bluuebunny/crossref_metadata_2025 huggingface dataset:
Fluorescent Quinolinium Derivative as Novel Mitochondria Probe and Function Modulator by Targeting Mitochondrial RNA
Authors: Wang Bo-Zheng , Zhou Ying-Chen , Lin Yu-Wei , Chen Xiu-Cai , Yu Ze-Yi , Xu Yao-Hao , Tan Jia-Heng , Huang Zhi-Shu , Chen Shuo-Bin
Published: March 2023

Mitochondria have a crucial role in regulating energy metabolism and their dysfunction has been linked to tumorigenesis. Cancer diagnosis and intervention have a great interest in the development of new agents that target biomolecules within mitochondria. However, monitoring and modulating mitochondria RNA (mtRNA), an essential component in mitochondria, in cells is challenging due to limited functional research and the absence of targeting agents. In this study, we designed and synthesized a fluorescent quinolinium derivative, QUCO-1, which actively lit up with mtRNA in both normal and cancer cells in vitro. Additionally, we evaluated the function of QUCO-1 as an mtRNA ligand and found that it effectively induced severe mitochondrial dysfunction and OXPHOS inhibition in RKO colorectal cancer cells. Treatment with QUCO-1 resulted in apoptosis, cell cycle blockage at the G2/M phase, and the effective inhibition of cell proliferation. Our findings suggest that QUCO-1 has great potential as a promising probe and therapeutic agent for mtRNA, with the potential for treating colorectal cancer.
Novel Steroidal[17,16-d]pyrimidines Derived from Epiandrosterone and Androsterone: Synthesis, Characterization and Configuration-Activity Relationships
Authors: Yang Fei , Liu Fang , Min Yong , Shi Liqiao , Liu Manli , Wang Kaimei , Ke Shaoyong , Gong Yan , Yang Ziwen
Published: March 2023

Two series of novel steroidal[17,16-d]pyrimidines derived from natural epiandrosterone and androsterone were designed and synthesized, and these compounds were screened for their potential anticancer activities. The preliminary bioassay indicated that some of these prepared compounds exhibited significantly good cytotoxic activities against human gastric cancer (SGC-7901), lung cancer (A549), and hepatocellular liver carcinoma (HepG2) cell lines compared with 5-fluorouracil (5-FU), epiandrosterone, and androsterone. Especially the respective pairs from epiandrosterone and androsterone showed significantly different inhibitory activities, and the possible configuration-activity relationships have also been summarized and discussed based on kinase assay and molecular docking, which indicated that the inhibition activities of these steroidal[17,16-d]pyrimidines might obviously be affected by the configuration of the hydroxyl group in the part of the steroidal scaffold.
Catalytic Asymmetric α-Functionalization of α-Branched Aldehydes
Authors: Vera Silvia , Landa Aitor , Mielgo Antonia , Ganboa Iñaki , Oiarbide Mikel , Soloshonok Vadim
Published: March 2023

Aldehydes constitute a main class of organic compounds widely applied in synthesis. As such, catalyst-controlled enantioselective α-functionalization of aldehydes has attracted great interest over the years. In this context, α-branched aldehydes are especially challenging substrates because of reactivity and selectivity issues. Firstly, the transient trisubstituted enamines and enolates resulting upon treatment with an aminocatalyst or a base, respectively, would exhibit attenuated reactivity; secondly, mixtures of E- and Z-configured enamines/enolates may be formed; and third, effective face-discrimination on such trisubstituted sp2 carbon intermediates by the incoming electrophilic reagent is not trivial. Despite these issues, in the last 15 years, several catalytic approaches for the α-functionalization of prostereogenic α-branched aldehydes that proceed in useful yields and diastereo- and enantioselectivity have been uncovered. Developments include both organocatalytic and metal-catalyzed approaches as well as dual catalysis strategies for forging new carbon–carbon and carbon–heteroatom (C-O, N, S, F, Cl, Br, …) bond formation at Cα of the starting aldehyde. In this review, some key early contributions to the field are presented, but focus is on the most recent methods, mainly covering the literature from year 2014 onward.
Poly(amidoamine) Dendrimer/Camptothecin Complex: From Synthesis to In Vitro Cancer Cell Line Studies
Authors: Oledzka Ewa , Paśnik Klaudia , Domańska Izabela , Zielińska-Pisklak Monika , Piotrowska Urszula , Sobczak Marcin , Szeleszczuk Łukasz , Laskowska Anna
Published: March 2023

Camptothecin (CPT), an alkaloid with potent anticancer activity, is still not used in clinical practice due to its high hydrophobicity, toxicity, and poor active-form stability. To address these shortcomings, our research focuses on the encapsulation of this drug in the poly(amidoamine) (PAMAM) dendrimer macromolecule. The PAMAM dendrimer/CPT complex was synthesized and thoroughly characterized. The in vitro drug release study revealed that the drug was released in a slow and controlled manner in acidic and physiological conditions and that more than 80% of the drug was released after 168 h of incubation. Furthermore, it was demonstrated that CPT was released with first-order kinetics and non-Fickian transport. The studies on the hemolytic activity of the synthesized complex indicated that it is hemocompatible for potential intravenous administration at a concentration ≤ 5 µg/mL. Additionally, the developed product was shown to reduce the viability of non-small-cell lung cancer cells (A549) in a concentration- and time-dependent manner, and cancer cells were more susceptible to the complex than normal fibroblasts. Lastly, molecular modeling studies revealed that the lactone or carboxylic forms of CPT had a significant impact on the shape and stability of the complex and that its formation with the lactone form of CPT was more energetically favorable for each subsequent molecule than the carboxylic form. The report represents a systematic and structured approach to develop a PAMAM dendrimer/CPT complex that can be used as an effective drug delivery system (DDS) for the potential treatment of non-small-cell lung cancer.
Research Progress on Chemical Constituents and Pharmacological Activities of Menispermi Rhizoma
Authors: Zhai Xuan , Wang Kangmin , Gao Xingyi , Yan Bin
Published: March 2023

Menispermi Rhizoma, the rhizome of Menispermum dauricum DC., is a traditional Chinese medicine, which has the effect of clearing away heat and detoxification, dispelling wind, and relieving pain. It is often used in the treatment of sore throat, enteritis, dysentery, and rheumatism. The chemical constituents of M. Rhizoma mainly include alkaloids, phenolic acids, quinones, cardiotonic glycosides, and so on. Modern pharmacological studies have proved that M. Rhizoma has the effects of anti-tumour, anti-inflammation, anti-oxidation, bacteriostasis, cardio-cerebrovascular protection, anti-depression and anti-Alzheimer’s disease. In recent years, the chemical constituents of M. Rhizoma have been found continuously, and the pharmacological studies have deepened gradually. This paper reviews the research progress on the chemical composition and pharmacological effects of M. Rhizoma, to provide a basis for further research and development of its medicinal value.
Vanadium Extraction from the Flotation Concentrate of Vanadium-Bearing Shale by Process of Non-Roasting Enhanced Acid Leaching and Thermodynamics
Authors: Tang Yue , Ye Guohua , Zuo Qi
Published: March 2023

The purpose of this work is to significantly improve the vanadium grade of vanadium-bearing shale after flotation preconcentration, which is conducive to reducing the acid consumption and industrial costs in the subsequently enhanced acid leaching of vanadium. Vanadium concentrate from vanadium-bearing shale enriched by flotation is used for acid-leaching feed. The leaching effects of two kinds of acid-leaching systems were compared, and the mechanism of acid leaching on the mineral structure was also described. The difficulty of spontaneous reactions of vanadium-bearing minerals such as garnet in an acid-leaching system was studied through thermodynamics. Additionally, several characterization methods were used to evaluate the improvement of leaching performance. The addition of oxidants and fluorinating aids strengthens the acid-leaching process, which greatly destroys the structure of a garnet, which is conducive to the extraction of vanadium in a flotation concentrate. The leaching efficiency can reach 94.86%, and the acid consumption is also reduced. Through the mechanism study of the leaching system, it is expected that when the enhanced acid-leaching process is put into industrial production, the effective leaching of vanadium can be accurately controlled, and the difficulty of subsequent vanadium enrichment and purification can be reduced.
Decoding the Conformational Selective Mechanism of FGFR Isoforms: A Comparative Molecular Dynamics Simulation
Authors: Zhang Mingyang , Yasen Miersalijiang , Lu Shaoyong , Ma De-Ning , Chai Zongtao
Published: March 2023

Fibroblast growth factor receptors (FGFRs) play critical roles in the regulation of cell growth, differentiation, and proliferation. Specifically, FGFR2 gene amplification has been implicated in gastric and breast cancer. Pan-FGFR inhibitors often cause large toxic side effects, and the highly conserved ATP-binding pocket in the FGFR1/2/3 isoforms poses an immense challenge in designing selective FGFR2 inhibitors. Recently, an indazole-based inhibitor has been discovered that can selectively target FGFR2. However, the detailed mechanism involved in selective inhibition remains to be clarified. To this end, we performed extensive molecular dynamics simulations of the apo and inhibitor-bound systems along with multiple analyses, including Markov state models, principal component analysis, a cross-correlation matrix, binding free energy calculation, and community network analysis. Our results indicated that inhibitor binding induced the phosphate-binding loop (P-loop) of FGFR2 to switch from the open to the closed conformation. This effect enhanced extensive hydrophobic FGFR2-inhibitor contacts, contributing to inhibitor selectivity. Moreover, the key conformational intermediate states, dynamics, and driving forces of this transformation were uncovered. Overall, these findings not only provided a structural basis for understanding the closed P-loop conformation for therapeutic potential but also shed light on the design of selective inhibitors for treating specific types of cancer.
Impact of Plastic-Related Compounds on P-Glycoprotein and Breast Cancer Resistance Protein In Vitro
Authors: Rosellini Matteo , Turunen Petri , Efferth Thomas
Published: March 2023

Plastic in oceans degrades to microplastics and nanoplastics, causing various problems for marine fauna and flora. Recently, microplastic has been detected in blood, breast milk and placenta, underlining their ability to enter the human body with still unknown effects. In addition, plastic contains other compounds such as plasticizers, antioxidants or lubricants, whose impact on human health is also elusive. On the cellular level, two transporters involved in cell protection and detoxification of xenobiotic compounds are the ABC-transporters P-glycoprotein (P-gp, MDR1, ABCB1) and breast cancer resistance protein (BCRP, ABCG2). Despite the great importance of these proteins to maintain the correct cellular balance, their interaction with plastic and related products is evasive. In this study, the possible interaction between different plastic-related compounds and these two transporters was investigated. Applying virtual compound screening and molecular docking of more than 1000 commercially available plastic compounds, we identified candidates most probably interacting with these two transporters. Cytotoxicity and uptake assays confirmed their toxic interaction on P-glycoprotein-overexpressing CEM/ADR5000 and BCRP-overexpressing MDA-MD-231-BCRP cell lines. To specifically visualize the results obtained on the P-glycoprotein inhibitor 2,2’-methylenebis(6-tert-butyl-4-methylphenol), we performed live cell time-lapse microscopy. Confocal fluorescence microscopy was used to understand the behavior of the molecule and the consequences that it has on the uptake of the well-known substrate doxorubicin and, in comparison, with the known inhibitor verapamil. Based on the results, we provide evidence that the compound in question is an inhibitor of the P-glycoprotein. Moreover, it is also possible that 2,2’-methylenebis(6-tert-butyl-4-methylphenol), together with three other compounds, may also inhibit the breast cancer resistance protein. This discovery implies that plastic-related compounds can not only harm the human body but can also inhibit detoxifying efflux pumps, which increases their toxic potential as these transporters lose their physiological functions.
Formation of Gold Nanoclusters from Goldcarbonyl Chloride inside the Metal-Organic Framework HKUST-1
Authors: Hassan Zeinab Mohamed , Guo Wei , Welle Alexander , Oestreich Robert , Janiak Christoph , Redel Engelbert
Published: March 2023

Gas-phase infiltration of the carbonylchloridogold(I), Au(CO)Cl precursor into the pores of HKUST-1 ([Cu3(BTC)2(H2O)2], Cu-BTC) SURMOFs (surface-mounted metal-organic frameworks; BTC = benzene-1,3,5-tricarboxylate) leads to Au(CO)Cl decomposition within the MOF through hydrolysis with the aqua ligands on Cu. Small Aux clusters with an average atom number of x ≈ 5 are formed in the medium-sized pores of the HKUST-1 matrix. These gold nanoclusters are homogeneously distributed and crystallographically ordered, which was supported by simulations of the powder X-ray diffractometric characterization. Aux@HKUST-1 was further characterized by scanning electron microscopy (SEM) and infrared reflection absorption (IRRA) as well as Raman spectroscopy, time-of-flight secondary ion mass spectrometry (ToF-SIMS), X-ray photoelectron spectroscopy (XPS) and inductively coupled plasma optical emission spectroscopy (ICP-OES).
Analysis of the Volatile Flavor Compounds of Pomegranate Seeds at Different Processing Temperatures by GC-IMS
Authors: Gao Lili , Zhang Lihua , Liu Jing , Zhang Xiao , Lu Yonghui
Published: March 2023

This study sought to reveal the mechanism of flavor generation when pomegranate seeds are processed, as well as the contribution of volatile organic components (VOCs) to flavor formation. Gas chromatography–ion mobility spectrometry (GC-IMS), combined with relative odor activity (ROAV) and statistical methods, was used for the analysis. The results showed that 54 compounds were identified from 70 peaks that appeared in the GC-IMS spectrum. Then, the ROAV results showed 17 key volatile components in processing pomegranate seeds, and 7 flavor components with large differential contributions were screened out using statistical methods. These included γ-butyrolactone, (E)-3-penten-2-one (dimer), pentanal, 1-propanethiol, octanal, and ethyl valerate (monomer). It is suggested that lipid oxidation and the Maillard reaction may be the main mechanisms of flavor formation during the processing of pomegranate seeds. Furthermore, this study lays the experimental and theoretical foundations for further research on the development of flavor products from pomegranate seeds.
A Novel Drug with Potential to Treat Hyperbilirubinemia and Prevent Liver Damage Induced by Hyperbilirubinemia: Carbon Dots Derived from Platycodon grandiflorum
Authors: Chen Rui , Ma Huagen , Li Xiaopeng , Wang Meijun , Yang Yunbo , Wu Tong , Zhang Yue , Kong Hui , Qu Huihua , Zhao Yan
Published: March 2023

Platycodon grandiflorum (PG) is a traditional Chinese medicine with a long history, but its active compounds have not been reported. In this study, novel carbon dots (CDs), PG-based CDs (PGC-CDs), were discovered and prepared from PG via calcinations and characterized by transmission electron microscopy; high-resolution transmission electron microscopy; X-ray diffraction, fluorescence, ultraviolet-visible, and Fourier-transform infrared spectrometers; X-ray photoelectron spectroscopy; and high-performance liquid chromatography. In addition, the safety and antioxidant activity of PGC-CDs was evaluated by RAW264.7 cells and LO2 cells. The therapeutic effects of PGC-CDs on hyperbilirubinemia and liver protection were evaluated in a bilirubin-induced hyperbilirubinemia mice model. The experiment confirmed that the diameter range of PGC-CDs was from 1.2 to 3.6 nm. PGC-CDs had no toxicity to RAW264.7 cells and LO2 cells at a concentration of 3.91 to 1000 µg/mL and could reduce the oxidative damage of cells caused by H2O2. PGC-CDs could inhibit the increase levels of bilirubin and inflammation factors and increase the levels of antioxidants and survival rate, demonstrating that PGC-CDs possessed anti-inflammatory and anti-oxidation activity. PGC-CDs may reduce the content of bilirubin, so as to reduce a series of pathological lesions caused by bilirubin, which has potential in treating hyperbilirubinemia and preventing liver damage induced by hyperbilirubinemia.
Are Non-Six-Membered Ring Defects Formed in Single-Walled Carbon Nanotubes Treated by a Fluorination–Defluorination Process?
Authors: Omoto Yoji , Morita Hiromu , Sato Yoshinori , Nishida Tetsuo , Motomiya Kenichi , Katsui Hirokazu , Goto Takashi , Sato Yoshinori
Published: March 2023

Single-walled carbon nanotubes (SWCNTs) modified by introducing non-six-membered ring defects, such as five- and seven-membered rings, have attracted considerable attention because their conductivity is enhanced by increasing the electronic density of states at the Fermi energy level. However, no preparation method exists to efficiently introduce non-six-membered ring defects into SWCNTs. Herein, we attempt to introduce non-six-membered ring defects into SWCNTs by defect rearrangement of the nanotube framework using a fluorination–defluorination process. Defect-introduced SWCNTs were fabricated from SWCNTs fluorinated at 25 °C for different reaction times. Their structures were evaluated, and their conductivities were measured by operating a temperature program. Structural analysis of the defect-induced SWCNTs using X-ray photoelectron spectroscopy, Raman spectroscopy, high-resolution transmission electron microscopy, and visible–near-infrared spectroscopy did not reveal the presence of non-six-membered ring defects in the SWCNTs but indicated the introduction of vacancy defects. Meanwhile, conductivity measurements performed by operating a temperature program showed that the defluorinated SWCNTs prepared from SWCNTs fluorinated for 3 min (deF-RT-3m) exhibited decreased conductivity owing to the adsorption of water molecules to non-six-membered ring defects, thereby implying the possibility of non-six-membered ring defects being introduced into deF-RT-3m.
The Influence of Dietary Interventions on Arterial Stiffness in Overweight and Obese Subjects
Authors: Stanek Agata , Grygiel-Górniak Bogna , Brożyna-Tkaczyk Klaudia , Myśliński Wojciech , Cholewka Armand , Zolghadri Samaneh
Published: March 2023

Arterial stiffness is often increased in overweight/obese subjects before the development of hypertension. It is also one of the earliest indicators of increased cardiovascular disease risk and can be considered a good predictor of the development of subclinical cardiovascular dysfunction. Arterial stiffness is a significant prognostic factor influencing cardiovascular risk, which dietary habits can modify. Obese patients should use the caloric-restricted diet because it augments aortic distensibility, diminishes pulse wave velocity (PWV), and increases the activity of endothelial nitric oxide synthases. High intake of saturated fatty acids (SFA), trans fats, and cholesterol, typical for the Western diet, impairs endothelial function and raises brachial-ankle PWV. The replacement of SFA with monounsaturated (MUFA) or polyunsaturated fatty acids (PUFA) derived from seafood and plants diminishes the risk of arterial stiffness. The dairy product intake (excluding butter) decreases PWV in the general population. The high-sucrose diet causes toxic hyperglycemia and increases arterial stiffness. Complex carbohydrates with a low glycemic index (including isomaltose) should be recommended to keep vascular health. The high sodium intake (>10 g/day), particularly associated with low potassium consumption, has a deleterious effect on arterial stiffness (↑ baPWV). Since vegetables and fruits are good sources of vitamins and phytochemicals, they should be recommended in patients with high PWV. Thus, the dietary recommendation to prevent arterial stiffness should be similar to the Mediterranean diet, which is rich in dairy products, plant oils, and fish, with a minimal red meat intake and five servings of fruits and vegetables daily.
Impact of Caloric Restriction and Exercise on Trimethylamine N-Oxide Metabolism in Women with Obesity
Authors: Battillo Daniel J. , Malin Steven K.
Published: March 2023

Trimethylamine N-oxide (TMAO) is linked to cardiovascular disease (CVD) through partly altered central hemodynamics. We sought to examine if a low-calorie diet plus interval exercise (LCD+INT) intervention reduces TMAO more than a low-calorie diet (LCD) program alone in relation to hemodynamics, prior to clinically meaningful weight loss. Women with obesity were randomized to 2 weeks of LCD (n = 12, ~1200 kcal/d) or LCD+INT (n = 11; 60 min/d, 3 min at 90% and 50% HRpeak, respectively). A 180 min 75 g OGTT was performed to assess fasting TMAO and precursors (carnitine, choline, betaine, and trimethylamine (TMA)) as well as insulin sensitivity. Pulse wave analysis (applanation tonometry) including augmentation index (AIx75), pulse pressure amplification (PPA), forward (Pf) and backward pressure (Pb) waveforms, and reflection magnitude (RM) at 0, 60, 120, and 180 min was also analyzed. LCD and LCD+INT comparably reduced weight (p < 0.01), fasting glucose (p = 0.05), insulin tAUC180min (p < 0.01), choline (p < 0.01), and Pf (p = 0.04). Only LCD+INT increased VO2peak (p = 0.03). Despite no overall treatment effect, a high baseline TMAO was associated with decreased TMAO (r = −0.45, p = 0.03). Reduced TMAO was related to increased fasting PPA (r = −0.48, p = 0.03). Lowered TMA and carnitine correlated with higher fasting RM (r = −0.64 and r = −0.59, both p < 0.01) and reduced 120 min Pf (both, r = 0.68, p < 0.01). Overall, treatments did not lower TMAO. Yet, people with high TMAO pre-treatment reduced TMAO after LCD, with and without INT, in relation to aortic waveforms.
Molecular Mechanisms for the Carnosine-Induced Activation of Muscle–Brain Interaction
Authors: Ishibashi Asuka , Udono Miyako , Sato Mikako , Katakura Yoshinori
Published: March 2023

Carnosine is known to improve brain function. The molecular basis for the carnosine-mediated interaction between intestinal cells and neuronal cells is that carnosine acts on intestinal cells and stimulates exosome secretion, which can induce neurite outgrowth in neuronal cells. This study aimed to infer the carnosine-mediated interaction between muscle cells and neuronal cells. The results revealed that carnosine induces muscle cell differentiation, as well as the secretion of exosomes and myokines that can act on neuronal cells. Carnosine acts not only on intestinal cells but also on muscle cells, stimulating the secretion of secretory factors including exosomes that induce neurite outgrowth in neuronal cells, as well as myokines known to be involved in neuronal cell activation. As the miRNAs in exosomes secreted from intestinal cells and muscle cells upon carnosine treatment are different, it could be assumed that carnosine acts on each cell to interact with neuronal cell through separate factors and mechanisms.
Unusual Cardiac Manifestations of a Pheochromocytoma in a Girl
Authors: D’Angelo Lisa , Parent Anne-Simone , Derwael Céline , Hustinx Roland , Seghaye Marie-Christine
Published: March 2023

We report the case of an 11-year-old girl who complained about severe asthenia, orthostatic dizziness and abdominal pain for 4 weeks. The primary investigation concluded on febrile urinary tract infection treated by antibiotics. Symptom persistence prompted cardiological and endocrinological investigations. A fluctuation in blood pressure, long QT interval, dilation of the aortic root and left ventricular hypertrophy were documented. Elevated levels of urinary catecholamines together with the presence of a right-sided adrenal mass shown via abdominal ultrasound and magnetic resonance imaging were highly suggestive of a pheochromocytoma. This was confirmed by through iodine-123-metaiodobenzylguathdine ([123I]-mIBG) scintigraphy. Genetic analysis allowed for the exclusion of pathogenic mutations in genes implicated in hereditary paragangliomas and pheochromocytomas but showed a rare somatic mutation in exon 3 of the von Hippel-Lindau gene. The patient was treated with a β-blocker and calcium channel antagonist and underwent laparoscopic right-sided adrenalectomy. Cardiac manifestations resolved soon after surgery indicating that they were secondary to the pheochromocytoma. After 5 years of follow-up, the patient remains asymptomatic without any sign of tumor recurrence. The presence of aortic root dilation, a prolonged QT-interval and left ventricular hypertrophy may be early cardiac manifestations of a pheochromocytoma in a child and should prompt this diagnosis to be evoked.
Comparative HPLC–DAD–ESI-QTOF/MS/MS Analysis of Bioactive Phenolic Compounds Content in the Methanolic Extracts from Flowering Herbs of Monarda Species and Their Free Radical Scavenging and Antimicrobial Activities
Authors: Kozyra Małgorzata , Biernasiuk Anna , Wiktor Magdalena , Kukula-Koch Wirginia , Malm Anna
Published: March 2023

Comparative analysis of flavonoids and phenolic acids composition, in plants of six species of Monarda from family Lamiaceae was carried out. The 70% (v/v) methanolic extracts of flowering herbs of Monarda citriodora Cerv. ex Lag., Monarda bradburiana L.C. Beck, Monarda didyma L., Monarda media Willd., Monarda fistulosa L. and Monarda punctata L. were analyzed for their polyphenol composition as well as antioxidant capacity and antimicrobial effect. Liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC–DAD–ESI-QTOF/MS/MS) was used to identify phenolic compounds. The in vitro antioxidant activity was assessed using a DPPH radical scavenging assay, while antimicrobial activity was measured by the broth microdilution method allowing for MIC (minimal inhibitory concentration) determination. The total polyphenol content (TPC) was assayed by the Folin–Ciocalteu method. The results showed the presence of eighteen different components including phenolic acids and flavonoids together with their derivatives. The presence of six constituents (gallic acid, hydroxybenzoic acid glucoside, ferulic acid, p-coumaric acid, luteolin-7-glucoside and apigenin-7-glucoside) was found to be dependent on the species. To differentiate the samples, the antioxidant activity of 70% (v/v) methanolic extracts was studied and expressed as a percent of DPPH radical inhibition and in EC50 values (mg/mL). The latter values were as follows: M. media (EC50 = 0.090 mg/mL), M. didyma (EC50 = 0.114 mg/mL), M. citriodora (EC50 = 0.139 mg/mL), M. bradburiana (EC50 = 0.141 mg/mL), M. punctata (EC50 = 0.150 mg/mL) and M. fistulosa (EC50 = 0.164 mg/mL). Moreover, all extracts indicated bactericidal activity against reference Gram-positive (MIC = 0.07–1.25 mg/mL) and Gram-negative bacteria (MIC = 0.63–10 mg/mL) as well as fungicidal effect towards yeasts (MIC = 1.25–10 mg/mL). Staphylococcus epidermidis and Micrococcus luteus were the most sensitive to them. All extracts showed promising antioxidant properties and noteworthy activity against the reference Gram-positive bacteria. Antimicrobial effect of the extracts against the reference Gram-negative bacteria as well as fungi (yeasts) from Candida spp. was slight. All extracts showed bactericidal and fungicidal effect. The obtained results indicated that the investigated extracts from Monarda spp. could be potential sources of natural antioxidants and antimicrobial agents, especially with activity towards Gram-positive bacteria. The differences in the composition and properties of the studied samples may influence the pharmacological effects of the studied species.
Phenotyping Indices of CYP450 and P-Glycoprotein in Human Volunteers and in Patients Treated with Painkillers or Psychotropic Drugs
Authors: Darnaud Léa , Delage Clément , Daali Youssef , Trouvin Anne-Priscille , Perrot Serge , Khoudour Nihel , Merise Nadia , Labat Laurence , Etain Bruno , Bellivier Frank , Lloret-Linares Célia , Bloch Vanessa , Curis Emmanuel , Declèves Xavier
Published: March 2023

Drug-metabolizing enzymes and drug transporters are key determinants of drug pharmacokinetics and response. The cocktail-based cytochrome P450 (CYP) and drug transporter phenotyping approach consists in the administration of multiple CYP or transporter-specific probe drugs to determine their activities simultaneously. Several drug cocktails have been developed over the past two decades in order to assess CYP450 activity in human subjects. However, phenotyping indices were mostly established for healthy volunteers. In this study, we first performed a literature review of 27 clinical pharmacokinetic studies using drug phenotypic cocktails in order to determine 95%,95% tolerance intervals of phenotyping indices in healthy volunteers. Then, we applied these phenotypic indices to 46 phenotypic assessments processed in patients having therapeutic issues when treated with painkillers or psychotropic drugs. Patients were given the complete phenotypic cocktail in order to explore the phenotypic activity of CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A, and P-glycoprotein (P-gp). P-gp activity was evaluated by determining AUC0–6h for plasma concentrations over time of fexofenadine, a well-known substrate of P-gp. CYP metabolic activities were assessed by measuring the CYP-specific metabolite/parent drug probe plasma concentrations, yielding single-point metabolic ratios at 2 h, 3 h, and 6 h or AUC0–6h ratio after oral administration of the cocktail. The amplitude of phenotyping indices observed in our patients was much wider than those observed in the literature for healthy volunteers. Our study helps define the range of phenotyping indices with “normal” activities in human volunteers and allows classification of patients for further clinical studies regarding CYP and P-gp activities.
Auranofin Targeting the NDM-1 Beta-Lactamase: Computational Insights into the Electronic Configuration and Quasi-Tetrahedral Coordination of Gold Ions
Authors: Tolbatov Iogann , Marrone Alessandro
Published: March 2023

Recently, the well-characterized metallodrug auranofin has been demonstrated to restore the penicillin and cephalosporin sensitivity in resistant bacterial strains via the inhibition of the NDM-1 beta-lactamase, which is operated via the Zn/Au substitution in its bimetallic core. The resulting unusual tetrahedral coordination of the two ions was investigated via the density functional theory calculations. By assessing several charge and multiplicity schemes, coupled with on/off constraining the positions of the coordinating residues, it was demonstrated that the experimental X-ray structure of the gold-bound NDM-1 is consistent with either Au(I)-Au(I) or Au(II)-Au(II) bimetallic moieties. The presented results suggest that the most probable mechanism for the auranofin-based Zn/Au exchange in NDM-1 includes the early formation of the Au(I)-Au(I) system, superseded by oxidation yielding the Au(II)-Au(II) species bearing the highest resemblance to the X-ray structure.
Blautia coccoides JCM1395T Achieved Intratumoral Growth with Minimal Inflammation: Evidence for Live Bacterial Therapeutic Potential by an Optimized Sample Preparation and Colony PCR Method
Authors: Nomura Shoko , Sukowati Erike W. , Shigeno Yuko , Takahashi Maiko , Kato Akari , Benno Yoshimi , Yamashita Fumiyoshi , Mukai Hidefumi
Published: March 2023

We demonstrate that Blautia coccoides JCM1395T has the potential to be used for tumor-targeted live bacterial therapeutics. Prior to studying its in vivo biodistribution, a sample preparation method for reliable quantitative analysis of bacteria in biological tissues was required. Gram-positive bacteria have a thick outer layer of peptidoglycans, which hindered the extraction of 16S rRNA genes for colony PCR. We developed the following method to solve the issue; the method we developed is as follows. The homogenates of the isolated tissue were seeded on agar medium, and bacteria were isolated as colonies. Each colony was heat-treated, crushed with glass beads, and further treated with restriction enzymes to cleave DNAs for colony PCR. With this method, Blautia coccoides JCM1395T and Bacteroides vulgatus JCM5826T were individually detected from tumors in mice intravenously receiving their mixture. Since this method is very simple and reproducible, and does not involve any genetic modification, it can be applied to exploring a wide range of bacterial species. We especially demonstrate that Blautia coccoides JCM1395T efficiently proliferate in tumors when intravenously injected into tumor-bearing mice. Furthermore, these bacteria showed minimal innate immunological responses, i.e., elevated serum tumor necrosis factor α and interleukin-6, similar to Bifidobacterium sp., which was previously studied as a therapeutic agent with a small immunostimulating effect.
Bacilli Rhizobacteria as Biostimulants of Growth and Production of Sesame Cultivars under Water Deficit
Authors: Lima Giliard Bruno Primo de , Gomes Erika Fernandes , Rocha Geisenilma Maria Gonçalves da , Silva Francisco de Assis , Fernandes Pedro Dantas , Machado Alexandre Paulo , Fernandes-Junior Paulo Ivan , Melo Alberto Soares de , Arriel Nair Helena Castro , Gondim Tarcisio Marcos de Souza , Lima Liziane Maria de
Published: March 2023

A strategy using bacilli was adopted aiming to investigate the mitigation of the effects of water deficit in sesame. An experiment was carried out in a greenhouse with 2 sesame cultivars (BRS Seda and BRS Anahí) and 4 inoculants (pant001, ESA 13, ESA 402, and ESA 441). On the 30th day of the cycle, irrigation was suspended for eight days, and the plants were subjected to physiological analysis using an infrared gas analyzer (IRGA). On the 8th day of water suspension, leaves were collected for analysis: superoxide dismutase, catalase, ascorbate peroxidase, proline, nitrogen, chlorophyll, and carotenoids. At the end of the crop cycle, data on biomass and vegetative growth characteristics were collected. Data were submitted for variance analysis and comparison of means by the Tukey and Shapiro–Wilk tests. A positive effect of inoculants was observed for all characteristics evaluated, contributing to improvements in plant physiology, induction of biochemical responses, vegetative development, and productivity. ESA 13 established better interaction with the BRS Anahí cultivar and ESA 402 with BRS Seda, with an increase of 49% and 34%, respectively, for the mass of one thousand seeds. Thus, biological indicators are identified regarding the potential of inoculants for application in sesame cultivation.
Indoor and Outdoor Cultures of Gracilaria chilensis: Determination of Biomass Growth and Molecular Markers for Biomass Quality Evaluation
Authors: Caroca-Valencia Sofía , Rivas Jorge , Araya Matías , Núñez Alejandra , Piña Florentina , Toro-Mellado Fernanda , Contreras-Porcia Loretto
Published: March 2023

Taking into consideration climate change scenarios, marine contamination, and a constantly expanding world population, seaweed aquaculture has become an important option for the large-scale production of high-quality biomass. Due to existing biological knowledge of Gracilaria chilensis, several cultivation strategies have been established for obtaining diverse biomolecules (lipids, fatty acids, pigments, among others) with nutraceutical properties. In this research, indoor and outdoor cultivation methodologies were applied to generate high biomass of G. chilensis with positive quality for productive purposes, where the quality was determined according to the concentrations of lipoperoxides and phenolic compounds and the total antioxidant capacity (TAC). The results showed that G. chilensis cultures, which were fertilized for three weeks with Basfoliar® Aktiv (BF) at concentrations of 0.05–1% v/v, obtained high biomass (1–1.3 kg m–2) and DGR (0.35–4.66% d–1), low lipoperoxides (0.5–2.8 µmol g–1 DT), and high phenolic compounds (0.4–0.92 µ eq. GA g–1 FT) and TAC (5–7.5 nmol eq. TROLOX g–1 FT) as compared with other culture media. Lower stress was determined under indoor cultures, due to the operative control of diverse physicochemical stressor parameters (T°, light intensity, photoperiod, among others). Therefore, the cultures developed allow scaling the biomass in productive terms and are suitable for obtaining compounds of interest.
Understanding the Geographic Patterns of Closely-Related Species of Paspalum (Poaceae) Using Distribution Modelling and Seed Germination Traits
Authors: Glison Nicolás , Romero David , Rosso Virginia , Guerrero José Carlos , Speranza Pablo Rafael
Published: March 2023

The sexual species of the Dilatata complex (Paspalum dasypleurum, P. flavescens, P. plurinerve, P. vacarianum, and P. urvillei) are closely related phylogenetically and show allopatric distributions, except P. urvillei. These species show microhabitat similarities and differences in germination traits. We integrated species distribution models (SDMs) and seed germination assays to determine whether germination divergences explain their biogeographic pattern. We trained SDMs in South America using species’ presence–absence data and environmental variables. Additionally, populations sampled from highly favourable areas in the SDMs of these species were grown together, and their seeds germinated at different temperatures and dormancy-breaking conditions. Differences among species in seed dormancy and germination niche breadth were tested, and linear regressions between seed dormancy and climatic variables were explored. SDMs correctly classified both the observed presences and absences. Spatial factors and anthropogenic activities were the main factors explaining these distributions. Both SDMs and germination analyses confirmed that the niche of P. urvillei was broader than the other species which showed restricted distributions, narrower germination niches, and high correlations between seed dormancy and precipitation regimes. Both approaches provided evidence about the generalist-specialist status of each species. Divergences in seed dormancy between the specialist species could explain these allopatric distributions.
Trait Mapping of Phenolic Acids in an Interspecific (Vaccinium corymbosum var. caesariense × V. darrowii) Diploid Blueberry Population
Authors: Herniter Ira A. , Kim Yurah , Wang Yifei , Havill Joshua S. , Johnson-Cicalese Jennifer , Muehlbauer Gary J. , Iorizzo Massimo , Vorsa Nicholi
Published: March 2023

Blueberries (Vaccinium sect. Cyanococcus) are a dietary source of phenolic acids, including chlorogenic acid (CGA) and related compounds such as acetylated caffeoylquinic acid (ACQA) and caffeoylarbutin (CA). These compounds are known to be potent antioxidants with potential health benefits. While the chemistry of these compounds has been extensively studied, the genetic analysis has lagged behind. Understanding the genetic basis for traits with potential health implications may be of great use in plant breeding. By characterizing genetic variation related to fruit chemistry, breeders can make more efficient use of plant diversity to develop new cultivars with higher concentrations of these potentially beneficial compounds. Using a large interspecific F1 population, developed from a cross between the temperate V. corymbosum var. ceasariense and the subtropical V. darrowii, with 1025 individuals genotyped using genotype-by-sequencing methods, of which 289 were phenotyped for phenolic acid content, with data collected across 2019 and 2020, we have identified loci associated with phenolic acid content. Loci for the compounds clustered on the proximal arm of Vc02, suggesting that a single gene or several closely associated genes are responsible for the biosynthesis of all four tested compounds. Within this region are multiple gene models similar to hydroxycinnamoyl CoA shikimate/quinate hydroxycinnamoyltransferase (HCT) and UDP glucose:cinnamate glucosyl transferase (UGCT), genes known to be involved in the CGA biosynthesis pathway. Additional loci on Vc07 and Vc12 were associated with caffeoylarbutin content, suggesting a more complicated biosynthesis of that compound.
Antifungal Activity and Effect of Plant-Associated Bacteria on Phenolic Synthesis of Quercus robur L.
Authors: Bilous Svitlana , Likhanov Artur , Boroday Vira , Marchuk Yurii , Zelena Liubov , Subin Oleksandr , Bilous Andrii
Published: March 2023

Europe’s forests, particularly in Ukraine, are highly vulnerable to climate change. The maintenance and improvement of forest health are high-priority issues, and various stakeholders have shown an interest in understanding and utilizing ecological interactions between trees and their associated microorganisms. Endophyte microbes can influence the health of trees either by directly interacting with the damaging agents or modulating host responses to infection. In the framework of this work, ten morphotypes of endophytic bacteria from the tissues of unripe acorns of Quercus robur L. were isolated. Based on the results of the sequenced 16S rRNA genes, four species of endophytic bacteria were identified: Bacillus amyloliquefaciens, Bacillus subtilis, Delftia acidovorans, and Lelliottia amnigena. Determining the activity of pectolytic enzymes showed that the isolates B. subtilis and B. amyloliquefaciens could not cause maceration of plant tissues. Screening for these isolates revealed their fungistatic effect against phytopathogenic micromycetes, namely Fusarium tricinctum, Botrytis cinerea, and Sclerotinia sclerotiorum. Inoculation of B. subtilis, B. amyloliquefaciens, and their complex in oak leaves, in contrast to phytopathogenic bacteria, contributed to the complete restoration of the epidermis at the sites of damage. The phytopathogenic bacteria Pectobacterium and Pseudomonas caused a 2.0 and 2.2 times increase in polyphenol concentration in the plants, respectively, while the ratio of antioxidant activity to total phenolic content decreased. Inoculation of Bacillus amyloliquefaciens and Bacillus subtilis isolates into oak leaf tissue were accompanied by a decrease in the total pool of phenolic compounds. The ratio of antioxidant activity to total phenolic content increased. This indicates a qualitative improvement in the overall balance of the oak leaf antioxidant system induced by potential PGPB. Thus, endophytic bacteria of the genus Bacillus isolated from the internal tissues of unripe oak acorns have the ability of growth biocontrol and spread of phytopathogens, indicating their promise for use as biopesticides.
Enhancement of Power Conversion Efficiency of Non-Fullerene Organic Solar Cells Using Green Synthesized Au–Ag Nanoparticles
Authors: Okai Victor , Chahul Habibat Faith , Shikler Rafi
Published: March 2023

Organic-based photovoltaics are excellent candidates for renewable energy alternatives to fossil fuels due to their low weight, low manufacturing cost, and, in recent years, high efficiency, which is now above 18%. However, one cannot ignore the environmental price of the fabrication procedure due to the usage of toxic solvents and high-energy input equipment. In this work, we report on the enhancement of the power conversion efficiency non-fullerene organic solar cells by incorporating green synthesised Au–Ag nanoparticles, using onion bulb extract, into the hole transport layer poly (3,4-ethylene dioxythiophene)-poly (styrene sulfonate) (PEDOT: PSS) of Poly[4,8-bis(5-(2-ethylhexyl)thiophen-2-yl)benzo[1,2-b;4,5-b′]dithiophene-2,6-diyl-alt-(4-(2-ethylhexyl)-3 fluorothieno[3,4-b]thiophene-)-2-carboxylate-2-6-diyl)]: 3,9-bis(2-methylene-(3-(1,1-dicyanomethylene)-indanone))-5,5,11,11-tetrakis(4-hexylphenyl)-dithieno[2,3-d:2′,3′-d′]-s-indaceno[1,2-b:5,6-b′]dithiophene (PTB7-Th: ITIC) bulk-heterojunction organic solar cells. Red onion has been reported to contain quercetin, which serves as a capping agent that covers bare metal nanoparticles, thus reducing exciton quenching. We found that the optimized volume ratio of NPs to PEDOT: PSS is 0.06:1. At this ratio, a 24.7% enhancement in power conversion efficiency of the cell is observed, corresponding to a 9.11% power conversion efficiency (PCE). This enhancement is due to an increase in the generated photocurrent and a decrease in the serial resistance and recombination, as extracted from the fitting of the experimental data to a non-ideal single diode solar cell model. It is expected that the same procedure can be applied to other non-fullerene acceptor-based organic solar cells, leading to an even higher efficiency with minimal effect on the environment.
PLA 3D Printing as a Straightforward and Versatile Fabrication Method for PDMS Molds
Authors: van der Borg Guus , Warner Harry , Ioannidis Melina , van den Bogaart Geert , Roos Wouter H.
Published: March 2023

3D printing is gaining traction in research and development as a way to quickly, cheaply, and easily manufacture polydimethylsiloxane (PDMS) molds. The most commonly used method is resin printing, which is relatively expensive and requires specialized printers. This study shows that polylactic acid (PLA) filament printing is a cheaper, more readily available alternative to resin printing, that does not inhibit the curing of PDMS. As a proof of concept, a PLA mold for PDMS-based wells was designed, and 3D printed. We introduce an effective method to smooth the printed PLA mold, based on chloroform vapor treatment. After this chemical post-processing step, the smoothened mold was used to cast a ring of PDMS prepolymer. The PDMS ring was attached to a glass coverslip after oxygen plasma treatment. The PDMS–glass well showed no leakage and was well suited to its intended use. When used for cell culturing, monocyte-derived dendritic cells (moDCs) showed no morphological anomalies, as tested by confocal microscopy, nor did they show an increase in cytokines, as tested using ELISA. This underlines the versatility and strength of PLA filament printing and exemplifies how it can be valuable to a researcher’s toolset.
Preventing the Collapse Behavior of Polyurethane Foams with the Addition of Cellulose Nanofiber
Authors: Ju Sanghyeon , Lee Ajeong , Shin Youngeun , Jang Hyekyeong , Yi Jin-Woo , Oh Youngseok , Jo Nam-Ju , Park Teahoon
Published: March 2023

Polyurethane foam manufacturing depends on its materials and processes. A polyol that contains primary alcohol is very reactive with isocyanate. Sometimes, this may cause unexpected problems. In this study, a semi-rigid polyurethane foam was fabricated; however, its collapse occurred. The cellulose nanofiber was fabricated to solve this problem, and a weight ratio of 0.25, 0.5, 1, and 3% (based on total parts per weight of polyols) of the nanofiber was added to the polyurethane foams. The effect of the cellulose nanofiber on the polyurethane foams’ rheological, chemical, morphological, thermal, and anti-collapse performances was analyzed. The rheological analysis showed that 3 wt% of the cellulose nanofiber was unsuitable because of the aggregation of the filler. It was observed that the addition of the cellulose nanofiber showed the improved hydrogen bonding of the urethane linkage, even if it was not chemically reacted with the isocyanate groups. Moreover, due to the nucleating effect of the cellulose nanofiber, the average cell area of the produced foams decreased according to the amount of the cellulose nanofiber present, and the average cell area especially was reduced about five times when it contained 1 wt% more of the cellulose nanofiber than the neat foam. Although the thermal stability declined slightly, the glass transition temperature shifted from 25.8 °C to 37.6, 38.2, and 40.1 °C by when the cellulose nanofiber increased. Furthermore, the shrinkage ratio after 14 days from the foaming (%shrinkage) of the polyurethane foams decreased 15.4 times for the 1 wt% cellulose nanofiber polyurethane composite.