Seven lower toxicity celastrol derivatives by biotransformation of Pestalotiopsis sp. LGT-1.

Biotransformation of toxic components by plant endophytes has become an effective method to reduce the toxicity of target compounds and discover lead compounds. In this context, an endophytic fungus, Pestalotiopsis sp. LGT-1, from Tripterygium wilfordii Hook F. (TwHF), was used to reduce the toxicity of celastrol which is also produced by TwHF and is considered an attractive molecule with a variety of biological activities. Seven celastrol derivatives (1-7) were isolated from the coculture fermentation broth of LGT-1 and celastrol. Their structures were elucidated by spectroscopic data analysis including 1D and 2D NMR, as well as HRESIMS. Their absolute configurations were determined by analysis of NOESY, ECD data and NMR calculations. In cell proliferation experiments, the toxicity of seven compounds was 10.11- to 1.24-fold lower in normal cells than the prototype compound celastrol. These derivatives serve as potential candidates for future pharmaceutical applications.

Secondary Metabolite Analysis of Phomopsis sp. LGT-5 Based on the Dual Guidance of Whole-Genome Sequencing and HPLC-Q-ToF-MS/MS.

Microorganisms produce a wealth of structurally diverse specialized metabolites with a remarkable range of biological activities. The Phomopsis sp. LGT-5 was obtained through tissue block and repeatedly crossed methods from Tripterygium wilfordii Hook. F. The antibacterial experiments of LGT-5 showed that it has high inhibitory activity against Staphylococcus aureus and Pseudomonas aeruginosa, and moderate inhibitory activity against Candida albicans. To research the generation of the antibacterial phenomenon of LGT-5 and provide support for further research and application, the whole genome sequencing (WGS) of LGT-5 was obtained by single-molecule real-time DNA sequencing platform Pacific Biosciences (PacBio) sequencing and Illumina paired-end sequencing. The final assembled LGT-5 genome is 54.79 Mb with a contig N50 of 290.07 kb; in addition, its secondary metabolites were detected through HPLC-Q-ToF-MS/MS. By comparing its MS/MS data, the secondary metabolites were analyzed based on visual network maps obtained on the Global Natural Products Social Molecular Networking (GNPS). The analysis results showed that the secondary metabolites of LGT-5 were triterpenes and various cyclic dipeptides.

Plant-beneficial Streptomyces dioscori SF1 potential biocontrol and plant growth promotion in saline soil within the arid and semi-arid areas.

Environmental challenges like salinity, drought, fungal phytopathogens, and pesticides directly or/and indirectly influence the environment and agricultural yields. Certain beneficial endophytic Streptomyces sp. can ameliorate environmental stresses and be utilized as crop growth promoters under adverse conditions. Herein, Streptomyces dioscori SF1 (SF1) isolated from seeds of Glycyrrhiza uralensis tolerated fungal phytopathogens and abiotic stresses (drought, salt, and acid base). Strain SF1 showed multifarious plant growth promotion characteristics, including the production of indole acetic acid (IAA), ammonia, siderophores, ACC deaminase, extracellular enzymes, the ability of potassium solubilization, and nitrogen fixation. The dual plate assay showed that strain SF1 inhibited 63.21 ± 1.53%, 64.84 ± 1.35%, and 74.19 ± 2.88% of Rhizoctonia solani, Fusarium acuminatum, and Sclerotinia sclerotiorum, respectively. The detached root assays showed that strain SF1 significantly reduced the number of rotten sliced roots, and the biological control effect on sliced roots of Angelica sinensis, Astragalus membranaceus, and Codonopsis pilosula was 93.33%, 86.67%, and 73.33%, respectively. Furthermore, the strain SF1 significantly increased the growth parameters and biochemical indicators of adversity in G. uralensis seedlings under drought and/or salt conditions, including radicle length and diameter, hypocotyl length and diameter, dry weight, seedling vigor index, antioxidant enzyme activity, and non-enzymatic antioxidant content. In conclusion, the strain SF1 can be used to develop environmental protection biological control agents, improve the anti-disease activity of plants, and promote plant growth in salinity soil within arid and semi-arid regions.

Strain-induced ordered Ge(Si) hut wires on patterned Si (001) substrates.

Ge/Si nanowires are predicted to be a promising platform for spin and even topological qubits. While for large-scale integration of these devices, nanowires with fully controlled positions and arrangements are a prerequisite. Here, we have reported ordered Ge hut wires by multilayer heteroepitaxy on patterned Si (001) substrates. Self-assembled GeSi hut wire arrays are orderly grown inside patterned trenches with post growth surface flatness. Such embedded GeSi wires induce tensile strain on the Si surface, which results in preferential nucleation of Ge nanostructures. Ordered Ge nano-dashes, disconnected wires and continuous wires are obtained correspondingly by tuning the growth conditions. These site-controlled Ge nanowires on a flattened surface lead to the ease of fabrication and large-scale integration of nanowire quantum devices.

Epitaxial Growth of Ordered In-Plane Si and Ge Nanowires on Si (001).

Controllable growth of wafer-scale in-plane nanowires (NWs) is a prerequisite for achieving addressable and scalable NW-based quantum devices. Here, by introducing molecular beam epitaxy on patterned Si structures, we demonstrate the wafer-scale epitaxial growth of site-controlled in-plane Si, SiGe, and Ge/Si core/shell NW arrays on Si (001) substrate. The epitaxially grown Si, SiGe, and Ge/Si core/shell NW are highly homogeneous with well-defined facets. Suspended Si NWs with four {111} facets and a side width of about 25 nm are observed. Characterizations including high resolution transmission electron microscopy (HRTEM) confirm the high quality of these epitaxial NWs.

InAs/GaAs quantum dot narrow ridge lasers epitaxially grown on SOI substrates for silicon photonic integration.

Monolithic integration of III-V laser sources on standard silicon-on-insulator (SOI) substrate has been recognized as an enabling technology for realizing Si-based photonic integration circuits (PICs). The Si-based ridge lasers employing III-V quantum dot (QD) materials are gaining significant momentum as it allows massive-scalable, streamlined fabrication of Si photonic integrated chips to be made cost effectively. Here, we present the successful fabrication of InAs/GaAs QD ridge lasers monolithically grown on {111}-faceted SOI hollow substrates. The as-cleaved Fabry-Perot (FP) narrow ridge laser is achieved with a relatively low threshold current of 50 mA at room temperature under pulse current operation. The maximum working temperature achieved is up to 80 oC. The promising lasing characteristics of such SOI-based InAs/GaAs QD ridge lasers with low threshold current and small footprint provide a viable route towards large-scale, low-cost integration of laser sources on SOI platform for silicon photonic integration purpose.

Phosphorus-free 1.5 µm InAs quantum-dot microdisk lasers on metamorphic InGaAs/SOI platform.

III-V semiconductor lasers epitaxially grown on silicon, especially on a silicon-on-insulator (SOI) platform, have been considered one of the most promising approaches to realize an integrated light source for silicon photonics. Although notable achievements have been reported on InP-based 1.5 µm III-V semiconductor lasers directly grown on silicon substrates, phosphorus-free 1.5 µm InAs quantum dot (QD) lasers on both silicon and SOI platforms are still uncharted territory. In this work, we demonstrate, to the best of our knowledge, the first phosphorus-free InAs QD microdisk laser epitaxially grown on SOI substrate emitting at the telecommunications S-band by growing metamorphic InAs/InGaAs QDs on (111)-faceted SOI hollow structures. The lasing threshold power for a seven-layer InAs QD microdisk laser with a diameter of 4 µm is measured as 234 µW at 200 K. For comparison, identical microdisk lasers grown on GaAs substrate are also characterized. The results obtained pave the way for an on-chip 1.5 µm light source for long-haul telecommunications.

Site-Controlled Uniform Ge/Si Hut Wires with Electrically Tunable Spin-Orbit Coupling.

Semiconductor nanowires have been playing a crucial role in the development of nanoscale devices for the realization of spin qubits, Majorana fermions, single photon emitters, nanoprocessors, etc. The monolithic growth of site-controlled nanowires is a prerequisite toward the next generation of devices that will require addressability and scalability. Here, combining top-down nanofabrication and bottom-up self-assembly, the growth of Ge wires on prepatterned Si (001) substrates with controllable position, distance, length, and structure is reported. This is achieved by a novel growth process that uses a SiGe strain-relaxation template and can be potentially generalized to other material combinations. Transport measurements show an electrically tunable spin-orbit coupling, with a spin-orbit length similar to that of III-V materials. Also, charge sensing between quantum dots in closely spaced wires is observed, which underlines their potential for the realization of advanced quantum devices. The reported results open a path toward scalable qubit devices using nanowires on silicon.

1310 nm InAs quantum-dot microdisk lasers on SOI by hybrid epitaxy.

Direct epitaxial growth of O-band InAs/GaAs quantum-dot laser on Si substrates has been rapidly developing over the past few years. But most of current methodologies are not fully compatible with silicon-on-insulator (SOI) technology, which is the essential platform for silicon photonic devices. By implementing an in situ III-V/Si hybrid growth technique with (111)-faceted Si hollow structures, we demonstrate the first optically pumped InAs/GaAs quantum-dot microdisk laser on SOI substrates grown by molecular beam epitaxy (MBE). The microdisk laser on SOI is characterized with threshold pump power as low as 0.39 mW and a Q factor of 3900 at room temperature. Additionally, the compared device performance of InAs quantum-dot microdisk lasers on GaAs, Si (001) and SOI are simultaneously studied with identical epi-structures.

Phytochemical Information and Biological Activities of Quinolizidine Alkaloids in Sophora: A Comprehensive Review.

Quinolizidine alkaloids, a main form of alkaloids found in the genus Sophora, have been shown to have many pharmacological effects. This review aims to summarize the photochemical reports and biological activities of quinolizidine alkaloids in Sophora. The collected information suggested that a total of 99 quinolizidine alkaloids were isolated and detected from different parts of Sophora plants, represented by lupinine-type, cytisine-type, sparteine-type, and matrine-type. However, quality control needs to be monitored because it could provide basic information for the reasonable and efficient use of quinolizidine alkaloids as medicines and raw materials. The nonmedicinal parts may be promising to be used as a source of quinolizidine alkaloid raw materials and to reduce the waste of resources and environmental pollution. In addition, the diversity of chemical compounds based on the alkaloid scaffold to make a biological compound library needs to be extended, which may reduce toxicity and find new bioactivities of quinolizidine alkaloids. The bioactivities most reported are in the fields of antitumor activity along with the effects on the cardiovascular system. However, those studies rely on theoretical research, and novel drugs based on quinolizidine alkaloids are expected.

Improved oral bioavailability for lutein by nanocrystal technology: formulation development, in vitro and in vivo evaluation.

Lutein is a kind of natural carotenoids possessing many pharmacological effects. The application of lutein was limited mainly due to its low oral bioavailability caused by poor aqueous solubility. Nanocrystal formulation of lutein was developed to improve the oral bioavailability in this study. The nanosuspension was prepared by the anti-solvent precipitation-ultrasonication method and optimized by Box-Behnken design, followed by freeze-drying to obtain lutein nanocrystals. The nanocrystals were characterized on their physical properties, in vitro dissolution and in vivo absorption performance. Lutein nanocrystals showed as tiny spheres with an average particle size of 110.7 nm. The result of diffractograms indicated that the percent crystallinity of lutein was 89.4% in coarse powder and then declined in nanocrystal formulation. The saturated solubility of lutein in water increased from 7.3 µg/ml for coarse powder up to 215.7 µg/ml for lutein nanocrystals. The dissolution rate of lutein nanocrystals was significantly higher than that of coarse powder or the physical mixture. The Cmax and AUC0-24 h of lutein nanocrystals after oral administration in rats was 3.24 and 2.28 times higher than those of lutein suspension, respectively. These results indicated that the nanocrystal formulation could significantly enhance the dissolution and absorption of lutein and might be a promising approach for improving its oral bioavailability.

Impact of chrysosplenetin, per se or in combination with artemisinin, on breast cancer resistance protein (Bcrp)/ABCG2 mRNA expression levels in mice small intestine

ABSTRACT Our previous work revealed that chrysosplenetin in combination with artemisinin inhibited in vivo P-glycoprotein (P-gp, one of classic multi-drug resistance proteins) mediated digoxin transportation activity by reversing the upregulated P-gp/Mdr1 mRNA expression levels by artemisinin. Therefore, chrysosplenetin might be a potential artemisinin-resistance reversal agent as a P-gp inhibitor. But it still remains unknown if chrysosplenetin has an impact on another pivotal multi-drug resistance protein, breast cancer resistance protein (Bcrp), which is co-expressed with P-gp in apical membrane of intestinal epithelial cell and overlaps some of the substrates and inhibitors. This study, therefore, further addressed the impact of chrysosplenetin, per se or in combination with artemisin, on Bcrp/ABCG2 mRNA expression levels in mice small intestine determined by western blot and real time-quantitative polymerase chain reaction (RT-qPCR) assay. The drugs were intragastrically administrated once per day for 7 days. Novobiocin, a known Bcrp inhibitor, was observed to have no impact on Bcrp/ABCG2 levels with or without artemisinin versus vehicle. Interestingly, artemisinin alone attenuated Bcrp level while chrysosplenetin alone increased it (p < 0.05). Relative mRNA level was significantly decreased when co-used with artemisinin and chrysosplenetin in ratio of 1:2 (p < 0.05). The discrepant results for chrysosplenetin on Bcrp/ABCG2 mRNA expressions might be closely related to the transcriptional or posttranscriptional regulation.

Chrysosplenetin, in the absence and presence of artemsininin, alters breast cancer resistance protein-mediated transport activity in Caco-2 cell monolayers using aristolochic acid I as a specific probe substrate

ABSTRACT The present study describes the impact of chrysosplenetin, in the absence and presence of artemisinin, on in vitro breast cancer resistance protein-mediated transport activity in Caco-2 cell monolayers using aristolochic acid I as a specific probe substrate. We observed that novobiocin, a known breast cancer resistance protein active inhibitor, increased Papp (AP-BL) of aristolochic acid I 3.13 fold (p < 0.05) but had no effect on Papp (BL-AP). Efflux ratio (PBA/PAB) declined 4.44 fold (p < 0.05). Novobiocin, consequently, showed a direct facilitation on the uptake of AAI instead of its excretion. Oppositely, both artemisinin and chrysosplenetin alone at dose of 10 µM significantly decreased Papp (BL-AP) instead of Papp (AP-BL). Chrysosplenetin alone attenuated the efflux ratio, which was suggestive of being as a potential breast cancer resistance protein suppressant. Oddly, Papp (BL-AP) as well as efflux ratio were respectively enhanced 2.52 and 2.58 fold (p < 0.05), when co-used with artemisinin and chrysosplenetin in ratio of 1:2. The potential reason remains unclear; it might be relative to binding sites competition between artemisinin and chrysosplenetin or the homodimer/oligomer formation of breast cancer resistance protein bridged by disulfide bonds, leading to an altered in vitro breast cancer resistance protein-mediated efflux transport function.

A new periplogenin cardenolide from the seeds of Antiaris toxicaria.

A new periplogenin cardenolide, periplogulcoside (1), together with three known cardenolides, was isolated from the seeds of Antiaris toxicaria. The structure of the new compound was characterized as periplogenin-3-O-ß-D-glucopyranosyl-(1 → 4)-ß-D-glucopyranoside (1) by spectroscopic methods including 1D and 2D NMR, HR-TOF-MS, and CD spectrometry, and the known compounds were identified by comparison of their NMR and HR-TOF-MS data with those reported in the literature. Compound 1 showed significant cytotoxicity against Hela and HepG-2 cell lines.

Rapid and sensitive detection of PRRSV by a reverse transcription-loop-mediated isothermal amplification assay.

A real-time monitoring reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed for the sensitive and specific detection of prototypic, prevalent North American porcine reproductive and respiratory syndrome virus (PRRSV) strains. As a higher sensitivity and specificity method than reverse transcription polymerase chain reaction (RT-PCR), the RT-LAMP method only used a turbidimeter, exhibited a detection limit corresponding to a 10(-4) dilution of template RNA extracted from 250 µL of 10(5) of the 50% tissue culture infective dose (TCID(50)) of PRRSV-containing cells, and no cross-reactivity was observed with other related viruses including porcine circovirus type 2, swine influenza virus, porcine rotavirus and classical swine fever virus. From forty-two field samples, 33 samples in the RT-LAMP assay was detected positive, whereas three of which were not detected by RT-PCR. Furthermore, in 33 strains of PRRSV, an identical detection rate was observed with the RT-LAMP assay to what were isolated using porcine alveolar macrophages. These findings demonstrated that the RT-LAMP assay has potential clinical applications for the detection of highly pathogenic PRRSV isolates, especially in developing countries.