RSC Advances

Studzińska, Sylwia; Skoczylas, Magdalena; Bocian, Szymon; Dembska, Anna; Buszewski, Bogusław

doi: 10.1039/d0ra01620apmid: 35498856

The main aim of the present study was the synthesis of an oligonucleotide-based material with high chemical stability, repeatability and specificity to complementary oligonucleotides. The oligonucleotides were attached to a silica gel surface modified with amino acids during one-step synthesis. The amount of the oligonucleotides immobilized on the support surface had an impact on adsorption effectiveness, due to steric interference. The adsorption capacity corresponds to 4.7 μg of complementary oligonucleotide per 1 mg of material, which reflects 50% of immobilized oligonucleotides. The presented results contain comprehensive studies on hybridization and release of fully complementary, partially complementary, non-complementary and antisense oligonucleotides from the newly synthesized adsorbent. The salt concentration and time period were the most influential parameters in the case of adsorption, while high temperature and low salt content were indispensable for effective desorption. Selectivity studies revealed that the adsorption percentage increases with the decreasing number of base mismatches. Consequently, the desorption of low complementarity oligonucleotides was always greater in comparison with the fully complementary sequence. Furthermore, it was shown that oligonucleotide-based materials may be successfully used for the extraction of antisense oligonucleotides and their metabolites from serum samples with recoveries ranging between 65 and 73%.

Al-Shakliah, Nasser S.; Attwa, Mohamed W.; Kadi, Adnan A.; AlRabiah, Haitham

doi: 10.1039/c9ra10871hpmid: 35498820

Infigratinib (INF) is a novel, small molecule that is orally administered to inhibit human fibroblast growth factor receptors (FGFRs), which are a family of receptor tyrosine kinases that may be upregulated in different tumor cell types. On 6 January 2020, the FDA granted fast track designation to INF for first-line treatment of cholangiocarcinoma. Prediction of susceptible sites of metabolism and reactivity pathways (cyanide and GSH) for INF was performed by the Xenosite web predictor tool. Then, we report the characterization and identification of in vitro, in vivo, and reactive intermediates of INF using liquid chromatography ion trap mass spectrometry (LC-ITMS). Finally, an in silico toxicity assessment of INF metabolites was carried out using the StarDrop DEREK module showing structural alerts. Rat liver microsomes (RLMs) and isolated perfused rat liver hepatocytes were incubated with INF in vitro and the generated metabolites were collected by protein precipitation. In vivo metabolism was evaluated by time-course urine sampling from Sprague-Dawley rats administered a single INF oral dose. A similar volume of acetonitrile was added to each collected urine sample and both organic and aqueous layers were analyzed by LC-ITMS to detect in vivo INF metabolites. N-Ethyl piperazine rings and benzene at part A of the INF structure are metabolized to form iminium and 1,4-benzoquinone, respectively, which are very reactive toward nucleophilic macromolecules. Incubation of INF with RLMs in the presence of 1.0 mM KCN and 1.0 mM glutathione was used to evaluate reactive metabolites potentially responsible for toxicities associated with INF. There were seven in vitro phase I metabolites, three in vitro phase II metabolites, three cyano adducts, and three GSH conjugate metabolites of INF detected by LC-ITMS. In vivo INF metabolites identified included four in vivo phase I and three in vivo phase II metabolites. In vitro and in vivo phase I metabolic pathways included N-dealkylation, N-demethylation, O-demethylation, hydroxylation, and dechlorination, while the in vivo phase II metabolic reaction was a direct conjugation of INF with glucuronic acid and sulphate.

Sun, Jingjing; Yang, Wude; Feng, Meichen; Liu, Qifang; Kubar, Muhammad Saleem

doi: 10.1039/d0ra00922apmid: 35498850

Variable selection is a critical step for spectrum modeling. In this study, a new method of variable interval selection based on random frog (RF), known as Interval Selection based on Random Frog (ISRF), is developed. In the ISRF algorithm, RF is used to search the most likely informative variables and then, a local search is applied to expand the interval width of the informative variables. Through multiple runs and visualization of the results, the best informative interval variables are obtained. This method was tested on three near infrared (NIR) datasets. Four variable selection methods, namely, genetic algorithm PLS (GA-PLS), random frog, interval random frog (iRF) and interval variable iterative space shrinkage approach (iVISSA) were used for comparison. The results show that the proposed method is very efficient to find the best interval variables and improve the model's prediction performance and interpretation.

Lekjing, Somwang; Venkatachalam, Karthikeyan

doi: 10.1039/d0ra01165gpmid: 35498825

Effects of germination time (3, 5 and 7 days) and kilning temperature (40, 50 and 60 °C) on the malting characteristics, biochemical properties and structural properties of HomChaiya rice were examined. Malting potential in terms of germination rate and germination capacity increased as the germination period of rice was prolonged. Diastatic potential, hot water extract and malting loss of rice gradually increased with germination time and with kilning temperature; in contrast, malting yield and viscosity of the samples decreased. Germination time significantly increased the α-amylase activity, but β-amylase activities increased when kilned at different temperatures. Total starch decreased and reducing sugar increased in rice with prolonged germination, and furthermore, the kilning temperature significantly influenced these changes. Higher kilning temperature and prolonged germination period increased the protease activity in rice, and consequently, soluble protein and free amino acids also increased. Among the twelve identified amino acids in the HomChaiya rice, aspartic acid, glutamic acid, asparagine, serine, arginine, isoleucine, tyrosine, and phenylalanine increased with germination time and kilning temperature. FTIR results showed that increased germination time and kilning temperature unfolded the carbohydrates, which is consistent with the enzymatic (α- and β-amylase) activities. XRD results also found higher peak intensities for rice when germinated longer and kilned at a higher temperature. The crystallinity of malted rice decreased with germination time. Ultrastructural changes showed that starch granules are more vulnerable to enzymatic attack upon extended germination time and at higher kilning temperatures.

Teixeira, Ricardo G.; Marques, Fernanda; Robalo, M. Paula; Fontrodona, Xavier; Garcia, M. Helena; Geninatti Crich, Simonetta; Viñas, Clara; Valente, Andreia

doi: 10.1039/d0ra01522apmid: 35498822

Ruthenium complexes of carboranyl ligands offer the possibility of dual action (chemo + radiotherapy) that might result in significant clinical benefits. In that frame, we describe herein the development of ruthenium–carboranyl complexes bearing bipyridyl derivatives with the general formula [3-CO-3,3-{κ2-4,4′-R2-2,2′-bipy}-closo-3,1,2-RuC2B9H11] (R = CH3, RuCB1 or R = CH2OH, RuCB2). Both compounds crystallized in the monoclinic system, showing the expected three-legged piano stool structure. The ruthenacarboranes are stable in cell culture media and were tested against two cell lines that have shown favorable clinical responses with BNCT, namely melanoma (A375) and glioblastoma (U87). RuCB1 shows no cytotoxic activity up to 100 μM while RuCB2 showed moderate activity for both cell lines. Cell distribution assays showed that RuCB2 presents high boron internalization that is proportional to the concentration used indicating that RuCB2 presents features to be further studied as a potential anticancer bimodal agent (chemo + radiotherapy).

Huang, Bobo; Zhang, Bin; Liang, Bo; Fang, Lu; Ye, Xuesong

doi: 10.1039/d0ra00905apmid: 35498837

Hepatocellular carcinoma (HCC) is one of the most common cancerous diseases, with a low 5 year survival rate. Global hypomethylation drives genomic instability, which is regarded as one biomarker for early diagnosis. Long interspersed nucleotide element-1 (LINE-1) makes up around 17% of the genome, and could be regarded as a surrogate marker for global DNA methylation. In this work, a gold nanoparticle (AuNP) modified carbon fiber microelectrode (CFME) with a diameter of 7 μm was applied for the first time to detect the methylation level of LINE-1, by distinguishing adsorption affinities between different DNA bases and AuNPs. Several parameters, including AuNP electrodeposition time, sample adsorption time, and DNA concentration have been analyzed and optimized. The detection limit of our assay was 0.1 nM with only 2 μL sample solution. And the CFME had an excellent sensitivity of 10% methylation change and had the capacity to distinguish only one methylated CpG site. The global DNA methylation level of real samples including cell lines and clinical tissues was tested. Higher signals of HCC cell lines and cancer tissues were observed respectively, compared with normal hepatic cell lines and normal tissues. This work provides a promising approach for HCC early diagnosis and prognosis.

Chao, Szu-Han; Yeh, Li-Hsien; Wu, Rudder T.; Kawagishi, Kyoko; Hsu, Shih-Chieh

doi: 10.1039/d0ra01900cpmid: 35498868

In this study, a novel patterned sapphire substrate (PSS) was used to obtain mesa-type light-emitting diodes (LED), which can efficiently reduce the threading dislocation densities. Silicon nitride (Si3N4) was used as a barrier to form the PSS, replacing the commonly used silicon dioxide (SiO2). The refractive index of Si3N4 is 2.02, which falls between those of sapphire (1.78) and GaN (2.4), so it can be used as a gradient refractive index (GRI) material, enhancing the light extraction efficiency (LEE) of light-emitting diodes. The simulation and experimental results obtained indicate that the LEE is enhanced compared with the conventional PSS-LED. After re-growing, we observed that an air void exists on the top of the textured Si3N4 layer due to GaN epitaxial lateral overgrowth (ELOG). Temperature-dependent PL was used to estimate the internal quantum efficiency (IQE) of the PSS-LED and that of the PSS-LED with the Si3N4 embedded air void (PSA-LED). The IQE of the PSA-LED is 4.56 times higher than that of the PSS-LED. Then, a TracePro optical simulation was used to prove that the air voids will affect the final luminous efficiency. The luminous efficiency of the four different structures considered is ranked as Si3N4 (PSN-LED) > PSA-LED > PSS-LED with SiO2 (PSO-LED) > PSS-LED. Finally, we fabricated LED devices with different thickness of the Si3N4 barrier. The device shows the best luminance–current–voltage (LIV) performance when the Si3N4 thickness is 220 nm.

Yaghoubian, Sima

doi: 10.1039/d0ra01219jpmid: 35498859

The adsorption of toluene and octane vapours on a homogenous silicon surface was measured under steady, thermal disequilibrium conditions where a vapour at a temperature TV is exposed to a solid surface at a lower temperature, TS. Zeta adsorption isotherm theory was used along with Gibbsian thermodynamics to examine the adsorption results analytically and to investigate the wetting conditions for these vapours. Further, from the prediction of the cluster distribution in the adsorbate, the conditions for the initiation of a liquid phase are predicted. Finally, the mechanism that determines the condensation mode of hydrocarbons on a silicon surface is investigated.

Liu, Xiao; Zhou, Jianhua; Xu, Zhen; Wang, Yixuan

doi: 10.1039/d0ra01412epmid: 35498873

The formation of a solid electrolyte interphase (SEI) between the anode surface and the electrolyte of lithium-ion batteries (LIBs) has been considered to be the most important yet the least understood issue of LIBs. To further our understanding in this regard, the density functional theory (DFT) B3PW91/6-311++G(3df,3pd) together with the implicit solvent model and the transition state theory were used for the first time to comprehensively explore the electroreduction mechanism of a novel additive, 4-chloromethyl-1,3,2-dioxathiolane-2-oxide (CMDO), and a few other solvents and additives, such as ethylene carbonate (EC), propylene carbonate (PC), dimethyl carbonate (DMC), fluoroethylene carbonate (FEC), and even ethylene sulfite (ES), for comparison. The one-electron reduction potential of Li+-coordinated compounds Li+(X) for forming decomposition precursors [c-Li+(X˙−)] decreases in the following sequence: CMDO (1.9–2.2 V vs. Li+/Li) ∼ ES(1.9 V) > FEC (0.7 V) > EC (0.47 V) > PC (0.45 V) > DMC (0.38 V); this implies that CMDO is reduced prior to other solvents or additives in the mixture. Although the ring opening of [c-Li+(CMDO˙−)] is the least kinetically favorable, as reflected by the highest energy barrier (Ea), i.e., CMDO (18.8–22.9 kcal mol−1) ∼ ES (23.4) > FEC (16.2) > PC (12.5) > EC (11.2) > DMC (8.0), CMDO still shows the highest overall reaction rate constant (∼1053 s−1) for forming an open ring radical [o-Li+(CMDO˙)−]. In addition, the termination reaction of [o-Li+(CMDO˙)−] for forming LiCl is thermodynamically more favorable than that of Li2SO3 or organic disulfite (LiSO3)2-R, which supports the experimental observation that the halogen-containing LiF or LiCl additives are predominant over all other halogen-containing species in the SEI layer. Moreover, the hybrid model by including the second solvation shell of Li+ via a supercluster [(CMDO)Li+(PC)2](PC)9 and the implicit solvent model (SMD) can result in a reduction potential (∼1.7 V) that is in excellent agreement with the experimental reduction peak.

Waimin, Jose Fernando; Nejati, Sina; Jiang, Hongjie; Qiu, Jake; Wang, Jianghsan; Verma, Mohit S.; Rahimi, Rahim

doi: 10.1039/c9ra10986bpmid: 35498852

Gut microbiota plays an important role in host physiology such as obesity, diabetes, and various neurological diseases. Thus, microbiome sampling is a fundamental approach towards better understanding of possible diseases. However, conventional sampling methods, such as endoscopies or colonoscopies, are invasive and cannot reach the entire small intestine. To address this need, a battery-less 3D-printed sampling capsule, which can collect microbiome samples throughout the entirety of the GI tract was designed. The capsule (9 mm × 15 mm) consists of a 3D printed acrylic housing, a fast-absorbing hydrogel, and a flexible PDMS membrane. Fluids containing samples of the microbial flora within the GI tract enter the device through a sampling aperture on the cap of the device. Once the microbiome enters the housing, the hydrogel absorbs the fluid and swells, effectively protecting the samples within its polymeric matrix, while also pushing on the flexible PDMS membrane to block the sampling aperture from further fluid exchange. The retrieved capsule can be readily disassembled due to the screw-cap design of the capsule and the hydrogel can be removed for further bacterial culture and analysis. As a proof of concept, the capsule's bacterial sampling efficiency and the ability to host microbial samples within the hydrogel in a sealed capsule were validated using a liquid culture containing Escherichia coli. The demonstrated technology provides a promising inexpensive tool for direct sampling and assessment of microbes throughout the GI tract and can enable new insights into the role of diet in mediating host–microbe interactions and metabolism.