bluuebunny/crossref_metadata_2025 huggingface dataset:
Recovery Strategies for Heavy Metal-Inhibited Biological Nitrogen Removal from Wastewater Treatment Plants: A Review
Authors: Mpongwana Ncumisa , Rathilal Sudesh , Tetteh Emmanuel K.
Published: September 2022

Biological nutrient removal is an integral part of a wastewater treatment plant. However, the microorganism responsible for nutrient removal is susceptible to inhibition by external toxicants such as heavy metals which have the potential to completely inhibit biological nutrient removal. The inhibition is a result of the interaction between heavy metals with the cell membrane and the deoxyribonucleic acid (DNA) of the cell. Several attempts, such as the addition of pretreatment steps, have been made to prevent heavy metals from entering the biological wastewater systems. However, the unexpected introduction of heavy metals into wastewater treatment plants result in the inhibition of the biological wastewater treatment systems. This necessitates the recovery of the biological process. The biological processes may be recovered naturally. However, the natural recovery takes time; additionally, the biological process may not be fully recovered under natural conditions. Several methods have been explored to catalyze the recovery process of the biological wastewater treatment process. Four methods have been discussed in this paper. These include the application of physical methods, chelating agents, external field energy, and biological accelerants. These methods are compared for their ability to catalase the process, as well as their environmental friendliness. The application of bio-accelerant was shown to be superior to other recovery strategies that were also reviewed in this paper. Furthermore, the application of external field energy has also been shown to accelerate the recovery process. Although EDTA has been gaining popularity as an alternative recovery strategy, chelating agents have been shown to harm the metal acquisition of bacteria, thereby affecting other metabolic processes that require heavy metals in small amounts. It was then concluded that understanding the mechanism of inhibition by specific heavy metals, and understanding the key microorganism in the inhibited process, is key to developing an effective recovery strategy.
Past, Present, and Future of Genome Modification in Escherichia coli
Authors: Mori Hirotada , Kataoka Masakazu , Yang Xi
Published: September 2022

Escherichia coli K-12 is one of the most well-studied species of bacteria. This species, however, is much more difficult to modify by homologous recombination (HR) than other model microorganisms. Research on HR in E. coli has led to a better understanding of the molecular mechanisms of HR, resulting in technical improvements and rapid progress in genome research, and allowing whole-genome mutagenesis and large-scale genome modifications. Developments using λ Red (exo, bet, and gam) and CRISPR-Cas have made E. coli as amenable to genome modification as other model microorganisms, such as Saccharomyces cerevisiae and Bacillus subtilis. This review describes the history of recombination research in E. coli, as well as improvements in techniques for genome modification by HR. This review also describes the results of large-scale genome modification of E. coli using these technologies, including DNA synthesis and assembly. In addition, this article reviews recent advances in genome modification, considers future directions, and describes problems associated with the creation of cells by design.
Manufactured Nano-Objects Confer Viral Protection against Cucurbit Chlorotic Yellows Virus (CCYV) Infecting Nicotiana benthamiana
Authors: Al-Zaban Mayasar I. , Alhag Sadeq K. , Dablool Anas S. , Ahmed Ahmed Ezzat , Alghamdi Saad , Ali Baber , Al-Saeed Fatimah A. , Saleem Muhammad Hamzah , Poczai Peter
Published: September 2022

Nanotechnology has emerged as a new tool to combat phytopathogens in agricultural crops. Cucurbit chlorotic yellows virus (CCYV) mainly infects Solanaceae crops and causes significant crop losses. Nanomaterials (NMs) may have efficacy against plant viruses, but the mechanisms underlying complex nanomaterials-plant-virus interactions remain elusive. We challenged Nicotiana benthamiana plants with GFP-tagged CCYV and observed morphological, physiological, and molecular changes in response to 21-d foliar exposure to nanoscale Fe and Zn and C60 fullerenes at 100 mg/L concentration for 21 days. We observed that in response to C60 (100 mg/L) treatment, plants displayed a normal phenotype while the viral infection was not seen until 5 days post-inoculation. On the contrary, Fe and Zn were unable to suppress viral progression. The mRNA transcriptional analysis for GFP and viral coat protein revealed that the transcripts of both genes were 5-fold reduced in response to C60 treatment. Evaluation of the chloroplast ultrastructure showed that NMs treatment maintained the normal chloroplast structure in the plants as compared to untreated plants. C60 upregulated the defense-related phytohormones (abscisic acid and salicylic acid) by 42–43%. Our results demonstrate the protective function of carbon-based NMs, with suppression of CCYV symptoms via inhibition of viral replication and systemic movement.
Using Waste Brine from Desalination Plant as a Source of Industrial Water in Copper Mining Industry
Authors: Cruz Constanza , Herrera-León Sebastián , Calisaya-Azpilcueta Daniel , Salazar Ruth , Cisternas Luis A. , Kraslawski Andrzej
Published: September 2022

One of the main challenges of seawater desalination is a large volume of waste brine production that is commonly discharged into the sea and may threaten the marine ecosystem. This is critical in regions where conventional water resources are scarce and desalinated seawater is an alternative to meet water demand. Especially in regions where the mining industry is a key player in the economic development. The novelty of this research consists in the determination of the potential use of waste brine, discharged from the reverse osmosis process, as a source of industrial water in copper mining industry. To enable the waste brine applicability, there should be reduced calcium and magnesium ions concentration for improving copper recovery in the froth flotation process. The flotation tests were conducted in a batch cell with synthetic minerals composed of chalcopyrite, kaolinite, and quartz using different water qualities. The results showed that treated waste brine significantly improved copper recovery compared to untreated waste brine and seawater. Similar copper recovery was achieved when flotation test was performed with tap water and treated waste brine. Therefore, treated waste brine could provide a suitable water quality required in the froth flotation process as an alternative non-conventional water resource.
Zn-Pb Dumps, Environmental Pollution and Their Recultivation, Case of Ruda Śląska-Wirek, S Poland
Authors: Huber Miłosz , Iakovleva Olga
Published: September 2022

This article describes the results of a study on the Zn-Pb heap, which is located in the center of the city of Ruda Śląska. The heap dates back to the 19th century but was rediscovered in the 21st century and abandoned. Located in the center of the city, it is eroded and contributes to the spreading of pollutants. The authors performed a study on the components of the dump using microscopic observations and geochemical analyses. The results indicate that the components of the heap are mobile, mainly due to the infiltration of meteoric waters affecting the contamination of soils and plants. The present work is devoted to a review of the state of the environment in the area of the heap and a proposal for its reclamation by covering it with an isolation layer or moving it to a protected place away from the city center. It is possible, in the future, to build an Environmental Education Center, for education and the monitoring of enrivonmental problems in Upper Silesia.
Genus Smenospongia: Untapped Treasure of Biometabolites—Biosynthesis, Synthesis, and Bioactivities
Authors: Ibrahim Sabrin R. M. , Fadil Sana A. , Fadil Haifa A. , Hareeri Rawan H. , Abdallah Hossam M. , Mohamed Gamal A.
Published: September 2022

Marine sponges continue to attract remarkable attention as one of the richest pools of bioactive metabolites in the marine environment. The genus Smenospongia (order Dictyoceratida, family Thorectidae) sponges can produce diverse classes of metabolites with unique and unusual chemical skeletons, including terpenoids (sesqui-, di-, and sesterterpenoids), indole alkaloids, aplysinopsins, bisspiroimidazolidinones, chromenes, γ-pyrones, phenyl alkenes, naphthoquinones, and polyketides that possessed diversified bioactivities. This review provided an overview of the reported metabolites from Smenospongia sponges, including their biosynthesis, synthesis, and bioactivities in the period from 1980 to June 2022. The structural characteristics and diverse bioactivities of these metabolites could attract a great deal of attention from natural-product chemists and pharmaceuticals seeking to develop these metabolites into medicine for the treatment and prevention of certain health concerns.
Dimethylaminoethyl Methacrylate/Diethylene Glycol Dimethacrylate Grafted onto Folate-Esterified Bagasse Xylan/Andrographolide Composite Nanoderivative: Synthesis, Molecular Docking and Biological Activity
Authors: Su Yue , Zhang Shufen , Li Heping , Zhao Bin , Tian Kexin , Zou Zhiming
Published: September 2022

As a biocompatible biomaterial, bagasse xylan (BX) has been widely used in the biomedical field. The low biological activity of andrographolide (AD) restricts its development, so AD with certain anticancer activity is introduced. We use chemical modification methods such as grafting and esterification to improve the biological activity and make a novel anticancer nanomaterial. On the basis of the esterification of a mixture of BX and AD with folic acid (FA), a novel anticancer nanoderivative of bagasse xylan/andrographolide folate-g-dimethylaminoethyl methacrylate (DMAEMA)/diethylene glycol dimethacrylate (DEGDMA) nanoparticles (FA-BX/AD-g-DMAEMA/DEGDMA NPs) was synthesized by introducing DMAEMA and DEGDMA monomers through a graft copolymerization and nanoprecipitation method. The effects of reaction temperature, reaction time, the initiator concentration and the mass ratio of FA-BX/AD to mixed monomers on the grafting rate (GR) were investigated. The structure of the obtained product was characterized by FTIR, SEM, XRD and DTG. Further, molecular docking and MTT assays were performed to understand the possible docking sites with the target proteins and the anticancer activity of the product. The results showed that the GR of the obtained product was 79% under the conditions of the initiator concentration 55 mmol/L, m (FA-BX/AD):m (mixed monomer) = 1:2, reaction temperature 50 °C and reaction time 5 h. The inhibition rate of FA-BX/AD-g-DMAEMA/DEGDMA NPs on human lung cancer cells (NCI-H460) can reach 39.77 ± 5.62%, which is about 7.6 times higher than that of BX. Therefore, this material may have potential applications in the development of anticancer drug or carriers and functional materials.
Recent Advances in the Modulation of Cholinergic Signaling
Authors: Dallanoce Clelia
Published: September 2022

In recent years, an impressive number of research studies have been conducted to improve the understanding of the structure and function of the cholinergic system, and significant progress has also been made in elucidating the roles of neuronal and non-neuronal acetylcholine (ACh) in the pathogenesis and treatment of human disease [...]
Nano-Based Co-Delivery System for Treatment of Rheumatoid Arthritis
Authors: Zhang Shixin , Zhang Miaomiao , Li Xiangyu , Li Ge , Yang Bo , Lu Xinyue , Gao Yang , Sun Fengying
Published: September 2022

A systemic autoimmune condition known as rheumatoid arthritis (RA) has a significant impact on patients’ quality of life. Given the complexity of RA’s biology, no single treatment can totally block the disease’s progression. The combined use of co-delivery regimens integrating various diverse mechanisms has been widely acknowledged as a way to make up for the drawbacks of single therapy. These days, co-delivery systems have been frequently utilized for co-treatment, getting over drug limitations, imaging of inflammatory areas, and inducing reactions. Various small molecules, nucleic acid drugs, and enzyme-like agents intended for co-delivery are frequently capable of producing the ability to require positive outcomes. In addition, the excellent response effect of phototherapeutic agents has led to their frequent use for delivery together with chemotherapeutics. In this review, we discuss different types of nano-based co-delivery systems and their advantages, limitations, and future directions. In addition, we review the prospects and predicted challenges for the combining of phototherapeutic agents with conventional drugs, hoping to provide some theoretical support for future in-depth studies of nano-based co-delivery systems and phototherapeutic agents.
Differential Expression and Localization of ADAMTS Proteinases in Proliferative Diabetic Retinopathy
Authors: Abu El-Asrar Ahmed M. , Nawaz Mohd Imtiaz , Allegaert Eef , Siddiquei Mohammad Mairaj , Ahmad Ajmal , Gikandi Priscilla , De Hertogh Gert , Opdenakker Ghislain
Published: September 2022

We analyzed the expression of ADAMTS proteinases ADAMTS-1, -2, -4, -5 and -13; their activating enzyme MMP-15; and the degradation products of proteoglycan substrates versican and biglycan in an ocular microenvironment of proliferative diabetic retinopathy (PDR) patients. Vitreous samples from PDR and nondiabetic patients, epiretinal fibrovascular membranes from PDR patients, rat retinas, retinal Müller glial cells and human retinal microvascular endothelial cells (HRMECs) were studied. The levels of ADAMTS proteinases and MMP-15 were increased in the vitreous from PDR patients. Both full-length and cleaved activation/degradation fragments of ADAMTS proteinases were identified. The amounts of versican and biglycan cleavage products were increased in vitreous from PDR patients. ADAMTS proteinases and MMP-15 were localized in endothelial cells, monocytes/macrophages and myofibroblasts in PDR membranes, and ADAMTS-4 was expressed in the highest number of stromal cells. The angiogenic activity of PDR membranes correlated significantly with levels of ADAMTS-1 and -4 cellular expression. ADAMTS proteinases and MMP-15 were expressed in rat retinas. ADAMTS-1 and -5 and MMP-15 levels were increased in diabetic rat retinas. HRMECs and Müller cells constitutively expressed ADAMTS proteinases but not MMP-15. The inhibition of NF-κB significantly attenuated the TNF-α-and-VEGF-induced upregulation of ADAMTS-1 and -4 in a culture medium of HRMECs and Müller cells. In conclusion, ADAMTS proteinases, MMP-15 and versican and biglycan cleavage products were increased in the ocular microenvironment of patients with PDR.
Rapid Identification of Wild Gentiana Genus in Different Geographical Locations Based on FT-IR and an Improved Neural Network Structure Double-Net
Authors: Zeng Pan , Li Xiaokun , Wu Xunxun , Diao Yong , Liu Yao , Liu Peizhong
Published: September 2022

Gentiana Genus, a herb mainly distributed in Asia and Europe, has been used to treat the damp heat disease of the liver for over 2000 years in China. Previous studies have shown significant differences in the compositional contents of wild Gentiana Genus samples from different geographical origins. Therefore, the traceable geographic locations of the wild Gentiana Genus samples are essential to ensure practical medicinal value. Over the last few years, the developments in chemometrics have facilitated the analysis of the composition of medicinal herbs via spectroscopy. Notably, FT-IR spectroscopy is widely used because of its benefit of allowing rapid, nondestructive measurements. In this paper, we collected wild Gentiana Genus samples from seven different provinces (222 samples in total). Twenty-one different FT-IR spectral pre-processing methods that were used in our experiments. Meanwhile, we also designed a neural network, Double-Net, to predict the geographical locations of wild Gentiana Genus plants via FT-IR spectroscopy. The experiments showed that the accuracy of the neural network structure Double-Net we designed can reach 100%, and the F1_score can reach 1.0.
Efficient Synthesis of 2-OH Thioglycosides from Glycals Based on the Reduction of Aryl Disulfides by NaBH4
Authors: Guo Yang-Fan , Luo Tao , Feng Guang-Jing , Liu Chun-Yang , Dong Hai
Published: September 2022

An improved method to efficiently synthesize 2-OH thioaryl glycosides starting from corresponding per-protected glycals was developed, where 1,2-anhydro sugars were prepared by the oxidation of glycals with oxone, followed by reaction of crude crystalline 1,2-anhydro sugars with NaBH4 and aryl disulfides. This method has been further used in a one-pot reaction to synthesize glycosyl donors having both “armed” and “NGP (neighboring group participation)” effects.
Pouteria macrophylla Fruit Extract Microemulsion for Cutaneous Depigmentation: Evaluation Using a 3D Pigmented Skin Model
Authors: Brathwaite Ana Clara N. , Alencar-Silva Thuany , Carvalho Larissa A. C. , Branquinho Maryana S. F. , Ferreira-Nunes Ricardo , Cunha-Filho Marcilio , Gelfuso Guilherme M. , Maria-Engler Silvya S. , Carvalho Juliana Lott , Silva Joyce K. R. , Gratieri Tais
Published: September 2022

Here, we verify the depigmenting action of Pouteria macrophylla fruit extract (EXT), incorporate it into a safe topical microemulsion and assess its effectiveness in a 3D pigmented skin model. Melanocytes-B16F10- were used to assess the EXT effects on cell viability, melanin synthesis, and melanin synthesis-related gene transcription factor expression, which demonstrated a 32% and 50% reduction of intra and extracellular melanin content, respectively. The developed microemulsion was composed of Cremophor EL®/Span 80 4:1 (w/w), ethyl oleate, and pH 4.5 HEPES buffer and had an average droplet size of 40 nm (PdI 0.40 ± 0.07). Skin irritation test with reconstituted epidermis (Skin Ethic RHETM) showed that the formulation is non-irritating. Tyrosinase inhibition was maintained after skin permeation in vitro, in which microemulsion showed twice the inhibition of the conventional emulsion (20.7 ± 2.2% and 10.7 ± 2.4%, respectively). The depigmenting effect of the microemulsion was finally confirmed in a 3D culture model of pigmented skin, in which histological analysis showed a more pronounced effect than a commercial depigmenting formulation. In conclusion, the developed microemulsion is a promising safe formulation for the administration of cutite fruit extract, which showed remarkable depigmenting potential compared to a commercial formulation.
pH and Reduction Dual-Responsive Nanogels as Smart Nanocarriers to Resist Doxorubicin Aggregation
Authors: Maruf Ali , Milewska Małgorzata , Lalik Anna , Wandzik Ilona
Published: September 2022

The use of smart nanocarriers that can modulate therapeutic release aided by biological cues can prevent undesirable cytotoxicity caused by the premature release of cytotoxic drugs during nanocarrier circulation. In this report, degradable nanocarriers based on pH/reduction dual-responsive nanogels were synthesized to encapsulate doxorubicin hydrochloride (DOX) and specifically boost the release of DOX in conditions characteristic of the cancer microenvironment. Nanogels containing anionic monomer 2-carboxyethyl acrylate (CEA) and N,N′-bis(acryloyl)cystamine (CBA) as a degradable crosslinker have been successfully synthesized via photoinitiated free radical polymerization. The loading process was conducted after polymerization by taking advantage of the electrostatic interaction between the negatively charged nanogels and the positively charged DOX. In this case, a high drug loading capacity (DLC) of up to 27.89% was achieved. The entrapment of DOX into a nanogel network could prevent DOX from aggregating in biological media at DOX concentrations up to ~160 µg/mL. Anionic nanogels had an average hydrodynamic diameter (dH) of around 90 nm with a negative zeta (ζ) potential of around −25 mV, making them suitable for targeting cancer tissue via the enhanced permeation effect. DOX-loaded nanogels formed a stable dispersion in different biological media, including serum-enriched cell media. In the presence of glutathione (GSH) and reduced pH, drug release was enhanced, which proves dual responsivity. An in vitro study using the HCT 116 colon cancer cell line demonstrated the enhanced cytotoxic effect of the NG-CBA/DOX-1 nanogel compared to free DOX. Taken together, pH/reduction dual-responsive nanogels show promise as drug delivery systems for anticancer therapy.
Natural Deep Eutectic Solvent-Based Microwave-Assisted Extraction of Total Flavonoid Compounds from Spent Sweet Potato (Ipomoea batatas L.) Leaves: Optimization and Antioxidant and Bacteriostatic Activity
Authors: Zhang Yuqin , Bian Shiquan , Hu Jing , Liu Gang , Peng Shouhua , Chen Hongjiang , Jiang Zhenying , Wang Tongyong , Ye Quan , Zhu Haibo
Published: September 2022

Natural deep eutectic solvents (NADESs) coupled with microwave-assisted extraction (MAE) were applied to extract total flavonoid compounds from spent sweet potato (Ipomoea batatas L.) leaves. In this study, ten different NADESs were successfully synthesized for the MAE. Based on single-factor experiments, the response surface methodology (RSM) was applied, and the microwave power, extraction temperature, extraction time, and solid–liquid ratio were further evaluated in order to optimize the yields of total flavonoid compounds. Besides, the extracts were recovered by macroporous resin for the biological activity detection of flavonoid compounds. As a result, NADES-2, synthesized by choline chloride and malic acid (molar ratio 1:2), exhibited the highest extraction yield. After that, the NADES-2-based MAE process was optimized and the optimal conditions were as follows: microwave power of 470 W, extraction temperature of 54 °C, extraction time of 21 min, and solid–liquid ratio of 70 mg/mL. The extraction yield (40.21 ± 0.23 mg rutin equivalents/g sweet potato leaves) of the model validation experiment was demonstrated to be in accordance with the predicted value (40.49 mg rutin equivalents/g sweet potato leaves). In addition, flavonoid compounds were efficiently recovered from NADES-extracts with a high recovery yield (>85%) using AB-8 macroporous resin. The bioactivity experiments in vitro confirmed that total flavonoid compounds had good DPPH and O2−· radical-scavenging activity, as well as inhibitory effects on E. coli, S. aureus, E. carotovora, and B. subtilis. In conclusion, this study provides a green and efficient method to extract flavonoid compounds from spent sweet potato leaves, providing technical support for the development and utilization of sweet potato leaves’ waste.
Design, Synthesis, and Evaluation of a Set of Carboxylic Acid and Phosphate Prodrugs Derived from HBV Capsid Protein Allosteric Modulator NVR 3-778
Authors: Ji Xiangkai , Jiang Xiangyi , Kobayashi Chisa , Ren Yujie , Hu Lide , Gao Zhen , Kang Dongwei , Jia Ruifang , Zhang Xujie , Zhao Shujie , Watashi Koichi , Liu Xinyong , Zhan Peng
Published: September 2022

Hepatitis B virus (HBV) capsid protein (Cp) is necessary for viral replication and the maintenance of viral persistence, having become an attractive target of anti-HBV drugs. To improve the water solubility of HBV capsid protein allosteric modulator (CpAM) NVR 3-778, a series of novel carboxylic acid and phosphate prodrugs were designed and synthesized using a prodrug strategy. In vitro HBV replication assay showed that these prodrugs maintained favorable antiviral potency (EC50 = 0.28–0.42 µM), which was comparable to that of NVR 3-778 (EC50 = 0.38 µM). More importantly, the cytotoxicity of prodrug N8 (CC50 > 256 µM) was significantly reduced compared to NVR 3-778 (CC50 = 13.65 ± 0.21 µM). In addition, the water solubility of prodrug N6 was hundreds of times better than that of NVR 3-778 in three phosphate buffers with various pH levels (2.0, 7.0, 7.4). In addition, N6 demonstrated excellent plasma and blood stability in vitro and good pharmacokinetic properties in rats. Finally, the hemisuccinate prodrug N6 significantly improved the candidate drug NVR 3-778’s water solubility and increased metabolic stability while maintaining its antiviral efficacy.
In Silico Study towards Repositioning of FDA-Approved Drug Candidates for Anticoronaviral Therapy: Molecular Docking, Molecular Dynamics and Binding Free Energy Calculations
Authors: Qayed Wesam S. , Ferreira Rafaela S. , Silva José Rogério A.
Published: September 2022

The SARS-CoV-2 targets were evaluated for a set of FDA-approved drugs using a combination of drug repositioning and rigorous computational modeling methodologies such as molecular docking and molecular dynamics (MD) simulations followed by binding free energy calculations. Six FDA-approved drugs including, Ouabain, Digitoxin, Digoxin, Proscillaridin, Salinomycin and Niclosamide with promising anti-SARS-CoV-2 activity were screened in silico against four SARS-CoV-2 proteins—papain-like protease (PLpro), RNA-dependent RNA polymerase (RdRp), SARS-CoV-2 main protease (Mpro), and adaptor-associated kinase 1 (AAK1)—in an attempt to define their promising targets. The applied computational techniques suggest that all the tested drugs exhibited excellent binding patterns with higher scores and stable complexes compared to the native protein cocrystallized inhibitors. Ouabain was suggested to act as a dual inhibitor for both PLpro and Mpro enzymes, while Digitoxin bonded perfectly to RdRp. In addition, Salinomycin targeted PLpro. Particularly, Niclosamide was found to target AAK1 with greater affinity compared to the reference drug. Our study provides comprehensive molecular-level insights for identifying or designing novel anti-COVID-19 drugs.
New 11-Methoxymethylgermacranolides from the Whole Plant of Carpesium divaricatum
Authors: Zhang Tao , Zhang Haixin , Lin Chunyu , Fu Lu , Zou Zhongmei
Published: September 2022

Eight new 11-methoxymethylgermacranolides (1–8) were isolated from the ethanol extract of the whole plant of Carpesium divaricatum. The planar structures and relative configurations of the new compounds were determined by detailed spectroscopic analysis. The absolute configuration of 1 was established by electronic circular dichroism (ECD) spectrum and X-ray crystallographic analysis, and the stereochemistry of the new compounds 2–8 were determined by similar ECD data with 1. The absolute configurations of 5 and 7 were further confirmed by using quantum chemical electronic circular dichroism (ECD) calculations. Compound 4 exhibited weak cytotoxicity against MCF-7 cells. Compound 8 could potently decrease PGE2 productions in LPS-induced RAW 264.7 cells.
Metabolic Study of Tetra-PEG-Based Hydrogel after Pelvic Implantation in Rats
Authors: Zuo Baoyan , Cao Mingxue , Tao Xiumei , Xu Xiaoyu , Leng Hongfei , Cui Yali , Bi Kaishun
Published: September 2022

In vivo metabolism of polyethylene glycol (PEG) hydrogels has rarely been studied. In this study, we prepared a chemically crosslinked hydrogel formulation using 14C-labeled tetra-armed poly (ethylene glycol) succinimidyl succinate (Tetra-PEG-SS) and 3H-labeled crosslinking agent for implantation into the pelvis of Sprague-Dawley (SD) rats. This radioactive labeling technique was used to investigate the radioactivity excretion rates in of feces and urine, the blood exposure time curve, and the radioactivity recovery rate in each tissue over time. We showed that the primary excretion route of the hydrogel was via urine (3H: about 86.4%, 14C: about 90.0%), with fewer portion through feces (3H: about 6.922%, 14C: about 8.16%). The hydrogel metabolites exhibited the highest distribution in the kidney, followed by the jejunal contents; The 3H and 14C radioactivity exposures in the remaining tissues were low. We also showed that the 3H and 14C radioactivity recovery rates in the blood were usually low (<0.10% g−1 at 12 h after implantation), even though, in theory, the hydrogel could be absorbed into the blood through the adjacent tissues. By using a combination of HPLC-MS/MS and offline radioactivity counting method, we established that the tetra-PEG-based hydrogel was mainly metabolized to lower-order PEG polymers and other low-molecular-weight substances in vivo.
Design, Synthesis, Electronic Properties, and X-ray Structural Characterization of Various Modified Electron-Rich Calixarene Derivatives and Their Conversion to Stable Cation Radical Salts
Authors: Rathore Rajendra , Lindeman Sergey V. , Abdelwahed Sameh H.
Published: September 2022

We have designed and synthesized electron-rich calixarene derivatives, which undergo reversible electrochemical oxidation in a well-accessible potential range that allows the ready preparation and isolation of the corresponding cation radicals. Preparation of mono- or tetra-radical cation can be achieved by using stable aromatic cation-radical salts such as MA+•, MB+•, and NAP+• as selective organic oxidants. The cation radicals of calixarenes are stable indefinitely at ambient temperatures and can be readily characterized by UV-vis-NIR spectroscopy. These cation radicals bind a single molecule of nitric oxide within its cavity with remarkable efficiency.
Design, Synthesis and Structure—Activity Relationships of Phenylalanine-Containing Peptidomimetics as Novel HIV-1 Capsid Binders Based on Ugi Four-Component Reaction
Authors: Ji Xiangkai , Li Jing , Sharma Prem , Jiang Xiangyi , Rathi Brijesh , Gao Zhen , Hu Lide , Kang Dongwei , De Clercq Erik , Cocklin Simon , Liu Chuanfeng , Pannecouque Christophe , Dick Alexej , Liu Xinyong , Zhan Peng
Published: September 2022

As a key structural protein, HIV capsid (CA) protein plays multiple roles in the HIV life cycle, and is considered a promising target for anti-HIV treatment. Based on the structural information of CA modulator PF-74 bound to HIV-1 CA hexamer, 18 novel phenylalanine derivatives were synthesized via the Ugi four-component reaction. In vitro anti-HIV activity assays showed that most compounds exhibited low-micromolar-inhibitory potency against HIV. Among them, compound I-19 exhibited the best anti-HIV-1 activity (EC50 = 2.53 ± 0.84 μM, CC50 = 107.61 ± 27.43 μM). In addition, I-14 displayed excellent HIV-2 inhibitory activity (EC50 = 2.30 ± 0.11 μM, CC50 > 189.32 μM) with relatively low cytotoxicity, being more potent than that of the approved drug nevirapine (EC50 > 15.02 μM, CC50 > 15.2 μM). Additionally, surface plasmon resonance (SPR) binding assays demonstrated direct binding to the HIV CA protein. Moreover, molecular docking and molecular dynamics simulations provided additional information on the binding mode of I-19 to HIV-1 CA. In summary, we further explored the structure—activity relationships (SARs) and selectivity of anti-HIV-1/HIV-2 of PF-74 derivatives, which is conducive to discovering efficient anti-HIV drugs.
Effect and Mechanism of Pharmaceutical Excipients on Berberine to Alleviate Ulcerative Colitis via Regulating Gut Microbiota
Authors: Wu Chenyang , Zheng Tingting , Chen Huan , Zou Peizhi , Zhang Mengxue , Wang Jinrui , Li Nan , Zhang Yun , Li Ying , Dong Zhengqi
Published: September 2022

Background: Various potential effect of drugs on alleviating diseases by regulating intestinal microbiome as well as the pharmaceutical excipients on gut microbiota has been revealed. However, the interaction between them is rarely investigated. Methods: Histological analysis, immunohistochemistry analysis, enzyme-linked immunosorbent assay (ELISA) analysis, RT-qPCR, and 16S rRNA analysis were utilized to explore the effect mechanism of the five excipients including hydroxypropyl methylcellulose (HPMC) F4M, Eudragit (EU) S100, chitosan (CT), pectin (PT), and rheum officinale polysaccharide (DHP) on berberine (BBR) to cure UC. Results: The combined BBR with PT and DHP group exhibited better therapeutic efficacy of UC with significantly increased colon length, and decreased hematoxylin-eosin (H&E) scores than other groups. Furthermore, the expression of tight junction ZO-1 and occludin in colon tissue were upregulated, and claudin-2 was downregulated. Ultimately, the serum content of tumor necrosis (TNF)-α, interleukin (IL)-1β, and IL-6 was decreased. Moreover, the combined BBR with PT significantly promoted the restoration of gut microbiota. The relative abundance of Firmicutes and Lactobacillus was significantly increased by the supplement of PT and DHP, and the relative abundance of Proteobacteria was downregulated. Conclusions: Our study may provide a new perspective that the selection of pharmaceutical excipients could be a crucial factor affecting the drugs’ therapeutic efficiency outcome.
Polygonatum sibiricum Polysaccharides Attenuate Lipopoly-Saccharide-Induced Septic Liver Injury by Suppression of Pyroptosis via NLRP3/GSDMD Signals
Authors: Xiao Linxia , Qi Liang , Zhang Guozhe , Liu Hongxia , Gu Yaqin , Zhang Lihu , Zhang Mingguang , Wu Hongyan
Published: September 2022

Sepsis is a systemic inflammatory response syndrome with high mortality. Acute liver injury is an independent predictor for poor prognosis in septic patients. Polygonatum sibiricum polysaccharides (PSP) have been reported to possess anti-inflammatory and hepatoprotective activities. To evaluate the effects of PSP on septic liver injury and demonstrate the potential molecular mechanisms, the septic acute liver injury (SALI) model was established in BALB/c mice via intraperitoneal injection of lipopolysaccharide (LPS). We found that PSP treatment could remarkably reduce the 48 h mortality rate of septic mice; alleviate liver histopathologic damage; lower the activity of neutrophil infiltration marker MPO in liver tissue; and decrease the levels of liver function indexes AST, ALT, ALP, and TBIL, inflammatory cytokines TNFα and IL-6, and pyroptosis-related inflammatory cytokines IL-18 and IL-1β in serum. TUNEL staining and detecting GSDMD-NT protein expression level in liver tissue revealed that PSP could restrain excessive pyroptosis. In addition, PSP treatment reversed the upregulations of mRNA expression levels of the NLRP3/GSDMD signals in the liver. Our results indicated the potential protective role of PSP against SALI by inhibiting pyroptosis via NLRP3/GSDMD signals.
The Effects of Transparency and Reliability of In-Vehicle Intelligent Agents on Driver Perception, Takeover Performance, Workload and Situation Awareness in Conditionally Automated Vehicles
Authors: Zang Jing , Jeon Myounghoon
Published: September 2022

In the context of automated vehicles, transparency of in-vehicle intelligent agents (IVIAs) is an important contributor to driver perception, situation awareness (SA), and driving performance. However, the effects of agent transparency on driver performance when the agent is unreliable have not been fully examined yet. This paper examined how transparency and reliability of the IVIAs affect drivers’ perception of the agent, takeover performance, workload and SA. A 2 × 2 mixed factorial design was used in this study, with transparency (Push: proactive vs. Pull: on-demand) as a within-subjects variable and reliability (high vs. low) as a between-subjects variable. In a driving simulator, 27 young drivers drove with two types of in-vehicle agents during the conditionally automated driving. Results suggest that transparency influenced participants’ perception on the agent and perceived workload. High reliability agent was associated with higher situation awareness and less effort, compared to low reliability agent. There was an interaction effect between transparency and reliability on takeover performance. These findings could have important implications for the continued design and development of IVIAs of the automated vehicle system.
Size-Dependent Phonon-Assisted Anti-Stokes Photoluminescence in Nanocrystals of Organometal Perovskites
Authors: Sekerbayev Kairolla , Taurbayev Yerzhan , Mussabek Gauhar , Baktygerey Saule , Pokryshkin Nikolay S. , Yakunin Valery G. , Utegulov Zhandos , Timoshenko Victor Yu.
Published: September 2022

Anti-Stokes photoluminescence (ASPL), which is an up-conversion phonon-assisted process of the radiative recombination of photoexcited charge carriers, was investigated in methylammonium lead bromide (MALB) perovskite nanocrystals (NCs) with mean sizes that varied from about 6 to 120 nm. The structure properties of the MALB NCs were investigated by means of the scanning and transmission electron microscopy, X-ray diffraction and Raman spectroscopy. ASPL spectra of MALB NCs were measured under near-resonant laser excitation with a photon energy of 2.33 eV and they were compared with the results of the photoluminescence (PL) measurements under non-resonant excitation at 3.06 eV to reveal a contribution of phonon-assisted processes in ASPL. MALB NCs with a mean size of about 6 nm were found to demonstrate the most efficient ASPL, which is explained by an enhanced contribution of the phonon absorption process during the photoexcitation of small NCs. The obtained results can be useful for the application of nanocrystalline organometal perovskites in optoelectronic and all-optical solid-state cooling devices.
Two-Dimensional Core-Shell Structure of Cobalt-Doped@MnO2 Nanosheets Grown on Nickel Foam as a Binder-Free Battery-Type Electrode for Supercapacitor Application
Authors: Moniruzzaman Md , Anil Kumar Yedluri , Pallavolu Mohan Reddy , Arbi Hammad Mueen , Alzahmi Salem , Obaidat Ihab M.
Published: September 2022

Herein, we present an interfacial engineering strategy to construct an efficient hydrothermal approach by in situ growing cobalt-doped@MnO2 nanocomposite on highly conductive nickel foam (Ni foam) for supercapacitors (SCs). The remarkably high specific surface area of Co dopant provides a larger contacting area for MnO2. In the meantime, the excellent retentions of the hierarchical phase-based pore architecture of the cobalt-doped surface could beneficially condense the electron transportation pathways. In addition, the nickel foam (Ni foam) nanosheets provide charge-transport channels that lead to the outstanding improved electrochemical activities of cobalt-doped@MnO2. The unique cobalt-doped@MnO2 nanocomposite electrode facilitates stable electrochemical architecture, multi-active electrochemical sites, and rapid electro-transports channels; which act as a key factor in enhancing the specific capacitances, stability, and rate capacities. As a result, the cobalt-doped@MnO2 nanocomposite electrode delivered superior electrochemical activities with a specific capacitance of 337.8 F g–1 at 0.5 A g–1; this is greater than pristine MnO2 (277.9 F g–1). The results demonstrate a worthy approach for the designing of high-performance SCs by the grouping of the nanostructured dopant material and metal oxides.
Sorafenib-Loaded Cu2−xSe Nanoparticles Boost Photothermal–Synergistic Targeted Therapy against Hepatocellular Carcinoma
Authors: Huang An-Tian , Du Jun , Liu Zhi-Yong , Zhang Guang-Cong , Abuduwaili Weinire , Yan Jia-Yan , Sun Jia-Lei , Xu Ru-Chen , Liu Tao-Tao , Shen Xi-Zhong , Dong Ling , Zhu Ji-Min , Li Yuhao
Published: September 2022

Hepatocellular carcinoma (HCC) accounts for the predominant form of liver malignancy and presents a leading cause of cancer-related death globally. Sorafenib (SOR), a first-line targeted drug for advanced HCC treatment, has a battery of untoward side effects. Photothermal therapy (PTT) has been utilized as an effective adjuvant in synergy with other approaches. However, little is known about the tumoricidal efficacy of combining SOR with PTT for HCC. Herein, a novel versatile nanoparticle, Cu2−xSe@SOR@PEG (CSP), that is based on a photothermal Cu2−xSe core and SOR for simultaneously reinforcing PTT and reducing the adverse effects of SOR was constructed. The synthesized CSP exhibited a remarkably enhanced therapeutic effect upon 808 nm laser irradiation via dampening HCC cell propagation and metastasis and propelling cell apoptosis. The intravenous administration of CSP substantially suppressed tumor growth in a xenograft tumor mouse model. It was noted that the CSP manifested low toxicity and excellent biocompatibility. Together, this work indicates a promising and versatile tool that is based on synergistic PTT and molecular-targeted therapy for HCC management.
Synthesis of Novel N4-Hydrocytidine Analogs as Potential Anti-SARS-CoV-2 Agents
Authors: Amblard Franck , LeCher Julia C. , De Ramyani , Goh Shu Ling , Li Chengwei , Kasthuri Mahesh , Biteau Nicolas , Zhou Longhu , Tber Zahira , Downs-Bowen Jessica , Zandi Keivan , Schinazi Raymond F.
Published: September 2022

Coronavirus disease 2019 (COVID-19) is an emerging global pandemic with severe morbidity and mortality caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Molnupiravir, an ester prodrug form of N4-hydroxycytidine (NHC), was recently emergency-use approved for the treatment of early SARS-CoV-2 infections. Herein, we report the synthesis and evaluation of a series of novel NHC analogs.
Semisolid Wet Sol–Gel Silica/Hydroxypropyl Methyl Cellulose Formulation for Slow Release of Serpin B3 Promotes Wound Healing In Vivo
Authors: Albiero Mattia , Fullin Alice , Villano Gianmarco , Biasiolo Alessandra , Quarta Santina , Bernardotto Simone , Turato Cristian , Ruvoletto Mariagrazia , Fadini Gian Paolo , Pontisso Patrizia , Morpurgo Margherita
Published: September 2022

Foot ulcerations are a disabling complication of diabetes and no treatment is currently available based on disease mechanisms. The protein serpin B3 (SB3) was identified as a positive biomarker of successful diabetic wound healing; therefore, its exogenous administration may promote healing. The topical administration of SB3 is challenging due to its protein nature. Physical entrapment in wet sol–gel silica can stabilize the protein’s conformation and permit its sustained delivery. However, irreversible syneresis and poor viscoelastic properties hamper wet sol–gel silica application as a semisolid vehicle. To overcome these limits, a sol–gel silica/hydroxypropylmethylcellulose (HPMC) hydrogel blend was developed. SB3 entrapped in 8% SiO2 wet sol–gel silica preserved its structure, was stabilized against denaturation, and was slowly released for at least three days. Blending a silica gel with an HPMC–glycerol (metolose-G) hydrogel permitted spreadability without affecting the protein’s release kinetics. When administered in vivo, SB3 in silica/metolose-G—but not in solution or in metolose-G alone—accelerated wound healing in SB3 knockout and diabetic mouse models. The results confirmed that SB3 is a new pharmacological option for the treatment of chronic ulcers, especially when formulated in a slow-releasing vehicle. Silica–metolose-G represents a novel type of semisolid dosage form which could also be applied for the formulation of other bioactive proteins.
Tyrosinase Inhibitory Ability and In Vitro, In Vivo Acute Oral and In Silico Toxicity Evaluation of Extracts Obtained from Algerian Fir (Abiesnumidica de Lannoy ex CARRIERE) Needles
Authors: Benouchenne Djamila , Bellil Ines , Tachour Sana Hazar , Akkal Salah , Djeghim Hanène , Kebaili Fethi Farouk , Nieto Gema , Khelifi Douadi
Published: September 2022

This study was designed to evaluate the tyrosinase inhibitory effect, in vitro, in vivo, and in silico toxicity of fractions isolated from A. numidica de Lannoy needles. The cytotoxicity of extracts was examined against Artemia salina larvae, while the toxicity of these extracts was tested by acute oral toxicity in mice; by administration of a dose of 2000 mg/kg b.w A. numidica leaves extracts. The blood samples were collected from the eye orbital sinus for further analysis of biochemical parameters. The absorption, distribution, metabolism, elimination, and toxicity (ADMET) properties were identified by the pkCSM web server. The data stated that ethyl acetate (EA) presented strong anti-tyrosinase apt. The results reported that ethyl acetate extract exhibited a strong inhibitory capacity against A. salina larvae with LD50 of 75.004 µg/mL. The data also showed that no mortality occurred, and no toxicity symptoms were observed in mice. The biochemical parameters revealed that both extracts significantly affected the hepatic profile by increasing ALT, AST, and alkaline phosphatase. Histopathological tests also confirmed that both fractions were toxic at this concentration on hepatic and renal tissues, with necrosis observed. The toxicity of molecules in silico revealed no effect on all examined biomolecules.It can be concluded that this plant was toxic on the liver and renal profiles and tissues at the dose studied.
Antibacterial, Anticandidal, and Antibiofilm Potential of Fenchone: In Vitro, Molecular Docking and In Silico/ADMET Study
Authors: Ahmad Wasim , Ansari Mohammad Azam , Yusuf Mohammad , Amir Mohd , Wahab Shadma , Alam Prawez , Alomary Mohammad N. , Alhuwayri Abdulrahman A. , Khan Maria , Ali Abuzer , Warsi Musarrat Husain , Ashraf Kamran , Ali Maksood
Published: September 2022

The aim of the present study is to investigate the effective antimicrobial and antibiofilm properties of fenchone, a biologically active bicyclic monoterpene, against infections caused by bacteria and Candida spp. The interactions between fenchone and three distinct proteins from Escherichia coli (β-ketoacyl acyl carrier protein synthase), Candida albicans (1, 3-β–D-glucan synthase), and Pseudomonas aeruginosa (Anthranilate-CoA ligase) were predicted using molecular docking and in silico/ADMET methods. Further, to validate the in-silico prediction, the antibacterial and antifungal potential of fenchone was evaluated against E. coli, P. aeruginosa, and C. albicans by determining minimum inhibitory concentration (MIC), minimum bacterial concentration (MBC), and minimum fungicidal concentration (MFC). The lowest MIC/MBC values of fenchone against E. coli and P. aeruginosa obtained was 8.3 ± 3.6/25 ± 0.0 and 266.6 ± 115.4/533.3 ± 230.9 mg/mL, respectively, whereas the MIC/MFC value for C. albicans was found to be 41.6 ± 14.4/83.3 ± 28.8 mg/mL. It was observed that fenchone has a significant effect on antimicrobial activity (p < 0.05). Our findings demonstrated that fenchone at 1 mg/mL significantly reduced the production of biofilm (p < 0.001) in E. coli, P. aeruginosa, and C. albicans by 70.03, 64.72, and 61.71%, respectively, in a dose-dependent manner when compared to control. Based on these results, it has been suggested that the essential oil from plants can be a great source of pharmaceutical ingredients for developing new antimicrobial drugs.
Seed Vigour and Morphological and Physiological Characteristics of Epimedium brevicornu Maxim: In Different Stages of Seed Development
Authors: Li Pengshu , Fan Jiarong , Song Chengli , Dong Xuehui , Kang Dingming
Published: September 2022

Epimedium brevicornu Maxim is a traditional Chinese medicinal plant with important value for curing several diseases, including liver cancer. Seed germination, field seedling emergence, and morphological and physiological traits were measured in developing seeds of E. brevicornu, which were collected at 7, 14, 21, 28, and 35 days after flowering. The results showed that with the fruit pericarp changing from lime green to dark red, the seed volume increased. Furthermore, the dry mass of seeds gradually increased from 0.011 g at 7 d to 0.275 g at 35 d, which was a significantly positive correlation with seed vigour (r = 0.980). The soluble protein content initially increased and then decreased to 11.09 mg/g and presented a maximum at 28 d; however, the soluble sugar content gradually declined to a minimum of 30.45 mg/g at 35 d, which was also significantly negatively correlated with seed vigour (r = −0.915). Furthermore, the unsaturated fatty acids (oleic acid and linoleic acid) increase with seed development. Abscisic acid (ABA) reached a maximum value of 18.45 ng/g at 28 d, and gibberellin (GA3), 3-Indoleacetic acid (IAA) and zeatin-riboside (ZR) initially increased and then decreased. These results suggest that the vigour of E. brevicornu seeds is closely associated with their stage of development, with the highest vigour observed at 28~35 d after flowering.