In-Tumor Biosynthetic Construction of Upconversion Nanomachines for Precise Near-Infrared Phototherapy.

Targeted construction of therapeutic nanoplatforms in tumor cells with specific activation remains appealing but challenging. Here, we design a cancer-motivated upconversion nanomachine (UCNM) based on porous upconversion nanoparticles (p-UCNPs) for precise phototherapy. The nanosystem is equipped with a telomerase substrate (TS) primer and simultaneously encapsulates 5-aminolevulinic acid (5-ALA) and d-arginine (d-Arg). After coating with hyaluronic acid (HA), it can readily get into tumor cells, where 5-ALA induces efficient accumulation of protoporphyrin IX (PpIX) via the inherent biosynthetic pathway, and the overexpressed telomerase prolonged the TS to form G-quadruplexes (G4) for binding the resulting PpIX as a nanomachine. This nanomachine can respond to near-infrared (NIR) light and promote the active singlet oxygen (1O2) production due to the efficiency of Förster resonance energy transfer (FRET) between p-UCNPs and PpIX. Intriguingly, such oxidative stress can oxidize d-Arg into nitric oxide (NO), which relieves the tumor hypoxia and in turn improves the phototherapy effect. This in situ assembly approach significantly enhances targeting in cancer therapy and might be of considerable clinical value.

Efficacy of acupuncture at ghost points combined with fluoxetine in treating depression: A randomized study.

BACKGROUND: Depression affects more than 350 million people worldwide. In China, 4.2% (54 million people) of the total population suffers from depression. Psychotherapy has been shown to change cognition, improve personality, and enhance the ability to cope with difficulties and setbacks. While pharmacotherapy can reduce symptoms, it is also associated with adverse reactions and relapse after drug withdrawal. Therefore, there has been an increasing emphasis placed on the use of non-pharmacological therapies for depression. The hypothesis of this study was that acupuncture at ghost points combined with fluoxetine would be more effective than fluoxetine alone for the treatment of depression. AIM: To investigate the efficacy of acupuncture at ghost points combined with fluoxetine for the treatment of patients with depression. METHODS: This randomized controlled trial included patients with mild to moderate depression (n = 160). Patients received either acupuncture at ghost points combined with fluoxetine (n = 80) or fluoxetine alone (control group, n = 80). Needles were retained in place for 30 min, 5 times a week; three treatment cycles were administered. The Mann-Whitney U test was used to compare functional magnet resonance imaging parameters, Hamilton depression rating scale (HAMD) scores, and self-rating depression scale (SDS) scores between the acupuncture group and control group. RESULTS: There were no significant differences in HAMD or SDS scores between the acupuncture group and control group, before or after 4 wk of treatment. The acupuncture group exhibited significantly lower HAMD and SDS scores than the control group after 8 wk of treatment (P < 0.05). The acupuncture group had significantly lower fractional Amplitude of Low Frequency Fluctuations values for the left anterior wedge leaf, left posterior cingulate gyrus, left middle occipital gyrus, and left inferior occipital gyrus after 8 wk. The acupuncture group also had significantly higher values for the right inferior frontal gyrus, right insula, and right hippocampus (P < 0.05). After 8 wk of treatment, the effective rates of the acupuncture and control groups were 51.25% and 36.25%, respectively (P < 0.05). CONCLUSION: The study results suggest that acupuncture at ghost points combined with fluoxetine is more effective than fluoxetine alone for the treatment of patients with mild to moderate depression.

Water-Soluble Cyclophanes Synthesized via the Zincke Reaction.

By taking advantage of the Zincke reaction, we successfully synthesized three macrocycles, each of which contains two bipyridinium units as the electron acceptors. Two of them contain sp2-hybridized atoms exclusively in the ring frameworks, while the third contains two methylene units. The third macrocycle is able to form 1:1 inclusion complexes with guests of complementary sizes. A pair of isomers, namely, phenanthrene and anthracene, could be separated by the third macrocycle.

Preparation and characterization of active oxidized starch films containing licorice residue extracts and its potential against methicillin-resistant S. aureus.

The antibacterial and antioxidant packaging films were fabricated by incorporating licorice residue extracts (LREs) into oxidized starch (OS) films. The bioactive fraction (BF) was firstly obtained from LREs by using bioassay-guided isolation method. The BF showed potent anti-Gram(+) bacteria effects, especially against methicillin-resistant S. aureus (MRSA) with MIC of 32.5 µg/mL. The present results also indicated that the addition of BF could significantly decrease the moisture content, water vapor permeability, light transmittance of OS films. Notably, the antibacterial and antioxidant activities of OS films significantly enhanced with the concentration of BF increasing. Moreover, the films with the highest concentration of BF showed the lowest tensile strength (4.23 MPa) and the highest elongation at break (63.89%). Meanwhile, the bioactive films could release bioactive compounds such as licochalcone A and licochalcone B into the alcoholic and fatty food simulants. Taken together, the active OS films containing LREs have the potential for application in food packaging films, due to its potential against MRSA and antioxidant activity as well as good physicochemical properties.

Rapid screening of lipase inhibitors in licorice extract by using porcine pancreatic lipase immobilized on Fe3O4 magnetic nanoparticles.

Chalcones, a class of natural lipase inhibitors, have received substantial attention from researchers in recent years. Although many kinds of chalcones are typically distributed in G. inflata, there is little literature about the anti-lipase activity of G. inflata extracts (GIEs). In the present study, a ligand fishing strategy for fast screening of lipase inhibitors from GIEs was thus proposed. Porcine pancreatic lipase (PPL) was firstly immobilized on carboxyl modified Fe3O4 magnetic nanoparticles (MNPs) to obtain PPL functionalized MNPs (PPL@MNPs), and then the PPL@MNPs were incubated with a bioactive fraction to fish out the ligands. Eight ligands were obtained and identified as one flavone together with seven chalcones. Licochalcone A, licochalcone D and licochalcone E inhibited pancreatic lipase (PL) with IC50 of 4.9, 3.2 and 5.8 µM, respectively. Meanwhile, investigation of the structure-activity relationship also revealed that isopentenyl and hydroxyl substituents at ring A were essential for the noncovalent inhibitory potency of the chalcones.

[Fermentation of cellulase with multiple types of Salvia miltiorrhiza residues and other solid wastes from Chinese materia medica industrialization].

The solid wastes of Chinese materia dedica industrialization represented by Salvia miltiorrhiza residues have a strong small-molecule bio-recalcitrance in the process of high-value utilization of biotransformation. Highly tolerant strains were bred to break bio-recalcitrance of Salvia miltiorrhiza residues and produce high-value added cellulose, which has a significant significance for recycling and industrial utilization of solid waste. In this study, a strain of fungus, Penicillium expansum SZ13, was found with small-molecule antibacterial substance tanshinone contained in Salvia miltiorrhiza residues by a biological method. The optimal enzyme production process and peak period of SZ13 were determined. It was found that SZ13 could maintain peak enzyme production for 5 days by degrading residues under the conditions of temperature 35 ℃, rotation speed 180 r·min~(-1), 5% of residues addition, and 5% seed solution addition. Meanwhile, the ability of SZ13 to degrade the enzyme production of multiple types of residues was explored. The results showed a high enzyme activity and stable enzyme production of SZ13 in the process of degrading residues. SZ13 could efficiently utilize various types of Chinese medicine residues, such as Salvia miltiorrhiza residues, to realize the high-value utilization of cellulose in multiple types of residues.

Comparative analysis of sixteen flavonoids from different parts of Sophora flavescens Ait. by ultra high-performance liquid chromatography-tandem mass spectrometry.

The root of Sophora flavescens Ait. has long been used as a crude drug in China and other Asian countries for thousands of years. The quinolizidine alkaloids and flavonoids are considered as the main bioactive components in this plant. To determine the distribution and content of the flavonoids in different organs of this plant, a rapid, sensitive and reproducible method was established using ultra-high-performance liquid chromatography coupled with a triple quadrupole electrospray tandem mass spectrometry. A total of sixteen flavonoids including five different types (isoflavones, pterocarpans, flavones, flavonols and prenylflavonoids) were simultaneously determined in 10 min. The established method was fully validated in terms of linearity, sensitivity, precision, repeatability as well as recovery and successfully applied in the methanolic extracts of S. flavescens parts (root, stem, leaf, pod and seed). The analysis results indicated that the distribution and contents of different type of flavonoids showed remarkable differences among the five organs of S. flavescens. This study might be useful for the rational utilization of S. flavescens resource.

High-throughput in vivo genetic and drug screening using femtosecond laser nano-surgery, and microfluidics.

We demonstrate microfluidic devices and imaging technologies for high-speed immobilization, cellular resolution imaging, and femtosecond laser micro-surgery of awake small-animals (C. elegans) for high-throughput in vivo genetic and drug screens on neural degeneration and regeneration.