bluuebunny/crossref_metadata_2025 huggingface dataset:
Loveringite from the Khamal Layered Mafic Intrusion: The First Occurrence in the Arabian Shield, Northwest Saudi Arabia
Authors: Abuamarah Bassam A. , Alshehri Fahad , Azer Mokhles K. , Asimow Paul D.
Published: January 2023

Loveringite, a rare member of the crichtonite group with nominal formula (Ca,Ce)(Ti,Fe,Cr,Mg)21O38, was found in the Khamal layered mafic intrusion, the first known locality for this mineral in the Arabian Shield. The Khamal intrusion, a large post-collisional mafic complex, is lithologically zoned, bottom to top, from olivine gabbro through gabbronorite, hornblende gabbro, anorthosite, and diorite to quartz diorite. Loveringite is found near the base of the complex, as an intercumulus phase in olivine gabbro. Most loveringite grains are homogeneous, although a few grains are zoned from cores rich in TiO2, Al2O3, Cr2O3, and CaO towards rims rich in FeO*, ZrO2, V2O3, Y2O3, and rare earth elements (REE). Petrographic relations indicate that loveringite formed after crystallization of cumulus olivine, pyroxenes, and plagioclase. Anhedral and corroded crystals of loveringite are surrounded by reaction rims of Mn-bearing ilmenite and baddeleyite, suggesting that the residual liquid evolved into and subsequently out of the stability field of loveringite. The budget of incompatible elements (Zr, Hf, REE, U, and Th) hosted in loveringite is anomalous for a primitive mafic liquid. Saturation in loveringite is likely the result of early contamination of the primary melt by anatexis of country rock, followed by isolation of evolving liquid in intercumulus space that restricted communication with the overlying magma chamber. The zoned crystals likely reflect diffusive equilibration between residual loveringite grains and their reaction rims of ilmenite.
Effect of Al2O3 on the Structural Properties of Water-Quenched Copper Slag Related to Pozzolanic Activity
Authors: Zhang Qinli , Deng Dengwen , Feng Yan , Wang Daolin , Liu Bin , Chen Qiusong
Published: January 2023

Water-quenched copper slag (WCS) modified with alumina (Al2O3) has been proven as a cement substitute; however, the effect of Al2O3 on structural properties of WCS related to pozzolanic activity has not been well investigated. The structural properties and the pozzolanic activity of WCS with different amounts of Al2O3 are characterized by X-ray diffraction, differential scanning calorimetry, Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, and the uniaxial compressive strength test. The results show that only amorphous exists in copper slag, and the stability of amorphous first increases and then decreases with the increase in the alumina content. The addition of alumina significantly improves the pozzolanic activity of WCS at 7 and 28 days, but it has little effect on the pozzolanic activity of WCS when the slag’s curing age is 3 days. The results also show the increase in the non-bridging oxygen content, the decrease in the degree of polymerization, and the transition from Q2 and Q4 to Q3 with the increase of alumina content. Moreover, the addition of aluminum will convert Si-O-Si into Si-O-Al. These experimental results show that the addition of alumina can improve the pozzolanic activity of WCS, which can be used to partially replace cement.
Acknowledgment to the Reviewers of Mining in 2022
Authors:   Mining Editorial Office
Published: January 2023

High-quality academic publishing is built on rigorous peer review [...]
Sustainable Synthesis, Antiproliferative and Acetylcholinesterase Inhibition of 1,4- and 1,2-Naphthoquinone Derivatives
Authors: Cabral Rafaela G. , Viegas Gonçalo , Pacheco Rita , Sousa Ana Catarina , Robalo Maria Paula
Published: January 2023

This work describes the design, sustainable synthesis, evaluation of electrochemical and biological properties against HepG2 cell lines, and AChE enzymes of different substituted derivatives of 1,4- and 1,2-naphthoquinones (NQ). A microwave-assisted protocol was optimized with success for the synthesis of the 2-substituted-1,4-NQ series and extended to the 4-substituted-1,2-NQ family, providing an alternative and more sustainable approach to the synthesis of naphthoquinones. The electrochemical properties were studied by cyclic voltammetry, and the redox potentials related to the molecular structural characteristics and the biological properties. Compounds were tested for their potential anti-cancer activity against a hepatocellular carcinoma cell line, HepG2, using MTT assay, and 1,2-NQ derivatives were found to be more active than their 1,4-NQ homologues (3a–f), with the highest cytotoxic potential found for compound 4a (EC50 = 3 μM). The same trend was found for the inhibitory action against acetylcholinesterase, with 1,2-NQ derivatives showing higher inhibition50µM than their 1,4-NQ homologues, with 4h being the most potent compound (Inhibition50µM = 85%). Docking studies were performed for the 1,2-NQ derivatives with the highest inhibitions, showing dual binding interactions with both CAS and PAS sites, while the less active 1,4-NQ derivatives showed interactions with PAS and the mid-gorge region.
Anthocyanins: Potential Therapeutic Approaches towards Obesity and Diabetes Mellitus Type 2
Authors: Franco-San Sebastián Denise , Alaniz-Monreal Samary , Rabadán-Chávez Griselda , Vázquez-Manjarrez Natalia , Hernández-Ortega Marcela , Gutiérrez-Salmeán Gabriela
Published: January 2023

Overweight and obesity are present in about three-quarters of the adult population in Mexico. The inflammatory mechanisms subjacent to visceral white adipose tissue are accountable for the initiation and development of cardiometabolic alterations, including type 2 diabetes. Lifestyle changes are pillars within its therapeutics and, thus, current dietary modifications should include not only hypocaloric prescriptions with balanced macronutrient intake, preferably by increasing the amount of whole grains, fruits, vegetables, nuts and legumes, but in concomitance, bioactive substances, such as anthocyanins, have been correlated with lower incidence of this disease.
Energy Level Prediction of Organic Semiconductors for Photodetectors and Mining of a Photovoltaic Database to Search for New Building Units
Authors: Saleh Jehad , Haider Sajjad , Akhtar Muhammad Saeed , Saqib Muhammad , Javed Muqadas , Elshahat Sayed , Kamal Ghulam Mustafa
Published: January 2023

Due to the large versatility in organic semiconductors, selecting a suitable (organic semiconductor) material for photodetectors is a challenging task. Integrating computer science and artificial intelligence with conventional methods in optimization and material synthesis can guide experimental researchers to develop, design, predict and discover high-performance materials for photodetectors. To find high-performance organic semiconductor materials for photodetectors, it is crucial to establish a relationship between photovoltaic properties and chemical structures before performing synthetic procedures in laboratories. Moreover, the fast prediction of energy levels is desirable for designing better organic semiconductor photodetectors. Herein, we first collected large sets of data containing photovoltaic properties of organic semiconductor photodetectors reported in the literature. In addition, molecular descriptors that make it easy and fast to predict the required properties were used to train machine learning models. Power conversion efficiency and energy levels were also predicted. Multiple models were trained using experimental data. The light gradient boosting machine (LGBM) regression model and Hist gradient booting regression model are the best models. The best models were further tuned to achieve better prediction ability. The reliability of our designed approach was further verified by mining the photovoltaic database to search for new building units. The results revealed that good consistency is obtained between experimental outcomes and model predictions, indicating that machine learning is a powerful approach to predict the properties of photodetectors, which can facilitate their rapid development in various fields.
Recent Advances in Supramolecular-Macrocycle-Based Nanomaterials in Cancer Treatment
Authors: Pan Zheng , Zhao Xinzhi , Li Qiushi , Zhang Zhanzhan , Liu Yang
Published: January 2023

Cancer is a severe threat to human life. Recently, various therapeutic strategies, such as chemotherapy, photodynamic therapy, and combination therapy have been extensively applied in cancer treatment. However, the clinical benefits of these therapeutics still need improvement. In recent years, supramolecular chemistry based on host–guest interactions has attracted increasing attention in biomedical applications to address these issues. In this review, we present the properties of the major macrocyclic molecules and the stimulus–response strategies used for the controlled release of therapeutic agents. Finally, the applications of supramolecular-macrocycle-based nanomaterials in cancer therapy are reviewed, and the existing challenges and prospects are discussed.
Efficient Bioconversion of Stevioside and Rebaudioside A to Glucosylated Steviol Glycosides Using an Alkalihalobacillus oshimesis-Derived Cyclodextrin Glucanotransferase
Authors: Zhang Ruiqin , Tang Ruiqi , Bi Jiahua , Shen Shanshan , Wu Qin , Chen Qihe , Li Yanjun
Published: January 2023

The enzymatic transglycosylation of steviol glycosides can improve the edulcorant quality of steviol glycosides. Cyclodextrin glucanotransferase (CGTase) is one of the most popular glucanotransferases applied in this reaction. Herein, the CGTase-producing strain Alkalihalobacillus oshimensis CGMCC 23164 was isolated from Stevia planting soil. Using mass spectrometry-based secretome profiling, a high-efficiency CGTase that converted steviol glycosides to glucosylated steviol glycosides was identified and termed CGTase-13. CGTase-13 demonstrated optimal transglycosylation activity with 10 g/L steviol glycoside and 50 g/L soluble starch as substrates at <40 °C. Under the above conditions, the conversion rate of stevioside and rebaudioside A, two main components of steviol glycosides, reached 86.1% and 90.8%, respectively. To the best of our knowledge, this is the highest conversion rate reported to date. Compared with Toruzyme® 3.0 L, the commonly used commercial enzyme blends, glucosylated steviol glycosides produced using CGTase-13 exhibited weaker astringency and unpleasant taste, faster sweetness onset, and stronger sweetness intensity. Thus, CGTase provides a novel option for producing high-quality glucosylated steviol glycoside products and has great potential for industrial applications.
Effect of Winemaking on Phenolic Compounds and Antioxidant Activities of Msalais Wine
Authors: Hou Xiaojie , Chen Shenghuizi , Pu Yunfeng , Wang Tingting , Xu Heng , Li Hu , Ma Peng , Hou Xujie
Published: January 2023

Msalais wine (MW) is a popular traditional wine with the cultural characteristics of a specific Chinese ethnic group. In this study, phenolic profiles and antioxidant characteristics were identified using chromatographic analysis. A total of thirty-eight compounds, including eight furans, eleven phenolic acids, fourteen flavonoids, and five others, were identified via LC-MS/QTOF. It was found that catechin is the most abundant phenolic compound in MW, followed by epicatechin, gallic acid, caffeic acid, rutin, and p-coumaric acid. Winemaking had a significant influence on the levels of phenols and antioxidant activity. Condensed juice (CJ) displayed the highest phenol and antioxidant activity levels, while the levels were significantly decreased during the fermentation process and gradually stabilized thereafter during the aging process. A correlation analysis between the polyphenols in Msalais and their antioxidant capacity was performed to determine which molecules contributed more to the antioxidant capacity in a complex mixture of polyphenols. All of the phenolic compounds, except ferulic acid, showed good correlation with DPPH, ABTS, and CUPRAC. Among them, resveratrol had the strongest antioxidant capacity, although its concentration was very low. Catechin also had a strong antioxidant capacity, which was positively correlated with its concentration. This indicates that the antioxidant activity of Msalais is related to the number, type, and structure of polyphenols.
In Vitro and In Silico Studies of Neolignans from Magnolia grandiflora L. Seeds against Human Cannabinoids and Opioid Receptors
Authors: Pandey Pankaj , Kumarihamy Mallika , Chaturvedi Krishna , Ibrahim Mohamed A. M. , Lambert Janet A. , Godfrey Murrell , Doerksen Robert J. , Muhammad Ilias
Published: January 2023

Magnolia grandiflora L. (Magnoliaceae) is a plant of considerable medicinal significance; its flowers and seeds have been used in various traditional remedies. Radioligand binding assays of n-hexane seeds extract showed displacement of radioligand for cannabinoid (CB1 and CB2) and opioid δ (delta), κ (kappa), and µ (mu) receptors. Bioactivity-guided fractionation afforded 4-O-methylhonokiol (1), magnolol (2), and honokiol (3), which showed higher binding to cannabinoid rather than opioid receptors in radioligand binding assays. Compounds 1–3, together with the dihydro analog of 2 (4), displayed selective affinity towards CB2R (Ki values of 0.29, 1.4, 1.94, and 0.99 μM, respectively), compared to CB1R (Ki 3.85, 17.82, 14.55, and 19.08 μM, respectively). An equal mixture of 2 and 3 (1:1 ratio) showed additive displacement activity towards the tested receptors compared to either 2 or 3 alone, which in turn provides an explanation for the strong displacement activity of the n-hexane extract. Due to the unavailability of an NMR or X-ray crystal structure of bound neolignans with the CB1 and CB2 receptors, a docking study was performed to predict ligand–protein interactions at a molecular level and to delineate structure-activity relationships (SAR) of the neolignan analogs with the CB1 and CB2 receptors. The putative binding modes of neolignans 1–3 and previously reported related analogs (4, 4a, 5, 5a, 6, 6a, and 6b) into the active site of the CB1 and CB2 receptors were assessed for the first time via molecular docking and binding free-energy (∆G) calculations. The docking and ∆G results revealed the importance of a hydroxyl moiety in the molecules that forms strong H-bonding with Ser383 and Ser285 within CB1R and CB2R, respectively. The impact of a shift from a hydroxyl to the methoxy group on experimental binding affinity to CB1R versus CB2R was explained through ∆G data and the orientation of the alkyl chain within the CB1R. This comprehensive SAR, influenced by the computational study and the observed in vitro displacement binding affinities, has indicated the potential of magnolia neolignans for developing new CB agonists for potential use as analgesics, anti-inflammatory agents, or anxiolytics.
Hydrogen Absorption Reactions of Hydrogen Storage Alloy LaNi5 under High Pressure
Authors: Sato Toyoto , Saitoh Hiroyuki , Utsumi Reina , Ito Junya , Nakahira Yuki , Obana Kazuki , Takagi Shigeyuki , Orimo Shin-ichi
Published: January 2023

Hydrogen can be stored in the interstitial sites of the lattices of intermetallic compounds. To date, intermetallic compound LaNi5 or related LaNi5-based alloys are known to be practical hydrogen storage materials owing to their higher volumetric hydrogen densities, making them a compact hydrogen storage method and allowing stable reversible hydrogen absorption and desorption reactions to take place at room temperature below 1.0 MPa. By contrast, gravimetric hydrogen density is required for key improvements (e.g., gravimetric hydrogen density of LaNi5: 1.38 mass%). Although hydrogen storage materials have typically been evaluated for their hydrogen storage properties below 10 MPa, reactions between hydrogen and materials can be facilitated above 1 GPa because the chemical potential of hydrogen dramatically increases at a higher pressure. This indicates that high-pressure experiments above 1 GPa could clarify the latent hydrogen absorption reactions below 10 MPa and potentially explore new hydride phases. In this study, we investigated the hydrogen absorption reaction of LaNi5 above 1 GPa at room temperature to understand their potential hydrogen storage capacities. The high-pressure experiments on LaNi5 with and without an internal hydrogen source (BH3NH3) were performed using a multi-anvil-type high-pressure apparatus, and the reactions were observed using in situ synchrotron radiation X-ray diffraction with an energy dispersive method. The results showed that 2.07 mass% hydrogen was absorbed by LaNi5 at 6 GPa. Considering the unit cell volume expansion, the estimated hydrogen storage capacity could be 1.5 times higher than that obtained from hydrogen absorption reaction below 1.0 MPa at 303 K. Thus, 33% of the available interstitial sites in LaNi5 remained unoccupied by hydrogen atoms under conventional conditions. Although the hydrogen-absorbed LaNi5Hx (x < 9) was maintained below 573 K at 10 GPa, LaNi5Hx began decomposing into NiH, and the formation of a new phase was observed at 873 K and 10 GPa. The new phase was indexed to a hexagonal or trigonal unit cell with a ≈ 4.44 Å and c ≈ 8.44 Å. Further, the newly-formed phase was speculated to be a new hydride phase because the Bragg peak positions and unit cell parameters were inconsistent with those reported for the La-Ni intermetallic compounds and La-Ni hydride phases.
Mesoporous Silica Nanoparticles Coated with Carboxymethyl Chitosan for 5-Fluorouracil Ocular Delivery: Characterization, In Vitro and In Vivo Studies
Authors: Alhowyan Adel Ali , Kalam Mohd Abul , Iqbal Muzaffar , Raish Mohammad , El-Toni Ahmed M. , Alkholief Musaed , Almomen Aliyah A. , Alshamsan Aws
Published: January 2023

This study investigates the development of topically applied non-invasive amino-functionalized silica nanoparticles (AMSN) and O-Carboxymethyl chitosan-coated AMSN (AMSN-CMC) for ocular delivery of 5-Fluorouracil (5-FU). Particle characterization was performed by the DLS technique (Zeta-Sizer), and structural morphology was examined by SEM and TEM. The drug encapsulation and loading were determined by the indirect method using HPLC. Physicochemical characterizations were performed by NMR, TGA, FTIR, and PXRD. In vitro release was conducted through a dialysis membrane in PBS (pH 7.4) using modified Vertical Franz diffusion cells. The mucoadhesion ability of the prepared nanoparticles was tested using the particle method by evaluating the change in zeta potential. The transcorneal permeabilities of 5-FU from AMNS-FU and AMSN-CMC-FU gel formulations were estimated through excised goat cornea and compared to that of 5-FU gel formulation. Eye irritation and ocular pharmacokinetic studies from gel formulations were evaluated in rabbit eyes. The optimum formulation of AMSN-CMC-FU was found to be nanoparticles with a particle size of 249.4 nm with a polydispersity of 0.429, encapsulation efficiency of 25.8 ± 5.8%, and drug loading capacity of 5.2 ± 1.2%. NMR spectra confirmed the coating of AMSN with the CMC layer. In addition, TGA, FTIR, and PXRD confirmed the drug loading inside the AMSN-CMC. Release profiles showed 100% of the drug was released from the 5-FU gel within 4 h, while AMSN-FU gel released 20.8% of the drug and AMSN-CMC-FU gel released around 55.6% after 4 h. AMSN-CMC-FU initially exhibited a 2.45-fold increase in transcorneal flux and apparent permeation of 5-FU compared to 5-FU gel, indicating a better corneal permeation. Higher bioavailability of AMSN-FU and AMSN-CMC-FU gel formulations was found compared to 5-FU gel in the ocular pharmacokinetic study with superior pharmacokinetics parameters of AMSN-CMC-FU gel. AMSN-CMC-FU showed 1.52- and 6.14-fold higher AUC0-inf in comparison to AMSN-FU and 5-FU gel, respectively. AMSN-CMC-FU gel and AMSN-FU gel were “minimally irritating” to rabbit eyes but showed minimal eye irritation potency in comparison to the 5 FU gel. Thus, the 5-FU loaded in AMSN-CMC gel could be used as a topical formulation for the treatment of ocular cancer.
Curcumin and Andrographolide Co-Administration Safely Prevent Steatosis Induction and ROS Production in HepG2 Cell Line
Authors: Pipitone Rosaria Maria , Zito Rossella , Lupo Giulia , Javed Ayesha , La Mantia Claudia , Di Maria Gabriele , Pratelli Giovanni , Di Salvo Francesca , Fontana Simona , Pucci Marzia , Carlisi Daniela , Grimaudo Stefania
Published: January 2023

Non-alcoholic fatty liver disease (NAFLD) is an emerging chronic liver disease worldwide. Curcumin and andrographolide are famous for improving hepatic functions, being able to reverse oxidative stress and release pro-inflammatory cytokines, and they are implicated in hepatic stellate cell activation and in liver fibrosis development. Thus, we tested curcumin and andrographolide separately and in combination to determine their effect on triglyceride accumulation and ROS production, identifying the differential expression of genes involved in fatty liver and oxidative stress development. In vitro steatosis was induced in HepG2 cells and the protective effect of curcumin, andrographolide, and their combination was observed evaluating cell viability, lipid and triglyceride content, ROS levels, and microarray differential gene expression. Curcumin, andrographolide, and their association were effective in reducing steatosis, triglyceride content, and ROS stress, downregulating the genes involved in lipid accumulation. Moreover, the treatments were able to protect the cytotoxic effect of steatosis, promoting the expression of survival and anti-inflammatory genes. The present study showed that the association of curcumin and andrographolide could be used as a therapeutic approach to counter high lipid content and ROS levels in steatosis liver, avoiding the possible hepatotoxic effect of curcumin. Furthermore, this study improved our understanding of the antisteatosis and hepatoprotective properties of a curcumin and andrographolide combination.
Aluminum Salen Complexes Modified with Unsaturated Alcohol: Synthesis, Characterization, and Their Activity towards Ring-Opening Polymerization of ε-Caprolactone and D,L-Lactide
Authors: Zaitsev Kirill V. , Trubachev Andrey D. , Oprunenko Yuri F. , Piskun Yuliya A. , Vasilenko Irina V. , Churakov Andrei V. , Kostjuk Sergei V.
Published: January 2023

A highly efficient one-step approach to the macromonomer synthesis using modified aluminum complexes as catalysts of ring-opening polymerization (ROP) of ε-caprolactone and D,L-lactide was developed. The syntheses, structures, and catalytic activities of a wide range of aluminum salen complexes, 3a-c, functionalized with unsaturated alcohol (HO(CH2)4OCH=CH2) are reported. X-Ray diffraction studies revealed a tetragonal pyramidal structure for 3c. Among the complexes 3a-c, the highest activity in bulk ROP of ε-caprolactone and D,L-lactide was displayed by 3b, affording polyesters with controlled molecular weights at low monomer to initiator ratios (Mn up to 15,000 g mol−1), relatively high polydispersities (Ð~1.8) and high number-average functionalities (Fn up to 85%).
Role of Fungi in Biodegradation of Imidazolium Ionic Liquids by Activated Sewage Sludge
Authors: Klein Joanna , Łuczak Justyna , Brillowska-Dąbrowska Anna
Published: January 2023

Ionic liquids (ILs), due to their specific properties, can play the role of persistent water contaminants. Fungi manifest the ability to decompose hardy degradable compounds, showing potential in the biodegradation of ILs, which has been studied extensively on sewage sludge; however, attention was drawn mainly to bacterial and not fungal species. The aim of the research was to determine the significance of fungi in ILs’ biodegradation to extend the knowledge and possibly point out ways of increasing their role in this process. The research included: the isolation and genetic identification of fungal strains potentially capable of [OMIM][Cl], [BMIM][Cl], [OMIM][Tf2N], and [BMIM][Tf2N] degradation, adjustment of the ILs concentration for biodegradability test by MICs determination and choosing strains with the highest biological robustness; inoculum adaptation tests, and finally primary biodegradation by OECD 301F test. The study, conducted for 2 mM [OMIM][Cl] as a tested substance and consortium of microorganisms as inoculum, resulted in an average 64.93% biodegradation rate within a 28-day testing period. For the individual fungal strain (Candida tropicalis), the maximum of only 4.89% biodegradation rate was reached in 10 days, then inhibited. Insight into the role of fungi in the biodegradation of ILs was obtained, enabling the creation of a complex overview of ILs toxicity and the possibilities of its biological use. However, only an inoculum consisting of a consortium of microorganisms enriched with a selected strain of fungi was able to decompose the IL, in contrast to that consisting only of an individual fungal strain.
Naphthalimide-Piperazine Derivatives as Multifunctional “On” and “Off” Fluorescent Switches for pH, Hg2+ and Cu2+ Ions
Authors: Pršir Kristina , Matić Mislav , Grbić Marlena , Mohr Gerhard J. , Krištafor Svjetlana , Steinberg Ivana Murković
Published: January 2023

Novel 1,8-naphthalimide-based fluorescent probes NI-1 and NI-2 were designed and screened for use as chemosensors for detection of heavy metal ions. Two moieties, methylpyridine (NI-1) and hydroxyphenyl (NI-2), were attached via piperazine at the C-4 position of the napthalimide core resulting in a notable effect on their spectroscopic properties. NI-1 and NI-2 are pH sensitive and show an increase in fluorescence intensity at around 525 nm (switch “on”) in the acidic environment, with pKa values at 4.98 and 2.91, respectively. Amongst heavy metal ions only Cu2+ and Hg2+ had a significant effect on the spectroscopic properties. The fluorescence of NI-1 is quenched in the presence of either Cu2+ or Hg2+ which is attributed to the formation of 1:1 metal-ligand complexes with binding constants of 3.6 × 105 and 3.9 × 104, respectively. The NI-1 chemosensor can be used for the quantification of Cu2+ ions in sub-micromolar quantities, with a linear range from 250 nM to 4.0 μM and a detection limit of 1.5 × 10−8 M. The linear range for the determination of Hg2+ is from 2 μM to 10 μM, with a detection limit of 8.8 × 10−8 M. Conversely, NI-2 behaves like a typical photoinduced electron transfer (PET) sensor for Hg2+ ions. Here, the formation of a complex with Hg2+ (binding constant 8.3 × 103) turns the green fluorescence of NI-2 into the “on” state. NI-2 showed remarkable selectivity towards Hg2+ ions, allowing for determination of Hg2+ concentration over a linear range of 1.3 μM to 25 μM and a limit of detection of 4.1 × 10−7 M.
Drugging the Undruggable Trypanosoma brucei Monothiol Glutaredoxin 1
Authors: Favaro Annagiulia , Bolcato Giovanni , Comini Marcelo A. , Moro Stefano , Bellanda Massimo , Sturlese Mattia
Published: January 2023

Trypanosoma brucei is a species of kinetoplastid causing sleeping sickness in humans and nagana in cows and horses. One of the peculiarities of this species of parasites is represented by their redox metabolism. One of the proteins involved in this redox machinery is the monothiol glutaredoxin 1 (1CGrx1) which is characterized by a unique disordered N-terminal extension exclusively conserved in trypanosomatids and other organisms. This region modulates the binding profile of the glutathione/trypanothione binding site, one of the functional regions of 1CGrx1. No endogenous ligands are known to bind this protein which does not present well-shaped binding sites, making it target particularly challenging to target. With the aim of targeting this peculiar system, we carried out two different screenings: (i) a fragment-based lead discovery campaign directed to the N-terminal as well as to the canonical binding site of 1CGrx1; (ii) a structure-based virtual screening directed to the 1CGrx1 canonical binding site. Here we report a small molecule that binds at the glutathione binding site in which the binding mode of the molecule was deeply investigated by Nuclear Magnetic Resonance (NMR). This compound represents an important step in the attempt to develop a novel strategy to interfere with the peculiar Trypanosoma Brucei redox system, making it possible to shed light on the perturbation of this biochemical machinery and eventually to novel therapeutic possibilities.
Analysis of Single-Step Pretreatments for Lignocellulosic Platform Isolation as the Basis of Biorefinery Design
Authors: Poveda-Giraldo Jhonny Alejandro , Garcia-Vallejo Maria Camila , Cardona Alzate Carlos Ariel
Published: January 2023

Biorefinery feasibility is highly influenced by the early design of the best feedstock transformation pathway to obtain value-added products. Pretreatment has been identified as the critical stage in biorefinery design since proper pretreatment influences subsequent reaction, separation, and purification processes. However, many pretreatment analyses have focused on preserving and valorizing six-carbon sugars for future use in bioconversion processes, leaving aside fractions such as hemicellulose and lignin. To date, there has been no pretreatment systematization for the removal of lignocellulosic fractions. This work defines pretreatment efficacy through operational, economic, environmental, and social indicators. Thus, using the data reported in the literature, as well as the results of the simulation schemes, a multi-criteria weighting of the best-performing schemes for the isolation or removal of cellulose, hemicellulose, and lignin was carried out. As a main result, it was concluded that dilute acid is the most effective for cellulose isolation and hemicellulose removal for producing platform products based on six- and five-carbon sugars, respectively. Additionally, the kraft process is the best methodology for lignin removal and its future use in biorefineries. The results of this work help to elucidate a methodological systematization of the pretreatment efficacy in the design of biorefineries as an early feasibility stage considering sustainability aspects.
Comparative Chemical Profiling and Citronellol Enantiomers Distribution of Industrial-Type Rose Oils Produced in China
Authors: Dobreva Ana , Nedeltcheva-Antonova Daniela
Published: January 2023

The chemical composition and aroma profile of industrial essential oils (EOs) from species of rose grown in China, including the native Kushui rose (R. sertata × R. rugosa) and R. rugosa Thunb. cv. Plena, and the recently introduced Damask rose (R. damascena Mill.), were studied in comparison by means of GC/MS and GC-FID. More than 150 individual compounds were detected in Chinese rose samples, of which 112 were identified and their quantitative content determined, representing 88.7%, 96.7% and 97.9% of the total EO content, respectively. It was found that the main constituents of the Chinese rose EOs were representatives of terpenoid compounds (mono- and sesquiterpenoids, predominantly) and aliphatic hydrocarbons. Comparative chemical profiling revealed different chemical composition and aroma profiles: while the R. damascena oil showed a balance between the eleoptene and stearoptene fractions of the oil (the average ratio between the main terpene alcohols and paraffins was 2.65), in the Kushui and R. rugosa oils, the odorous liquid phase strongly dominated over the stearopten, with a ratio of 16.91 and 41.43, respectively. The most abundant terpene was citronellol, ranging from 36.69% in R. damascena to 48.32% in R. rugosa oil. In addition, the citronellol enantiomers distribution, which is an important marker for rose oil authenticity, was studied for the first time in R. rugosa oil.
Studies on the Complexation of Platinum(II) by Some 4-Nitroisoxazoles and Testing the Cytotoxic Activity of the Resulting Complexes
Authors: Mastalarz Henryk , Mastalarz Agnieszka , Wietrzyk Joanna , Milczarek Magdalena , Kochel Andrzej , Regiec Andrzej
Published: January 2023

Two novel platinum(II) complexes (1 and 2) were synthesized by the reaction of the appropriate 3,5-dimethyl-4-nitroisoxazole with K2PtCl4 and characterized by elemental analysis, ESI MS spectrometry, 1H NMR and far-IR spectroscopy. The structure of trans complex 2 was additionally confirmed by X-ray diffraction. The cytotoxicity of the investigated compounds was examined in vitro on three human cancer cell lines (MCF-7 breast, ES-2 ovarian and A-549 lung adenocarcinomas) in both normoxia and hypoxia conditions. LogPs of complexes were measured using the shake-flask method. The trans complex 2 showed much better cytotoxic activity than cisplatin for all the tested cancer cell lines. Cis complex 1 was inferior to its trans isomer against all the cancer lines tested in normoxia conditions but proved superior to the reference cisplatin against the MCF-7 and A549 lines, and showed similar activity to cisplatin against the ES-2 line. To gain additional information that may facilitate the explanation of the pharmacological activity of the tested compounds, cellular platinum uptake and stability in L-glutathione solution were determined for both compounds 1 and 2.
Delphinidin-3-rutinoside from Blackcurrant Berries (Ribes nigrum): In Vitro Antiproliferative Activity and Interactions with Other Phenolic Compounds
Authors: Miladinovic Bojana , Faria Miguel Ângelo , Ribeiro Mafalda , Sobral Maria Madalena Costa , Ferreira Isabel M. P. L. V. O.
Published: January 2023

Blackcurrant berries (Rigrum L.) are of great interest for food scientists/technologists as a source of delphinidin-3-rutinoside (D3R). This is an uncommon phenolic compound in diets that unveils potent antiproliferative activity besides its colour. Other phenolic compounds, such as chlorogenic acid (CA) and epicatechin (EC), also known by their antiproliferative effects, are abundant in foods and beverages. To design smart food/supplements combinations containing blackcurrant and improved anticancer properties at the gastrointestinal level, there is the need for more data concerning the combined effects of those molecules. In this work, synergistic, additive, or antagonistic effects against gastric and intestinal cancers of D3R, CA, and EC were assessed in vitro. The antiproliferative activity of D3R, CA, and EC, alone and in binary combinations (D3R+CA, D3R+EC, and CA+EC) on NCI-N87 (gastric) and Caco-2 (intestinal) cells, was assessed following the Chou-Talalay theorem at equipotent contributions (i.e., (IC50)1/(IC50)2). D3R presented the strongest antiproliferative activity of the single molecules tested, with IC50 values of 24.9 µM and 102.5 µM on NCI-N87 and Caco-2 cells, respectively. The combinations D3R+CA and CA+EC were synergic against NCI-N87 until IC50 and IC75, respectively, while D3R+EC shifted from slight antagonism to synergism at higher doses. On Caco-2 cells, antagonism at low doses and synergism at high doses was observed. Therefore, the synergisms observed on the gastric cancer model at low doses occurred on the colon model only at high doses. Data herein described is vital to the targeted smart design of foods and supplements, as it is foreseen that the same combination of phenolic compounds causes different interactions/effects depending on the dose and gastrointestinal compartment.
Acid-Triggered Switchable Near-Infrared/Shortwave Infrared Absorption and Emission of Indolizine-BODIPY Dyes
Authors: Saucier Matthew A. , Smith Cameron , Kruse Nicholas A. , Hammer Nathan I. , Delcamp Jared H.
Published: January 2023

Fluorescent organic dyes that absorb and emit in the near-infrared (NIR, 700–1000 nm) and shortwave infrared (SWIR, 1000–1700 nm) regions have the potential to produce noninvasive high-contrast biological images and videos. BODIPY dyes are well known for their high quantum yields in the visible energy region. To tune these chromophores to the NIR region, fused nitrogen-based heterocyclic indolizine donors were added to a BODIPY scaffold. The indolizine BODIPY dyes were synthesized via microwave-assisted Knoevenagel condensation with indolizine aldehydes. The non-protonated dyes showed NIR absorption and emission at longer wavelengths than an aniline benchmark. Protonation of the dyes produced a dramatic 0.35 eV bathochromic shift (230 nm shift from 797 nm to 1027 nm) to give a SWIR absorption and emission (λmaxemis = 1061 nm). Deprotonation demonstrates that material emission is reversibly switchable between the NIR and SWIR.
Impact of Ag/ZnO Reinforcements on the Anticancer and Biological Performances of CA@Ag/ZnO Nanocomposite Materials
Authors: Alahmadi Nadiyah , Hussein Mahmoud A.
Published: January 2023

In this study, an unpretentious, non-toxic, and cost-effective dissolution casting method was utilized to synthesize a group of anticancer and biologically active hybrid nanocomposite materials containing biopolymer cellulose acetate. Pristine ZnO and Ag(0.01, 0.05, 0.1)/ZnO hybrid nanofillers based on variable Ag NP loadings were prepared via green procedures in the presence of gum arabic (GA). The chemical structures and the morphological features of the designed nanocomposite materials were investigated by PXRD, TEM, SEM, FTIR, TGA, and XPS characterization techniques. The characterization techniques confirmed the formation of CA@Ag(0.01, 0.05, 0.1)/ZnO hybrid nanocomposite materials with an average crystallite size of 15 nm. All investigated materials showed two degradation steps. The thermal stability of the fabricated samples was ranked in the following order: CA/ZnO < CA@Ag(0.01)/ZnO < CA@Ag(0.05)/ZnO = CA@Ag(0.1)/ZnO. Hence, the higher Ag doping level slightly enhanced the thermal stability. The developed nanocomposites were tested against six pathogens and were used as the target material to reduce the number of cancer cells. The presence of Ag NPs had a positive impact on the biological and the anticancer activities of the CA-reinforced Ag/ZnO composite materials. The CA@Ag(0.1)/ZnO hybrid nanocomposite membrane had the highest antimicrobial activity in comparison to the other fabricated materials. Furthermore, the developed CA@Ag(0.1)/ZnO hybrid nanocomposite material effectively induced cell death in breast cancer.
Glycoproteomic Analysis of Urinary Extracellular Vesicles for Biomarkers of Hepatocellular Carcinoma
Authors: Li Dejun , Jia Shengnan , Wang Shuyue , Hu Lianghai
Published: January 2023

Hepatocellular carcinoma (HCC) accounts for the most common form of primary liver cancer cases and constitutes a major health problem worldwide. The diagnosis of HCC is still challenging due to the low sensitivity and specificity of the serum α-fetoprotein (AFP) diagnostic method. Extracellular vesicles (EVs) are heterogeneous populations of phospholipid bilayer-enclosed vesicles that can be found in many biological fluids, and have great potential as circulating biomarkers for biomarker discovery and disease diagnosis. Protein glycosylation plays crucial roles in many biological processes and aberrant glycosylation is a hallmark of cancer. Herein, we performed a comprehensive glycoproteomic profiling of urinary EVs at the intact N-glycopeptide level to screen potential biomarkers for the diagnosis of HCC. With the control of the spectrum-level false discovery rate ≤1%, 756 intact N-glycopeptides with 154 N-glycosites, 158 peptide backbones, and 107 N-glycoproteins were identified. Out of 756 intact N-glycopeptides, 344 differentially expressed intact N-glycopeptides (DEGPs) were identified, corresponding to 308 upregulated and 36 downregulated N-glycopeptides, respectively. Compared to normal control (NC), the glycoproteins LG3BP, PIGR and KNG1 are upregulated in HCC-derived EVs, while ASPP2 is downregulated. The findings demonstrated that specific site-specific glycoforms in these glycoproteins from urinary EVs could be potential and efficient non-invasive candidate biomarkers for HCC diagnosis.
A Novel Approach to Develop New and Potent Inhibitors for the Simultaneous Inhibition of Protease and Helicase Activities of HCV NS3/4A Protease: A Computational Approach
Authors: Riaz Muhammad , Rehman Ashfaq Ur , Waqas Muhammad , Khalid Asaad , Abdalla Ashraf N. , Mahmood Arif , Hu Junjian , Wadood Abdul
Published: January 2023

Infection of hepatitis C (HCV) is a major threat to human health throughout the world. The current therapy program suffers from restricted efficiency and low tolerance, and there is serious demand frr novel medication. NS3/4A protease is observed to be very effective target for the treatment of HCV. A data set of the already reported HCV NS3/4A protease inhibitors was first docked into the NS3/4A protease (PDB ID: 4A92A) active sites of both protease and helicase sites for calculating the docking score, binding affinity, binding mode, and solvation energy. Then the data set of these reported inhibitors was used in a computer-based program “RECAP Analyses” implemented in MOE to fragment every molecule in the subset according to simple retrosynthetic analysis rules. The RECAP analysis fragments were then used in another computer-based program “RECAP Synthesis” to randomly recombine and generate synthetically reasonable novel chemical structures. The novel chemical structures thus produced were then docked against HCV NS3/4A. After a thorough validation of all undertaken steps, based on Lipinski’s rule of five, docking score, binding affinity, solvation energy, and Van der Waal’s interactions with HCV NS3/4A, 12 novel chemical structures were identified as inhibitors of HCV NS3/4A. The novel structures thus designed are hoped to play a key role in the development of new effective inhibitors of HCV.
A Colorimetric Method for the Rapid Estimation of the Total Cannabinoid Content in Cannabis Samples
Authors: Jornet-Martínez Neus , Biosca-Micó Josep , Campíns-Falcó Pilar , Herráez-Hernández Rosa
Published: January 2023

A colorimetric method for the estimation of the total content of cannabinoids in cannabis samples is proposed. The assay is based on the reaction of these compounds with the reagent Fast Blue B (FBB), which has been immobilized into polydimethylsiloxane (PDMS). The reaction and detection conditions have been established according to the results obtained for the individual cannabinoids Δ9-tetrahydrocannabidiol (THC), cannabidiol (CBD), and cannabinol (CBN), as well as for ethanolic extracts obtained from cannabis samples after ultrasonication. In contact with the extract and under basic conditions, the reagent diffuses from the PDMS device, producing a red-brown solution. The absorbances measured at 500 nm after only 1 min of exposure to the FBB/PDMS composites led to responses proportional to the amounts of the cannabinoids in the reaction media. Those absorbances have been then transformed in total cannabinoid content using CBD as a reference compound. The potential utility of the proposed conditions has been tested by analyzing different cannabis samples. The selectivity towards other plants and drugs has been also evaluated. The present method is proposed as a simple and rapid alternative to chromatographic methods for the estimation of the total content of cannabinoids.
Design, Synthesis and Antitumor Activity of Novel Selenium-Containing Tepotinib Derivatives as Dual Inhibitors of c-Met and TrxR
Authors: Hu Jinhui , Chen Li , Lu Zhonghui , Yao Han , Hu Yunfei , Feng Luanqi , Pang Yanqing , Wu Jia-Qiang , Yu Zhiling , Chen Wen-Hua
Published: January 2023

Cellular mesenchymal–epithelial transition factor (c-Met), an oncogenic transmembrane receptor tyrosine kinase (RTK), plays an essential role in cell proliferation during embryo development and liver regeneration. Thioredoxin reductase (TrxR) is overexpressed and constitutively active in most tumors closely related to cancer recurrence. Multi-target-directed ligands (MTDLs) strategy provides a logical approach to drug combinations and would adequately address the pathological complexity of cancer. In this work, we designed and synthesized a series of selenium-containing tepotinib derivatives by means of selenium-based bioisosteric modifications and evaluated their antiproliferative activity. Most of these selenium-containing hybrids exhibited potent dual inhibitory activity toward c-Met and TrxR. Among them, compound 8b was the most active, with an IC50 value of 10 nM against MHCC97H cells. Studies on the mechanism of action revealed that compound 8b triggered cell cycle arrest at the G1 phase and caused ROS accumulations by targeting TrxR, and these effects eventually led to cell apoptosis. These findings strongly suggest that compound 8b serves as a dual inhibitor of c-Met and TrxR, warranting further exploitation for cancer therapy.
Electrochemical Removal of Nitrogen Compounds from a Simulated Saline Wastewater
Authors: Iovino Pasquale , Fenti Angelo , Galoppo Simona , Najafinejad Mohammad Saleh , Chianese Simeone , Musmarra Dino
Published: January 2023

In the last few years, many industrial sectors have generated and discharged large volumes of saline wastewater into the environment. In the present work, the electrochemical removal of nitrogen compounds from synthetic saline wastewater was investigated through a lab-scale experimental reactor. Experiments were carried out to examine the impacts of the operational parameters, such as electrolyte composition and concentration, applied current intensity, and initial ammoniacal nitrogen concentration, on the total nitrogen removal efficiency. Using NaCl as an electrolyte, the NTOT removal was higher than Na2SO4 and NaClO4; however, increasing the initial NaCl concentration over 250 mg·L−1 resulted in no benefits for the NTOT removal efficiency. A rise in the current intensity from 0.05 A to 0.15 A resulted in an improvement in NTOT removal. Nevertheless, a further increase to 0.25 A led to basically no enhancement of the efficiency. A lower initial ammoniacal nitrogen concentration resulted in higher removal efficiency. The highest NTOT removal (about 75%) was achieved after 90 min of treatment operating with a NaCl concentration of 250 mg·L−1 at an applied current intensity of 0.15 A and with an initial ammoniacal nitrogen concentration of 13 mg·L−1. The nitrogen degradation mechanism proposed assumes a series–parallel reaction system, with a first step in which NH4+ is in equilibrium with NH3. Moreover, the nitrogen molar balance showed that the main product of nitrogen oxidation was N2, but NO3− was also detected. Collectively, electrochemical treatment is a promising approach for the removal of nitrogen compounds from impacted saline wastewater.
Modified Supporting Materials to Fabricate Form Stable Phase Change Material with High Thermal Energy Storage
Authors: Yu Chengbin , Song Youngseok
Published: January 2023

Thermal energy storage (TES) is vital to the absorption and release of plenty of external heat for various applications. For such storage, phase change material (PCM) has been considered as a sustainable energy material that can be integrated into a power generator. However, pure PCM has a leakage problem during the phase transition process, and we should fabricate a form stable PCM composite using some supporting materials. To prevent the leakage problem during the phase transition process, two different methods, microencapsulation and 3D porous infiltration, were used to fabricate PCM composites in this work. It was found that both microsphere and 3D porous aerogel supported PCM composites maintained their initial solid state without any leakage during the melting process. Compared with the microencapsulated PCM composite, the 3D porous aerogel supported PCM exhibited a relatively high weight fraction of working material due to its high porosity. In addition, the cross-linked graphene aerogel (GCA) could reduce volume shrinkage effectively during the infiltration process, and the GCA supported PCM composite kept a high latent heat (∆H) and form stability.