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Proteases, as one of the most significant kind of digestive enzymes, are closely related to a variety of physiological processes and diseases. Herein, a black phosphorus nanosheets (BPs) based sensitive fluorometric method for protease detection and inhibitor screening is proposed. The aqueous solution of perylene probe (probe 1) displays a strong fluorescence. BPs, as novel discovered two-dimensional (2D) materials, can adsorb probe 1 through electrostatic interactions, which causes fluorescence quenching of probe 1. Histone can control the interactions between the perylene probe and BPs, which can be further regulated by the introduction of a protease. Thus, the protease activity can be monitored by detecting the fluorescence intensity changes of probe 1. The method is label free, sensitive and selective. As low as 1 ng/mL trypsin can be easily detected.

A sensitive sandwich immunoassay for the sensing of human epididymis protein 4 (HE4) is developed based on aggregation-induced emission probe doped silica nanoparticles. Fluorescent silica nanoparticles (TSiO2) with excellent performance were prepared using a tetraphenylethylene based probe (TPE-C4-4) to produce a controlled aggregation effect, and HE4 was detected using antibody-functionalized fluorescent silica nanoparticles. The fluorescent silica nanoparticles possess good photophysical properties. The TSiO2 NPs were surface modified with carboxyl groups, and the antibody was covalently attached onto the surface of the nanoparticles. In addition, magnetic beads were modified with N-hydroxysulfosuccinimide sodium salt (NHS) on their surface, capable of forming stable peptide bonds with the antibody. TSiO2 NPs modified by an antibody and the magnetic beads modified by an antibody were used for the sandwich immunoassay for HE4 protein. The assay is quite sensitive and selective. The detection limit of HE4 is estimated to be 40 pM. The assay shows promising applications for the early diagnosis of ovarian cancer and the development of ovarian cancer-related drugs.

Objective: The purpose of this meta-analysis of longitudinal studies is to determine the safety and efficacy of artesunate combined with other forms of adjunctive therapies for severe malaria.Methods: Following the PRISMA guidelines, we searched multiple databases with the search terms “artesunate” and “adjunctive therapy” and “severe malaria” in July 2020. If the search showed a randomized controlled trial, the study was included in this meta-analysis. The random-effects model was used to calculate the combined incidence rate and relative risk or risk difference.Results: This meta-analysis included nine longitudinal studies with 724 participants. We found that the mortality rates in the artesunate monotherapy group and the artesunate + adjuvant therapy group are similar (RD = −0.02, 95% confidence interval: −0.06–0.02). The incidence of adverse reactions in the artesunate monotherapy group and the artesunate + adjuvant therapy group was also similar.Conclusion: No significant differences in safety and efficacy were observed between the artesunate monotherapy group and the artesunate + adjuvant therapy group. Higher quality and rigorously designed randomized controlled studies are needed to validate our findings.

Background and purpose Activation of the human pregnane X receptor (PXR; NR1I2) has potential therapeutic uses for inflammatory bowel disease (IBD). Imperatorin (IMP), a naturally occurring coumarin, is the main bioactive ingredient of Angelica dahurica Radix, which is regularly used to treat the common cold and intestinal disorders. However, there are no data on the protective effects of IMP against IBD. Experimental approach The effects of IMP on PXR-modulated cytochrome P450 3A4 (CYP3A4) expression were assessed using a PXR transactivation assay, a mammalian two-hybrid assay, a competitive ligand-binding assay, analysis of CYP3A4 mRNA and protein expression levels and measurement of CYP3A4 activity using a cell-based reporter gene assay and in vitro model. The inhibitory effects of IMP on NF-κB activity were evaluated by a reporter assay and NF-κB p65 nuclear translocation. The anti-IBD effects of IMP were investigated in a dextran sulphate sodium (DSS)-induced colitis mouse model. Colon inflammatory cytokines were assessed by elisa. Key results IMP activated CYP3A4 promoter activity, recruited steroid receptor coactivator 1 to the ligand-binding domain of PXR and increased the expression and activity of CYP3A4. PXR knockdown substantially reduced IMP-induced increase in CYP3A4 expression. Furthermore, IMP-mediated PXR activation suppressed the nuclear translocation of NF-κB and down-regulated LPS-induced expression of pro-inflammatory genes. Nevertheless, PXR knockdown partially reduced the IMP-mediated inhibition of NF-κB. IMP ameliorated DSS-induced colitis by PXR/NF-κB signalling. Conclusions and implications IMP acts as a PXR agonist to attenuate DSS-induced colitis by suppression of the NF-κB-mediated pro-inflammatory response in a PXR/NF-κB-dependent manner.

A novel and efficient approach has been established for the synthesis of silver nanoclusters capped silica nanoparticles (SiO 2 @AgNCs). These nanoclusters (AgNCs) capped silica nanoparticles were utilized as a novel ratiometric photoluminescence (PL) nanosensor for extremely sensitive and selective detection of I − and S 2− ions. The AgNCs were prepared in situ on the silica nanoparticles through polyethyleneimine (PEI) template approach. While dual PL emissions of AgNCs (at 500 nm) and luminescent silica nanoparticles (at 602 nm) formed the basis for the ratiometric sensing. The PL emission of AgNCs was strongly quenched by I − (or S 2− ), while that of luminescent silica nanoparticles was hardly affected. The PL emission intensity ratio of AgNCs and the luminescent silica nanoparticles was defined as I 500 /I 602 . A good linear relationship between the I 500 /I 602 value and the concentration of I − (or S 2− ) was observed, and the limit of detection (LOD) was estimated to be 57 nM for I − and 62 nM for S 2− . In addition, the fluorescence images of the SiO 2 @AgNCs nanosensor changed from white to orange upon exposure to different concentrations of I − (or S 2− ) (0–250 μM), which could be clearly distinguished by the naked eye. The SiO 2 @AgNCs nanosensor exhibited good selectivity against other analytes, and I − or S 2− ions could be separately detected via the introduction of proper masking agents. Furthermore, the detection of I − and S 2− in real water samples was also demonstrated.

A fluorescence turn-on assay for alkaline phosphatase (ALP) activity is developed through the controlled release of polyethyleneimine-capped copper nanoclusters (PEI-capped CuNCs) from the MnO2 nanosheets. In an aqueous solution, the positively charged PEI-capped CuNCs could be adsorbed onto the surface of the negatively charged MnO2 nanosheets. Such adsorption through favorable electrostatic interactions could efficiently quench the nanocluster fluorescence emission via resonance energy transfer from the PEI-capped CuNCs to the MnO2 nanosheets. 2-Phospho-l-ascorbic acid (AAP) could be hydrolyzed to l-ascorbic acid (AA) in the presence of ALP. AA could reduce MnO2 into Mn2+ and trigger the disintegration of the MnO2 nanosheets. As a result, the CuNCs were released and the quenched fluorescence was recovered efficiently. The detection strategy is simple, inexpensive, sensitive, selective, with low toxicity, and has better biocompatibility. The newly fabricated biosensor for ALP activity will potentially make it a robust candidate for numerous biological and biomedical applications.

A sensitive and selective luminescent nanoprobe (referred to as DEPN) is designed for the determination of Cu(II) ions. DEPN shows two emission peaks, one at 602 nm and caused by [Ru(bpy)3]2+, the other (peaking at 500 nm) caused by silver nanoclusters (AgNCs). The luminescence of the ruthenium complex is inert and acts as the internal reference signal, while that of the AgNCs is quenched by Cu(II) ions. Under 350 nm photoexcitation, a linear relationship is found between the ratio of emission intensity (I500/I602) and the concentration of Cu(II) ions in the 0.1–16 μM range. The detection limit of Cu(II) ions is estimated to be 50 nM. The DEPN was applied to the determination of Cu(II) ions in (spiked) water samples, and to intracellular imaging of Cu(II) in HeLa cells using confocal fluorescence microscopy.

A bright white light emitting benzoperylene probe-polyethyleneimine capped quantum dot nanocomposite has been synthesized for the first time. The negatively charged benzoperylene probe with a carboxylic acid functional group tends to self-assemble in the presence of a polycation, and exhibits distinct induced excimer fluorescence. Phosphorescence emitting manganese doped zinc sulfide quantum dots (Mn-ZnS QDs) were capped with polyethyleneimine (PEI). The PEI capped Mn-ZnS QDs were used to induce the benzoperylene probe self-assembly. A bright white light emitting nanocomposite was obtained both in solution and in solid state. The white emission has Commission Internationale de l'Eclairage (CIE) coordinates of (0.33, 0.32), a color-rendering index (CRI) of 72.61 and correlated color temperature (CCT) of 5697 K. Multiple color emissions from blue to orange could also be obtained in a controllable manner via simple adjustment of the ratio of the PEI capped Mn-ZnS QDs and the benzoperylene probe. The nanocomposite displays good photo, chemical and long-term stability. A strong white light emitting LED device based on the nanocomposite was demonstrated.

AIDS, a serious fatal disease caused by the human immunodeficiency virus (HIV), is an epidemic disease for which no effective vaccine has been established. The current therapeutic interventions for AIDS have limited efficacy because they are unable to clear HIV infections and the continuous occurrence of resistant HIV strains. Therefore, the exploitation of new drugs to prevent the spread of AIDS remains a high priority. In this study, the effects of icariin and its metabolite anhydroicaritin on SIV/HIV replication were investigated. In CEM × 174 cells and PBMC cells, both icariin and anhydroicaritin can significantly inhibit HIV-1 or SIVmac251 replication. Furthermore, molecular docking studies revealed that icariin and anhydroicaritin can act on both HIV reverse transcriptase and protease but could not bind to integrase. Reverse transcriptase and protease inhibition biological assays showed that both icariin and anhydroicaritin could significantly inhibit only HIV reverse transcriptase. In summary, the two compounds can significantly inhibit HIV/SIV in vitro and their targets may be mainly involved with HIV reverse transcriptase.

Three pairs of new spirocyclic alkaloid enantiomers eurotinoids A–C (1–3), as well as a known biogenetically related racemate dihydrocryptoechinulin D (4) were isolated from a marine-derived fungus Eurotium sp. SCSIO F452. Their structures were determined by spectroscopic analyses and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 represent the first two “meta” products from a non-stereoselective [4 + 2] Diels-Alder cycloaddition presumably between an enone group of a diketopiperazine alkaloid and a diene group of a benzaldehyde derivative via a new head-to-tail coupling mode biosynthetically, while 3 and 4 were “ortho” products. Their enantiomers exhibited different antioxidative and cytotoxic activities. The modes of action were investigated by a preliminary molecular docking study.

In this work, the α-conformation (individual locally separated chain) of the conjugated polymer poly(9,9-dioctylfluorene) (PFO) in dilute solution is studied by the following three points: the Mark-Houwink exponent a, the fractal dimension D, and the form factor R(g)/R(h). From the result of a, the α-conformation of PFO is considered to have a semirigid chain conformation in dilute solution. We establish the mathematical relationship between the Mark-Houwink exponent a and the fractal dimension D in dilute solution. To prove the rationality of this mathematical relationship, the classic polymer polystyrene (PS) is used for comparison. According to the result of D, it can be known that the α-conformation of PFO has a relatively loose and extended chain conformation. Moreover, we use light scattering to get the form factor R(g)/R(h) of the PFO solution in which the α-conformation and β-conformation coexist. It is found that R(g)/R(h) increases with the proportion of α-conformation, which indicates that the α-conformation of PFO has a loose and extended chain conformation, and this result agrees well with the conclusions drawn from a and D. On the basis of the fact that the β-conformation (ordered conformation) and α-conformation of PFO can transform into each other in solution, this work is significant for the control of the β-conformation and will have a potential meaning to increase the charge carrier mobility and efficiency from the PFO solution to films.

In this work, the effects of solvation and desolvation on the β phase of poly(9,9-dioctylfluorene) (PFO) are studied. The content of β phase is approximately calculated for comparison. The content of β phase can be enhanced up to 40% by the solvation effect and become a metastable state; the desolvation effect is a dynamic process and can enhance the content of β phase remarkably by 18%age units. It is found that the contents of β phase are always changing with the aggregation degrees of PFO chains. To fully understand it, the concepts of mesoscopic aggregates and macroscopic aggregates are proposed and well proved by the filtration experiment. In the solution (the ethanol content less than 30%), the mesoscopic aggregates are beneficial to enhance the content of β phase; in the solution (the ethanol content more than 40%), which is close to the condensed state of fabricated optoelectronic film, the macroscopic aggregates can make the content of β phase not only much higher but also stable. The content of ...

In this work, the solvent field and temperature are used to explore the mutual transformation dynamic process and mechanism between the α-conformation and β-conformation in poly(9,9-dioctylfluorene) (PFO) precursor solution. The conformational transformation of the PFO chain is researched by UV-vis absorption spectra and the proportions of the β-conformation are quantitatively calculated. The corresponding variation trend of the aggregation structure is researched using a static and dynamic light scattering (SLS/DLS) method. It is found that the mutual transformation processes between the α-conformation and β-conformation are reversible in essence. Especially in the transformation processes, the complicated relationship between the β-conformation and the aggregation structure is understood, that is the aggregation structure promotes formation of the β-conformation under solvent field, then the conformational transformation of the β-conformation promotes the dissociation of the aggregation structure under temperature. The above results give an insight into the β-conformation and the aggregation structure of PFO in theory. Furthermore, under the temperature, we find that both two transformation steps have good linear correlations, which indicates that using temperature can be considered as a good method to accurately control the proportion of β-conformation in actual applications, and it will help us to get the desired proportion of the β-conformation in PFO precursor solution so as to make the charge carrier mobility of optoelectronic films increased and device performance better.