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1.
Nature ; 607(7919): 480-485, 2022 07.
Article in English | MEDLINE | ID: mdl-35859196

ABSTRACT

Pyroelectricity describes the generation of electricity by temporal temperature change in polar materials1-3. When free-standing pyroelectric materials approach the 2D crystalline limit, how pyroelectricity behaves remained largely unknown. Here, using three model pyroelectric materials whose bonding characters along the out-of-plane direction vary from van der Waals (In2Se3), quasi-van der Waals (CsBiNb2O7) to ionic/covalent (ZnO), we experimentally show the dimensionality effect on pyroelectricity and the relation between lattice dynamics and pyroelectricity. We find that, for all three materials, when the thickness of free-standing sheets becomes small, their pyroelectric coefficients increase rapidly. We show that the material with chemical bonds along the out-of-plane direction exhibits the greatest dimensionality effect. Experimental observations evidence the possible influence of changed phonon dynamics in crystals with reduced thickness on their pyroelectricity. Our findings should stimulate fundamental study on pyroelectricity in ultra-thin materials and inspire technological development for potential pyroelectric applications in thermal imaging and energy harvesting.

2.
Nucleic Acids Res ; 52(12): 7142-7157, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38804263

ABSTRACT

DHH/DHHA1 family proteins have been proposed to play critical roles in bacterial resistance to environmental stresses. Members of the most radioresistant bacteria genus, Deinococcus, possess two DHH/DHHA1 family proteins, RecJ and RecJ-like. While the functions of Deinococcus radiodurans RecJ (DrRecJ) in DNA damage resistance have been well characterized, the role and biochemical activities of D. radiodurans RecJ-like (DrRecJ-like) remain unclear. Phenotypic and transcriptomic analyses suggest that, beyond DNA repair, DrRecJ is implicated in cell growth and division. Additionally, DrRecJ-like not only affects stress response, cell growth, and division but also correlates with the folding/stability of intracellular proteins, as well as the formation and stability of cell membranes/walls. DrRecJ-like exhibits a preferred catalytic activity towards short single-stranded RNA/DNA oligos and c-di-AMP. In contrast, DrRecJ shows no activity against RNA and c-di-AMP. Moreover, a crystal structure of DrRecJ-like, with Mg2+ bound in an open conformation at a resolution of 1.97 Å, has been resolved. Subsequent mutational analysis was conducted to pinpoint the crucial residues essential for metal cation and substrate binding, along with the dimerization state, necessary for DrRecJ-like's function. This finding could potentially extend to all NrnA-like proteins, considering their conserved amino acid sequence and comparable dimerization forms.


Subject(s)
Bacterial Proteins , Deinococcus , Deinococcus/genetics , Deinococcus/metabolism , Bacterial Proteins/metabolism , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Models, Molecular , Crystallography, X-Ray , Amino Acid Sequence , DNA Repair
3.
Biochem Biophys Res Commun ; 722: 150160, 2024 08 30.
Article in English | MEDLINE | ID: mdl-38795453

ABSTRACT

Carbene transfer reactions have emerged as pivotal methodologies for the synthesis of complex molecular architectures. Heme protein-catalyzed carbene transfer reactions have shown promising results on model compounds. However, their limited substrate scope has hindered their application in natural product functionalization. Building upon the foundation of previously published work on a carbene transferase-myoglobin variant, this study employs computer-aided protein engineering to design myoglobin variants, using either docking or the deep learning-based LigandMPNN method. These variants were utilized as catalysts in carbene transfer reactions with a selection of monoterpene substrates featuring C-C double bonds, leading to seven target products. This cost-effective methodology broadens the substrate scope for heme protein-catalyzed reactions, thereby opening novel pathways for research in heme protein functionalities and offering fresh perspectives in the synthesis of bioactive molecules.


Subject(s)
Methane , Monoterpenes , Myoglobin , Myoglobin/chemistry , Methane/chemistry , Methane/analogs & derivatives , Monoterpenes/chemistry , Monoterpenes/metabolism , Protein Engineering/methods , Transferases/chemistry , Transferases/metabolism , Molecular Docking Simulation
4.
Chemistry ; 30(10): e202302936, 2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38012074

ABSTRACT

Protein engineering of cytochrome P450s has enabled these biocatalysts to promote a variety of abiotic reactions beyond nature's repertoire. Integrating such non-natural transformations with microbial biosynthetic pathways could allow sustainable enzymatic production of modified natural product derivatives. In particular, trifluoromethylation is a highly desirable modification in pharmaceutical research due to the positive effects of the trifluoromethyl group on drug potency, bioavailability, and metabolic stability. This study demonstrates the biosynthesis of non-natural trifluoromethyl-substituted cyclopropane derivatives of natural monoterpene scaffolds using an engineered cytochrome P450 variant, P411-PFA. P411-PFA successfully catalyzed the transfer of a trifluoromethyl carbene from 2-diazo-1,1,1-trifluoroethane to the terminal alkenes of several monoterpenes, including L-carveol, carvone, perilla alcohol, and perillartine, to generate the corresponding trifluoromethylated cyclopropane products. Furthermore, integration of this abiotic cyclopropanation reaction with a reconstructed metabolic pathway for L-carveol production in Escherichia coli enabled one-step biosynthesis of a trifluoromethylated L-carveol derivative from limonene precursor. Overall, amalgamating synthetic enzymatic chemistry with established metabolic pathways represents a promising approach to sustainably produce bioactive natural product analogs.


Subject(s)
Biological Products , Cyclohexane Monoterpenes , Cytochrome P-450 Enzyme System , Cytochrome P-450 Enzyme System/metabolism , Monoterpenes/metabolism , Escherichia coli/metabolism , Cyclopropanes/chemistry , Biological Products/metabolism
5.
BMC Biol ; 21(1): 42, 2023 02 24.
Article in English | MEDLINE | ID: mdl-36829173

ABSTRACT

BACKGROUND: The nuclease NurA and the ATPase/translocase HerA play a vital role in repair of double-strand breaks (DSB) during the homologous recombination in archaea. A NurA-HerA complex is known to mediate DSB DNA end resection, leading to formation of a free 3' end used to search for the homologous sequence. Despite the structures of individual archaeal types of NurA and HerA having been reported, there is limited information regarding the molecular mechanisms underlying this process. Some bacteria also possess homologs of NurA and HerA; however, the bacterial type of this complex, as well as the detailed mechanisms underlying the joining of NurA-HerA in DSB DNA end resection, remains unclear. RESULTS: We report for the first time the crystal structures of Deinococcus radiodurans HerA (drHerA) in the nucleotide-free and ADP-binding modes. A D. radiodurans NurA-HerA complex structure was constructed according to a low-resolution cryo-electron microscopy map. We performed site-directed mutagenesis to map the drNurA-HerA interaction sites, suggesting that their interaction is mainly mediated by ionic links, in contrast to previously characterized archaeal NurA-HerA interactions. The key residues responsible for the DNA translocation activity, DNA unwinding activity, and catalytic activities of the drNurA-HerA complex were identified. A HerA/FtsK-specific translocation-related motif (TR motif) that guarantees the processivity of double-stranded DNA (dsDNA) translocation was identified. Moreover, a mechanism for the translocation-regulated resection of the 5' tail of broken dsDNA and the corresponding generation of a recombinogenic 3' single-stranded DNA tail by the drNurA-HerA complex was elucidated. CONCLUSIONS: Our work provides new insights into the mechanism underlying bacterial NurA-HerA-mediated DSB DNA end resection, and the way this complex digests the 5' tail of a DNA duplex and provides long 3' free end for strand invasion in the bacterial homologous recombination process.


Subject(s)
Adenosine Triphosphatases , Bacteria , Cryoelectron Microscopy , Adenosine Triphosphatases/genetics , Bacteria/genetics , DNA Repair , DNA , DNA, Bacterial , Archaea/genetics
6.
Molecules ; 29(4)2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38398519

ABSTRACT

To enhance the bioavailability and antihypertensive effect of the anti-depressant drug citalopram hydrobromide (CTH) we developed a sustained-release transdermal delivery system containing CTH. A transdermal diffusion meter was first used to determine the optimal formulation of the CTH transdermal drug delivery system (TDDS). Then, based on the determined formulation, a sustained-release patch was prepared; its physical characteristics, including quality, stickiness, and appearance, were evaluated, and its pharmacokinetics and irritation to the skin were evaluated by applying it to rabbits and rats. The optimal formulation of the CTH TDDS was 49.2% hydroxypropyl methyl cellulose K100M, 32.8% polyvinylpyrrolidone K30, 16% oleic acid-azone, and 2% polyacrylic acid resin II. The system continuously released an effective dose of CTH for 24 h and significantly enhanced its bioavailability, with a higher area under the curve, good stability, and no skin irritation. The developed CTH TDDS possessed a sustained-release effect and good characteristics and pharmacokinetics; therefore, it has the potential for clinical application as an antidepressant.


Subject(s)
Citalopram , Skin Absorption , Rats , Rabbits , Animals , Citalopram/pharmacology , Citalopram/metabolism , Delayed-Action Preparations/pharmacology , Administration, Cutaneous , Skin , Drug Delivery Systems , Transdermal Patch
7.
J Cell Physiol ; 238(8): 1909-1920, 2023 08.
Article in English | MEDLINE | ID: mdl-37357506

ABSTRACT

Human embryonic stem cells (hESCs) have great potential for developmental biology and regenerative medicine. However, extensive apoptosis often occurs when hESCs respond to various stresses or injuries. Understanding the molecular control and identifying new factors associated with hESC survival are fundamental to ensure the high quality of hESCs. In this study, we report that PRPF8, an RNA spliceosome component, is essential for hESC survival. PRPF8 knockdown (KD) induces p53 protein accumulation and activates the p53 pathway, leading to apoptosis in hESCs. Strikingly, silencing of p53 rescues PRPF8 KD-induced apoptosis, indicating that PRPF8 KD triggers hESC apoptosis through activating the p53 pathway. In search for the mechanism by which p53 pathway is activated by PRPF8 KD, we find that PRPF8 KD alters alternative splicing of many genes, including PIRH2 which encodes an E3 ubiquitin ligase of p53. PIRH2 has several isoforms such as PIRH2A, PIRH2B, and PIRH2C. Intriguingly, PRPF8 KD specifically increases the transcript level of the PIRH2B isoform, which lacks a RING domain and E3 ligase activity. Functionally, PIRH2B KD partially rescues the reduction in cell numbers and upregulation of P21 caused by PRPF8 KD in hESCs. The finding suggests that PRPF8 controls alternative splicing of PIRH2 to maintain the balance of p53 pathway activity and survival of hESCs. The PRPF8/PIRH2/p53 axis identified here provides new insights into how p53 pathway and hESC survival are precisely regulated at multiple layers, highlighting an important role of posttranscriptional machinery in supporting hESC survival.


Subject(s)
Alternative Splicing , Tumor Suppressor Protein p53 , Humans , Alternative Splicing/genetics , Protein Isoforms/genetics , Protein Isoforms/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolism , Ubiquitination
8.
Small ; 19(42): e2302935, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37322314

ABSTRACT

Organic-inorganic hybrid materials often face a stability challenge. ß-ZnTe(en)0.5 , which uniquely has over 15-year real-time degradation data, is taken as a prototype structure to demonstrate an accelerated thermal aging method for assessing the intrinsic and ambient-condition long-term stability of hybrid materials. Micro-Raman spectroscopy is used to investigate the thermal degradation of ß-ZnTe(en)0.5 in a protected condition and in air by monitoring the temperature dependences of the intrinsic and degradation-product Raman modes. First, to understand the intrinsic degradation mechanism, the transition state of the degradation is identified, then using a density functional theory, the intrinsic energy barrier between the transition state and ground state is calculated to be 1.70 eV, in excellent agreement with the measured thermal degradation barrier of 1.62 eV in N2 environment. Second, for the ambient-condition degradation, a reduced thermal activation barrier of 0.92 eV is obtained due to oxidation, corresponding to a projected ambient half-life of 40 years at room temperature, in general agreement with the experimental observation of no apparent degradation over 15 years. Furthermore, the study reveals a mechanism, conformation distortion enhanced stability, which plays a pivotal role in forming the high kinetic barrier, contributing greatly to the impressive long-term stability of ß-ZnTe(en)0.5 .

9.
J Transl Med ; 21(1): 739, 2023 10 19.
Article in English | MEDLINE | ID: mdl-37858181

ABSTRACT

BACKGROUND: Hepatic ischemia-reperfusion (IR) injury is the primary reason for complications following hepatectomy and liver transplantation (LT). Insulin-induced gene 2 (Insig2) is one of several proteins that anchor the reticulum in the cytoplasm and is essential for metabolism and inflammatory responses. However, its function in IR injury remains ambiguous. METHODS: Insig2 global knock-out (KO) mice and mice with adeno-associated-virus8 (AAV8)-delivered Insig2 hepatocyte-specific overexpression were subjected to a 70% hepatic IR model. Liver injury was assessed by monitoring hepatic histology, inflammatory responses, and apoptosis. Hypoxia/reoxygenation stimulation (H/R) of primary hepatocytes and hypoxia model induced by cobalt chloride (CoCl2) were used for in vitro experiments. Multi-omics analysis of transcriptomics, proteomics, and metabolomics was used to investigate the molecular mechanisms underlying Insig2. RESULTS: Hepatic Insig2 expression was significantly reduced in clinical samples undergoing LT and the mouse IR model. Our findings showed that Insig2 depletion significantly aggravated IR-induced hepatic inflammation, cell death and injury, whereas Insig2 overexpression caused the opposite phenotypes. The results of in vitro H/R experiments were consistent with those in vivo. Mechanistically, multi-omics analysis revealed that Insig2 is associated with increased antioxidant pentose phosphate pathway (PPP) activity. The inhibition of glucose-6-phosphate-dehydrogenase (G6PD), a rate-limiting enzyme of PPP, rescued the protective effect of Insig2 overexpression, exacerbating liver injury. Finally, our findings indicated that mouse IR injury could be attenuated by developing a nanoparticle delivery system that enables liver-targeted delivery of substrate of PPP (glucose 6-phosphate). CONCLUSIONS: Insig2 has a protective function in liver IR by upregulating the PPP activity and remodeling glucose metabolism. The supplementary glucose 6-phosphate (G6P) salt may serve as a viable therapeutic target for alleviating hepatic IR.


Subject(s)
Hepatocytes , Insulins , Liver Diseases , Reperfusion Injury , Animals , Mice , Antioxidants/metabolism , Apoptosis/genetics , Glucose/metabolism , Hepatectomy/adverse effects , Hepatocytes/metabolism , Hepatocytes/pathology , Hypoxia/complications , Hypoxia/genetics , Hypoxia/metabolism , Insulins/metabolism , Liver/blood supply , Liver/injuries , Liver/metabolism , Liver/pathology , Liver Diseases/genetics , Liver Diseases/metabolism , Liver Diseases/pathology , Liver Diseases/surgery , Liver Transplantation/adverse effects , Phosphates/metabolism , Phosphates/pharmacology , Reperfusion Injury/genetics , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Reperfusion Injury/prevention & control
10.
Inorg Chem ; 62(19): 7376-7384, 2023 May 15.
Article in English | MEDLINE | ID: mdl-37134020

ABSTRACT

Copper-based halides have been found to be a new family of lead-free materials with high stability and superior optoelectrical properties. In this work, we report the photoluminescence of the known (C8H14N2)CuBr3 and the discovery of three new compounds, (C8H14N2)CuCl3, (C8H14N2)CuCl3·H2O, and (C8H14N2)CuI3, which all exhibit efficient light emissions. All these compounds have monoclinic structures with the same space group (P21/c) and zero-dimensional (0D) structures, which can be viewed as the assembly of promising aromatic molecules and different copper halide tetrahedrons. Upon the irradiation of deep ultraviolet light, (C8H14N2)CuCl3, (C8H14N2)CuBr3,, and (C8H14N2)CuI3 show green emission peaking at ∼520 nm with a photoluminescent quantum yield (PLQY) of 3.38, 35.19, and 17.81%, while (C8H14N2)CuCl3·H2O displays yellow emission centered at ∼532 nm with a PLQY of 2.88%. A white light-emitting diode (WLED) was successfully fabricated by employing (C8H14N2)CuBr3 as a green emitter, demonstrating the potential of copper halides for applications in the green lighting field.

11.
J Chem Phys ; 158(24)2023 Jun 28.
Article in English | MEDLINE | ID: mdl-37358218

ABSTRACT

Silver sulfide in monoclinic phase (α-Ag2S) has attracted significant attention owing to its metal-like ductility and promising thermoelectric properties near room temperature. However, first-principles studies on this material by density functional theory calculations have been challenging as both the symmetry and atomic structure of α-Ag2S predicted from such calculations are inconsistent with experimental findings. Here, we propose that a dynamical approach is imperative for correctly describing the structure of α-Ag2S. The approach is based on a combination of ab initio molecular dynamics simulation and deliberately chosen density functional considering both proper treatment of the van der Waals interaction and on-site Coulomb interaction. The obtained lattice parameters and atomic site occupations of α-Ag2S are in good agreement with experimental data. A stable phonon spectrum at room temperature can be obtained from this structure, which also yields a bandgap in accord with experimental measurements. The dynamical approach thus paves the way for studying this important ductile semiconductor in not only thermoelectric but also optoelectronic applications.

12.
J Nanobiotechnology ; 21(1): 475, 2023 Dec 10.
Article in English | MEDLINE | ID: mdl-38072936

ABSTRACT

This study presents the first-ever synthesis of samarium-doped indium vanadate nanosheets (IVONSs:Sm) via microemulsion-mediated solvothermal method. The nanosheets were subsequently utilized as a nano-matrix in laser desorption/ionization mass spectrometry (LDI-MS). It was discovered that the as-synthesized IVONSs:Sm possessed the following advantages: improved mass spectrometry signal, minimal matrix-related background, and exceptional stability in negative-ion mode. These qualities overcame the limitations of conventional matrices and enabled the sensitive detection of small biomolecules such as fatty acids. The negative-ion LDI mechanism of IVONSs:Sm was examined through the implementation of density functional theory simulation. Using IVONSs:Sm-assisted LDI-MS, fingerprint recognitions based on morphology and chemical profiles of endogenous/exogenous compounds were also achieved. Notably, crucial characteristics such as the age of an individual's fingerprints and their physical state could be assessed through the longitudinal monitoring of particular biomolecules (e.g., ascorbic acid, fatty acid) or the specific biomarker bilirubin glucuronide. Critical information pertinent to the identification of an individual would thus be facilitated by the analysis of the compounds underlying the fingerprint patterns.


Subject(s)
Indium , Vanadates , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Fatty Acids , Lasers
13.
Anal Chem ; 94(29): 10451-10461, 2022 07 26.
Article in English | MEDLINE | ID: mdl-35830232

ABSTRACT

The simultaneous analysis of diversified biomarkers with high sensitivity and in a point-of-care (POC) manner is of great significance for facile and early cancer diagnosis. Herein, we develop a target amplification-assisted ratiometric fluorescence assay (TARFA) platform integrating the dual-amplification strategy and colorimetric readout technology for sensitive and specific detection of two malignancy-associated biomarkers. Meanwhile, the NIR-excited alkaline-earth sulfide nanodots (ASNDs) with an ultrasmall (<10 nm) diameter and tunable emission wavelength are employed to replace commonly UV/visible light-excited fluorescent labels to minimize background interference from the sample matrix. Unique advantages of the ASNDs, together with superiority of consecutive signal amplification of enzymatic target recycling (ETR) and hybridization chain reaction (HCR), realize the pg/mL-range detection limit in specifically recognizing the vascular endothelial growth factor (VEGF) and soluble interleukin-6 receptors (sIL-6R). The combination detection of the dual analyte exhibits an improved sensitivity for cancer diagnosis. The addition of the target biomarkers leads to an increasingly ratiometric RGB signal, and quantification based on the ratio-dependent signal is more reliable rather than measuring the absolute RGB signals. Moreover, perceptible color transformation makes the TARFA platform competent for visual analysis of the target analytes as convenient as reading the pH indicator strip, and hue-based image analysis also improves the method with fine precision by quantitatively identifying the visual color. This work provides a new kind of NIR-excited aptasensing platform with a low detection limit, high throughput, and great portability, which also highlights the potential of the ASNDs in biomolecular fluorescent labeling.


Subject(s)
Biosensing Techniques , Neoplasms , Biomarkers, Tumor , Coloring Agents , Humans , Limit of Detection , Neoplasms/diagnosis , Nucleic Acid Hybridization , Vascular Endothelial Growth Factor A
14.
Chemistry ; 28(32): e202200234, 2022 Jun 07.
Article in English | MEDLINE | ID: mdl-35357741

ABSTRACT

In recent years all-solid-state sodium-ion batteries (SS-SIBs) have drawn significant attention due to their potential to be safer and lower cost than lithium-ion batteries. However, the lack of sodium solid-state electrolytes with high ionic conductivity has become one of the major challenges. Here, with first-principles computation we took NaCuZrS3 , consisting of earth-abundant and environmentally benign elements only, as an example to study Na-ion transport in the post-perovskite-like structure and used computation-guided design to improve its potential as a solid-state electrolyte. With ab initio molecular dynamics simulation and nudged elastic band calculation, we studied possible diffusion mechanisms in this material and found that Na ion interstitials have a favorable migration barrier of 0.22 eV, which is among the smallest in the literature reported values. Considering the large formation energy of Frenkel defects, we proposed doping strategy to introduce extra Na interstitials in the material. Our study suggests that the post-perovskite-like sulfides are worth of exploration for applications in SS-SIBs.

15.
J Biochem Mol Toxicol ; 36(7): e23055, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35373417

ABSTRACT

ß-Amyloid toxicity (Aß) is an important pathological factor of Alzheimer's disease (AD). Studies have shown that genistein can reduce the toxicity of Aß to a certain extent; however, the specific mechanism is still uncertain. In the study, we applied Caenorhabditis elegans strains expressing Aß peptides to evaluate the role of genistein inhibiting Aß toxicity and the undying mechanism. Genistein influencing the sterol metabolism pathway, the HSP-16.2 pathway, and lipofuscin in different strains of C. elegans were studied using reverse transcription-polymerase chain reaction, fluorescence labeling, RNA interference (RNAi), and so forth. Our results showed that genistein alleviated the paralysis of transgenic C. elegans strains. Furthermore, in AD C. elegans, genistein reduced the fluorescence of lipofuscin, downregulated the messenger RNA (mRNA) level of vit-3 and vit-6 which were related to the sterol metabolism pathway, significantly increased the mRNA level and protein level of HSP-16.2, increased the nuclear translocation of the DAF-16 transcription factor and increased the survival rate after heat stress, which was closely associated with HSP-16.2 levels. However, the paralysis-alleviating effect of genistein was greatly reduced because of RNAi-mediated inhibition of hsp-16.2, indicating that the anti-Aß toxicity effect of genistein was greatly dependent on HSP-16.2. The above results suggest that genistein inhibiting the toxicity of Aß in C. elegans, is involved in the modulation of the sterol metabolism pathway by promoting transcription factor DAF-16 translocation into the nucleus, increasing the expression level of HSP-16.2, and reducing the levels of lipofuscin through its antioxidant activity.


Subject(s)
Alzheimer Disease , Caenorhabditis elegans Proteins , Animals , Caenorhabditis elegans/genetics , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Forkhead Transcription Factors/genetics , Forkhead Transcription Factors/metabolism , Forkhead Transcription Factors/pharmacology , Genistein/pharmacology , Lipofuscin/metabolism , Lipofuscin/pharmacology , Paralysis , RNA, Messenger/metabolism , Signal Transduction , Sterols/pharmacology , Transcription Factors/genetics , Transcription Factors/metabolism
16.
Int J Mol Sci ; 23(21)2022 Oct 27.
Article in English | MEDLINE | ID: mdl-36361834

ABSTRACT

In this study, we developed a sustained-release transdermal delivery system containing losartan potassium (LP) and verapamil hydrochloride (VPH). LP and VPH have low bioavailability and long half-life. Therefore, the development of an optimum administration mode is necessary to overcome these drawbacks and enhance the antihypertensive effect. A transdermal diffusion meter was used to determine the optimal formulation of LP-VPH transdermal drug delivery systems (TDDS). Based on in vitro results, a sustained-release patch was prepared. Physical characteristics, including quality, stickiness, and appearance, were evaluated in vitro, while pharmacokinetics and skin irritation were evaluated in vivo. The results showed that 8.3% polyvinyl alcohol, 74.7% polyvinylpyrrolidone K30, 12% oleic acid-azone, and 5% polyacrylic acid resin II provided an optimized TDDS product for effective administration of LP and VPH. Furthermore, in vitro and in vivo release tests showed that the system continuously released LP and VPH for 24 h. The pharmacokinetic results indicated that although the maximum concentration was lower, both the area under the curve from 0-time and the mean residence time of the prepared patch were significantly higher than those of the oral preparations. Furthermore, the prepared LP-VPH transdermal patch showed good stability and no skin irritation. The developed LP-VPH TDDS showed a sustained-release effect and good characteristics and pharmacokinetics; therefore, it is an ideal formulation.


Subject(s)
Losartan , Verapamil , Delayed-Action Preparations/pharmacokinetics , Skin Absorption , Administration, Cutaneous , Drug Delivery Systems/methods
17.
Small ; 17(4): e2006279, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33373112

ABSTRACT

Cs2 SnI6 perovskite displays excellent air stability and a high absorption coefficient, promising for photovoltaic and optoelectronic applications. However, Cs2 SnI6 -based device performance is still low as a result of lacking optimized synthesis approaches to obtain high quality Cs2 SnI6 crystals. Here, a new simple method to synthesize single crystalline Cs2 SnI6 perovskite at a liquid-liquid interface is reported. By controlling solvent conditions and Cs2 SnI6 supersaturation at the liquid-liquid interface, Cs2 SnI6 crystals can be obtained from 3D to 2D growth with controlled geometries such as octahedron, pyramid, hexagon, and triangular nanosheets. The formation mechanisms and kinetics of complex shapes/geometries of high quality Cs2 SnI6 crystals are investigated. Freestanding single crystalline 2D nanosheets can be fabricated as thin as 25 nm, and the lateral size can be controlled up to sub-millimeter regime. Electronic property of the high quality Cs2 SnI6 2D nanosheets is also characterized, featuring a n-type conduction with a high carrier mobility of 35 cm2 V-1 s-1 . The interfacial reaction-controlled synthesis of high-quality crystals and mechanistic understanding of the crystal growth allow to realize rational design of materials, and the manipulation of crystal growth can be beneficial to achieve desired properties for potential functional applications.

18.
Mikrochim Acta ; 188(1): 29, 2021 01 06.
Article in English | MEDLINE | ID: mdl-33409815

ABSTRACT

A new metal-organic framework compound (MOF@MOF, NUZ-8) comprised of NH2-UiO-66 and ZIF-8 under the polyvinylpyrrolidone (PVP) as the structure modifier was synthesized through an internal extended growth method (IEGM). The resulting NUZ-8 emerged the unreported unique polyhedron shape and showed considerable specific surface area (1466.1862 m2/g), excellent adsorption capacity, and fluorescence. NUZ-8 was used as a probe for the rapid optical detection of natural antioxidant quercetin (QCT). Its outstanding selectivity and sensitivity to QCT are derived from the fact that NH2-UiO-66 acted as an optical tentacle to perceive QCT in virtue of its luminescence advantages, and ZIF-8 realized the selective enrichment of the QCT through its electron-rich framework structure. The experiments were carried out at an excitation wavelength of 335 nm and an emission wavelength range of 370-530 nm. Under conditions of the investigation, this probe realized the rapid detection of QCT and considerable adsorption capacity with wide linearity (0.3-80 µM), a low detection limit (0.14 µM), and acceptable recoveries (84.0-97.0%) in red wine samples, properties which were superior to many other detection platforms. The synthesis and the use of the above polyhedral composite provide guidance for the application of the IEGM in enhancing chemical sensing and instant determination of drugs.Graphical abstract Flow chart of this paper.


Subject(s)
Antioxidants/analysis , Fluorescent Dyes/chemistry , Metal-Organic Frameworks/chemistry , Quercetin/analysis , Adsorption , Antioxidants/chemistry , Limit of Detection , Phthalic Acids/chemistry , Povidone/chemistry , Quercetin/chemistry , Spectrometry, Fluorescence , Wine/analysis
19.
Analyst ; 145(13): 4436-4441, 2020 Jul 07.
Article in English | MEDLINE | ID: mdl-32469359

ABSTRACT

Anti-Stokes fluorescence induced by near-IR (NIR) radiation is particularly advantageous for the bioassay of complex samples, but most of the commonly used NIR-induced fluorescence nanomaterials such as up-conversion nanoparticles (UCNPs) do not exhibit satisfactory fluorescence intensity and work against achieving a highly sensitive bioassay. In this study, we a construct sensitive and specific bacteria biosensor based on the NIR-stimulated CaS: Eu, Sm, Mn and SrS: Ce, Sm, Mn nanoparticles. The fluorescent nanoparticles are conjugated with bacteria recognition fragments. In addition, the independent emission bands of these two types of fluorescent nanoparticles make it possible to detect and quantify Gram-positive strain and Gram-negative strain, simultaneously. Intense fluorescence and magnetic enrichment of magneto-fluorescence systems enable bacteria discrimination with the naked eye and improve sensitivity in trace bacteria detection (<20 CFU mL-1). The linear relationship between the fluorescence intensity and bacterial concentration is established with a detection range of 25-106 CFU mL-1. Furthermore, this NIR-excited assay strategy demonstrates better anti-interference capability than UV/visible-excited assay methods, showing high potential and practical value for medical diagnostics and bacteria monitoring.


Subject(s)
Bacteriological Techniques/methods , Escherichia coli/isolation & purification , Fluorescent Dyes/chemistry , Metal Nanoparticles/chemistry , Staphylococcus aureus/isolation & purification , Animals , Calcium Compounds/chemistry , Calcium Compounds/radiation effects , Escherichia coli/chemistry , Fluorescence , Food Contamination/analysis , Infrared Rays , Limit of Detection , Magnetic Phenomena , Metal Nanoparticles/radiation effects , Metals, Heavy/chemistry , Metals, Heavy/radiation effects , Microscopy, Fluorescence , Milk/microbiology , Polymyxin B/chemistry , Spectrometry, Fluorescence , Staphylococcus aureus/chemistry , Sulfides/chemistry , Sulfides/radiation effects , Teicoplanin/chemistry
20.
Anal Bioanal Chem ; 411(27): 7293-7301, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31598741

ABSTRACT

A simple, sensitive, and naked-eye assay of metformin (MET), based on the host-guest molecular recognition of cucurbit[6]uril (CB[6])-modified silver nanoparticles, has been developed for the first time. The molecular recognition between CB[6] and MET is initially demonstrated and the related recognition mechanism is further discussed. CB[6]-modified AgNPs were first synthesized and then characterized by UV-vis spectroscopy, Fourier transform infrared spectroscopy, and transmission electron microscopy. The solution behavior of CB[6] in the presence of AgNO3 was also studied, and the correlative result revealed that AgNPs could combine with the carbonyl portals of CB[6]. On the basis of the molecular recognition of CB[6] and the surface plasmon resonance effect of AgNPs, CB[6]-modified AgNPs were used as visual probes to detect MET. In CB[6]-modified AgNP solution, the aggregation of CB[6]-modified AgNPs induced by MET triggered changes of color and the UV-vis absorption spectrum, which laid the foundation for the visual identification and spectrophotometric determination of MET. Under the optimized detection conditions, the UV-vis spectral assay had a good linear relationship in the range from 3 to 750 µM, and the limit of detection was 1 µM. According to the color changes, the minimum concentration recognized by the naked eye was about 75 µM. Furthermore, this assay has high selectivity for coexisting interferents and was also applied to MET detection in human urine samples. This strategy provides a novel and facile tool for highly selective and sensitive detection of MET. Graphical abstract.


Subject(s)
Bridged-Ring Compounds/chemistry , Hypoglycemic Agents/urine , Imidazoles/chemistry , Metal Nanoparticles/chemistry , Metformin/urine , Silver/chemistry , Colorimetry , Humans , Limit of Detection , Metal Nanoparticles/ultrastructure , Spectrophotometry, Ultraviolet/methods , Urinalysis/methods
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