The phenylalanine-tyrosine-dopa-dopamine pathway provides dopamine to the brain. In this process, tyrosine hydroxylase (TH) is the rate-limiting enzyme that hydroxylates tyrosine and generates ...levodopa (L-dopa) with tetrahydrobiopterin (BH
) as a coenzyme. Here, we show that oral berberine (BBR) might supply H
through dihydroberberine (reduced BBR produced by bacterial nitroreductase) and promote the production of BH
from dihydrobiopterin; the increased BH
enhances TH activity, which accelerates the production of L-dopa by the gut bacteria. Oral BBR acts in a way similar to vitamins. The L-dopa produced by the intestinal bacteria enters the brain through the circulation and is transformed to dopamine. To verify the gut-brain dialog activated by BBR's effect, Enterococcus faecalis or Enterococcus faecium was transplanted into Parkinson's disease (PD) mice. The bacteria significantly increased brain dopamine and ameliorated PD manifestation in mice; additionally, combination of BBR with bacteria showed better therapeutic effect than that with bacteria alone. Moreover, 2,4,6-trimethyl-pyranylium tetrafluoroborate (TMP-TFB)-derivatized matrix-assisted laser desorption mass spectrometry (MALDI-MS) imaging of dopamine identified elevated striatal dopamine levels in mouse brains with oral Enterococcus, and BBR strengthened the imaging intensity of brain dopamine. These results demonstrated that BBR was an agonist of TH in Enterococcus and could lead to the production of L-dopa in the gut. Furthermore, a study of 28 patients with hyperlipidemia confirmed that oral BBR increased blood/fecal L-dopa by the intestinal bacteria. Hence, BBR might improve the brain function by upregulating the biosynthesis of L-dopa in the gut microbiota through a vitamin-like effect.
The fabrication of anion‐coordinated assemblies into functional soft materials remains a major challenge. To this end, four C2‐symmetric anion‐binding ligands equipped with ortho‐phenylene‐bridged ...bis(urea) and amine or amide ends were designed, which generated A2L3 triple helical architectures upon self‐assembly with phosphate ions. Hierarchical intermolecular hydrogen bonds among the terminal amine/amide groups and urea moieties resulted in the formation of functional gels. The obtained gels were further applied for conductive adhesion between different surfaces, displaying excellent flexibility and selective wettability. The viscoelastic gels constructed from anion‐coordinated assemblies described in this work represent the first example of a new class of anion‐coordination‐driven smart materials.
A series of C2‐symmetric anion‐binding ligands equipped with ortho‐phenylene‐bridged bis(urea) and amine/amide ends were designed, which could firstly self‐assemble into triple helicates by coordination with phosphate ions and subsequently form gels through multiple intermolecular hydrogen bonds. The obtained gels exhibit effective and stable adhesive properties, selective wettability, and conductivity.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
•Influence of temperatures and water contents on the piezoresistivity is studied.•Electrical resistance was used to sense temperature and water content.•Equivalent circuit diagram of CNFM with ...temperature and water content was obtained.
Influence of temperatures and water contents on the electrical resistance and piezoresistivity of carbon nanofibers (CNFs) cement mortar were investigated in this paper. Electrochemical impedance spectroscopy (EIS) and equivalent circuits were determined to explore the conductive and mechanical mechanism. Results indicated that the electrical resistance decreased with the increasing CNFs dosages in all environments. When CNFs content was less than 1.5%, the electrical resistance of dried specimens with environment temperature ranging from −30 °C to 20 °C increased linearly with the ascending temperature. However, when the temperature ranged from 20 °C to 40 °C, the electrical resistance decreased with one dimensional Gauss function with the increasing temperature. While, when dried CNFs mortar possessed the CNFs content of 1.5%, 2.0% and 2.5% or specimens were in water saturated state, the resistance of all specimens and temperatures conformed to one dimensional Gauss function. Moreover, when CNFs mortars were at the temperature of 20 °C, the relationship between electrical resistance and water contents could be described as exponential function of 10. Additionally, CNFs mortar with 2.5% CNFs performed favorable piezoresistivity. The strain-sensing performance of CNFs mortar deteriorated when temperature decreased from 20 °C to −30 °C. When temperature was higher than 20 °C, self-sensing property became worse with the increasing temperature. Nevertheless, the sensitivity of CNFs mortar first decreased and then increased with the increasing water contents. CNFs mortar samples in dried state and 20 °C showed the optimum self-sensing performance. Furthermore, the EIS curves were sensitive to temperatures and water contents and effective to reveal the conductive mechanism.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Spermatozoa released from testes undergo a maturation process and acquire the capacity to fertilize ova through epididymal transit. The epididymis is divided into four regions, each with unique ...morphology, gene profile, luminal microenvironment and distinct function. To study the functions of relevant genes in the epididymal initial segment (IS), a novel IS-specific mouse model, Lcn9-Cre knock-in (KI) mouse line was generated via CRISPR/Cas9 technology. The TAG stop codon was replaced by a 2A-NLS-Cre cassette, resulting in the co-expression of Lcn9 and Cre recombinase. IS-specific Cre expression was first observed from postnatal day 17. Using the Rosa26.sup.tdTomato reporter mice, the Cre-mediated DNA recombination was detected exclusively in principal cells. The epididymal IS-specific Cre activity in vivo was further confirmed using Lcn9-Cre mice crossed with a mouse strain carrying Tsc1 floxed alleles (Tsc1.sup.flox/+). Cre expression did not affect either normal development or male fecundity. Different from any epididymis-specific Cre mice reported previously, the novel Lcn9-Cre mouse line can be used to introduce entire IS-specific conditional gene editing for gene functional study.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Optically active β‐amino alcohols are very useful chiral intermediates frequently used in the preparation of pharmaceutically active substances. Here, a novel cyclohexylamine oxidase (ArCHAO) was ...identified from the genome sequence of Arthrobacter sp. TYUT010‐15 with the R‐stereoselective deamination activity of β‐amino alcohol. ArCHAO was cloned and successfully expressed in E. coli BL21, purified and characterized. Substrate‐specific analysis revealed that ArCHAO has high activity (4.15 to 6.34 U mg−1 protein) and excellent enantioselectivity toward the tested β‐amino alcohols. By using purified ArCHAO, a wide range of racemic β‐amino alcohols were resolved, (S)‐β‐amino alcohols were obtained in >99 % ee. Deracemization of racemic β‐amino alcohols was conducted by ArCHAO‐catalyzed enantioselective deamination and transaminase‐catalyzed enantioselective amination to afford (S)‐β‐amino alcohols in excellent conversion (78–94 %) and enantiomeric excess (>99 %). Preparative‐scale deracemization was carried out with 50 mM (6.859 g L−1) racemic 2‐amino‐2‐phenylethanol, (S)‐2‐amino‐2‐phenylethanol was obtained in 75 % isolated yield and >99 % ee.
Coming to a resolution: Enantioselective cascade biocatalysis for deracemization of racemic β‐amino alcohols was conducted by employing cyclohexylamine oxidase and ω‐transaminase. (S)‐β‐amino alcohols were obtained in excellent conversions and ee values.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Three-phase wireless power transfer (WPT) systems have compact coil structures, canceled triplen harmonics, and less dc -link current ripple, which are suitable for wireless electric vehicle (EV) ...charging systems. Most three-phase WPT systems are based on two-level inverters. Alternately, three-level (TL) inverters have the potential to further promote the performance of EV chargers by reducing the electromagnetic interference (EMI) and the voltage stress of power switches. However, the unbalance of the neutral point (NP) voltage is a problem for traditional TL inverters. This article proposes a TL three-phase WPT system for EV wireless charging, which is based on a T-type neutral point clamp (TNPC) inverter. The modeling, coil structure, and switching pattern of the proposed system are analyzed in detail. Furthermore, a novel output regulation method based on vector control is proposed for the WPT system. Also, a NP voltage balance strategy is proposed to enhance the reliability of the TL inverter. Both simulations and an experimental prototype based on SIC- MOSFET are given to verify the effectiveness of the proposed three-phase WPT system and control method.
Intratumoral injection is a palliative treatment that aims at further improvement in the survival and quality of life of patients with advanced or recurrent carcinomas, or cancer patients with severe ...comorbidities or those with a poor performance status.
In this study, a solvent-injection method was used to prepare paclitaxel-cholesterol complex-loaded lecithin-chitosan nanoparticles (PTX-CH-loaded LCS_NPs) for intratumoral injection therapy, and the physicochemical properties of NPs were well characterized.
The particle size and zeta potential of PTX-CH-loaded LCS_NPs were 142.83±0.25 nm and 13.50±0.20 mV, respectively. Release behavior of PTX from PTX-CH-loaded LCS_NPs showed a pH-sensitive pattern. The result of cell uptake assay showed that PTX-CH-loaded LCS_NPs could effectively enter cells via the energy-dependent caveolae-mediated endocytosis and macropinocytosis in company with the Golgi apparatus. Meanwhile, PTX-CH-loaded LCS_NPs had a better ability to induce cell apoptosis than PTX solution. The in vivo antitumor results suggested that PTX-CH-loaded LCS_NPs effectively inhibited mouse mammary cancer growth and metastasis to distant organs and significantly improved the survival rate of tumor-bearing mice by intratumoral administration.
In general, our study demonstrated that PTX-CH-loaded LCS_NPs used for palliative treatment by intratumoral injection showed improved safety and antitumor efficacy, which provided an alternative approach in the field of palliative chemotherapy.
Abstract
The alterations in the gut microbiota have been reported to be correlated with the development of depression. The purpose of this study was to investigate the changes of intestinal ...microbiota in depressed patients after antidepressant treatment. We recruited 30 MDD patients (MDD group) and 30 healthy controls (control group). The MDD group received individualized treatment with escitalopram at a maximum dose of 20 mg/day. After depressive symptoms improved to a HAMD scale score > 50%, a fecal sample was collected again and used as the follow-up group. The differences of gut microbiota between patients and controls, the characteristics of gut microbiota under treatment and the potential differences in metabolic functions were thus investigated. The Firmicutes/Bacteroidetes ratio was significantly different within three groups, and the ratio of follow-up group was significantly lower than those of the other two groups. Alpha diversity was significantly higher in MDD group than those of the other groups, and the alpha diversity was not significantly different between control and follow-up groups. The beta diversity of some patients resembled participants in the control group. The metabolic function of gut microbiota after treatment was still different from that of the control group. This study suggests that the intestinal flora of depressed patients has a tendency to return to normal under escitalopram treatment.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
A tris(pentafluorophenyl)borane‐catalyzed oxidation reaction of α‐diazoesters (α‐diazo amides) with dimethyl sulfoxide has been developed. The reaction proceeds under metal free conditions to afford ...a series α‐ketoesters and α‐ketoamides. The synthetic utility of this protocol is demonstrated through synthetic transformations and scaled‐up synthesis.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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