RSC Advances

Zhou, Wenjie; Ye, Shandong; Luo, Rong; Wu, Li-Min; Wang, Wei

doi: 10.1039/c9ra00020hpmid: 35517700

Depression is the leading cause of disability worldwide, and its treatment represents a major clinical challenge. The hypothalamus–pituitary–adrenal (HPA) axis has been known to play a crucial role in depression and serves as a target for antidepressants. Acid-sensing ion channels (ASICs) are widely expressed in the nervous system and may be implicated in depression. Whether ASICs could act on the HPA axis to affect depression-related behaviors is not fully understood. In this study, we investigated the effect of inhibition of ASICs on the HPA axis activity in chronic stress-subjected rats. We found that treatment with the ASIC selective antagonist amiloride reversed chronic stress-induced elevation of adrenocorticotropic hormone (ACTH) and corticosterone in serum, which is reflective of the HPA axis activity. In addition, amiloride also alleviated chronic stress-induced anhedonia-like behavior. These results suggest that inhibition of ASICs may act on the HPA axis to alleviate the symptoms of depression.

Cheng, Taofang; Ye, Ji; Li, Huiliang; Dong, Hongyuan; Xie, Ning; Mi, Nan; Zhang, Zhen; Zou, Jingtao; Jin, Huizi; Zhang, Weidong

doi: 10.1039/c8ra10100kpmid: 35517662

The compound Dan Zhi Tablet (DZT), a reputable traditional Chinese medicine prescription, is widely used for the treatment of ischemic stroke in clinic. However, its systematic chemical constituents have rarely been elucidated, which hampers its quality evaluation, the study of bioactive constituents and the mechanism of action interpretation. In this study, we developed a combination of multidimensional data acquisition and data processing strategy with the aim to globally and comprehensively identify the chemical constituents in DZT based on UPLC-TWIMS-QTOFMS. First, multidimensional acquisition modes (MSE, Fast DDA and HDMSE) were performed on UPLC-TWIMS-QTOFMS. Second, targeted characterizations of the known compounds and their analogues present in DZT were carried out on the basis of the corresponding commercial standards or Mass2Motifs. Third, untargeted identification of unknown compounds in DZT was performed by extracting shared Mass2Motifs from the raw fragmentation spectra. Finally, the coeluting isomers were characterized using a precursor and/or product ion mobility. Consequently, 202 compounds were detected from DZT: 29 of them were unambiguously identified by comparison with reference compounds, 29 unknown compounds were discovered in specific medicinal materials, and ten pairs of coeluting isomers, which could not be distinguished using conventional MSE or Fast-DDA, were resolved using HDMSE only. This strategy was successfully used for the rapid and global identification of complex compounds including known, unknown and coeluting isomeric compounds in DZT and provided helpful chemical information for further quality control, pharmacology and active mechanism research on DZT.

Lucero-Acuña, Armando; Gutiérrez-Valenzuela, Cindy Alejandra; Esquivel, Reynaldo; Guzmán-Zamudio, Roberto

doi: 10.1039/c9ra00821gpmid: 35517657

In this study we describe a mathematical analysis that considers the temperature effects of the controlled drug release process from biodegradable poly-d,l-lactide-co-glycolide (PLGA) nanoparticles. Temperature effects are incorporated and applied to two drug release models. The first one consists of a two-stage release process that considers only simultaneous contributions of initial burst and nanoparticle degradation–relaxation (BR model). The second one is a three release stage model that considers, additionally, a simultaneous drug diffusion (BRD model) step. In these models, the temperature dependency of the release parameters, initial burst constant, kb, the rate of degradation–relaxation constant, kr, time to achieve 50% of release, tmax, and effective diffusion coefficient constant (De), are determined using mathematical expressions analogous to the Arrhenius equation. The temperature dependent models are used to analyze the release of previously encapsulated Rhodamine 6G dye as a model drug in polyethylene glycol modified PLGA nanoparticles. The experimental data used to develop the mathematical model was obtained from release studies carried out in phosphate buffer pH 7.4 at 37 °C, 47 °C, and 57 °C. Multiphasic release behaviors with an overall increase rate associated with the incubation temperature were observed. The study incorporates a parametrical analysis that can evaluate diverse temperature variation effects of the controlled release parameters for the two models.

Heintges, Gaël H. L.; Hendriks, Koen H.; Colberts, Fallon J. M.; Li, Mengmeng; Li, Junyu; Janssen, René A. J.

doi: 10.1039/c9ra00816kpmid: 35517690

The effect of gradually replacing the branched alkyl side chains of a diketopyrrolopyrrole (DPP) conjugated polymer by linear side chains containing branched siloxane end groups on the photovoltaic performance of blends of these polymers with a common fullerene acceptor is investigated. With an increasing proportion of siloxane side chains, the molecular weight and solubility of the polymers decreases. While the siloxane containing polymers exhibit a higher hole mobility in field-effect transistors, their performance in solar cells is less than the polymer with only alkyl sides chains. Using grazing-incidence wide-angle X-ray scattering, transmission electron microscopy, and fluorescence spectroscopy we identify two main reasons for the reduced performance of siloxane containing polymers in solar cells. The first one is a somewhat coarser phase-separated morphology with slightly wider polymer fibers. This is unexpected as often the fiber width is inversely correlated with polymer solubility. The second one is stronger non-radiative decay of the pristine polymers containing siloxane side chains.

Babu, Lavanya Thilak; Jadhav, Gajanan Raosaheb; Paira, Priyankar

doi: 10.1039/c9ra01498epmid: 35517674

A series of quinoxaline-2-hydroxyphenylbenzothiazole scaffolds were synthesized and characterized using NMR, UV, fluorescence spectroscopy and LCMS. These newly synthesized compounds were found to be cytotoxic in human epithelioid cervix carcinoma (HeLa) and human colon cancer cell lines (Caco-2). Selectivity of the compounds 7e and 7g are more than 9 fold higher in Caco-2 cells with respect to the normal cell line HEK-293. The most fluorescent compound 7e has displayed high cytoselectivity, significant cellular uptake in HeLa cells and strong binding efficacy with DNA and BSA. The most potent compound 7g has primarily classified as BCS class 4 and BDDCS class 4.

Xu, Zhilong; Fan, Lei; Ni, Xiangying; Han, Jie; Guo, Rong

doi: 10.1039/c8ra10201epmid: 35517654

Tin (Sn) has wide prospects in applications as an anode electrode material for Li-ion batteries, due to its high theoretical specific capacity. However, the large volume expansion of Sn during the charge–discharge process causes a performance reduction of lithium-ion batteries (LIBs). Here, Sn encapsulated N-doped porous carbon fibers (Sn/NPCFs) were synthesized through an electrospinning method with a pyrolysis process. This structure was beneficial for the lithium ion/electron diffusion and buffered the large volume change. By adjusting the amount of Sn, the hybrid carbon fibers with different Sn/carbon ratios could be prepared, and the morphology, composition and properties of the Sn/NPCFs were characterized systematically. The results indicated that the Sn/NPCFs with a Sn-precursor/polymer weight ratio at 0.5 : 1 showed the best cycling stability and specific capacity, preserving the specific capacity of 400 mA h g−1 at the current density of 500 mA g−1 even after 100 cycles.

Ortega-Villarreal, Ana Sofia; Hernández-Fernández, Eugenio; Jensen, Christopher; Valdivia-Berroeta, Gabriel A.; Garrard, Samuel; López, Israel; Smith, Stacey J.; Christensen, Kenneth A.; Reyes-González, Miguel A.; Michaelis, David J.

doi: 10.1039/c9ra00108epmid: 35517661

A series of eight new ethyl (Z)-benzotriazolyl acrylates 6a–d and 7a–d have been synthesized by conventional heating and microwave irradiation from ethyl benzotriazolyl acetates 3 and 4 with the corresponding aromatic aldehydes. This work reports the synthetic approach and spectroscopic characterization (1H, 13C-NMR, HRMS) of all the synthesized compounds. X-ray diffraction analyses were performed for molecules 6a, 7a and 7d. Photophysical properties of compounds were evaluated. Finally, compound 6a was tested in a human cell line and showed low to no cytotoxicity at relevant concentrations. Initial testing demonstrates its potential use as a fluid-phase fluorescent marker for live cell imaging.

Zhang, Xueying; Ikram, Muhammad; Liu, Zhi; Teng, Lei; Xue, Jialing; Wang, Di; Li, Li; Shi, Keying

doi: 10.1039/c9ra00526apmid: 35517683

To develop an ultra-sensitive and selective NOx gas sensor with an ultra-low detection limit, expanded graphite/NiAl layered double hydroxide (EG/NA) nanowires were synthesized by using hydrothermal method with EG as a template and adjusting the amount of urea in the reaction. X-ray diffraction and transmission electron microscopy showed EG/NA3 nanowires with a diameter of 5–10 nm and a length greater than 100 nm uniformly dispersed on the expanded graphite nanosheet (>8 layers). The synergy between NiAl layered double hydroxide (NiAl-LDH) and expanded graphite (EG) improved the gas sensing properties of the composites. As expected, gas sensing tests showed that EG/NA composites have superior performance over pristine NiAl-LDH. In particular, the EG/NA3 nanowire material exhibited an ultra-high response (Ra/Rg = 17.65) with ultra-fast response time (about 2 s) to 100 ppm NOx, an ultra-low detection limit (10 ppb) and good selectivity at room temperature (RT, 24 ± 2 °C), which could meet a variety of application needs. Furthermore, the enhancement of the sensing response was attributed to the nanowire structure formed by NiAl-LDH in the EG interlayer and the conductive nanonetwork of interwoven nanowires.

Krishnan, Siva Kumar; Singh, Eric; Singh, Pragya; Meyyappan, Meyya; Nalwa, Hari Singh

doi: 10.1039/c8ra09577apmid: 35517682

Biosensors with high sensitivity, selectivity and a low limit of detection, reaching nano/picomolar concentrations of biomolecules, are important to the medical sciences and healthcare industry for evaluating physiological and metabolic parameters. Over the last decade, different nanomaterials have been exploited to design highly efficient biosensors for the detection of analyte biomolecules. The discovery of graphene has spectacularly accelerated research on fabricating low-cost electrode materials because of its unique physical properties, including high specific surface area, high carrier mobility, high electrical conductivity, flexibility, and optical transparency. Graphene and its oxygenated derivatives, including graphene oxide (GO) and reduced graphene oxide (rGO), are becoming an important class of nanomaterials in the field of biosensors. The presence of oxygenated functional groups makes GO nanosheets strongly hydrophilic, facilitating chemical functionalization. Graphene, GO and rGO nanosheets can be easily combined with various types of inorganic nanoparticles, including metals, metal oxides, semiconducting nanoparticles, quantum dots, organic polymers and biomolecules, to create a diverse range of graphene-based nanocomposites with enhanced sensitivity for biosensor applications. This review summarizes the advances in two-dimensional (2D) and three-dimensional (3D) graphene-based nanocomposites as emerging electrochemical and fluorescent biosensing platforms for the detection of a wide range of biomolecules with enhanced sensitivity, selectivity and a low limit of detection. The biofunctionalization and nanocomposite formation processes of graphene-based materials and their unique properties, surface functionalization, enzyme immobilization strategies, covalent immobilization, physical adsorption, biointeractions and direct electron transfer (DET) processes are discussed in connection with the design and fabrication of biosensors. The enzymatic and nonenzymatic reactions on graphene-based nanocomposite surfaces for glucose- and cholesterol-related electrochemical biosensors are analyzed. This review covers a very broad range of graphene-based electrochemical and fluorescent biosensors for the detection of glucose, cholesterol, hydrogen peroxide (H2O2), nucleic acids (DNA/RNA), genes, enzymes, cofactors nicotinamide adenine dinucleotide (NADH) and adenosine triphosphate (ATP), dopamine (DA), ascorbic acid (AA), uric acid (UA), cancer biomarkers, pathogenic microorganisms, food toxins, toxic heavy metal ions, mycotoxins, and pesticides. The sensitivity and selectivity of graphene-based electrochemical and fluorescent biosensors are also examined with respect to interfering analytes present in biological systems. Finally, the future outlook for the development of graphene based biosensing technology is outlined.

Atapour, Mehdi; Amoabediny, Ghasem; Ahmadzadeh-Raji, Mojgan

doi: 10.1039/c8ra09659gpmid: 35517687

In this paper, an optical-electrochemical nano-biosensor was introduced for measuring Cu2+ ion concentrations in water. A multi-step procedure was used to fabricate the transparent-conductive biosensor platform consisting of an l-cysteine–gold nanoparticle-based sandwich structure. First, colloidal gold nanoparticles (GNPs) were synthesized according to the Turkevich–Frens method with some modifications and then functionalized with l-cysteine molecules (GNP/l-cys). Then, cyclic voltammetry was preformed in buffered solutions containing HAuCl4·3H2O for gold nanoparticle electrodeposition on cleaned ITO glasses. The GNP-electrodeposited ITO glasses (ITO/GNPs) were thermally treated in air atmosphere for 1 hour at a temperature of 300 °C. Following the procedure, the gold nanoparticles on ITO/GNPs substrates were functionalized with l-cysteine to prepare ITO/GNPs/l-cys substrates. Finally, the sandwich-type substrates of ITO/GNPs/l-cys⋯Cu2+⋯l-cys/GNPs were fabricated by accumulation of Cu2+ ions using an open circuit technique performed in copper ion buffer solutions in the presence of previously produced colloidal GNP/l-cys nanoparticles. The effective parameters including GNP/l-cys solution volume, pre-concentration pH and pre-concentration time on the LSPR and SWV responses were investigated and optimized. The fabricated transparent-conductive platforms were successfully assessed as a nano-biosensor for detection of copper ions using two different methods of square wave voltammetry (SWV) and localized surface plasmon resonance (LSPR). As a result, the proposed biosensor showed a high sensitivity, selectivity and a wide detectable concentration range to copper ions. The total linear range and the limit of detection (LOD) of the nano-biosensor were 10–100 000 nM (0.6–6354.6 ppb) and below 5 nM (0.3 ppb), respectively. The results demonstrated the potential of combining two different optical and electrochemical methods for quantitation of the single analyte on the same biosensor platform and obtaining richer data. Also, these results indicated that the developed LSPR-SWV biosensor was superior to many other copper biosensors presented in the literature in terms of linear range and LOD. The developed nano-biosensor was successfully applied in the determination of trace Cu2+ concentration in actual tap water samples.