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The World Health Organization declared monkeypox a global public health emergency on 23 July 2022. This disease was caused by the monkeypox virus (MPXV), which was first identified in 1958 in Denmark. The MPXV is a member of the Poxviridae family, the Chordopoxvirinae subfamily, and the genus Orthopoxvirus, which share high similarities with the vaccinia virus (the virus used to produce the smallpox vaccine). For the initial stage of infection, the MPXV needs to attach to the human cell surface glycosaminoglycan (GAG) adhesion molecules using its E8 protein. However, up until now, neither a structure for the MPXV E8 protein nor a specific cure for the MPXV exists. This study aimed to search for small molecules that inhibit the MPXV E8 protein, using computational approaches. In this study, a high-quality three-dimensional structure of the MPXV E8 protein was retrieved by homology modeling using the AlphaFold deep learning server. Subsequent molecular docking and molecular dynamics simulations (MDs) for a cumulative duration of 2.1 microseconds revealed that ZINC003977803 (Diosmin) and ZINC008215434 (Flavin adenine dinucleotide-FAD) could be potential inhibitors against the E8 protein with the MM/GBSA binding free energies of -38.19 ± 9.69 and -35.59 ± 7.65 kcal·mol -1 , respectively.

In this work, we present and analyze a design of an absorber-waveguide system combining a highly sensitive waveguide array concept with a resonant selective absorber. The waveguide part is composed of an array of coupled strip waveguides and is therefore called a coupled strip array (CSA). The CSA is then coupled to the end of a slab Tamm plasmon (STP-) resonator, which is composed of a quasicrystal-like reflector formed by the patterning of a silicon slab and an interfacing tungsten slab. The concept describes an emitter-waveguide or waveguide-detector system featuring selective plasmon-enhanced resonant absorption or emission. These are crucial properties for corresponding optical on-chip integrated devices in context with evanescent field absorption sensing in fluids or gases, for example. Thus, the concept comprises a valuable and more cost-effective alternative to quantum cascade lasers. We designed the lateral dimensions of the STP resonator via a simple quasi-crystal approach and achieved strong narrowband resonances (emittance and Q -factors up to 85% and 88, respectively) for different silicon thicknesses and substrate materials (air and silicon oxide). Moreover, we analyze and discuss the sensitivity of the complete emitter-waveguide system in dependence on the slab thickness. This reveals the crucial correlation between the expected sensitivity assigned to the absorber-waveguide system and field confinement within the silicon.

Background: Dengue virus and Japanese encephalitis virus are two common flaviviruses that are spread widely by Aedes and Culex mosquitoes. Livestock keeping is vital for cities; however, it can pose the risk of increasing the mosquito population. Our study explored how livestock keeping in and around a large city is associated with the presence of mosquitoes and the risk of them spreading flaviviruses., Methods: An entomological study was conducted in 6 districts with 233 households with livestock, and 280 households without livestock, in Hanoi city. BG-Sentinel traps and CDC light traps were used to collect mosquitoes close to animal farms and human habitats. Adult mosquitoes were counted, identified to species level, and grouped into 385 pools, which were screened for flaviviruses using a pan-flavivirus qPCR protocol and sequencing., Results: A total of 12,861 adult mosquitoes were collected at the 513 households, with 5 different genera collected, of which the Culex genus was the most abundant. Our study found that there was a positive association between livestock keeping and the size of the mosquito population-most predominantly between pig rearing and Culex species ( p < 0.001). One pool of Cx. tritaeniorhynchus , collected in a peri-urban district, was found to be positive for Japanese encephalitis virus., Conclusions: The risk of flavivirus transmission in urban areas of Hanoi city due to the spread of Culex and Aedes mosquitoes could be facilitated by livestock keeping.

In this study, we investigate the potential of one-dimensional plasmonic grating structures to serve as a platform for, e.g., sensitive refractive index sensing. This is achieved by comparing numerical simulations to experimental results with respect to the excitation of surface plasmon polaritons (SPPs) in the mid-infrared region. The samples, silver-coated poly-silicon gratings, cover different grating depths in the range of 50 nm-375 nm. This variation of the depth, at a fixed grating geometry, allows the active tuning of the bandwidth of the SPP resonance according to the requirements of particular applications. The experimental setup employs a tunable quantum cascade laser (QCL) and allows the retrieval of angle-resolved experimental wavelength spectra to characterize the wavelength and angle dependence of the SPP resonance of the specular reflectance. The experimental results are in good agreement with the simulations. As a tendency, shallower gratings reveal narrower SPP resonances in reflection. In particular, we report on 2.9 nm full width at half maximum (FWHM) at a wavelength of 4.12 µm and a signal attenuation of 21%. According to a numerical investigation with respect to a change of the refractive index of the dielectric above the grating structure, a spectral shift of 4122nmRIU can be expected, which translates to a figure of merit (FOM) of about 1421 RIU-1. The fabrication of the suggested structures is performed on eight-inch silicon substrates, entirely accomplished within an industrial fabrication environment using standard microfabrication processes. This in turn represents a decisive step towards plasmonic sensor technologies suitable for semiconductor mass-production.

ABCG2 is an ABC membrane protein reverse transport pump, which removes toxic substances such as medicines out of cells. As a result, drug bioavailability is an unexpected change and negatively influences the ADMET (absorption, distribution, metabolism, excretion, and toxicity), leading to multi-drug resistance (MDR). Currently, in spite of promising studies, screening for ABCG2 inhibitors showed modest results. The aim of this study was to search for small molecules that could inhibit the ABCG2 pump. We first used the WISS MODEL automatic server to build up ABCG2 homology protein from 655 amino acids. Pharmacophore models, which were con-structed based on strong ABCG2 inhibitors (IC 50 < 1 μM), consist of two hydrophobic (Hyd) groups, two hydrogen bonding acceptors (Acc2), and an aromatic or conjugated ring (Aro|PiR). Using molecular docking method, 714 substances from the DrugBank and 837 substances from the TCM with potential to inhibit the ABCG2 were obtained. These chemicals maybe favor synthesized or extracted and bioactivity testing.

Inhibition of human pancreatic lipase, a crucial enzyme in dietary fat digestion and absorption, is a potent therapeutic approach for obesity treatment. In this study, human pancreatic lipase inhibitory activity of aurone derivatives was explored by molecular modeling approaches. The target protein was human pancreatic lipase (PDB ID: 1LPB). The 3D structures of 82 published bioactive aurone derivatives were docked successfully into the protein catalytic active site, using AutoDock Vina 1.5.7.rc1. Of them, 62 compounds interacted with the key residues of catalytic trial Ser152-Asp176-His263. The top hit compound ( A14 ), with a docking score of -10.6 kcal⋅mol -1 , was subsequently submitted to molecular dynamics simulations, using GROMACS 2018.01. Molecular dynamics simulation results showed that A14 formed a stable complex with 1LPB protein via hydrogen bonds with important residues in regulating enzyme activity (Ser152 and Phe77). Compound A14 showed high potency for further studies, such as the synthesis, in vitro and in vivo tests for pancreatic lipase inhibitory activity.

Acetylcholinesterase (AChE) and β-secretase (BACE-1) have become attractive therapeutic targets for Alzheimer's disease (AD). Flavones are flavonoid derivatives with various bioactive effects, including AChE and BACE-1 inhibition. In the present work, a series of 14 flavone derivatives was synthesized in relatively high yields (35-85%). Six of the synthetic flavones ( B4 , B5 , B6 , B8 , D6 and D7 ) had completely new structures. The AChE and BACE-1 inhibitory activities were tested, giving pIC 50 3.47-4.59 (AChE) and 4.15-5.80 (BACE-1). Three compounds ( B3 , D5 and D6 ) exhibited the highest biological effects on both AChE and BACE-1. A molecular docking investigation was conducted to explain the experimental results. These molecules could be employed for further studies to discover new structures with dual action on both AChE and BACE-1 that could serve as novel therapies for AD.

Acetylcholinesterase (AChE) and beta-secretase (BACE-1) are two attractive targets in the discovery of novel substances that could control multiple aspects of Alzheimer's disease (AD). Chalcones are the flavonoid derivatives with diverse bioactivities, including AChE and BACE-1 inhibition. In this study, a series of N -substituted-4-phenothiazine-chalcones was synthesized and tested for AChE and BACE-1 inhibitory activities. In silico models, including two-dimensional quantitative structure-activity relationship (2D-QSAR) for AChE and BACE-1 inhibitors, and molecular docking investigation, were developed to elucidate the experimental process. The results indicated that 13 chalcone derivatives were synthesized with relatively high yields (39-81%). The bioactivities of these substances were examined with pIC 50 3.73-5.96 (AChE) and 5.20-6.81 (BACE-1). Eleven of synthesized chalcones had completely new structures. Two substances AC4 and AC12 exhibited the highest biological activities on both AChE and BACE-1. These substances could be employed for further researches. In addition to this, the present study results suggested that, by using a combination of two types of predictive models, 2D-QSAR and molecular docking, it was possible to estimate the biological activities of the prepared compounds with relatively high accuracy.

Acetylcholinesterase (AChE) and beta-secretase (BACE-1) are the two crucial enzymes involved in the pathology of Alzheimer's disease. The former is responsible for many defects in cholinergic signaling pathway and the latter is the primary enzyme in the biosynthesis of beta-amyloid as the main component of the amyloid plaques. These both abnormalities are found in the brains of Alzheimer's patients. In this study, in silico models were developed, including 3D-pharmacophore, 2D-QSAR (two-dimensional quantitative structure-activity relationship), and molecular docking, to screen virtually a database of compounds for AChE and BACE-1 inhibitory activities. A combinatorial library containing more than 3 million structures of curcumin and flavonoid derivatives was generated and screened for drug-likeness and enzymatic inhibitory bioactivities against AChE and BACE-1 through the validated in silico models. A total of 47 substances (two curcumins and 45 flavonoids), with remarkable predicted pIC 50 values against AChE and BACE-1 ranging from 4.24-5.11 (AChE) and 4.52-10.27 (BACE-1), were designed. The in vitro assays on AChE and BACE-1 were performed and confirmed the in silico results. The study indicated that, by using in silico methods, a series of curcumin and flavonoid structures were generated with promising predicted bioactivities. This would be a helpful foundation for the experimental investigations in the future. Designed compounds which were the most feasible for chemical synthesis could be potential candidates for further research and lead optimization.

Among conductive oxide materials, niobium doped titanium dioxide has recently emerged as a stimulating and promising contestant for numerous applications. With carrier concentration tunability, high thermal stability, mechanical and environmental robustness, this is a material-of-choice for infrared plasmonics, which can substitute indium tin oxide (ITO). In this report, to illustrate great advantages of this material, we describe successful fabrication and characterization of niobium doped titanium oxide nanoantenna arrays aiming at surface-enhanced infrared absorption spectroscopy. The niobium doped titanium oxide film was deposited with co-sputtering method. Then the nanopatterned arrays were prepared by electron beam lithography combined with plasma etching and oxygen plasma ashing processes. The relative transmittance of the nanostrip and nanodisk antenna arrays was evaluated with Fourier transform infrared spectroscopy. Polarization dependence of surface plasmon resonances on incident light was examined confirming good agreements with calculations. Simulated spectra also present red-shift as length, width or diameter of the nanostructures increase, as predicted by classical antenna theory.

On the search for the practical plasmonic materials beyond noble metals, aluminum has been emerging as a favorable candidate as it is abundant and offers the possibility of tailoring the plasmonic resonance spanning from ultra-violet to the infrared range. In this letter, in combination with the numerical electromagnetic simulations, we experimentally study the dark-field scattering spectral mapping of plasmonic resonance from the free-standing Al bowtie antenna arrays and correlate their strong nearfield enhancement with the sensing capability by means of surface-enhanced Raman spectroscopy. The spatial matching of plasmonic and Raman mapping puts another step to realize a very promising application of free-standing Al bowtie antennas for plasmonic sensing.

We propose and experimentally demonstrate a compact design for membrane-supported wavelength-selective infrared (IR) bolometers. The proposed bolometer device is composed of wavelength-selective absorbers functioning as the efficient spectroscopic IR light-to-heat transducers that make the amorphous silicon (a-Si) bolometers respond at the desired resonance wavelengths. The proposed devices with specific resonances are first numerically simulated to obtain the optimal geometrical parameters and then experimentally realized. The fabricated devices exhibit a wide resonance tunability in the mid-wavelength IR atmospheric window by changing the size of the resonator of the devices. The measured spectral response of the fabricated device wholly follows the pre-designed resonance, which obviously evidences that the concept of the proposed wavelength-selective IR bolometers is realizable. The results obtained in this work provide a new solution for on-chip MEMS-based wavelength-selective a-Si bolometers for practical applications in IR spectroscopic devices.

Spectrally selective detection is of crucial importance for diverse modern spectroscopic applications such as multi-wavelength pyrometry, non-dispersive infrared gas sensing, biomedical analysis, flame detection, and thermal imaging. This paper reports a quad-wavelength hybrid plasmonic-pyroelectric detector that exhibited spectrally selective infrared detection at four wavelengths-3.3, 3.7, 4.1, and 4.5 μm. The narrowband detection was achieved by coupling the incident infrared light to the resonant modes of the four different plasmonic perfect absorbers based on Al-disk-array placed on a Al 2 O 3 -Al bilayer. These absorbers were directly integrated on top of a zinc oxide thin film functioning as a pyroelectric transducer. The device was fabricated using micro-electromechanical system (MEMS) technology to optimize the spectral responsivity. The proposed detector operated at room temperature and exhibited a responsivity of approximately 100-140 mV/W with a full width at half maximum of about 0.9-1.2 μm. The wavelength tunability, high spectral resolution, compactness and robust MEMS-based platform of the hybrid device demonstrated a great advantage over conventional photodetectors with bandpass filters, and exhibited impressive possibilities for miniature multi-wavelength spectroscopic devices.

Chemically diverse heterocyclic chalcones were prepared and evaluated for cytotoxicity, aiming to push forward potency and selectivity. They were tested against rhabdomyosarcoma (RMS) and noncancerous cell line (LLC-PK1). The influence of heteroaryl patterns on rings A and B was studied. Heterocycle functionalities on both rings, such as phenothiazine, thiophene, furan and pyridine were evaluated. Notably, the introduction of three methoxy groups at positions 3, 4, 5 on ring B appears to be critical for cytotoxicity. The best compound, with potent and selective cytotoxicity (IC50 = 12.51 μM in comparison with the value 10.84 μM of paclitaxel), contains a phenothiazine moiety on ring A and a thiophene heterocycle on ring B. Most of the potential compounds only show weak cytoxicity on the noncancerous cell line LLC-PK1.

Shape memory behavior of crystalline shape memory polyurethane (SPU) reinforced with graphene, which utilizes melting temperature as a shape recovery temperature, was examined with various external actuating stimuli such as direct heating, resistive heating, and infrared (IR) heating. Compatibility of graphene with crystalline SPU was adjusted by altering the structure of the hard segment of the SPU, by changing the structure of the graphene, and by changing the preparation method of the graphene/SPU composite. The SPU made of aromatic 4,4'-diphenylmethane diisocyanate (MSPU) exhibited better compatibility with graphene, having an aromatic structure, compared to that made of the aliphatic hexamethylene diisocyanate. The finely dispersed graphene effectively reinforced MSPU, improved shape recovery of MSPU, and served effectively as a filler, triggering shape recovery by resistive or IR heating. Compatibility was enhanced when the graphene was modified with methanol. This improved shape recovery by direct heating, but worsened the conductivity of the composite, and consequently the efficiency of resistive heating for shape recovery also declined. Graphene modified with methanol was more effective than pristine graphene in terms of shape recovery by IR heating.

A series of simple heterocyclic chalcone analogues have been synthesized by Claisen Schmidt condensation reactions between substituted benzaldehydes and heteroaryl methyl ketones and evaluated for their antibacterial activity. The structures of the synthesized chalcones were established by IR and ¹H-NMR analysis. The biological data shows that compounds p₅, f₆ and t₅ had strong activities against both susceptible and resistant Staphylococcus aureus strains, but not activity against a vancomycin and methicillin resistant Staphylococcus aureus isolated from a human sample. The structure and activity relationships confirmed that compounds f₅, f₆ and t₅ are potential candidates for future drug discovery and development.

Benzo[c]phenanthridine (BCP) derivatives were identified as topoisomerase I (TOP-I) targeting agents with pronounced antitumor activity. In this study, hologram-QSAR, 2D-QSAR and 3D-QSAR models were developed for BCPs on topoisomerase I inbibitory activity and cytotoxicity against seven tumor cell lines including RPMI8402, CPT-K5, P388, CPT45, KB3-1, KBV-1and KBH5.0. The hologram, 2D, and 3D-QSAR models were obtained with the square of correlation coefficient R² = 0.58-0.77, the square of the crossvalidation coefficient q² = 0.41-0.60 as well as the external set's square of predictive correlation coefficient r² = 0.5-0.80. Moreover, the assessment method based on reliability test with confidence level of 95% was used to validate the predictive power of QSAR models and to prevent over-fitting phenomenon of classical QSAR models. Our QSAR model could be applied to design new analogues of BCPs with higher antitumor and topoisomerase I inhibitory activity.

Benzo[c]phenanthridine (BCP) derivatives were identified as topoisomerase I (TOP-I) targeting agents with pronounced antitumor activity. In this study, a support vector machine model was performed on a series of 73 analogues to classify BCP derivatives according to TOP-I inhibitory activity. The best SVM model with total accuracy of 93% for training set was achieved using a set of 7 descriptors identified from a large set via a random forest algorithm. Overall accuracy of up to 87% and a Matthews coefficient correlation (MCC) of 0.71 were obtained after this SVM classifier was validated internally by a test set of 15 compounds. For two external test sets, 89% and 80% BCP compounds, respectively, were correctly predicted. The results indicated that our SVM model could be used as the filter for designing new BCP compounds with higher TOP-I inhibitory activity.