Berberine and magnolol exert cooperative effects on ulcerative colitis in mice by self-assembling into carrier-free nanostructures.

The risk of ulcerative colitis (UC) is increasing worldwide with limited success using classical drugs, which has underscored the development of novel agents. Recently, carrier-free molecular assembly has been proven to be an effective drug delivery system, but it has yet to be examined for UC drug development using phytochemicals. Based on traditional Chinese medicine compatibility and potential medicinal uses, a pair of natural compounds, berberine (BBR) and magnolol (MAG), were found to self-assemble into nanostructures in aqueous solutions. Spectral analysis revealed that the assembly mechanisms of BBR and MAG were mediated through charge interactions and π-π stacking. Pharmacokinetic studies and animal imaging showed that BBR-MAG self-assembly (BM) effectively promoted the oral bioavailability and biodistribution of BBR in the colon. BM exhibited superior effects in regulating inflammatory factors, maintaining colon barrier integrity, and regulating gut microbiota in a dextran sulfate sodium salt-induced colitis mouse model. Additionally, no apparent signs of toxicity were observed, suggesting that BM has a favorable safety profile. This study presents a new strategy for UC management and highlights the cooperative effects of combined phytochemicals.

High-Strength, Large-Deformation, Dual Cross-Linking Network Liquid Crystal Elastomers Based on Quadruple Hydrogen Bonds.

Liquid crystal elastomers (LCEs) with large deformation under external stimuli have attracted extensive attention in various applications such as soft robotics, 4D printing, and biomedical devices. However, it is still a great challenge to reduce the damage to collimation and enhance the mechanical and actuation properties of LCEs simultaneously. Here, we construct a new method of a double cross-linking network structure to improve the mechanical properties of LCEs. The ureidopyrimidinone (UPy) group with quadruple hydrogen bonds was used as the physical cross-linking unit, and pentaerythritol tetra(3-mercaptopropionate) was used as the chemical cross-link. The LCEs showed a strong mechanical tensile strength of 8.5 MPa and excellent thermally induced deformation (50%). In addition, the introduction of quadruple hydrogen bonds endows self-healing ability to extend the service life of LCEs. This provides a generic strategy for the fabrication of high-strength LCEs, inspiring the development of actuators and artificial muscles.

Neuroprotective effects of fecal microbiota transplantation on MPTP-induced Parkinson's disease mice: Gut microbiota, glial reaction and TLR4/TNF-α signaling pathway.

Parkinson's disease (PD) patients display alterations in gut microbiota composition. However, mechanism between gut microbial dysbiosis and pathogenesis of PD remains unexplored, and no recognized therapies are available to halt or slow progression of PD. Here we identified that gut microbiota from PD mice induced motor impairment and striatal neurotransmitter decrease on normal mice. Sequencing of 16S rRNA revealed that phylum Firmicutes and order Clostridiales decreased, while phylum Proteobacteria, order Turicibacterales and Enterobacteriales increased in fecal samples of PD mice, along with increased fecal short-chain fatty acids (SCFAs). Remarkably, fecal microbiota transplantation (FMT) reduced gut microbial dysbiosis, decreased fecal SCFAs, alleviated physical impairment, and increased striatal DA and 5-HT content of PD mice. Further, FMT reduced the activation of microglia and astrocytes in the substantia nigra, and reduced expression of TLR4/TNF-α signaling pathway components in gut and brain. Our study demonstrates that gut microbial dysbiosis is involved in PD pathogenesis, and FMT can protect PD mice by suppressing neuroinflammation and reducing TLR4/TNF-α signaling.

Unexpected Neuroprotective Effects of Loganin on 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Induced Neurotoxicity and Cell Death in Zebrafish.

1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP), which induces the pathological characteristics of Parkinson's disease in rodents, also specifically targets dopaminergic neurons in zebrafish embryos and larvae. Loganin, a traditional Chinese drug, was reported to regulate immune function and possess anti-inflammatory and anti-shock effects. Here, we investigate the role of loganin in MPTP-induced Parkinson-like abnormalities in zebrafish. MPTP treatment-induced abnormal development, in larvae, such as pericardium edema, increased yolk color, yolk sac edema, and retarded yolk sac resorption, as well as defects in brain development. Loganin could block MPTP-induced defects, with little toxicity to the eggs. Results of whole mount in situ hybridization showed loganin prevented the loss of both dopaminergic neurons and locomotor activity, exhibited by larvae treated with MPTP. In addition, loganin significantly rescued MPTP-induced neurotoxicity on PC12 cells, possibly through the suppression of PI3K/Akt/mTOR axis and JNK signaling pathways. In conclusion, loganin blocks MPTP-induced neurotoxicity and abnormal development in zebrafish. J. Cell. Biochem. 118: 615-628, 2017. © 2016 Wiley Periodicals, Inc.

Neuroprotective Effects of Loganin on MPTP-Induced Parkinson's Disease Mice: Neurochemistry, Glial Reaction and Autophagy Studies.

Parkinson's disease (PD) is a progressive neurodegenerative disease, involving resting tremor and bradykinesia, for which no recognized therapies or drugs are available to halt or slow progression. In recent years, natural botanic products have been considered relatively safe, with limited side effects, and are expected to become an important source for clinical mediation of PD in the future. Our study focuses on the ability of loganin, a compound derived from fruits of cornus, to mediate neuroprotection in a mouse model of PD. Mice were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) with a dosage of 30 mg/kg daily for 5 days to establish a subacute PD model and treated with loganin. Locomotor activity was assessed by a pole test, then mice were euthanized at 1 and 3 days after the last treatment, and brain tissue was prepared for subsequent assays. Loganin rescued decrease of dopamine levels and tyrosine hydroxylase (TH) expression in the striatum, and shortened total locomotor activity (TLA) time of mice. Furthermore, loganin alleviated microglia and astrocyte activation, and suppressed TNF-α and caspase-3 expression through a c-Abl-p38-NFκB pathway. Loganin also downregulated LC3-II and Drp1 expression, and decreased the level of acidic vesicular organelles (AVOs). Loganin exerts neuroprotective effects on MPTP-induced PD mice by decreasing inflammation, autophagy, and apoptosis, suggesting that loganin could serve as a therapeutic drug to ameliorate PD. J. Cell. Biochem. 118: 3495-3510, 2017. © 2017 Wiley Periodicals, Inc.

Intradiencephalon injection of histamine inhibited the recovery of locomotor function of spinal cord injured zebrafish.

Human spinal cord injury (SCI) usually causes irreversible disability beneath the injured site due to poor neural regeneration. On the contrary, zebrafish show significant regenerative ability after SCI, thus is usually worked as an animal model for studying neuroregeneration. Most of the previous SCI studies focused on the local site of SCI, the supraspinal-derived signals were rarely mentioned. Here we showed that intradiencephalon injection of histamine (HA) inhibited the locomotor recovery in adult zebrafish post-SCI. Immunofluorescence results showed that intradiencephalon HA administration increased the activated microglia 3 days post injury (dpi), promoted the proliferation of radial glial cells at 7 dpi and affected the morphology of radial glial cells at 11 dpi. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) results showed that intradiencephalon HA administration also reduced the expression of neurotrophic factors including brain-derived neurotrophic factor (BDNF) and insulin-like growth factor1 (IGF-1) at the lesion site, however, had no effect on the expression of pro-inflammatory factors such as TNF-alpha and IL-1 beta. Hence, our data suggested that exogenous intradiencephalon HA retarded locomotor recovery in spinal cord injured zebrafish via modulating the repair microenvironment.

Nitrogen-Doped Carbon Activated in Situ by Embedded Nickel through the Mott-Schottky Effect for the Oxygen Reduction Reaction.

The development of low-cost non-precious-metal electrocatalysts with high activity and stability in the oxygen reduction reaction (ORR) remains a great challenge. Heteroatom-doped carbon materials are receiving increased attention in research as effective catalysts. However, the uncontrolled doping of heteroatoms into a carbon matrix tends to inhibit the activity of a catalyst. Here, the in situ activation of a uniquely structured nitrogen-doped carbon/Ni composite catalyst for the ORR is demonstrated. This well-designed catalyst is composed of a nitrogen-doped carbon shell and embedded metallic nickel. The embedded Ni nanoparticles, dispersed on stable alumina with a high specific surface area for protecting them from agglomeration and in an unambiguous composite structure, are electron-donating and are shielded by the nitrogen-doped carbon from oxidation/dissolution in harsh environments. The electronic structure of the nitrogen-doped carbon shell is modulated by the transfer of electrons at the interface of nitrogen-doped carbon-Ni heterojunctions owing to the Mott-Schottky effect. The electrochemically active surface area result implies that the active sites do not relate to Ni directly and the enhanced catalytic activity mainly arises from the modulation of nitrogen-doped carbon by nickel. XPS and theoretical calculations suggest that the donated electrons are transferred to pyridinic N primarily, which ought to enhance the catalytic activity intrinsically. Benefiting from these transferred electrons, the half-wave potential of the nitrogen-doped carbon/Ni composite catalyst is 94 mV positively shifted compared to the Ni-free sample.

Hydrological characteristics of the Bering Sea in the summer of 2019.

Based on the data of three CTD sections in the northern, northeastern and western Bering Sea of 2019 voyage of Chinese National Arctic Research Expedition (CHINARE), this paper analyzes and studies the hydrological characteristics of the water mass distribution, layered structure, and cline characteristics in different sea areas of the Bering Sea. The results indicate that the hydrological characteristics of the Bering Sea in the summer of 2019 are different from those in the past and that the water mass is warming in many locations. The maximum water temperature reaches 11.13 °C, and the maximum thickness of the warm water is about 32 m. The water mass composition and characteristics of the north-northeast-west sections are significantly different: the BL section has the highest salinity, while the BS section has the lowest salinity, and both the lowest temperature and the largest temperature variation appear in the BL section. The stratification characteristics in all sea areas are noteworthy. In the deep-water seas, there are three types of water masses: upper water (BSW), middle water (BIW) and deep water (BDW) from top to bottom, while two main water masses appear in the shelf waters with the Alaska Coastal Water (ACW) overlies the Bering Sea Shelf Water (BSW). Along the Bering Sea Slope Current (BSC), the water mass is essentially steady. Statically unstable hydrological inversion structure appears near the bottom of the three stations at the northern end of the BL section.

MYC Oncogene: A Druggable Target for Treating Cancers with Natural Products.

Various diseases, including cancers, age-associated disorders, and acute liver failure, have been linked to the oncogene, MYC. Animal testing and clinical trials have shown that sustained tumor volume reduction can be achieved when MYC is inactivated, and different combinations of therapeutic agents including MYC inhibitors are currently being developed. In this review, we first provide a summary of the multiple biological functions of the MYC oncoprotein in cancer treatment, highlighting that the equilibrium points of the MYC/MAX, MIZ1/MYC/MAX, and MAD (MNT)/MAX complexes have further potential in cancer treatment that could be used to restrain MYC oncogene expression and its functions in tumorigenesis. We also discuss the multifunctional capacity of MYC in various cellular cancer processes, including its influences on immune response, metabolism, cell cycle, apoptosis, autophagy, pyroptosis, metastasis, angiogenesis, multidrug resistance, and intestinal flora. Moreover, we summarize the MYC therapy patent landscape and emphasize the potential of MYC as a druggable target, using herbal medicine modulators. Finally, we describe pending challenges and future perspectives in biomedical research, involving the development of therapeutic approaches to modulate MYC or its targeted genes. Patients with cancers driven by MYC signaling may benefit from therapies targeting these pathways, which could delay cancerous growth and recover antitumor immune responses.

Hedyotislongiramulis (Rubiaceae), a new species from south China.

Hedyotislongiramulissp. nov. (Rubiaceae) is described from Guangdong Province, China. It is similar to H.caudatifolia but differs in having puberulent, more or less tetragonal and decussately sulcate juvenile stems, waxy leaf surface, short inflorescence peduncles, high length ratio of corolla lobe to tube, and subglobose capsules. The phylogenetic analysis reveals that H.longiramulis is sister to H.pubirachis. Dimorphism concerning pollen size was observed in the heterostylous flowers. The complete chloroplast genome of the new species comprises a typical quadripartite structure of 153,616 bp in length, with two inverted repeats of 25,457 bp, a large single-copy of 85,050 bp and a small single-copy of 17,652 bp. It contains 112 unique genes, including 79 protein-coding genes, 29 tRNA genes, and four rRNA genes, the GC content of the chloroplast genome is 32.4%. The new species is provisionally evaluated as "Least Concern" because it is common and well-protected in two Provincial Nature Reserves.

Positive effects of steamed Polygonatum sibiricum polysaccharides including a glucofructan on fatty acids and intestinal microflora.

Steam-processed Polygonatum sibiricum (PS) has been used as food for thousands of years. However, fewer studies concentrated on the effects of polysaccharides (SPSP) from the steamed PS on the intestinal tract. With fermentation in vitro, we investigated the impact of SPSP on the fatty acids and microbiotas. Results showed significant increases in short-chain fatty acids (SCFAs) like acetic acid and propionic acid, and long-chain fatty acids (LCFAs) like cis, cis, cis-9,12,15-linolenic acid, cis-6-octadecenoic acid, and cis-9-octadecenoic acid after 12 h. The positive-associated beneficial microbiotas were observed with proliferation like Parabacteroides and Bifidobacterium. Harmful microbiota like Shigella showed decreased abundance. Further, a small molecule polysaccharide was separated from the SPSP with the structure of one glucose and ten fructose, which significantly increased SCFAs and LCFAs contents during fermentation. The potential benefits of SPSP were proved by the analysis of fatty acid levels and the intestinal microbiotas during fermentation.

Abnormal neurotransmission of GABA and serotonin in Caenorhabditis elegans induced by Fumonisin B1.

Fumonisin B1 (FB1) is a neurodegenerative mycotoxin synthesized by Fusarium spp., but the potential neurobehavioral toxicity effects in organisms have not been characterized clearly. Caenorhabditis elegans (C. elegans) has emerged as a promising model organism for neurotoxicological studies due to characteristics such as well-functioning nervous system and rich behavioral phenotypes. To investigate whether FB1 has neurobehavioral toxicity effects on C. elegans, the motor behavior, neuronal structure, neurotransmitter content, and gene expression related with neurotransmission of C. elegans were determined after exposed to 20-200 µg/mL FB1 for 24 h and 48 h, respectively. Results showed that FB1 caused behavioral defects, including body bends, head thrashes, crawling distance, mean speed, mean amplitude, mean wavelength, foraging behavior, and chemotaxis learning ability in a dose-, and time-dependent manner. In addition, when C. elegans was exposed to FB1 at a concentration of 200 µg/mL for 24 h and above 100 µg/mL for 48 h, the GABAergic and serotonergic neurons were damaged, but no effect on dopaminergic, glutamatergic, and cholinergic neurons. The relative content of GABA and serotonin decreased significantly. Furthermore, abnormal expression of mRNA levels associated with GABA and serotonin were found in nematodes treated with FB1, such as unc-30, unc-47, unc-49, exp-1, mod-5, cat-1, and tph-1. The neurobehavioral toxicity effect of FB1 may be mediated by abnormal neurotransmission of GABA and serotonin. This study provides useful information for understanding the neurotoxicity of FB1.

Morphology and molecules support the new monotypic genus Parainvolucrella (Rubiaceae) from Asia.

Parainvolucrella R.J. Wang, a new monotypic genus for P.scabra (Wall. ex Kurz) M.D.Yuan & R.J.Wang, new combination, is segregated from the Hedyotis-Oldenlandia complex, based on morphological and molecular evidence. Phylogenetically, the new genus is sister to Scleromitrion, from which it differs by a combination of morphological characters: herbaceous habit, terminal inflorescence with subtended leaves, heterostylous flowers, indehiscent fruits and pollen with double microreticulate tectum. A key to the genera of the Hedyotis-Oldenlandia complex in China is provided for further identification.

Rapid determination of adenosine deaminase kinetics using fast-scan cyclic voltammetry.

Adenosine deaminase is an enzyme involved in purine metabolism and its inhibitors are used as anticancer and antiviral drugs. In this study, we show that fast-scan cyclic voltammetry at carbon-fiber microelectrodes can be used to study the kinetics of adenosine deaminase by electrochemically monitoring decreases in adenosine concentration. Buffer and salt concentrations were shown to affect the enzyme kinetics and the inhibition by erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and deoxycoformycin (DCF). In a Tris buffer containing salts that mimic cerebrospinal fluid, EHNA and DCF showed non-competitive inhibition with a K(i) of 1.7 +/- 0.6 nM and 1.2 +/- 0.2 nM, respectively. However, removing the divalent cations from the Tris buffer caused the inhibition to be competitive and reduced the K(i) for DCF by two orders of magnitude. In phosphate-buffered saline, the K(i) was 1.0 +/- 0.2 nM for EHNA and 3.6 +/- 0.3 pM for DCF, similar to literature values. Adenosine deaminase was also competitively inhibited by AgNO(3), showing it is susceptible to silver toxicity. Caffeine was found to increase adenosine deaminase activity. This is a fast, easy method for screening drug effects on enzyme kinetics and could be applied to other enzymatic reactions where there is a significant difference in the electroactivity of the reactant and product.

Identifying Novel Anti-Osteoporosis Leads with a Chemotype-Assembly Approach.

In this paper, we applied a chemotype-assembly approach for ligand-based drug discovery (LBDD) to discover novel anti-osteoporosis leads. With this new approach, we identified 12 chemotypes and derived 18 major chemotype assembly rules from 245 known anti-osteoporosis compounds. Then, we selected 19 compounds from an in-house compound library using chemotype-assembly approach for anti-osteoporosis assays, which resulted in 13 hits. Based on structural features in these 13 compounds, we synthesized 50 possible anti-osteoporosis compounds from the anti-osteoporosis chemotypes by means of click chemistry techniques and discovered a compound (10a, IC50 = 2 nM) with nanomolar activity. Compound 10a was then proved to be an anti-osteoporosis lead since it can prevent bone loss in vivo.

Ternary Heterostructural Pt/CNx/Ni as a Supercatalyst for Oxygen Reduction.

We report here a supercatalyst for oxygen reduction of Pt/CNx/Ni in a unique ternary heterostructure, in which the Pt and the underlying Ni nanoparticles are separated by two to three layers of nitrogen-doped carbon (CNx), which mediates the transfer of electrons from the inner Ni to the outer Pt and protects the Ni against corrosion at the same time. The well-engineered low-Pt catalyst shows ∼780% enhanced specific mass activity or 490% enhanced specific surface activity compared with a commercial Pt/C catalyst toward oxygen reduction. More importantly, the exceptionally strong tune on the Pt by the unique structure makes the catalyst superbly stable, and its mass activity of 0.72 A/mgPt at 0.90 V (well above the US Department of Energy's 2020 target of 0.44 A/mgPt at 0.90 V) after 50,000 cyclic voltammetry cycles under acidic conditions is still better than that of the fresh commercial catalyst.

Neuroprotective effects of Astilbin on MPTP-induced Parkinson's disease mice: Glial reaction, α-synuclein expression and oxidative stress.

Astilbin (AST), a dihydro-flavonol glycoside, is a major bioactive ingredient in Astilbe thunbergii, Engelhardia roxburghiana, Smilax corbularia and Erythroxylum gonocladum, and has been shown to have anti-inflammatory, antioxidative and neuroprotective effects, suggesting potential therapeutic value in the treatment of Parkinson's disease (PD). We explored the neuroprotective effects of AST in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mice. Mice were administered with MPTP (30 mg/kg, i.p) daily for 5 days, to establish a subacute Parkinson's disease model, followed by daily treatment with AST or saline for 7 days. Pole and traction tests showed that AST ameliorated the impaired motor functions in MPTP-induced Parkinson's disease mice. High performance liquid chromatography analysis revealed that AST treatment prevented MPTP-induced decreases in striatal dopamine levels. Immunofluorescence assays showed that AST reduced the loss of dopaminergic neurons and the activation of microglia and astrocytes in the substantia nigra. Western blot analyses revealed that AST suppressed α-synuclein overexpression and activated PI3K/Akt in the striatum following MPTP treatment. AST also prevented the MPTP-induced reduction in total superoxide dismutase and glutathione activity in the striatum. AST exerts neuroprotective effects on MPTP-induced PD mice by suppressing gliosis, α-synuclein overexpression and oxidative stress, suggesting that AST could serve as a therapeutic drug to ameliorate PD.

Backside calibration chronopotentiometry: using current to perform ion measurements by zeroing the transmembrane ion flux.

A recent new direction in ion-selective electrode (ISE) research utilizes a stir effect to indicate the disappearance of an ion concentration gradient across a thin ion-selective membrane. This zeroing experiment allows one to evaluate the equilibrium relationship between front and backside solutions contacting the membrane by varying the backside solution composition. This method is attractive since the absolute potential during the measurement is not required, thus avoiding standard recalibrations from the sample solution and a careful control of the reference electrode potential. We report here on a new concept to alleviate the need to continuously vary the composition of the backside solution. Instead, transmembrane ion fluxes are counterbalanced at an imposed critical current. A theoretical model illustrates the relationship between the magnitude of this critical current and the concentration of analyte and countertransporting ions and is found to correspond well with experimental results. The approach is demonstrated with lead(II)-selective membranes and protons as dominating interference ions, and the concentration of Pb(2+) was successfully measured in tap water samples. The principle was further evaluated with calcium-selective membranes and magnesium as counterdiffusing species, with good results. Advantages and limitations arising from the kinetic nature of the perturbation technique are discussed.

Reversible detection of proteases and their inhibitors by a pulsed chronopotentiometric polyion-sensitive electrode.

Polymer membrane electrodes operated by pulsed chronopotentiometry have recently been introduced to replace traditional ion-selective electrodes for a number of applications. While ion-selective electrodes for the polycation protamine have been reported, for instance, a pulsed chronopotentiometric readout mode (called here pulstrode) provides improved stability and reproducibility while exhibiting sufficient selectivity for the direct detection of protamine in undiluted whole blood samples. Here, such protamine-sensitive pulstrodes are applied for the real-time detection of the activity of the protease trypsin and its soybean inhibitor. This is possible because small fragments produced by the trypsin digestion are not detectable by the protamine-sensing membrane. The real-time response to the proteolytic reaction is shown to exhibit good reproducibility and reversibility, and the initial reaction rate is dependent on the concentration of the protease and its inhibitor.