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The 3C protease (3Cpro) is an important enzyme for developing therapeutic medicines against some severe viral infections. In order to discover new classes of antiviral agents, 42 novel selenenyl sulfides were prepared and characterized by 1H NMR, 13C NMR, 77Se NMR and HRMS. The target compounds demonstrated promising inhibitions against 3Cpro from either enterovirus 71 (EV71) or coxsackievirus B3 (CVB3), as well as desirable cell-based antiviral activity against these viruses. Among them, 11f displayed the most potent IC50 value of 0.28 ± 0.05 μM against EV71-3Cpro, and the strongest IC50 value of 0.72 ± 0.15 μM against CVB3, with a selectivity index of 51.5 against Hela cell, superior to the control drug rupintrivir. In addition, molecular docking was undertaken to predict a possible binding mode for compound 11f, and a comparative molecular field analysis (CoMFA) model was subsequently generated to understand the structure-activity relationships. Overall, the present research has provided some new insights to design a distinct family of antiviral compounds.

High-cadence, multiwavelength observations have continuously revealed the diversity of tidal disruption events (TDEs), thus greatly advancing our knowledge and understanding of TDEs. In this work, we conducted an intensive optical-UV and X-ray follow-up campaign of TDE AT 2023lli and found a remarkable month-long bump in its UV/optical light curve nearly 2 months prior to maximum brightness. The bump represents the longest separation time from the main peak among known TDEs to date. The main UV/optical outburst declines as t ^−4.10 , making it one of the fastest-decaying optically selected TDEs. Furthermore, we detected sporadic X-ray emission 30 days after the UV/optical peak, accompanied by a reduction in the period of inactivity. It is proposed that the UV/optical bump could be caused by the self-intersection of the stream debris, whereas the primary peak is generated by the reprocessed emission of the accretion process. In addition, our results suggest that episodic X-ray radiation during the initial phase of decline may be due to the patched obscurer surrounding the accretion disk, a phenomenon associated with the inhomogeneous reprocessing process. The double TDE scenario, in which two stars are disrupted in sequence, is also a possible explanation for producing the observed early bump and main peak. We anticipate that the multicolor light curves of TDEs, especially in the very early stages, and the underlying physics can be better understood in the near future with the assistance of dedicated surveys such as the deep high-cadence survey of the 2.5 m Wide Field Survey Telescope.

Background: Bed bugs are blood-feeding insects and are an important urban pest. Bed bugs are nocturnal insects and hide in cracks in walls and beds during the day. The study aims to: (1) determine the bed bugs species that infest Iraq, their infestation source, and their distribution; (2) determine the level of awareness and concern regarding bed bugs among the Iraqi community. Methods: Between 2020 and 2021, a survey of bed bug infestation dynamics was conducted in 18 infested sites located in major cities across eight governorates. The 23-item online survey was distributed over social media to Iraqi citizens between June and July 2022 to survey on their familiarity with bed bug habitat, medical significance, transmission, pre­vention, control measures, and concerns. Results: There were a total of 1104 bed bugs collected. Based on the morphological characteristics, bed bugs collected from eight Iraqi governorates are identified as Cimex hemipterus. Besides, a high rate of bed bug infestation was ob­served in workers' dormitories. The online questionnaire was answered by 1843 respondents and based on the feedback, most respondents (55.3%) have no awareness of bed bug infestations, while around 43.8% are somewhat concerned about bed bug infestations in Iraq. Conclusion: Only tropical bed bugs, C. hemipterus were found in all sampled sites. Bed bug infestations are mainly caused by migrant workers and the reuse of second-hand furniture and clothing. The results suggest that the Iraqi gov­ernment should organize more proper demonstrations on bed bug awareness for the public.

IntroductionThe complement system is a key component of the innate immune system, and its aberrant activation underlies the pathophysiology of various diseases. Zilucoplan is a macrocyclic peptide that binds and inhibits the cleavage/activation of human complement component 5 (C5). We present in vitro and ex vivo data on the mechanism of action of zilucoplan for the inhibition of C5 activation, including two clinically relevant C5 polymorphisms at R885.MethodsThe interaction of zilucoplan with C5, including for clinical C5 R885 variants, was investigated using surface plasmon resonance (SPR), hemolysis assays, and ELISA. The interference of C5b6 formation by zilucoplan was investigated by native gel analysis and hemolysis assay. The permeability of zilucoplan in a reconstituted basement membrane was assessed by the partition of zilucoplan on Matrigel-coated transwell chambers.ResultsZilucoplan specifically bound human complement C5 with high affinity, competitively inhibited the binding of C5 to C3b, and blocked C5 cleavage by C5 convertases and the assembly of the cytolytic membrane attack complex (MAC, or C5b9). Zilucoplan fully prevented the in vitro activation of C5 clinical variants at R885 that have been previously reported to respond poorly to eculizumab treatment. Zilucoplan was further demonstrated to interfere with the formation of C5b6 and inhibit red blood cell (RBC) hemolysis induced by plasmin-mediated non-canonical C5 activation. Zilucoplan demonstrated greater permeability than a monoclonal C5 antibody in a reconstituted basement membrane model, providing a rationale for the rapid onset of action of zilucoplan observed in clinical studies.ConclusionOur findings demonstrate that zilucoplan uses a dual mode of action to potently inhibit the activation of C5 and terminal complement pathway including wild-type and clinical R885 variants that do not respond to eculizumab treatment. These data may be relevant to the clinically demonstrated benefits of zilucoplan.

Broad emission lines of active galactic nuclei (AGNs) originate from the broad-line region (BLR), consisting of dense gas clouds in orbit around an accreting supermassive black hole. Understanding the geometry and kinematics of this region is crucial for gaining insights into the physics and evolution of AGNs. Conventional velocity-resolved reverberation mapping may face challenges in disentangling the degeneracy between intricate motion and geometry of this region. To address this challenge, new key constraints are required. Here, we report the discovery of an asymmetric BLR using a novel technique: velocity-resolved ionization mapping, which can map the distance of emitting gas clouds by measuring Hydrogen line ratios at different velocities. By analyzing spectroscopic monitoring data, we find that the Balmer decrement is anticorrelated with the continuum and correlated with the lags across broad emission line velocities. Some line ratio profiles deviate from the expectations for a symmetrically virialized BLR, suggesting that the redshifted and blueshifted gas clouds may not be equidistant from the supermassive black hole (SMBH). This asymmetric geometry might represent a formation imprint, provide new perspectives on the evolution of AGNs, and influence SMBH mass measurements.

We present JefiAtten, a novel neural network model employing the attention mechanism to solve Maxwell’s equations efficiently. JefiAtten uses self-attention and cross-attention modules to understand the interplay between charge density, current density, and electromagnetic fields. Our results indicate that JefiAtten can generalize well to a range of scenarios, maintaining accuracy across various spatial distribution and handling amplitude variations. The model showcases an improvement in computation speed after training, compared to traditional integral methods. The adaptability of the model suggests potential for broader applications in computational physics, with further refinements to enhance its predictive capabilities and computational efficiency. Our work is a testament to the efficacy of integrating attention mechanisms with numerical simulations, marking a step forward in the quest for data-driven solutions to physical phenomena.

We report the discovery of a faint optical tidal disruption event (TDE) in the nearby star-forming galaxy NGC 3799. Identification of the TDE is based on its position at the galaxy nucleus, a light curve declining as t ^−5/3 , a blue continuum with an almost constant blackbody temperature of ∼12,000 K, broad (≈15,000 km s ^−1 ) Balmer lines, and characteristic He ii 4686 Å emission. The light curve of AT 2023clx peaked at an absolute magnitude of −17.16 mag in the g band and a maximum blackbody bolometric luminosity of 4.56 × 10 ^42 erg s ^−1 , making it the faintest TDE discovered to date. With a redshift of 0.01107 and a corresponding luminosity distance of 47.8 Mpc, it is also the closest optical TDE ever discovered to the best of our knowledge. Furthermore, our analysis of Swift/XRT observations of AT 2023clx yields a very tight 3 σ upper limit of 9.53 × 10 ^39 erg s ^−1 in the range 0.3–10 keV. AT 2023clx, together with very few other faint TDEs such as AT 2020wey, prove that there are probably a large number of faint TDEs yet to be discovered at higher redshifts, which is consistent with the prediction of luminosity functions (LFs). The upcoming deeper optical time-domain surveys, such as the Legacy Survey of Space and Time and the Wide Field Survey Telescope, will discover more TDEs at even lower luminosities, allowing for a more precise constraint of the low end of the LF.

Methicillin-resistant Staphylococcus aureus (MRSA) is a worldwide health threat and has already tormented humanity during its long history, creating an urgent need for the development of new classes of antibacterial agents. In this study, twenty-one novel sulfonylurea derivatives containing phenyl-5-vinyl and pyrimidinyl-4-aryl moieties were designed and synthesized, among which, nine compounds exhibited inhibitory potencies against Gram-positive bacterial strains: MRSA (Chaoyang clinical isolates), S. aureus ATCC6538, vancomycin-resistant Enterococci-309 (VRE-309), and Bacillus subtilis ATCC 6633. Especially, 9i and 9q demonstrated inhibitory activities against the four bacterial strains with minimum inhibitory concentrations (MICs) of 0.78–1.56 μg/mL, and quite a few of other MRSA clinical strains with MICs of 0.78 μg/mL, superior to those of the positive controls vancomycin (MIC of 1 μg/mL) and methicillin (MIC of >200 μg/mL). This is the very first time that sulfonylurea derivatives have been identified as promising inhibitors against different MRSA clinical isolates. In addition, all the MIC values of the synthesized compounds against Candida albicans were greater than 100 μg/mL. Since the reported anti-Candida activities of sulfonylureas were due to acetohydroxyacid synthase (AHAS) inhibition, the molecular target against MRSA for the target sulfonylureas was thought to be a different mode of action. Density functional theory (DFT) calculations were finally performed to understand the structure–activity relationships, based on which, significant differences were observed between their HOMO maps for compounds with strong antibacterial activities and weak anti-MRSA effects. The present results hence provide valuable guidance for the discovery of novel agents to treat bacterial infections, especially against MRSA.

We have calculated the directed flow v_{1} and charge-dependent directed flow Δv_{1} of pions and protons in Au+Au collisions at sqrt[s_{NN}]=200 GeV by solving the coupled Boltzmann-Maxwell equations self-consistently. Our numerical results show that v_{1} for pions and protons are all negative in the positive midrapidity region and have similar behavior and magnitude. In contrast we find a quite different behavior in Δv_{1} for pions and protons. The difference lies in that Δv_{1} for protons mainly comes from pressure gradients of the medium, while the dominant contribution to Δv_{1} for pions is from electromagnetic fields. Our results indicate that the effect of the electric field will slightly exceed that of the magnetic field and lead to a small negative slope of Δv_{1} for pions.

Abstract The Lower Cretaceous Xiagou Formation contains the major source rocks for the crude oils discovered in the Qingxi Sag and the South Uplift in the Jiuquan Basin, northwestern China. The Xiagou Formation source rock was formed in a closed, anoxic, reducing, alkaline lacustrine environment with a high salinity. Its high content of brittle minerals is favorable for the fracturing of reservoirs in source rock formations in the Qingxi Sag. The Xiagou Formation contains a great number of fair to excellent source rocks, and their organic matter (OM) came chiefly from plankton/algae and high plants as well as possibly bacterial organisms. The Xiagou Formation source rocks mainly contain Type II OM and some Type III and Type I OM, with good oil-generating potential. The source rock maturity is mainly in the early-mature and mature stages, and its Ro value corresponding to oil peak is about 0.8%, which is lower than classic oil peak Ro value of 1.0%; therefore, a great deal of hydrocarbon was generated before the classic oil peak Ro = 1.0%. Mature source rock in the Xiagou Formation tends to be distributed in the older members and at a greater depth. There is a better exploration potential of tight oil in the deep Qingxi Sag.

AIM: To assess the effects of small incision lenticule extraction (SMILE) surgery on the corneal endothelium at 1d to 1mo postoperatively. METHODS: A retrospective, observational study was conducted on 47 patients (47 eyes) who received SMILE surgery. Patients were grouped according to contact lens wear condition. The corneal endothelium was examined preoperatively and at 1d, 1wk and 1mo postoperatively. The corneal endothelium was analyzed for endothelial cell density (ECD), percentage of hexagonal cells, and coefficient of variation (CV) of cell size. RESULTS: There were no significant decrease in the ECD, percentage of hexagonal cells or increase in CV at 1d, 1wk and 1mo postoperatively (P>0.05). However, there was a small increase of ECD by 2.88% in contact lens wearers (78.26±113.62 cell/mm2, P

The role of pro-inflammatory macrophage activation in cardiovascular disease (CVD) is a complex one amenable to network approaches. While an indispensible tool for elucidating the molecular underpinnings of complex diseases including CVD, the interactome is limited in its utility as it is not specific to any cell type, experimental condition or disease state. We introduced context-specificity to the interactome by combining it with co-abundance networks derived from unbiased proteomics measurements from activated macrophage-like cells. Each macrophage phenotype contributed to certain regions of the interactome. Using a network proximity-based prioritization method on the combined network, we predicted potential regulators of macrophage activation. Prediction performance significantly increased with the addition of co-abundance edges, and the prioritized candidates captured inflammation, immunity and CVD signatures. Integrating the novel network topology with transcriptomics and proteomics revealed top candidate drivers of inflammation. In vitro loss-of-function experiments demonstrated the regulatory role of these proteins in pro-inflammatory signaling.

Aiming at the problem of limited resources and operational time combat air defense combat, naval combat formation analysis dynamic resources scheduling needs, on the basis of the establishment of ship dynamic scheduling model of warship formation combat resources dynamic combat formation resource scheduling, the operational resources and operational objectives, relationship between reasonable allocation of resources to play the warship formation combat operations the maximum efficiency. The design of three kinds of air defense command models: centralized platform free attack mode, command mode, request attack mode of air defense strategy, put forward the dynamic scheduling hybrid algorithm for solving the model, according to the naval fleet air defense combat scenario example for simulation. The simulation results show that the air defense strategy with the request attack mode can have effects on multi-target attacks under the shared combat situation, and the hybrid algorithm based on combat resource dynamic scheduling can meet the real-time operational requirements.

Terrestrial LiDAR provides many disciplines with an effective and efficient means of producing realistic three-dimensional models of real world objects. With the advent of mobile terrestrial LiDAR, this ability has been expanded to include the rapid collection of three-dimensional models of large urban scenes. For all its usefulness, it does have drawbacks. One of the major problems faced by the LiDAR industry today is the automatic removal of outlying data points from LiDAR point clouds. This paper discusses the development and combined implementation of two methods of performing outlier detection in georeferenced point clouds. These methods made use of the raw data available from most time-of-flight mobile terrestrial LiDAR scanners in both the temporal and spatial domains. The first method involved a moving fixed interval smoother derived from the well-known position velocity acceleration Kalman Filter. The second method fitted a quadratic curved surface to sections of LiDAR data. The combined use of these routines is discussed through examples with real LiDAR data.

Chronic renal disease (CRD) accelerates atherosclerosis and cardiovascular calcification. Statins reduce low-density lipoprotein-cholesterol levels in patients with CRD, however, the benefits of statins on cardiovascular disease in CRD remain unclear. This study has determined the effects of pitavastatin, the newest statin, on arterial inflammation and calcification in atherogenic mice with CRD.CRD was induced by 5/6 nephrectomy in cholesterol-fed apolipoprotein E-deficient mice. Mice were randomized into three groups: control mice, CRD mice, and CRD mice treated with pitavastatin. Ultrasonography showed that pitavastatin treatment significantly attenuated luminal stenosis in brachiocephalic arteries of CRD mice. Near-infrared molecular imaging and correlative Mac3 immunostaining demonstrated a significant reduction in macrophage accumulation in pitavastatin-treated CRD mice. Pitavastatin treatment reduced levels of osteopontin in plasma and atherosclerotic lesions in CRD mice, but did not produce a significant reduction in calcification in atherosclerotic plaques as assesses by histology. CRD mice had significantly higher levels of phosphate in plasma than did control mice, which did not change by pitavastatin. In vitro, pitavastatin suppressed the expression of osteopontin in peritoneal macrophages stimulated with phosphate or calcium/phosphate in concentrations similar to those found in human patients with CRD.Our study provides in vivo evidence that pitavastatin reduces inflammation within atherosclerotic lesions in CRD mice.

In the title compound, C12H12O7, the dihedral angles between the benzene ring and the mean planes of the 3-carboxymethoxy, 1-carboxymethoxy and acetyl substituents are 8.67 (7), 7.81 (6) and 10.3 (18)°, respectively. In the crystal, molecules are linked by typical carboxylic acid O—H...O hydrogen bonds, forming a zigzag chain. C—H...O interactions also occur.

In the title compound, [Cd(NCS)2(C4H6N4O2)2]n, the CdII cation is located on an inversion center and is coordinated by two N and two S atoms from four SCN− anions and two N atoms from two 3-(1H-tetrazol-1-yl)propanoic acid (Htzp) ligands in a distorted octahedral geometry. The SCN− anions bridge the CdII cations into a layer structure parallel to (100). A weak intramolecular C—H...N interaction occurs. The layers are further assembled into a three-dimensional supramolecular structure via classical O—H...O hydrogen bonds.

In the title compound, C10H12O2, the substituted benzene ring is inclined at a dihedral angle of 75.9 (1)° to the almost planar butan-2-one substituent (r.m.s. deviation = 0.02 Å). In the crystal, intermolecular O—H...O hydrogen bonds link the molecules into chains along the a axis.

Background: Bed bugs are blood-feeding insects and are an important urban pest. Bed bugs are nocturnal insects and hide in cracks in walls and beds during the day. The study aims to: (1) determine the bed bugs species that infest Iraq, their infestation source, and their distribution; (2) determine the level of awareness and concern regarding bed bugs among the Iraqi community. Methods: Between 2020 and 2021, a survey of bed bug infestation dynamics was conducted in 18 infested sites located in major cities across eight governorates. The 23-item online survey was distributed over social media to Iraqi citizens between June and July 2022 to survey on their familiarity with bed bug habitat, medical significance, transmission, prevention, control measures, and concerns. Results: There were a total of 1104 bed bugs collected. Based on the morphological characteristics, bed bugs collected from eight Iraqi governorates are identified as Cimex hemipterus. Besides, a high rate of bed bug infestation was observed in workers' dormitories. The online questionnaire was answered by 1843 respondents and based on the feedback, most respondents (55.3%) have no awareness of bed bug infestations, while around 43.8% are somewhat concerned about bed bug infestations in Iraq. Conclusion: Only tropical bed bugs, C. hemipterus were found in all sampled sites. Bed bug infestations are mainly caused by migrant workers and the reuse of second-hand furniture and clothing. The results suggest that the Iraqi government should organize more proper demonstrations on bed bug awareness for the public. [ABSTRACT FROM AUTHOR]