AcOH-Catalyzed Rearrangements of Benzo[e][1,4]diazepin-2(and 3)-ones: Easy Access to 1,4-Dihydroquinazolines and Their Condensed Analogues.

Presented herein is a novel synthesis of new 2-(quinolin-4-yl)-1,4-dihydroquinazoline systems 8, in which the acid-catalyzed rearrangement of spiro[benzo[e][1,4]diazepine-3,4'-quinolin]-2(1H)-ones generated in situ from 3-(2-aminophenyl)-5H-benzo[e][1,4]diazepin-2(1H)-ones 6 with acetone and alkylmethyl ketones has been realized as an important step. An attempt to synthesize isomeric 2-(2-aminophenyl)-5H-benzo[e][1,4]diazepin-3(4H)-one 6'a by hydrolysis of the corresponding N-{2-[5H-benzo[e][1,4]diazepin-3(4H)-on-2-yl]phenyl}acetamide 5'a led to a new heterocyclic system, 6-methyl-8,13-dihydro-13aH-quinazolino[4,3-b]quinazolin-5-ium 13a-carboxylate 14, as a result of an unexpected rearrangement. In addition, it is noteworthy that during the hydrolysis of N-{2-[5H-benzo[e][1,4]diazepin-2(1H)-on-3-yl]phenyl}acetamides 5, the not previously described 14-dihydro-5H-14,5a-(epimino[1,2]benzo)benzo[5,6][1,4]diazepin[2,1-b]quinazolin-6(7H)-ones 7 were unexpectedly obtained.

The venom of Habrobracon hebetor induces alterations in host metabolism.

The ability of parasitic wasps to manipulate a host's metabolism is under active investigation. Components of venom play a major role in this process. In the present work, we studied the effect of the venom of the ectoparasitic wasp Habrobracon hebetor on the metabolism of the greater wax moth host (Galleria mellonella). We identified and quantified 45 metabolites in the lymph (cell-free hemolymph) of wax moth larvae on the second day after H. hebetor venom injection, using NMR spectroscopy and liquid chromatography coupled with mass spectrometry. These metabolites included 22 amino acids, nine products of lipid metabolism (sugars, amines and alcohols) and four metabolic intermediates related to nitrogenous bases, nucleotides and nucleosides. An analysis of the larvae metabolome suggested that the venom causes suppression of the tricarboxylic acid cycle, an increase in the number of free amino acids in the lymph, an increase in the concentration of trehalose in the lymph simultaneously with a decrease in the amount of glucose, and destructive processes in the fat body tissue. Thus, this parasitoid venom not only immobilizes the prey but also modulates its metabolism, thereby providing optimal conditions for the development of larvae.

Population Structure and Antimicrobial Resistance in Campylobacter jejuni and C. coli Isolated from Humans with Diarrhea and from Poultry, East Africa.

Campylobacteriosis and antimicrobial resistance (AMR) are global public health concerns. Africa is estimated to have the world's highest incidence of campylobacteriosis and a relatively high prevalence of AMR in Campylobacter spp. from humans and animals. Few studies have compared Campylobacter spp. isolated from humans and poultry in Africa using whole-genome sequencing and antimicrobial susceptibility testing. We explored the population structure and AMR of 178 Campylobacter isolates from East Africa, 81 from patients with diarrhea in Kenya and 97 from 56 poultry samples in Tanzania, collected during 2006-2017. Sequence type diversity was high in both poultry and human isolates, with some sequence types in common. The estimated prevalence of multidrug resistance, defined as resistance to >3 antimicrobial classes, was higher in poultry isolates (40.9%, 95% credible interval 23.6%-59.4%) than in human isolates (2.5%, 95% credible interval 0.3%-6.8%), underlining the importance of antimicrobial stewardship in livestock systems.

Correction: Golovko et al. Ambient Dose and Dose Rate Measurement in SNOLAB Underground Laboratory at Sudbury, Ontario, Canada. Sensors 2023, 23, 1945.

We have found a discrepancy in the reported exposure time for passive sensors, specifically TLDs, in the original manuscript entitled "Ambient Dose and Dose Rate Measurement in SNOLAB Underground Laboratory at Sudbury, Ontario, Canada" [...].

Relativistic Exact Two-Component Coupled-Cluster Study of Molecular Sensitivity Factors for Nuclear Schiff Moments.

Relativistic exact two-component coupled-cluster calculations of molecular sensitivity factors for nuclear Schiff moments (NSMs) are reported. We focus on molecules containing heavy nuclei, especially octupole-deformed nuclei. Analytic relativistic coupled-cluster gradient techniques are used and serve as useful tools for identifying candidate molecules that sensitively probe for physics beyond the Standard Model in the hadronic sector. Notably, these tools enable straightforward "black-box" calculations. Two competing chemical mechanisms that contribute to the NSM are analyzed, illuminating the physics of ligand effects on NSM sensitivity factors.

Kazakhstan Has an Unexpected Diversity of Medicinal Plants of the Genus Acorus (Acoraceae) and Could Be a Cradle of the Triploid Species A. calamus.

The Acorus calamus group, or sweet flag, includes important medicinal plants and is classified into three species: A. americanus (diploid), A. verus (tetraploid), and A. calamus (sterile triploid of hybrid origin). Members of the group are famous as components of traditional Indian medicine, and early researchers suggested the origin of the sweet flag in tropical Asia. Subsequent research led to an idea of the origin of the triploid A. calamus in the Amur River basin in temperate Asia, because this was the only region where both diploids and tetraploids were known to co-occur and be capable of sexual reproduction. Contrary to this hypothesis, triploids are currently very rare in the Amur basin. Here, we provide the first evidence that all three species occur in Kazakhstan. The new records extend earlier data on the range of A. verus for c. 1800 km. Along the valley of the Irtysh River in Kazakhstan and the adjacent Omsk Oblast of Russia, A. verus is recorded in the south, A. americanus in the north, and A. calamus is common in between. We propose the Irtysh River valley as another candidate for a cradle of the triploid species A. calamus. It is possible that the range of at least one parent species (A. americanus) has contracted through competition with its triploid derivative species, for which the Irtysh River floods provide a tool for downstream range expansion. We refine our earlier data and show that the two parent species have non-overlapping ranges of variation in a quantitative metric of leaf aerenchyma structure.

Non-viral-mediated gene transfer of OX40 ligand for tumor immunotherapy.

Background: Immune checkpoint blockade (ICB) is rapidly becoming a standard of care in the treatment of many cancer types. However, the subset of patients who respond to this type of therapy is limited. Another way to promote antitumoral immunity is the use of immunostimulatory molecules, such as cytokines or T cell co-stimulators. The systemic administration of immunotherapeutics leads to significant immune-related adverse events (irAEs), therefore, the localized antitumoral action is needed. One way to achieve this is intratumoral non-viral gene-immune therapy, which allows for prolonged and localized gene expression, and multiple drug administration. In this study, we combined the previously described non-viral gene delivery system, PEG-PEI-TAT copolymer, PPT, with murine OX40L-encoding plasmid DNA. Methods: The resulting OX40L/PPT nanoparticles were characterized via gel mobility assay, dynamic light scattering analysis and in vitro transfection efficiency evaluation. The antitumoral efficacy of intratumorally (i.t.) administered nanoparticles was estimated using subcutaneously (s.c.) implanted CT26 (colon cancer), B16F0 (melanoma) and 4T1 (breast cancer) tumor models. The dynamics of stromal immune cell populations was analyzed using flow cytometry. Weight loss and cachexia were used as irAE indicators. The effect of combination of i.t. OX40L/PPT with intraperitoneal PD-1 ICB was estimated in s.c. CT26 tumor model. Results: The obtained OX40L/PPT nanoparticles had properties applicable for cell transfection and provided OX40L protein expression in vitro in all three investigated cancer models. We observed that OX40L/PPT treatment successfully inhibited tumor growth in B16F0 and CT26 tumor models and showed a tendency to inhibit 4T1 tumor growth. In B16F0 tumor model, OX40L/PPT treatment led to the increase in antitumoral effector NK and T killer cells and to the decrease in pro-tumoral myeloid cells populations within tumor stroma. No irAE signs were observed in all 3 tumor models, which indicates good treatment tolerability in mice. Combining OX40L/PPT with PD-1 ICB significantly improved treatment efficacy in the CT26 subcutaneous colon cancer model, providing protective immunity against CT26 colon cancer cells. Conclusion: Overall, the anti-tumor efficacy observed with OX40L non-viral gene therapy, whether administered alone or in combination with ICB, highlights its potential to revolutionize cancer gene therapy, thus paving the way for unprecedented advancements in the cancer therapy field.

A Comparative Study of Electrochemical Reduction of Levulinic Acid on Various Electrodes in Organic Solvents.

Studies on the electrochemical hydrogenation (ECH) of levulinic acid (LA) to valeric acid (VA) or γ-valerolactone (GVL) have mainly focused on the electrochemical reduction of LA in acidic aqueous solutions. However, the narrow range of applied potentials has hindered understanding of some mechanistic aspects of LA electrochemical conversion. Earlier, we discovered that employing proton-deficient non-aqueous reaction media provides more comprehensive insights into the mechanism of LA electrochemical reduction. Here, we conducted further investigations into the LA electroreduction process using cyclic voltammetry in various organic solvents on a Pt electrode and on various electrode materials in acetonitrile, both with and without the addition of proton donors. The products of the ECH processes were identified using HPLC. The solvent nature, the presence of proton donors, the electrode material, and the applied potential strongly influence the LA electroreduction process. This study reveals that LA, in the presence proton donors, can undergo electrochemical reduction through different pathways, depending on the difference (ΔE1/2) between the reduction half-wave potential of protons and LA on a certain electrode. When the difference is large, the LA reduction is incomplete and the formation of GVL is observed. Under the close reduction potentials of protons and LA, LA can be completely reduced to VA.

Cyanoacetohydrazide as a Novel Derivatization Agent for the Determination of UHPLC-HRMS Steroids in Urine.

The possibility of cyanoacetohydrazide usage as a novel derivatizing agent is demonstrated in the presented article, and a comparison with hydroxylamine as the most commonly used reagent is provided. Optimal conditions for steroid derivatization with cyanoacetohydrazide are provided. According to the collected data, the maximum yield of derivatives was observed at pH 2.8 within 70 min at 40 °C with 5 ng/mL limit of detection for all investigated analytes. It was shown that cyanoacetohydrazide derivatives produces both syn- and anti-forms as well as hydroxylamine, and their ratios were evaluated and shown in presented work. An efficiency enchantment from two to up to five times was achieved with a novel derivatization reagent. Its applicability for qualitative analysis of steroids in urine was presented at real samples. Additionally, the reproducible fragmentation of the derivatizing agent in collision-induced dissociation offers opportunities for simplified non-targeted steroidomic screening. Furthermore, cyanoacetohydrazide increases ionization efficiency in positive mode, which can eliminate the need for redundant high-resolution instrument runs required for both positive and negative mode analyses.

Segregated Conductive Polymer Composite with Fe3O4-Decorated Graphite Nanoparticles for Microwave Shielding.

Graphite nanoplatelets (GNPs)-the segregated ultra-high molecular weight polyethylene (UHMWPE)-based composites with hybrid filler-decorated with Fe3O4 were developed. Using X-ray diffraction and scanning electron microscopy, it was shown that the decorated component has the shape of separate granules, or their clusters were distributed evenly over the GNPs surface. The individual Fe3O4 nanoparticles are predominantly rounded, with diameters of approximately 20-60 nm. The use of GNPs/Fe3O4 as a filler leads to significant decreases in the percolation limit φc, 0.97 vol% vs. 0.56 vol% for GNPs/UHMWPE- and (GNPs/Fe3O4)/UHMWPE segregated composite material (SCM), respectively. Modification of the GNP surface with Fe3O4 leads to an essential improvement in the electromagnetic interference shielding due to enhanced microwave absorption in the 26-37 GHz frequency range in its turn by abundant surface functional groups and lattice defects of GNPs/Fe3O4 nanoparticles.

Superelectrophilic Activation of Phosphacoumarins towards Weak Nucleophiles via Brønsted Acid Assisted Brønsted Acid Catalysis.

The electrophilic activation of various substrates via double or even triple protonation in superacidic media enables reactions with extremely weak nucleophiles. Despite the significant progress in this area, the utility of organophosphorus compounds as superelectrophiles still remains limited. Additionally, the most common superacids require a special care due to their high toxicity, exceptional corrosiveness and moisture sensitivity. Herein, we report the first successful application of the "Brønsted acid assisted Brønsted acid" concept for the superelectrophilic activation of 2-hydroxybenzo[e][1,2]oxaphosphinine 2-oxides (phosphacoumarins). The pivotal role is attributed to the tendency of the phosphoryl moiety to form hydrogen-bonded complexes, which enables the formation of dicationic species and increases the electrophilicity of the phosphacoumarin. This unmasks the reactivity of phosphacoumarins towards non-activated aromatics, while requiring only relatively non-benign trifluoroacetic acid as the reaction medium.

Interleukin-10 deficiency induces thoracic perivascular adipose tissue whitening and vascular remodeling.

Perivascular adipose tissue (PVAT) is an adipose layer, surrounding blood vessels, with a local modulatory role. Interleukin-10 (IL-10) has been shown to modulate vascular tissue. This study aimed to characterize the endogenous role of IL-10 in vascular remodeling, and PVAT phenotyping. Thoracic aortic segments from control (C57BL/6J) and IL-10 knockout (IL-10-/-) male mice were used. Analyzes of aorta/PVAT morphometry, and elastin, collagen and reticulin deposition were performed. Tissue uncoupling protein 1 (UCP1) was accessed by Western blotting. Endogenous absence of IL-10 reduced total PVAT area (p = 0.0310), and wall/lumen ratio (p = 0.0024), whereas increased vascular area and thickness (p < 0.0001). Total collagen deposition was augmented in IL-10-/-, but under polarized light, the reduction of collagen-I (p = 0.0075) and the increase of collagen-III (p = 0.0055) was found, simultaneously with reduced elastic fibers deposition (p = 0.0282) and increased deposition of reticular fibers (p < 0.0001). Adipocyte area was augmented in the IL-10 absence (p = 0.0225), and UCP1 expression was reduced (p = 0.0420). Moreover, relative frequency of white adipose cells and connective tissue was augmented in IL-10-/- (p < 0.0001), added to a reduction in brown adipose cells (p < 0.0001). Altogether, these data characterize aorta PVAT from IL-10-/- as a white-like adipocyte phenotype. Endogenous IL-10 prevents vascular remodeling and favors a brown-like adipocyte phenotype, suggesting a modulatory role for IL-10 in PVAT plasticity.

Understanding Cu(i) local environments in MOFs via63/65Cu NMR spectroscopy.

The field of metal-organic frameworks (MOFs) includes a vast number of hybrid organic and inorganic porous materials with wide-ranging applications. In particular, the Cu(i) ion exhibits rich coordination chemistry in MOFs and can exist in two-, three-, and four-coordinate environments, which gives rise to many structural motifs and potential applications. Direct characterization of the structurally and chemically important Cu(i) local environments is essential for understanding the sources of specific MOF properties. For the first time, 63/65Cu solid-state NMR has been used to investigate a variety of Cu(i) sites and local coordination geometries in Cu MOFs. This approach is a sensitive probe of the local Cu environment, particularly when combined with density functional theory calculations. A wide range of structurally-dependent 63/65Cu NMR parameters have been observed, including 65Cu quadrupolar coupling constants ranging from 18.8 to 74.8 MHz. Using the data from this and prior studies, a correlation between Cu quadrupolar coupling constants, Cu coordination number, and local Cu coordination geometry has been established. Links between DFT-calculated and experimental Cu NMR parameters are also presented. Several case studies illustrate the feasibility of 63/65Cu NMR for investigating and resolving inequivalent Cu sites, monitoring MOF phase changes, interrogating the Cu oxidation number, and characterizing the product of a MOF chemical reaction involving Cu(ii) reduction to Cu(i). A convenient avenue to acquire accurate 65Cu NMR spectra and NMR parameters from Cu(i) MOFs at a widely accessible magnetic field of 9.4 T is described, with a demonstrated practical application for tracking Cu(i) coordination evolution during MOF anion exchange. This work showcases the power of 63/65Cu solid-state NMR spectroscopy and DFT calculations for molecular-level characterization of Cu(i) centers in MOFs, along with the potential of this protocol for investigating a wide variety of MOF structural changes and processes important for practical applications. This approach has broad applications for examining Cu(i) centers in other weight-dilute systems.

Ultrasound Diagnosis and Near-Infrared Spectroscopy in the Study of Encephalopathy in Neonates Born under Asphyxia: Narrative Review.

Brain injury resulting from adverse events during pregnancy and delivery is the leading cause of neonatal morbidity and disability. Surviving neonates often suffer long-term motor, sensory, and cognitive impairments. Birth asphyxia is among the most common causes of neonatal encephalopathy. The integration of ultrasound, including Doppler ultrasound, and near-infrared spectroscopy (NIRS) offers a promising approach to understanding the pathology and diagnosis of encephalopathy in this special patient population. Ultrasound diagnosis can be very helpful for the assessment of structural abnormalities associated with neonatal encephalopathy such as alterations in brain structures (intraventricular hemorrhage, infarcts, hydrocephalus, white matter injury) and evaluation of morphologic changes. Doppler sonography is the most valuable method as it provides information about blood flow patterns and outcome prediction. NIRS provides valuable insight into the functional aspects of brain activity by measuring tissue oxygenation and blood flow. The combination of ultrasonography and NIRS may produce complementary information on structural and functional aspects of the brain. This review summarizes the current state of research, discusses advantages and limitations, and explores future directions to improve applicability and efficacy.

Rationalizing Graphene-ZnO Composites for Gas Sensing via Functionalization with Amines.

The rational design of composites based on graphene/metal oxides is one of the pillars for advancing their application in various practical fields, particularly gas sensing. In this study, a uniform distribution of ZnO nanoparticles (NPs) through the graphene layer was achieved, taking advantage of amine functionalization. The beneficial effect of amine groups on the arrangement of ZnO NPs and the efficiency of their immobilization was revealed by core-level spectroscopy, pointing out strong ionic bonding between the aminated graphene (AmG) and ZnO. The stability of the resulting Am-ZnO nanocomposite was confirmed by demonstrating that its morphology remains unchanged even after prolonged heating up to 350 °C, as observed by electron microscopy. On-chip multisensor arrays composed of both AmG and Am-ZnO were fabricated and thoroughly tested, showing almost tenfold enhancement of the chemiresistive response upon decorating the AmG layer with ZnO nanoparticles, due to the formation of p-n heterojunctions. Operating at room temperature, the fabricated multisensor chips exhibited high robustness and a detection limit of 3.6 ppm and 5.1 ppm for ammonia and ethanol, respectively. Precise identification of the studied analytes was achieved by employing the pattern recognition technique based on linear discriminant analysis to process the acquired multisensor response.

Modulation of polyaniline memristive device switching voltage by nucleotide-free analogue of vitamin B12.

Memristive devices offer essential properties to become a part of the next-generation computing systems based on neuromorphic principles. Organic memristive devices exhibit a unique set of properties which makes them an indispensable choice for specific applications, such as interfacing with biological systems. While the switching rate of organic devices can be easily adjusted over a wide range through various methods, controlling the switching potential is often more challenging, as this parameter is intricately tied to the materials used. Given the limited options in the selection conductive polymers and the complexity of polymer chemical engineering, the most straightforward and accessible approach to modulate switching potentials is by introducing specific molecules into the electrolyte solution. In our study, we show polyaniline (PANI)-based device switching potential control by adding nucleotide-free analogue of vitamin B12, aquacyanocobinamide, to the electrolyte solution. The employed concentrations of this molecule, ranging from 0.2 to 2 mM, enabled organic memristive devices to achieve switching potential decrease for up to 100 mV, thus providing a way to control device properties. This effect is attributed to strong aromatic interactions between PANI phenyl groups and corrin macrocycle of the aquacyanocobinamide molecule, which was supported by ultraviolet-visible spectra analysis.

The NCBI Comparative Genome Viewer (CGV) is an interactive visualization tool for the analysis of whole-genome eukaryotic alignments.

We report a new visualization tool for analysis of whole-genome assembly-assembly alignments, the Comparative Genome Viewer (CGV) (https://ncbi.nlm.nih.gov/genome/cgv/). CGV visualizes pairwise same-species and cross-species alignments provided by National Center for Biotechnology Information (NCBI) using assembly alignment algorithms developed by us and others. Researchers can examine large structural differences spanning chromosomes, such as inversions or translocations. Users can also navigate to regions of interest, where they can detect and analyze smaller-scale deletions and rearrangements within specific chromosome or gene regions. RefSeq or user-provided gene annotation is displayed where available. CGV currently provides approximately 800 alignments from over 350 animal, plant, and fungal species. CGV and related NCBI viewers are undergoing active development to further meet needs of the research community in comparative genome visualization.

Composite Coatings Applied to Fresh and Blanched Chayote (Sechium edule) and Modeling of the Drying Kinetics and Sorption Isotherms.

Sustainable methods such as convective drying have regained interest in reducing the loss and waste of food produce. Combined with techniques like blanching and edible coatings, they could serve as useful tools in food processing development. Composite coatings comprising pectin, soy protein isolate, and xanthan gum were optimized using response surface methodology with the Box-Behnken design. This optimization aimed to investigate their effects on the moisture content, water activity, total color, and rehydration ratio of fresh and blanched chayote slices. Additionally, the study explored the modeling of the drying kinetics and sorption isotherms of chayote (Sechium edule) slices. Soy protein and xanthan gum were found to primarily influence the moisture content (ranging from 5.44% to 9.93%), and pectin influenced water activity (033 to 0.53) of the fresh-coated chayote, while pectin affected the aw (2.13-8.28) and rehydration of the blanch-coated chayote. The optimized formulations for both fresh and blanched chayote were utilized to assess the drying kinetics behavior and sorption isotherms. The best fit (R2: 0.996 to 0.999) was achieved with the parabolic model for thin-layer materials. Furthermore, the sorption isotherms of chayote displayed a Type IV behavior, with the BET model being the most suitable for describing the sorption behavior of materials with low water activity. The predicted values offer valuable data for optimizing processing conditions to enhance the quality and stability of dried chayote.

From a humorous post to a detailed quantum-chemical study: isocyanate synthesis revisited.

Isocyanates play an essential role in modern manufacturing processes, especially in polyurethane production. There are numerous synthesis strategies for isocyanates both under industrial and laboratory conditions, which do not prevent searching for alternative highly efficient synthetic protocols. Here, we report a detailed theoretical investigation of the mechanism of sulfur dioxide-catalyzed rearrangement of phenylnitrile oxide into phenyl isocyanate, which was first reported in 1977. The DLPNO-CCSD(T) method and up-to-date DFT protocols were used to perform a highly accurate quantum-chemical study of the rearrangement mechanism. An overview of various organic and inorganic catalysts has revealed other potential catalysts, such as sulfur trioxide and selenium dioxide. Furthermore, the present study elucidated how substituents in phenylnitrile oxide influence reaction kinetics. This study was performed by a self-organized collaboration of scientists initiated by a humorous post on the VK social network.