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Background: The efficacy of transanal endorectal pull-through (TERPT) in treating classic Hirschsprung's disease may be enhanced by incorporating laparoscopic-assisted endorectal pull-through (LERPT). This study was done to compare the long-term outcomes of TERPT and LERPT in the treatment of classic segment Hirschsprung's disease., Methods: Longitudinal study., Results: Between 2015 and 2019, a total of 154 patients underwent pull-through procedures. Of these, 113 were treated with TERPT and 41 with LERPT. The median operative time was significantly shorter for TERPT (109.5 min) compared to LERPT (144.6 min; p < 0.001). In terms of long-term outcomes, no significant differences were observed between the two procedures regarding complication rates and stooling patterns., Conclusions: Both TERPT and LERPT are effective surgical approaches for children with classic segment Hirschsprung's disease. The study found no significant differences in long-term outcomes between the two techniques., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A new fluorescent sensor based on diethylaminosalicylaldehyde-thiosemicarbazide (DST) was studied using a combination of density functional theory calculations and experimental investigations. DST was able to detect the metal ions Ag + and Hg 2+ in the presence of various competing metal ions and anions, with detection limits of 0.45 and 0.34 µM, respectively. The DST sensor could operate in a fully aqueous environment and within a wide pH range from 5 to 9. Density functional theory studies supported the experimental findings in determining the stable structures of the DST sensor and the complexes between DST and the Ag + and Hg 2+ ions, as well as elucidating the fluorescence ON-OFF mechanism in the DST sensor and the complexes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

An investigation into the corrosion inhibition properties of L-tryptophan (TP) and 5-hydroxy-L-tryptophan (5-OH-TP) for mild steel in a 1.0 M HCl acidic medium was conducted using experimental and theoretical methods. Results obtained from polarization curve measurements reveal that TP and 5-OH-TP are effective mixed-type inhibitors, exhibiting the highest inhibition efficiencies of 91.22% and 94.05%, respectively, at a temperature of 293 K and a concentration of 10 -2 M. However, their inhibition efficiencies gradually decline with increasing temperature, reaching the lowest values of 70.65% for TP and 73.55% for 5-OH-TP at a concentration of 10 -4 M and a temperature of 323 K. The adsorption of TP and 5-OH-TP on the steel surface follows the Langmuir isotherm, suggesting monolayer adsorption. Electrochemical impedance spectroscopy analysis indicates that the adsorbed inhibitors form a protective film, effectively shielding the steel from corrosive agents in the solution. Notably, 5-OH-TP consistently exhibits superior inhibition efficiency compared to TP, attributed to the presence of polar OH groups that facilitate stronger bonding of the inhibitor molecule with the metal surface. Quantum chemical parameters and molecular dynamics simulations further confirm the superior corrosion inhibition ability of 5-OH-TP over TP in acidic environments. In particular, the binding energies of protonated TP at the N3 position and 5-OH-TP at the N4 position are 556.40 and 579.27 kJ mol -1 , respectively.

An assessment of the free radical scavenging potential of 4-amino-5-phenyl-4H-1,2,4-triazole-3-thiol (AT) and 4-amino-5-(4-pyridyl)-4H-1,2,4-triazole-3-thiol (AP) involved a combination of experimental methodologies and theoretical calculations. In the 2,2-diphenyl-1-picrylhydrazyl (DPPH • ) assay, AT exhibited an heightened efficacy in scavenging DPPH • radicals compared to AP. This was evidenced by the notably lower IC 50DPPH value observed for AT (1.3 × 10 -3 ± 0.2 × 10 -3 M) in comparison to AP (2.2 × 10 -3 ± 0.1 × 10 -3 M). Similarly, in the 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) (ABTS • + ) test, AT exhibited superior ability in neutralizing ABTS •+ free radical cations compared to AP, with the computed IC 50ABTS values of 4.7 × 10 -5 ± 0.1 × 10 -5 M for AT and 5.5 × 10 -5 ± 0.2 × 10 -5 M for AP. Density functional theory served as the tool for evaluating the correlation between structural attributes and the antioxidant efficacy of the studied molecules. The findings highlighted the flexibility of hydrogen atoms within NH and NH 2 groups to nucleophilic attacks, indicative of their pivotal role in the scavenging mechanism. Furthermore, investigations into the interactions between AT and AP with the free radical HOO • revealed predominantly the reaction via the hydrogen atom transfer mechanism. Both experimental observations and theoretical deductions collectively affirmed AT's superior free radical scavenging ability over AP in the gas phase and ethanol., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Alchemical binding free energy calculations are one of the most accurate methods for estimating ligand-binding affinity. Assessing the accuracy of the approach over protein targets is one of the most interesting issues. The free energy difference of binding between a protein and a ligand was calculated via the alchemical approach. The alchemical approach exhibits satisfactory accuracy over four targets, including AmpC beta-lactamase (AmpC); glutamate receptor, ionotropic kainate 1 (GluK1); heat shock protein 90 (Hsp90); and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro). In particular, the correlation coefficients between calculated binding free energies and the respective experiments over four targets range from 0.56 to 0.86. The affinity computed via free energy perturbation (FEP) simulations is overestimated over the experimental value. Particularly, the electrostatic interaction free energy rules the binding process of ligands to AmpC and GluK1. However, the van der Waals (vdW) interaction free energy plays an important role in the ligand-binding processes of HSP90 and SARS-CoV-2 Mpro. The obtained results associate with the hydrophilic or hydrophobic properties of the ligands. This observation may enhance computer-aided drug design., Competing Interests: There are no conficts to declare., (This journal is © The Royal Society of Chemistry.)

In Southeast Asia, breast cancer is the most prevalent cancer among women and ranks as the second leading cause of cancer-related deaths. This systematic review and meta-analysis, encompassing 27 observational cohort studies with a minimum one-year follow-up period, aimed to examine temporal trends in breast cancer survival rates. Among the subset of five out of eleven Southeast Asian nations with available data, our analysis revealed pooled survival rates of 88.8 % at 1 year, 73.8 % at 3 years, 70.8 % at 5 years, and 49.3 % at 10 years for breast cancer patients. The mean age at diagnosis was 50.77±10.07 years, with 52.81 % of patients presenting with positive lymph nodes. Notably, stages I and II remained predominant even five years post-diagnosis. Although an overall amelioration in survival rates transpired over the preceding four decades, a noticeable exception pertained to the 3-year rate, demonstrating limited improvement. These findings underscore the pressing need for enhanced research efforts, particularly in countries within the region that lack survival data, to enable accurate estimations. Furthermore, our review also emphasizes the crucial need for future comprehensive, well-designed studies to delve into the factors behind survival rate disparities in Southeast Asia and the younger age at diagnosis compared to other regions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study investigated the microbial community of a two-stage anaerobic membrane bioreactor (2S-AnMBR) co-digesting food waste and food court wastewater. The hydrolysis reactor (HR) was dominated by Bacteroidetes and Firmicutes phylum, with genus Lactobacillus enriched due to food waste fermentation. The up-flow anaerobic sludge blanket (UASB) was dominated by genus such as Methanobacterium and Methanosaeta. The presence of Methanobacterium (91 %) and Methanosaeta (7.5 %) suggested that methane production pathways inevitably undergo both hydrogenotrophic and acetoclastic methanogenesis. Hydrogen generated during hydrolysis fermentation in the HR contributed to methane production in the UASB via hydrogenotrophic pathways. However, the low abundance of Methanosaeta in the UASB can be attributed to the limited inffluent of volatile fatty acids (VFA) and the competitive presence of acetate-consuming bacteria Acinetobacter. The UASB exhibited more excellent dispersion and diversity of metabolic pathways compared to the HR, indicating efficient methane production., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Rosmarinic acid ( RA ) is reported in separate studies to be either an inducer or reliever of oxidative stress, and this contradiction has not been resolved. In this study, we present a comprehensive examination of the radical scavenging activity of RA using density functional theory calculations in comparison with experimental data. In model physiological media, RA exhibited strong HO • radical scavenging activity with overall rate constant values of 2.89 × 10 10 and 3.86 × 10 9 M -1 s -1 . RA is anticipated to exhibit excellent scavenging properties for HOO • in an aqueous environment ( k overall = 3.18 × 10 8 M -1 s -1 , ≈2446 times of Trolox) following the hydrogen transfer and single electron transfer pathways of the dianion state. The neutral form of the activity is equally noteworthy in a lipid environment ( k overall = 3.16 × 10 4 M -1 s -1 ) by the formal hydrogen transfer mechanism of the O6(7,15,16)-H bonds. Chelation with RA may prevent Cu(II) from reduction by the ascorbic acid anion (AA - ), hence blocking the OIL-1 pathway, suggesting that RA in an aqueous environment also serves as an OIL-1 antioxidant. The computational findings exhibit strong concurrence with the experimental observations, indicating that RA possesses a significant efficacy as a radical scavenger in physiological environments.

In this work, we developed a thin membrane of boehmite-polyvinyl alcohol composite (BOPOM) (diameter ∼ 5 cm) grafted ZIF-67 combing sol-gel and in-situ growth methods. The fabricated materials were characterized using FT-IR, SEM, XRD, TGA, XPS, and N 2 sorption techniques. Results indicate that ZIF-67 nanocrystals were well-grafted into the AlOOH-PVA matrix with reduced crystallite size. Furthermore, the decorated ZIF-67 offered additional porous structures and adsorption sites onto the membrane, enhancing their removal efficiency towards Cr 6+ compared to the undecorated and pristine ZIF-67. At pH ∼5.5, the harvested ZIF-67/BOPOM exhibited the highest Cr 6+ uptake capacity of ∼56.4 mg g -1 . Kinetic studies showed that the chromium adsorption on the prepared materials obeyed the pseudo-second-order model, and the kinetic parameters followed the order ZIFF-67/BOPOM (0.020 mg g -1 min -1 ) > BOPOM (0.011 mg g -1 min -1 ) > ZIF-67 (0.006 mg g -1 min -1 ). Notably, the adsorption mechanism study revealed that adsorbed Cr 6+ was reduced to Cr 3+ , and the reduction yield was boosted owing to grafting ZIF-67 into the BOPOM. In addition, the fabricated ZIF-67/BOPOM can simultaneously remove Cr 6+ and methyl orange dye (MO) in the solution due to their synergetic effects on each other. Furthermore, the hybrid membrane ZIF-67/BOPOM showed a chromium removal efficiency of ∼78.2% after four successive adsorption-desorption cycles. This study indicates that grafting nanocrystals ZIF-67 onto the super-platform boehmite-PVA is a promising strategy to harvest an adsorbent with a high adsorption ability, cost-effectiveness, and reduced secondary pollution risks., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The first oral drug for the treatment of COVID-19, Paxlovid, has been authorized; however, nirmatrelvir, a major component of the drug, is reported to be associated with some side effects. Moreover, the appearance of many novel variants raises concerns about drug resistance, and designing new potent inhibitors to prevent viral replication is thus urgent. In this context, using a hybrid approach combining machine learning (ML) and free energy simulations, 6 compounds obtained by modifying nirmatrelvir were proposed to bind strongly to SARS-CoV-2 Mpro. The structural modification of nirmatrelvir significantly enhances the electrostatic interaction free energy between the protein and ligand and slightly decreases the vdW term. However, the vdW term is the most important factor in controlling the ligand-binding affinity. In addition, the modified nirmatrelvir might be less toxic to the human body than the original inhibitor., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Developing low-cost and highly effective adsorbent materials to decolorate wastewater is still challenging in the industry. In this study, TiO 2 -modified Al 2 O 3 microspheres with different TiO 2 contents were produced by spray pyrolysis, which is rapid and easy to scale up. Results reveal that the modification of γ-Al 2 O 3 with TiO 2 reduced the crystallite size of Al 2 O 3 and generated more active sites in the composite sample. The as-synthesized Al 2 O 3 -TiO 2 microspheres were applied to remove anionic methyl orange (MO) and cationic rhodamine B (RB) dyes in an aqueous solution using batch and continuous flow column sorption processes. Results show that the Al 2 O 3 microspheres modified with 15 wt% of TiO 2 exhibited the maximum adsorbing capacity of ∼41.15 mg g -1 and ∼32.28 mg g -1 for MO and RB, respectively, exceeding the bare γ-Al 2 O 3 and TiO 2 . The impact of environmental complexities on the material's reactivity for the organic pollutants was further delineated by adjusting the pH and adding coexisting ions. At pH ∼5.5, the TiO 2 /Al 2 O 3 microspheres showed higher sorption selectivity towards MO. In the continuous flow column removal, the TiO 2 /Al 2 O 3 microspheres achieved sorption capacities of ∼31 mg g -1 and ∼19 mg g -1 until the breakthrough point for MO and RB, respectively. The findings reveal that TiO 2 -modified Al 2 O 3 microspheres were rapidly prepared by spray pyrolysis, and they effectively treated organic dyes in water in batch and continuous flow removal processes., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Inhibiting the biological activity of SARS-CoV-2 Mpro can prevent viral replication. In this context, a hybrid approach using knowledge- and physics-based methods was proposed to characterize potential inhibitors for SARS-CoV-2 Mpro. Initially, supervised machine learning (ML) models were trained to predict a ligand-binding affinity of ca. 2 million compounds with the correlation on a test set of R = 0.748 ± 0.044 . Atomistic simulations were then used to refine the outcome of the ML model. Using LIE/FEP calculations, nine compounds from the top 100 ML inhibitors were suggested to bind well to the protease with the domination of van der Waals interactions. Furthermore, the binding affinity of these compounds is also higher than that of nirmatrelvir, which was recently approved by the US FDA to treat COVID-19. In addition, the ligands altered the catalytic triad Cys145 - His41 - Asp187, possibly disturbing the biological activity of SARS-CoV-2., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Elsevier B.V. All rights reserved.)

Co-digestion of organic waste and wastewater is receiving increased attention as a plausible waste management approach toward energy recovery. However, traditional anaerobic processes for co-digestion are particularly susceptible to severe organic loading rates (OLRs) under long-term treatment. To enhance technological feasibility, this work presented a two-stage Anaerobic Membrane Bioreactor (2 S-AnMBR) composed of a hydrolysis reactor (HR) followed by an anaerobic membrane bioreactor (AnMBR) for long-term co-digestion of food waste and kitchen wastewater. The OLRs were expanded from 4.5, 5.6, and 6.9 kg COD m -3 d -1 to optimize biogas yield, nitrogen recovery, and membrane fouling at ambient temperatures of 25-32 °C. Results showed that specific methane production of UASB was 249 ± 7 L CH 4 kg -1 COD removed at the OLR of 6.9 kg TCOD m -3 d -1 . Total Chemical Oxygen Demand (TCOD) loss by hydrolysis was 21.6% of the input TCOD load at the hydraulic retention time (HRT) of 2 days. However, low total volatile fatty acid concentrations were found in the AnMBR, indicating that a sufficiently high hydrolysis efficiency could be accomplished with a short HRT. Furthermore, using AnMBR structure consisting of an Upflow Anaerobic Sludge Blanket Reactor (UASB) followed by a side-stream ultrafiltration membrane alleviated cake membrane fouling. The wasted digestate from the AnMBR comprised 42-47% Total Kjeldahl Nitrogen (TKN) and 57-68% total phosphorous loading, making it suitable for use in soil amendments or fertilizers. Finally, the predominance of fine particles (D10 = 0.8 μm) in the ultrafiltration membrane housing (UFMH) could lead to a faster increase in trans-membrane pressure during the filtration process., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Primary and secondary antioxidant activities of pyridoxal have been investigated by using density functional theory (DFT) at the M05-2X level combined with 6-311++G(d,p) basis set for non-metallic atoms and LanL2DZ for metallic ions. The former has been examined by its free radical scavenging activity towards HOO ● , HO ● , and NO 2 ● via different mechanisms including formal hydrogen transfer (FHT), proton transfer (PT), single electron transfer (SET), and radical adduct formation (RAF). The latter has been accomplished through its transition metal-chelating ability with Fe(III)/Fe(II) and Cu(II)/Cu(I) ions. The results show that pyridoxal illustrates as an efficient radical scavenger, especially, for HO ● and NO 2 ● in water. The overall rate constants (k overall ) for the reactions with HOO ● , HO ● , and NO 2 ● radicals are 1.30 × 10 4 , 5.76 × 10 9 , and 1.43 × 10 9  M -1 s -1 , respectively. The SET from the anionic state is the most dominant for the HOO ● and NO 2 ● scavenging reactions, while both RAF and SET contribute largely to the reaction with highly reactive HO ● radicals. Moreover, the anionic form of pyridoxal demonstrates a better role as a metal chelator than the neutral. However, the pro-oxidant risks of the formed complexes could be observed if there are superoxide radical anion (O 2 ●- ) and ascorbate (Asc - ) in aqueous media., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Oxoberberine (OB, 2,10-dihydroxy-3,9-dimethoxy-8-oxo-protoberberine, artathomsonine), which was isolated from Artabotrys thomsonii, was shown to exhibit potent antioxidant activity in vitro , however that is the only reported evidence of the radical scavenging activity of this compound thus far. In the present study, thermodynamic and kinetic calculations were used to determine the free radical scavenging activity of OB against a range of biologically important species, under physiological conditions. In the first part the activity is calculated against the HOO˙ radical that is both biologically important and a reference radical for comparison. It was found that OB has high antiradical capacity against HOO˙ in both lipid medium and water at physiological pH with k overall = 1.33 × 10 5 and 1.73 × 10 6 M -1 s -1 , respectively. The formal hydrogen transfer mechanism defined the activity in nonpolar environments, whereas in the aqueous solution the single electron transfer competes with the hydrogen transfer pathway. The results showed that, in lipid medium, the HOO˙ trapping capability of OB is better than typical antioxidants such as Trolox, BHT, resveratrol and ascorbic acid. Similarly, the activity of OB in water at pH 7.4 is roughly 19 and 7 times faster than those of Trolox and BHT, respectively, but slightly lower than the activities of resveratrol or ascorbic acid. In the second part, it was found that OB also exhibits high activity against other typical free radicals such as CH 3 O˙, CH 3 OO˙, CCl 3 OO˙, NO 2 , SO 4 ˙ - , DPPH and ABTS˙ + with k f ranging from 2.03 × 10 5 to 5.74 × 10 7 M -1 s -1 . Hence, it is concluded that OB is a promising radical scavenger in the physiological environment., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Direct and indirect antioxidant activities of rosmarinic acid (RA) based on HOO˙/CH 3 OO˙ radical scavenging and Fe(iii)/Fe(ii) ion chelation were theoretically studied using density functional theory at the M05-2X/6-311++G(2df,2p) level of theory. First, four antioxidant mechanisms including hydrogen atom transfer (HAT), radical adduct formation (RAF), proton loss (PL) and single electron transfer (SET) were investigated in water and pentyl ethanoate (PEA) phases. Regarding the free radical scavenging mechanism, HAT plays a decisive role with overall rate coefficients of 1.84 × 10 3 M -1 s -1 (HOO˙) and 4.49 × 10 3 M -1 s -1 (CH 3 OO˙) in water. In contrast to PL, RAF and especially SET processes, the HAT reaction in PEA is slightly more favorable than that in water. Second, the [Fe(iii)(H 2 O) 6 ] 3+ and [Fe(ii)(H 2 O) 6 ] 2+ ion chelating processes in an aqueous phase are both favorable and spontaneous especially at the O5, site-1, and site-2 positions with large negative Δ r G 0 values and great formation constant K f . Finally, the pro-oxidant risk of RA - was also considered via the Fe(iii)-to-Fe(ii) complex reduction process, which may initiate Fenton-like reactions forming reactive HO˙ radicals. As a result, RA - does not enhance the reduction process when ascorbate anions are present as reducing agents, whereas the pro-oxidant risk becomes remarkable when superoxide anions are found. The results encourage further attempts to verify the speculation using more powerful research implementations of the antioxidant activities of rosmarinic acid in relationship with its possible pro-oxidant risks., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The spread of severe acute respiratory syndrome coronavirus 2 novel coronavirus (SARS-CoV-2) worldwide has caused the coronavirus disease 2019 (COVID-19) pandemic. A hundred million people were infected, resulting in several millions of death worldwide. In order to prevent viral replication, scientists have been aiming to prevent the biological activity of the SARS-CoV-2 main protease (3CL pro or Mpro). In this work, we demonstrate that using a reasonable combination of deep-learning calculations and atomistic simulations could lead to a new approach for developing SARS-CoV-2 main protease (Mpro) inhibitors. Initially, the binding affinities of the natural compounds to SARS-CoV-2 Mpro were estimated via atomistic simulations. The compound tomatine, thevetine, and tribuloside could bind to SARS-CoV-2 Mpro with nanomolar/high-nanomolar affinities. Secondly, the deep-learning (DL) calculations were performed to chemically alter the top-lead natural compounds to improve ligand-binding affinity. The obtained results were then validated by free energy calculations using atomistic simulations. The outcome of the research will probably boost COVID-19 therapy., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Highly porous 3d transition metal oxide nanostructures are opening up the exciting area of oxygen evolution reaction (OER) catalysts in alkaline medium thanks to their good thermal and chemical stability, excellent physiochemical properties, high specific surface area and abundant nanopores. In this paper, highly porous Co-doped NiO nanorods were successfully synthesized by a simple hydrothermal method. The porous rod-like nanostructures were preserved with the added cobalt dopant ranging from 1 to 5 at% but were broken into aggregated nanoparticles at higher concentrations of additional cobalt. The catalytic activity of Co-doped NiO nanostructures for OER in an alkaline medium was assayed. The 5%Co-NiO sample showed a drastically enhanced activity. This result could originate from the combination of advantageous characteristics of highly porous NiO nanorods such as large surface area and high porosity as well as the important role of Co dopant that could provide more catalytic active sites, leading to an enhanced catalytic activity of the nanocatalyst., (© 2021 The Authors.)

Preventing the biological activity of SARS-CoV-2 main protease using natural compounds is of great interest. In this context, using a combination of AutoDock Vina and fast pulling of ligand simulations, eleven marine fungi compounds were identified that probably play as highly potent inhibitors for preventing viral replication. In particular, four compounds including M15 (3- O -(6- O -α-l-arabinopyranosyl)-β-d-glucopyranosyl-1,4-dimethoxyxanthone), M8 ( wailupemycins H ), M11 (cottoquinazolines B), and M9 ( wailupemycins I ) adopted the predicted ligand-binding free energy of -9.87, -9.82, -9.62, and -9.35 kcal mol -1 , respectively, whereas the other adopted predicted ligand-binding free energies in the range from -8.54 to -8.94 kcal mol -1 . The results were obtained using a combination of Vina and FPL simulations. Notably, although, AutoDock4 adopted higher accurate results in comparison with Vina, Vina is proven to be a more suitable technique for rapidly screening ligand-binding affinity with a large database of compounds since it requires much smaller computing resources. Furthermore, FPL is better than Vina to classify inhibitors upon ROC-AUC analysis., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Antioxidant and UV absorption activities of three aaptamine derivatives including piperidine[3,2- b ]demethyl(oxy)aaptamine (C1), 9-amino-2-ethoxy-8-methoxy-3 H -benzo[de][1,6]naphthyridine-3-one (C2), and 2-( sec -butyl)-7,8-dimethoxybenzo[de]imidazo[4,5,1- ij ][1,6]-naphthyridin-10(9 H )-one (C3) were theoretically studied by density functional theory (DFT). Direct antioxidant activities of C1-C3 were firstly evaluated via their intrinsic thermochemical properties and the radical scavenging activity of the potential antioxidants with the HOO˙/HO˙ radicals via four mechanisms, including: hydrogen atom transfer (HAT), single electron transfer (SET), proton loss (PL) and radical adduct formation (RAF). Kinetic calculation reveals that HOO˙ scavenging in water occurs via HAT mechanism with C1 ( k app , 7.13 × 10 6 M -1 s -1 ) while RAF is more dominant with C2 ( k app , 1.40 × 10 5 M -1 s -1 ) and C3 ( k app , 2.90 × 10 5 M -1 s -1 ). Antioxidant activity of aaptamine derivatives can be classified as C1 > C3 > C2. Indirect antioxidant properties based on Cu(i) and Cu(ii) ions chelating activity were also investigated in aqueous phase. All three studied compounds show spontaneous and favorable Cu(i) ion chelating activity with Δ G 0 being -15.4, -13.7, and -15.7 kcal mol -1 , whereas Δ G 0 for Cu(ii) chelation are -10.4, -10.8, and -2.2 kcal mol -1 for C1, C2 and C3, respectively. In addition, all compounds show UVA and UVB absorption; in which the excitations are determined mostly as π-π* transition. Overall, the results suggest the potential applications of the aaptamines in pharmaceutics and cosmetics, i.e. as a sunscreen and antioxidant ingredient., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Anthraquinones (ANQs) isolated from Paederia plants are known to have antidiarrheal, antitussive, anthelmintic, analgesic, anti-inflammatory, antihyperlipidemic, antihyperglycaemic, and antimicrobial activities. The antioxidant properties were also noted but not confirmed thus far. In this study, the superoxide and hydroperoxide radical scavenging activities of six ANQs were evaluated using a computational approach. The results suggest that the ANQs exhibit low HOO • antiradical activity in all environments, including the gas phase ( k < 10 2 M -1 s -1 ). In contrast, the ANQs might exert excellent O 2 •- radical scavenging activity, particularly in aqueous solution. The rate constants of the superoxide anion scavenging in water (at pH = 7.4) range from 3.42 × 10 6 to 3.70 × 10 8 M -1 s -1 . Compared with typical antioxidants such as ascorbic acid and quercetin, the superoxide anion scavenging activity of ANQs is significantly higher. Thus, the ANQs are promising O 2 •- radical scavengers in polar media., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Fraxin (FX) (7-hydroxy-6-methoxycoumarin 8-glucoside) is a typical natural product of the coumarin family. This compound was shown to protect endothelial cells from oxidative stress; however, the nature of its antioxidant properties is still ambiguous. In this study, we report on a systematic evaluation of the radical scavenging activity of FX using a two-tier protocol based on thermodynamic and kinetic calculations. The results show that FX has moderate activity in the aqueous physiological environment against a range of radicals including HO˙, CCl 3 O˙, CCl 3 OO˙, NO 2 , , and HOO˙. The latter was examined in detail due to the prevalence of HOO˙ as a source of oxidative stress in biological systems. HOO˙ scavenging activity was promising in the gas phase but low in physiological environments with k overall = 1.57 × 10 6 , 3.13 × 10 2 and 2.68 × 10 3 M -1 s -1 in the gas phase, pentyl ethanoate and water solvents, respectively. The formal hydrogen transfer mechanism at the O7-H bond dominates the hydroperoxyl radical scavenging of FX in the nonpolar media, whereas, in the polar environment, the activity is exerted by the single electron transfer mechanism of the anion state. This activity falls behind typical antioxidants such as Trolox, ascorbic acid, and trans -resveratrol under the studied conditions. Thus FX may have multiple health benefits, but it is not an outstanding natural antioxidant., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

SARS-CoV-2 rapidly infects millions of people worldwide since December 2019. There is still no effective treatment for the virus, resulting in the death of more than one million patients. Inhibiting the activity of SARS-CoV-2 main protease (Mpro), 3C-like protease (3CLP), is able to block the viral replication and proliferation. In this context, our study has revealed that in silico screening for inhibitors of SARS-CoV-2 Mpro can be reliably done using the monomeric structure of the Mpro instead of the dimeric one. Docking and fast pulling of ligand (FPL) simulations for both monomeric and dimeric forms correlate well with the corresponding experimental binding affinity data of 24 compounds. The obtained results were also confirmed via binding pose and noncovalent contact analyses. Our study results show that it is possible to speed up computer-aided drug design for SARS-CoV-2 Mpro by focusing on the monomeric form instead of the larger dimeric one., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Syringic acid (SA) is a natural phenolic acid found in vegetables, fruits, and other plant-based foods. A range of biological activities were proposed for this compound including anticancer, antimicrobial, anti-inflammation, and anti-diabetic activities, as well as antioxidant and antinitrosant properties. In this study, the focus is on the latter two. The HO • , HOO • , NO, and NO 2 scavenging activities of SA were evaluated in physiological environments by kinetic and thermodynamic calculations. The computed rate constants of the HO • radical scavenging of SA were 4.63 × 10 9 and 9.77 × 10 7 M -1 s -1 in polar and nonpolar solvents, respectively. A comparison with the experimentally determined rate constant in aqueous solution yields a k calculated / k experimental ratio of 0.3, thus the computed kinetic data are reasonably accurate. SA exhibited excellent HOO • and NO 2 scavenging activity in water ( k overall (HOO • ) = 1.53 × 10 8 M -1 s -1 and k overall (NO 2 ) = 1.98 × 10 8 M -1 s -1 ), whereas it did not show NO scavenging activity in any of the studied environments. In lipid medium, SA exhibited weak activity. Thus, in polar environments, the HOO • radical scavenging of SA is 1.53 times higher than that of ascorbic acid. Consistently, SA is a promising antioxidant and antinitrosant agent in polar environments.

The substituent effects on the N-H bond dissociation enthalpies (BDE), ionization energies (IE), acidities (proton affinity, PA), and radical scavenging behavior of 3,7-disubstituted phenoxazines (PhozNHs) and 3,7-disubstituted phenothiazines (PhtzNHs) were determined using density functional theory, with the M05-2X functional in conjunction with the 6-311++G(d,p) basis set. These thermochemical parameters calculated in both gas phase and benzene solution with respect to the changes in several different substituents including halogen, electron-withdrawing, and electron-donating groups at both 3 and 7 positions in both PhozNHs and PhtzNHs systems were analyzed in terms of the inherent relationships between them with some quantitative substituent effect parameters. The kinetic rate constants of hydrogen-atom exchange reactions between PhozNH and PhtzNH derivatives with the HOO • radical were also calculated, and the effects of the substituents on the kinetic behaviors of these reactions were thereby quantitatively evaluated., Competing Interests: The authors declare no competing financial interest., (© 2020 American Chemical Society.)

Herein, a novel fluorescent sensor has been developed for the detection of biothiols based on theoretical calculations of the stability constant of the complex between a Cu 2+ ion and ( E )-3-((2-(benzo[ d ]thiazol-2-yl)hydrazono)methyl)-7-(diethylamino) coumarin (BDC) as a fluorescent ligand. In this study, on the basis of density functional theory method, the Gibbs free energy of ligand-exchange reaction and the solvation model were carried out using thermodynamic cycles. The obtained results are in good agreement with the experimental data. The BDC-Cu 2+ complex can be used as a fluorescent sensor for the detection of biothiols in the presence of non-thiol containing amino acids, with a detection limit for cysteine at 0.3 μM. Moreover, theoretical calculations of excited states were used to elucidate variations in the fluorescence properties. The computed results show that the excited doublet states D 2 and D 1 are dark doublet states, which quench the fluorescence of the complex., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Mactanamide ( MA ) is a diketopiperazine isolated from marine fungi of the genus Aspergillus . This compound is known as a natural antioxidant from experimental studies, yet this activity has not been successfully modeled thus far. In this work, the hydroperoxyl radical scavenging activity of MA was evaluated in the gas phase and physiological environments by thermodynamic and kinetic calculations. The results revealed that the HOO • radical scavenging of MA in the lipid media follows the formal hydrogen transfer mechanism via hydrogen abstraction at the O11-H bond. In the aqueous solution, however, the antioxidant activity follows the sequential proton loss electron transfer mechanism. The rate constant of the HOO • scavenging of MA in the polar environment is about 1045 times ( k overall = 2.23 × 10 6 M -1 s -1 ) higher than that in the lipid medium ( k overall = 2.20 × 10 3 M -1 s -1 ). In polar media, the HOO • radical scavenging activity of MA is therefore 18 times higher than that of Trolox, the reference compound when assessing antioxidant activity. The results presented here align well with the experimental data, validating the mechanistic pathways and thus providing useful insights into the antioxidant activity of MA ., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Ribavirin and remdesivir have been preclinically reported as potential drugs for the treatment of SARS-CoV-2 infection, while light silver tetrylene complexes (NHE Ph -AgCl and (NHE Ph -AgCl) 2 with E = C, Si, and Ge) have gained significant interest due to their promising applicability on the cytological scale. Firstly, the structures and bonding states of silver-tetrylene complexes (NHE-Ag) and bis-silver-tetrylene complexes (NHE-Ag-bis) were investigated using density functional theory (DFT) at the BP86 level with the def2-SVP and def2-TZVPP basis sets. Secondly, the inhibitory capabilities of the carbene complexes (NHC-Ag and NHC-Ag-bis) and the two potential drugs (ribavirin and remdesivir) on human-protein ACE2 and SARS-CoV-2 protease PDB6LU7 were evaluated using molecular docking simulation. The carbene ligand NHC bonds in a head-on configuration with AgCl and (AgCl) 2 , whereas, the other NHE (E = Si and Ge) tetrylene ligands bond in a side-on mode to the metal fragments. The bond dissociation energy (BDE) of the NHE-Ag bond in the complex families follows the order of NHC-Ag > NHSi-Ag > NHGe-Ag and NHSi-Ag-bis > NHGe-Ag-bis > NHC-Ag-bis. The natural bond orbital analysis implies that the [NHE Ph →AgCl] and [(NHE Ph ) 2 →(AgCl) 2 ] donations are derived mainly from the σ- and π-contributions of the ligands. The docking results indicate that both the ACE2 and PDB6LU7 proteins are strongly inhibited by silver-carbene NHC-Ag, bis-silver-carbene NHC-Ag-bis, ribavirin, and remdesivir with the docking score energy values varying from -17.5 to -16.5 kcal mol -1 and -16.9 to -16.6 kcal mol -1 , respectively. The root-mean-square deviation values were recorded to be less than 2 Å in all the calculated systems. Thus, the present study suggests that silver-carbene NHC-Ag and bis-silver-carbene NHC-Ag-bis complexes are potential candidates to inhibit ACE2 and PDB6LU7, and thus potentially conducive to prevent infection caused by the SARS-CoV-2 virus., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Stabilization for tetrylone complexes, which carry ylidone(0) ligands [(CO) 5 W-X (YCp*) 2 ] (X = Ge, Sn, Pb; Y = B-Tl), has become an active theoretical research because of their promising application. Structure, bonding, and quantum properties of the transition-metal donor-acceptor complexes were theoretically investigated at the level of theory BP86 with several types of basis sets including SVP, TZVPP, and TZ2P+. The optimized structures reveal that all ligands X (YCp*) 2 are strongly bonded in tilted modes to the metal fragment W(CO) 5 , and Cp* rings are mainly η 5 -bonded to atom X. DFT-based bonding analysis results in an implication that the stability of W-X bond strength primarily stems from the donation (CO) 5 W ← X(YCp*) 2 formed by both σ- and π-bondings and the electrostatic interaction Δ E elstat . The W-X bond possesses a considerable polarizability toward atom X, and analysis on its hybridization is either sp 2 -characteristic or mainly p-characteristic. EDA-NOCV-based results further imply that the ligands XY perform as significant σ-donors but minor π-donors. The visual simulations of NOCV pairs and the deformation densities assemble a comprehensive summary on different components of the chemical bond via σ- and π-types in the complexes. This work contributes to the literature as an in-depth overview on predicted molecular structures and quantum parameters of the complexes [(CO) 5 W-X(YCp*) 2 ] (X = Ge, Sn, Pb; Y = B-Tl), conducive to either further theoretical reference or extending experimental research., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

A novel coumarin derivative ( 5 ) was synthesized and used as a colorimetric and fluorescent probe for selective detection of Cu 2+ ions in the presence of other metal ions, with the detection limits of 5.7 and 4.0 ppb, respectively. Cu 2+ ion reacts with probe 5 to form a 1:1 stoichiometry complex, resulting in a remarkable redshift of absorption maximum from 460 to 510 nm, as well as almost completely quenching fluorescence intensity of probe 5 at the wavelength of 536 nm. These changes can be distinctly observed by naked eyes. In addition, the working pH range of probe 5 is wide and suitable for physiological conditions, thus probe 5 may be used for detection of Cu 2+ ions in living cells. The stable structures of probe 5 and its 1:1 complex with Cu 2+ ion were optimized at the PBE0/6-31+G(d) level of theory. The presence and characteristics of bonds in compounds were studied through atoms in a molecule and natural bond orbital analysis. The formation of the complex led to a strong transfer of electron density from probe 5 as a ligand to Cu 2+ ion, resulting in breaking the π-electron conjugated system, which is the cause of fluorescence quenching and color change of 5- Cu 2+ complex., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

[This corrects the article DOI: 10.1021/acsomega.0c00772.]., (Copyright © 2020 American Chemical Society.)

GC-MS was applied to identify 24 main substances in Melaleuca cajuputi essential oil ( TA ) extracted from fresh cajeput leaves through steam distilling. The inhibitory capability of active compounds in the TA from Thua Thien Hue, Vietnam over the Angiotensin-Converting Enzyme 2 (ACE2) protein in human body - the host receptor for SARS-CoV-2 and the main protease (PDB6LU7) of the SARS-CoV-2 using docking simulation has been studied herein. The results indicate that the ACE2 and PDB6LU7 proteins were strongly inhibited by 10 out of 24 compounds accounting for 70.9% in the TA . The most powerful anticoronavirus activity is expressed in the order: Terpineol ( TA2 ) ≈ Guaiol ( TA5 ) ≈ Linalool ( TA19 ) > Cineol ( TA1 ) > β-Selinenol ( TA3 ) > α-Eudesmol ( TA4 ) > γ-Eudesmol ( TA7 ). Interestingly, the synergistic interactions of these 10 substances of the TA exhibit excellent inhibition into the ACE2 and PDB6LU7 proteins. The docking results orient that the natural Melaleuca cajuputi essential oil is considered as a valuable resource for preventing SARS-CoV-2 invasion into human body., Competing Interests: The authors declare no conflict of interest., (© 2020 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim.)

Eighteen active substances, including 17 organosulfur compounds found in garlic essential oil (T), were identified by GC-MS analysis. For the first time, using the molecular docking technique, we report the inhibitory effect of the considered compounds on the host receptor angiotensin-converting enzyme 2 (ACE2) protein in the human body that leads to a crucial foundation about coronavirus resistance of individual compounds on the main protease (PDB6LU7) protein of SARS-CoV-2. The results show that the 17 organosulfur compounds, accounting for 99.4% contents of the garlic essential oil, have strong interactions with the amino acids of the ACE2 protein and the main protease PDB6LU7 of SARS-CoV-2. The strongest anticoronavirus activity is expressed in allyl disulfide and allyl trisulfide, which account for the highest content in the garlic essential oil (51.3%). Interestingly, docking results indicate the synergistic interactions of the 17 substances, which exhibit good inhibition of the ACE2 and PDB6LU7 proteins. The results suggest that the garlic essential oil is a valuable natural antivirus source, which contributes to preventing the invasion of coronavirus into the human body., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Depsidones are secondary metabolites in lichens with a range of potential health benefits. Among others, these compounds are believed to exhibit high hydroxyl radical and superoxide scavenging abilities, warranting a detailed investigation of their antioxidant properties. In this study, the radical scavenging activity of natural depsidones from Ramalina lichenized fungi was investigated in silico. Calculations of the thermodynamic parameters suggested that the main radical scavenging pathway follows the formal hydrogen transfer (FHT) mechanism; however, unexpectedly low rate constants were found in the CH 3 OO • scavenging reaction. Establishing that the depsidones are mostly ionized in an aqueous environment suggested that the single-electron transfer (SET) mechanism should not be ruled out. Consistently, depsidones were revealed to be excellent HO • and O 2 •- scavengers in aqueous solutions ( k = 4.60 × 10 5 - 8.60 × 10 9 M -1 s -1 and k = 2.60 × 10 8 - 8.30 × 10 9 M -1 s -1 , respectively) following the sequential proton loss electron transfer (SPLET) mechanism. These results suggest that natural fungal depsidones are potent hydroxyl and superoxide radical scavengers in aqueous solutions., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

A mercury sensor ( N -(rhodamine-6G)lactam-ethylenediamine-4-dimethylamino-cinnamaldehyde-RLED) based on the Hg 2+ -promoted hydrolysis reaction has been designed and developed with a combination of theoretical calculations and experimental investigations. The interaction between RLED and Hg 2+ goes through a fast-initial stage with formation of a 1:1 complex, followed by a slow hydrolysis process. The formation of durable intermediate complexes is due to quite a long hydrolysis reaction time. As a result, RLED can selectively detect Hg 2+ in the presence of other metal ions, with a detection limit of 0.08 μM for the colorimetric method, and of 0.008 μM with the fluorescent method. In addition, the RLED sensor can work in a solution with a small amount of organic solvent, with a wide pH range from 5 to 10. The time-dependent density functional theory has been used for investigations of the excitation and de-excitation processes in RLED, intermediate complexes, and reaction products, thereby clarifying the changes in the fluorescence intensity before and after the RLED interacts with Hg 2+ ions.

Paclitaxel is one of the most effective chemotherapeutic agents for treating various types of cancer. However, the clinical application of paclitaxel in cancer treatment is considerably limited due to its poor water solubility and low therapeutic index. Thus, it requires an urgent solution to improve therapeutic efficacy of paclitaxel. In this study, folate decorated paclitaxel loaded PLA-TPGS nanoparticles were prepared by a modified emulsification/solvent evaporation method. The obtained nanoparticles were characterized by Field Emission Scanning Electron Microscopy (FESEM), Fourier Transform Infrared (FTIR) and Dynamic Light Scattering (DLS) method. The spherical nanoparticles were around 50 nm in size with a narrow size distribution. Targeting effect of nanoparticles was investigated in vitro on cancer cell line and in vivo on tumor bearing nude mouse. The results indicated the effective targeting of folate decorated paclitaxel loaded copolymer nanoparticles on cancer cells both in vitro and in vivo.

A new rhodamine-ethylenediamine-nitrothiourea conjugate (RT) was synthesized and its sensing property as a fluorescent chemodosimeter toward metal ions was explored in water media. Analytical results from absorption and fluorescence spectra revealed that the addition of Hg(2+) ions to the aqueous solution of the chemodosimeter RT caused a distinct fluorescence OFF-ON response with a remarkable visual color change from colorless to pink; however, no clear spectral and color changes were observed from other metal ions including: Zn(2+) , Cu(2+) , Cd(2+) , Pb(2+) , Ag(+) , Fe(2+) , Cr(3+) , Co(3+) , Ni(2+) , Ca(2+) , Mg(2+) , K(+) and Na(+) . The sensing results and the molecular structure suggested that a Hg(2+) -induced a desulfurization reaction and cyclic guanylation of the thiourea moiety followed by ring-opening of the rhodamine spirolactam in RT are responsible for a distinct fluorescence turn-on signal, indicating that RT is a remarkably sensitive and selective chemodosimeter for Hg(2+) ions in aqueous solution. Hg(2+) within a concentration range from 0.1 to 25 μM can be determined using RT as a chemodosimeter and a detection limit of 0.04 μM is achieved., (Copyright © 2014 John Wiley & Sons, Ltd.)