatives and results of the studies evaluating effect of their length on immunogenic properties of the conjugates with protein carriers are overviewed. [ABSTRACT FROM AUTHOR]

Conjugation of cell-penetrating peptides to anticancer peptides is an effective strategy to enhance tumor treatment. The hybrid peptide, kla-TAT, by attaching the TAT peptide to the C-terminus of the pro-apoptotic peptide kla exhibited strong anticancer activity when co-administration with other peptide, but the systematic mechanism was not clear. In this study, the mechanisms of action of kla-TAT including the uptake pathway, distribution in cytoplasm, apoptosis-inducing ability and micro-morphology were investigated. The results indicated that the hybrid peptide internalized into A549 cells through two transmembrane mechanisms: endocytosis mediated by the clathrin-mediated endocytosis route and the rapid membrane disruption mechanism. Peptides that were endocytosed could interact with the mitochondrial membrane, while peptides internalized by disrupting the cell membrane caused disruption of the mitochondrial membrane. Thus, the hybrid kla-TAT peptide transfers through the cell membrane, inducing apoptosis by destroying the mitochondrial membrane and causethe expression of cyclin-D1 down-regulation. Meanwhile, the changes of the micro-morphology of the cancer cells was detected using atomic force microscope (AFM) and scanning electron microscope (SEM), which provided the visualized evidence for the mechanism of the peptides. [ABSTRACT FROM AUTHOR]