Room temperature, cascadable, all-optical polariton universal gates.

Today, almost all information processing is performed using electronic logic circuits operating at several gigahertz frequency. All-optical logic holds the promise to allow for up to three orders of magnitude higher speed. Whereas essential all-optical transistor functionalities were demonstrated across a range of platforms, utilising them to implement a complete Boolean logic gate set and in particular negation, i.e. switching off an optical signal with another, weaker, optical signal, poses a major challenge. Here, we realize a cascadable NOT gate by introducing the concept of non-ground-state polariton amplification in organic semiconductor microcavities under non-resonant optical excitation. We unravel the importance of vibron-mediated stimulated scattering in room temperature operation of the inverter. Moreover, we extend the concept to a multi-input universal NOR logic gate, where in the presence of any of the input signals non-ground-state amplification supersedes spontaneous ground-state condensation, resulting in a NOR gate with ~1 ps switching time. The realisation of an ultrafast universal logic gate constitutes an essential step for more complex optical circuitry that could boost information processing applications.

5-Aza-adenine Derivatives for Crop-Protection: Multicomponent Synthesis, Experimental and Theoretical Structural Analysis.

A microwave-assisted synthesis of 7-amino-1,2,4-triazolo[1,5-a][1,3,5]triazine-2-propanamides was developed using a three-component, catalyst-free reaction of cyanamide and trimethyl orthoformate with 3-(5-amino-1H-1,2,4-triazol-3-yl)propanamides (3). The reaction tolerated structurally diverse substrates and proceeded chemo- and regio-selectively, affording the target compounds in high purity in 5-10 minutes. The convenient chromatography-free isolation and purification of the products add practicality to this method. The structural features of the prepared compounds were investigated using dynamic NMR spectroscopy, X-ray crystallography and computational chemistry calculations. X-ray crystallography performed on a representative compound, 3-(7-amino-1,2,4-triazolo[1,5-a][1,3,5]triazin-2-yl)-N-(4-benzyl)propenamide (4l), showed the overall molecular conformation to adopt the shape of the letter C. Notable localisation of π-electron density is found within the 1,2,4-triazolo[1,5-a][1,3,5]triazine system; a relatively short C-NH2 bond is consistent with restricted rotation about this bond. This study also presents a detailed analysis of the molecular interactions in 4l using DFT and QTAIM methods with a focus on the hydrogen-bonding and π-stacking interactions that influence the molecular packing of 4l. The findings reveal the significant roles of N-H···O, N-H···N and C-H···N interactions, along with electrostatically enhanced π···π contacts. A broad screening for insecticidal, fungicidal and herbicidal properties identified several compounds with potent herbicidal activity against Matricaria inodora.

Repair and DNA Polymerase Bypass of Clickable Pyrimidine Nucleotides.

Clickable nucleosides, most often 5-ethynyl-2'-deoxyuridine (EtU), are widely used in studies of DNA replication in living cells and in DNA functionalization for bionanotechology applications. Although clickable dNTPs are easily incorporated by DNA polymerases into the growing chain, afterwards they might become targets for DNA repair systems or interfere with faithful nucleotide insertion. Little is known about the possibility and mechanisms of these post-synthetic events. Here, we investigated the repair and (mis)coding properties of EtU and two bulkier clickable pyrimidine nucleosides, 5-(octa-1,7-diyn-1-yl)-U (C8-AlkU) and 5-(octa-1,7-diyn-1-yl)-C (C8-AlkC). In vitro, EtU and C8-AlkU, but not C8-AlkC, were excised by SMUG1 and MBD4, two DNA glycosylases from the base excision repair pathway. However, when placed into a plasmid encoding a fluorescent reporter inactivated by repair in human cells, EtU and C8-AlkU persisted for much longer than uracil or its poorly repairable phosphorothioate-flanked derivative. DNA polymerases from four different structural families preferentially bypassed EtU, C8-AlkU and C8-AlkC in an error-free manner, but a certain degree of misincorporation was also observed, especially evident for DNA polymerase ß. Overall, clickable pyrimidine nucleotides could undergo repair and be a source of mutations, but the frequency of such events in the cell is unlikely to be considerable.

Probing the Conformational Restraints of DNA Damage Recognition with ß-L-Nucleotides.

The DNA building blocks 2'-deoxynucleotides are enantiomeric, with their natural ß-D-configuration dictated by the sugar moiety. Their synthetic ß-L-enantiomers (ßLdNs) can be used to obtain L-DNA, which, when fully substituted, is resistant to nucleases and is finding use in many biosensing and nanotechnology applications. However, much less is known about the enzymatic recognition and processing of individual ßLdNs embedded in D-DNA. Here, we address the template properties of ßLdNs for several DNA polymerases and the ability of base excision repair enzymes to remove these modifications from DNA. The Klenow fragment was fully blocked by ßLdNs, whereas DNA polymerase κ bypassed them in an error-free manner. Phage RB69 DNA polymerase and DNA polymerase ß treated ßLdNs as non-instructive but the latter enzyme shifted towards error-free incorporation on a gapped DNA substrate. DNA glycosylases and AP endonucleases did not process ßLdNs. DNA glycosylases sensitive to the base opposite their cognate lesions also did not recognize ßLdNs as a correct pairing partner. Nevertheless, when placed in a reporter plasmid, pyrimidine ßLdNs were resistant to repair in human cells, whereas purine ßLdNs appear to be partly repaired. Overall, ßLdNs are unique modifications that are mostly non-instructive but have dual non-instructive/instructive properties in special cases.

Proton Sponge Zwitterions with Positively and Negatively Charged Hydrogen Bonds: Extremely Polar Organic Compounds and Interplay of [NHN]+ and [NHN]- Properties.

Six previously unknown zwitterions with positively and negatively charged [NHN] hydrogen bonds were synthesized by acylation of 4,5-bis(dimethylamino)-1-tosylamino-8-aminonaphthalene with subsequent alkaline treatment of the resulting 8-acylamino derivatives. Using NMR and XRD measurements in conjunction with quantum chemical DFT/PBE1PBE/6-311++G(d,p) calculations, it was shown that the negatively charged [NHN]- bond in such compounds commonly differs from the [NHN]+ bond by significantly lower linearity, higher asymmetry, and moderate to strong paramagnetic shift of the chelated NH proton signal. Among other remarkable findings, the most important are (1) unusually high polarity (µ = 21-26 D) of the obtained zwitterions, (2) sharp difference in structures of the solid 1,8-bis(tosylated) zwitterion (BTZ) grown from MeCN or DMF, and (3) registration for one of the stereoisomers of BTZ with the record short [NHN]- hydrogen bridge (N···N = 2.510 Å) almost reaching the theoretical limit (2.50 Å) for the [NHN]+ hydrogen bond.

From land to water: "Sunken" T-maze for associated learning in cichlid fish.

The study introduced and evaluated learning paradigms for Maylandia callainos cichlids using a modified version of the rodent T-maze, filled with tank water (the "sunken" modification). Both male and female fish underwent training in two distinct conditioning paradigms. Firstly, simple operant conditioning involved placing a food reward in either the right or left compartment. Cichlids demonstrated the ability to purposefully find the bait within 6 days of training, with a persistent place preference lasting up to 6 days. Additionally, the learning dynamics varied with sex: female cichlids exhibited reduction in latency to visit the target compartment and consume the bait, along with a decrease in the number of errors 3 and 4 days earlier than males, respectively. Secondly, visually-cued operant conditioning was conducted, with a food reward exclusively placed in the yellow compartment, randomly positioned on the left or right side of the maze during each training session. Visual learning persisted for 10 days until reaction time improvement plateaued. Color preference disappeared after 4 consecutive check-ups, with no sex-related interference. For further validation of visually-cued operant conditioning paradigm, drugs MK-801 (dizocilpine) and caffeine, known to affect performance in learning tasks, were administered intraperitoneally. Chronic MK-801 (0.17 mg/kg) impaired maze learning, resulting in no color preference development. Conversely, caffeine administration enhanced test performance, increasing precision in fish. This developed paradigm offers a viable approach for studying learning and memory and presents an effective alternative to rodent-based drug screening tools, exhibiting good face and predictive validity.

Transient Interphase Microtubules Appear in Differentiating Sponge Cells.

Microtubules are an indispensable component of all eukaryotic cells due to their role in mitotic spindle formation, yet their organization and number can vary greatly in the interphase. The last common ancestor of all eukaryotes already had microtubules and microtubule motor proteins moving along them. Sponges are traditionally regarded as the oldest animal phylum. Their body does not have a clear differentiation into tissues, but it contains several distinguishable cell types. The choanocytes stand out among them and are responsible for creating a flow of water with their flagella and increasing the filtering and feeding efficiency of the sponge. Choanocyte flagella contain microtubules, but thus far, observing a developed system of cytoplasmic microtubules in non-flagellated interphase sponge cells has been mostly unsuccessful. In this work, we combine transcriptomic analysis, immunofluorescence, and electron microscopy with time-lapse recording to demonstrate that microtubules appear in the cytoplasm of sponge cells only when transdifferentiation processes are activated. We conclude that dynamic cytoplasmic microtubules in the cells of sponges are not a persistent but rather a transient structure, associated with cellular plasticity.

Three-component cascade reaction of 3-ketonitriles, 2-unsubstituted imidazole N-oxides, and aldehydes.

A three-component condensation of 2-unsubstituted imidazole N-oxides, 3-ketonitriles, and aldehydes is described. The reaction proceeds via sequential Knoevenagel condensation/Michael addition under mild, catalyst-free conditions with various substrates. Furthermore, the corresponding 2-functionalized imidazole N-oxides can be further dehydrated to (Z)-2-aroyl-3-(1H-imidazol-2-yl)-acrylonitriles, which may also be directly prepared by changing the reaction conditions as a cascade of Knoevenagel condensation/Michael addition/dehydration.

Green Light from Red-Emitting Nanocrystals: Broadband, Low-Threshold Lasing from Colloidal Quantum Shells in Optical Nanocavities.

Spherical semiconductor nanoplatelets, known as quantum shells (QSs), have captured significant interest for their strong suppression of Auger recombination, which leads to long multiexciton lifetimes and wide optical gain bandwidth. Yet, the realization of benefits associated with the multiexciton lasing regime using a suitably designed photonic cavity remains elusive. Here, we demonstrate broadly tunable lasing from close-packed films of CdS/CdSe/CdS QSs deposited over nanopillar arrays on Si substrates. Wide spectral tuning of the stimulated emission in QSs with a fixed bandgap value was achieved by engaging single exciton (λX ∼ 634 nm), biexciton (λBX ∼ 627 nm), and multiple exciton (λMX ∼ 615-565 nm) transitions. The ensemble-averaged gain threshold of ∼ 2.6 electron-hole pairs per QS particle and the low photonic cavity fluence threshold of ∼4 µJ/cm2 were attributed to Auger suppression. The tuning of the lasing emission closely aligns with our model predictions achieved by varying the array period while preserving mode confinement and quality (Q) factors. These results mark a notable step toward the development of colloidal nanocrystal lasers.

How I diagnose systemic mastocytosis.

OBJECTIVES: Systemic mastocytosis (SM) is a neoplasm of mast cells (MCs) characterized by their proliferation in extracutaneous organs. Systemic mastocytosis includes several entities with different clinical courses and prognoses. The rarity of this disease and the diversity of clinical and morphologic presentation make the diagnosis of SM very challenging. The aim of this review is to share our approach to the diagnosis of SM. METHODS: We present 4 cases that highlight the spectrum of clinical and laboratory features of SM and outline the diagnostic process with an emphasis on morphology. RESULTS: Pathology and laboratory medicine play a key role in investigation of SM, as correct diagnosis requires integration of morphologic, molecular, and serologic findings. In addition to awareness of microscopic findings in SM, a pathologist must keep abreast with an expanding menu of ancillary studies, particularly molecular testing. CONCLUSIONS: Systemic mastocytosis is a challenging diagnosis that requires not only a demonstration of a clonal proliferation of MCs but also a correct subclassification based on the recently updated criteria.

Oxygen tracer diffusion in amorphous hafnia films for resistive memory.

The oxygen diffusion rate in hafnia (HfO2)-based resistive memory plays a pivotal role in enabling nonvolatile data retention. However, the information retention times obtained in HfO2 resistive memory devices are many times higher than the expected values obtained from oxygen diffusion measurements in HfO2 materials. In this study, we resolve this discrepancy by conducting oxygen isotope tracer diffusion measurements in amorphous hafnia (a-HfO2) thin films. Our results show that the oxygen tracer diffusion in amorphous HfO2 films is orders of magnitude lower than that of previous measurements on monoclinic hafnia (m-HfO2) pellets. Moreover, oxygen tracer diffusion is much lower in denser a-HfO2 films deposited by atomic layer deposition (ALD) than in less dense a-HfO2 films deposited by sputtering. The ALD films yield similar oxygen diffusion times as experimentally measured device retention times, reconciling this discrepancy between oxygen diffusion and retention time measurements. More broadly, our work shows how processing conditions can be used to control oxygen transport characteristics in amorphous materials without long-range crystal order.

Luminescent Er3+ based single molecule magnets with fluorinated alkoxide or aryloxide ligands.

We report the synthesis, structures, and magnetic and luminescence properties of a series of new mono- and dinuclear Er3+ complexes derived from sterically demanding aryloxide and fluorinated alkoxide ligands: [4-tBu-2,6-(Ph2CH)2C6H2O]3Er(THF) (1), [(C6F5)3CO]3Er(Me3SiOH) (2), [(C6F5)3CO]3Er[(Me3Si)2NH] (3), [(C6F5)3CO]3Er(C6H5CH3) (4), [(C6F5)3CO]3Er(o-Me2NC6H4CH3) (5) and {[Ph(CF3)2CO]2Er(µ2-OC(CF3)2Ph)}2 (6). In compounds 1, 2, and 4, the Er3+ ion is four-coordinated and adopts a distorted trigonal pyramidal geometry, while in 3, 5, and 6, the coordination geometry of Er3+ is impacted by the presence of several relatively short Er⋯F distances, making them rather 6-coordinated. All compounds behave as field-induced Single Molecule Magnets (SMMs) and exhibit an Er3+ characteristic near infrared (NIR) emission associated with the 4I13/2 → 4I15/2 transition with a remarkably long lifetime going up to 73 µs, which makes them multifunctional luminescent SMMs. The deconvolution of the NIR emission spectra allowed us to provide a direct probe of the crystal field splitting in these compounds, which was correlated with magnetic data.

Review of the bicolora Fang and binghami Hampson species-groups of the genus Ovipennis Hampson with descriptions of five new species from Southwestern China and Indochina (Lepidoptera, Erebidae, Arctiinae, Lithosiini).

The Ovipennis bicolora Fang, 1986 and Ovipennis binghami Hampson, 1903 species-groups are reviewed. The identities of the records of O.binghami reported outside of its type locality are clarified. Ovipennis bicolora is rediscovered with the male and female genitalia illustrated for the first time. The male and female genitalia of O.thomasi ern, 2009 are illustrated for the first time and its specific status is confirmed. Five new species are described: O.hanae S.-Y. Huang, Volynkin & ern, sp. n. (Southwestern China), O.regina Volynkin, ern, S.-Y. Huang & Saldaitis, sp. n. (Northern Thailand and Southwestern China), O.takia Volynkin, S.-Y. Huang & ern, sp. n. (Western and Central Thailand), O.kitchingi Volynkin, S.-Y. Huang & ern, sp. n. (Northern Thailand), and O.sapa Volynkin, S.-Y. Huang, ern & Saldaitis, sp. n. (Northern Vietnam). Adults and genitalia of the new species are illustrated and compared with its congeners.

Heterologous Prime-Boost with Immunologically Orthogonal Protein Nanoparticles for Peptide Immunofocusing.

Protein nanoparticles are effective platforms for antigen presentation and targeting effector immune cells in vaccine development. Encapsulins are a class of protein-based microbial nanocompartments that self-assemble into icosahedral structures with external diameters ranging from 24 to 42 nm. Encapsulins from Mxyococcus xanthus were designed to package bacterial RNA when produced in E. coli and were shown to have immunogenic and self-adjuvanting properties enhanced by this RNA. We genetically incorporated a 20-mer peptide derived from a mutant strain of the SARS-CoV-2 receptor binding domain (RBD) into the encapsulin protomeric coat protein for presentation on the exterior surface of the particle. This immunogen elicited conformationally-relevant humoral responses to the SARS-CoV-2 RBD. Immunological recognition was enhanced when the same peptide was presented in a heterologous prime/boost vaccination strategy using the engineered encapsulin and a previously reported variant of the PP7 virus-like particle, leading to the development of a selective antibody response against a SARS-CoV-2 RBD point mutant. While generating epitope-focused antibody responses is an interplay between inherent vaccine properties and B/T cells, here we demonstrate the use of orthogonal nanoparticles to fine-tune the control of epitope focusing.

6-Aryl-4-cycloamino-1,3,5-triazine-2-amines: synthesis, antileukemic activity, and 3D-QSAR modelling.

Despite significant progress in immunotherapy and chimeric antigen receptor T cell therapy of leukemia, chemotherapy is the major treatment option for the disease. Therefore, the development of potent and safe drugs for standard and targeted chemotherapy of leukemia remains an important task for medicinal chemists. A library of 94 diverse 6-aryl-4-cycloamino-1,3,5-triazine-2-amines was prepared using a one-pot microwave-assisted protocol, which involves a three-component reaction of cyanoguanidine, aromatic aldehydes and cyclic amines, and subsequent dehydrogenative aromatization of the dihydrotriazine intermediates in the presence of alkali. The cytotoxic properties of prepared compounds were evaluated against the leukemic Jurkat T cell line and the selectivity of the 24 most active compounds was also assessed using a normal fibroblast MRC-5 cell line, indicating selective antiproliferative activity against leukemic cells. The structure-activity relationship was analysed, and the prepared 3D-QSAR model was found to predict the antileukemic activity of the compounds with reasonable accuracy. In the cell morphology study, both apoptosis and necrosis features were observed in Jurkat T cells after treatment with the most active compound.

Characterizing Aptamer Interaction with the Oncolytic Virus VV-GMCSF-Lact.

Aptamers are currently being investigated for their potential to improve virotherapy. They offer several advantages, including the ability to prevent the aggregation of viral particles, enhance target specificity, and protect against the neutralizing effects of antibodies. The purpose of this study was to comprehensively investigate an aptamer capable of enhancing virotherapy. This involved characterizing the previously selected aptamer for vaccinia virus (VACV), evaluating the aggregation and molecular interaction of the optimized aptamers with the recombinant oncolytic virus VV-GMCSF-Lact, and estimating their immunoshielding properties in the presence of human blood serum. We chose one optimized aptamer, NV14t_56, with the highest affinity to the virus from the pool of several truncated aptamers and built its 3D model. The NV14t_56 remained stable in human blood serum for 1 h and bound to VV-GMCSF-Lact in the micromolar range (Kd ≈ 0.35 µM). Based on dynamic light scattering data, it has been demonstrated that aptamers surround viral particles and inhibit aggregate formation. In the presence of serum, the hydrodynamic diameter (by intensity) of the aptamer-virus complex did not change. Microscale thermophoresis (MST) experiments showed that NV14t_56 binds with virus (EC50 = 1.487 × 109 PFU/mL). The analysis of the amplitudes of MST curves reveals that the components of the serum bind to the aptamer-virus complex without disrupting it. In vitro experiments demonstrated the efficacy of VV-GMCSF-Lact in conjunction with the aptamer when exposed to human blood serum in the absence of neutralizing antibodies (Nabs). Thus, NV14t_56 has the ability to inhibit virus aggregation, allowing VV-GMCSF-Lact to maintain its effectiveness throughout the storage period and subsequent use. When employing aptamers as protective agents for oncolytic viruses, the presence of neutralizing antibodies should be taken into account.

Controlling the Quality of Nanodrugs According to Their New Property-Radiothermal Emission.

Previous studies have shown that complexly shaped nanoparticles (NPs) have their intrinsic radiothermal emission in the millimeter range. This article presents a method for controlling the quality of nanodrugs-immunobiological preparations (IBPs)-based on the detection of their intrinsic radiothermal emissions. The emissivity of interferon (IFN) medicals, determined without opening the primary package, is as follows (µW/m2): IFN-α2b-80 ± 9 (105 IU per package), IFN-ß1a-40 ± 5 (24 × 106 IU per package), IFN-γ-30 ± 4 (105 IU per package). The emissivity of virus-like particles (VLP), determined using vaccines Gam-VLP-multivac (120 µg) in an injection bottle (crimp cap vials), was as follows: 12 ± 1 µW/m2, Gam-VLP-rota vaccines-9 ± 1 µW/m2. This study shows the reproducibility of emissivity over the course of a year, subject to the storage conditions of the immunobiological products. It has been shown that accelerated aging and a longer shelf life are accompanied by the coagulation of active NPs, and lead to a manyfold drop in emissivity. The dependence of radiothermal emission on temperature has a complex, non-monotonic nature. The emission intensity depends on the form of dosage, but remains within the order of magnitude for IFN-α2b for intranasal aqueous solution, ointments, and suppositories. The possibility of the remote quantitative control of the first phases of the immune response (increased synthesis of IFNs) to the intranasal administration of VLP vaccines has been demonstrated in experimental animals.

α-Umpolung/Michael Addition/Quaternization Tandem Reaction to provide α-Imido-ß-phosphonium Propanoates with Broad Spectrum of Biological Activity.

This paper has been supported by the Kazan Federal University Strategic Academic Leadership Program ('PRIORITY-2030'). HRMS data were obtained in the CSF-SAC FRC KSC RAS by support of the State Assignment of the Federal Research Center "Kazan Scientific Center", Russian Academy of Sciences. A.D.V, conducted studies of anticancer activity with financial support form the government assignment for FRC Kazan Scientific Center of RAS.

Anomalous isotope effect on the optical bandgap in a monolayer transition metal dichalcogenide semiconductor.

Isotope effects have received increasing attention in materials science and engineering because altering isotopes directly affects phonons, which can affect both thermal properties and optoelectronic properties of conventional semiconductors. However, how isotopic mass affects the optoelectronic properties in 2D semiconductors remains unclear because of measurement uncertainties resulting from sample heterogeneities. Here, we report an anomalous optical bandgap energy red shift of 13 (±7) milli-electron volts as mass of Mo isotopes is increased in laterally structured 100MoS2-92MoS2 monolayers grown by a two-step chemical vapor deposition that mitigates the effects of heterogeneities. This trend, which is opposite to that observed in conventional semiconductors, is explained by many-body perturbation and time-dependent density functional theories that reveal unusually large exciton binding energy renormalizations exceeding the ground-state renormalization energy due to strong coupling between confined excitons and phonons. The isotope effect on the optical bandgap reported here provides perspective on the important role of exciton-phonon coupling in the physical properties of two-dimensional materials.

Pre-transplant kidney quality evaluation using photoacoustic imaging during normothermic machine perfusion.

Due to the shortage of kidneys donated for transplantation, surgeons are forced to use the organs with an elevated risk of poor function or even failure. Although the existing methods for pre-transplant quality evaluation have been validated over decades in population cohort studies across the world, new methods are needed as long as delayed graft function or failure in a kidney transplant occurs. In this study, we explored the potential of utilizing photoacoustic (PA) imaging during normothermic machine perfusion (NMP) as a means of evaluating kidney quality. We closely monitored twenty-two porcine kidneys using 3D PA imaging during a two-hour NMP session. Based on biochemical analyses of perfusate and produced urine, the kidneys were categorized into 'non-functional' and 'functional' groups. Our primary focus was to quantify oxygenation (sO2) within the kidney cortical layer of depths 2 mm, 4 mm, and 6 mm using two-wavelength PA imaging. Next, receiver operating characteristic (ROC) analysis was performed to determine an optimal cortical layer depth and time point for the quantification of sO2 to discriminate between functional and non-functional organs. Finally, for each depth, we assessed the correlation between sO2 and creatinine clearance (CrCl), oxygen consumption (VO2), and renal blood flow (RBF). We found that hypoxia of the renal cortex is associated with poor renal function. In addition, the determination of sO2 within the 2 mm depth of the renal cortex after 30 min of NMP effectively distinguishes between functional and non-functional kidneys. The non-functional kidneys can be detected with the sensitivity and specificity of 80% and 85% respectively, using the cut-off point of sO2 < 39%. Oxygenation significantly correlates with RBF and VO2 in all kidneys. In functional kidneys, sO2 correlated with CrCl, which is not the case for non-functional kidneys. We conclude that the presented technique has a high potential for supporting organ selection for kidney transplantation.