Haperforatones A-M, thirteen undescribed limonoids from Harrisonia perforata with anti-inflammatory activity.

UPLC-Q-TOF-MS combined with mass defect filtering strategies were applied for the phytochemical investigation of Harrisonia perforata, leading to the isolation of thirteen undescribed limonoids named haperforatones A-M (1-13) and seventeen known compounds (14-30). Particularly, haperforatones D-E (4-5) have an unprecedented A, B, C, D-seco-6, 7-nor-C-24-limonoid skeleton, structurally stripped of the five-membered lactone ring B and formed a double bond at the C-5 and C-10 positions. Their 2D structures and relative configurations were identified using spectroscopic data. The absolute configurations of 1, 4, and 6 were established via X-ray diffraction crystallography. All 30 compounds were evaluated for anti-inflammatory potential in LPS-induced Raw 264.7 cell lines. Among those tested compounds, the most potent activity against LPS-induced NO generation was demonstrated by haperforatone F (6), with the IC50 value of inhibition NO production of 7.2 µM. Additionally, 6 could significantly inhibit IL-1ß and IL-6 release and markedly downregulate the protein expression level of iNOS in the LPS-stimulated RAW264.7 cells at 10 µM. The possible mechanism of NO inhibition of 6 was also investigated using molecular docking, which revealed the interaction of compound 6 with the iNOS protein.

Lindenane sesquiterpenoid dimers from Chloranthus japonicus improve LDL uptake by regulating PCSK9 and LDLR.

UPLC-TOF-MS/MDF directed phytochemical research of Chloranthus japonicus led to the isolation of 46 lindenane sesquiterpenoid dimers, which included 13 new analogs. Their structures with absolute configurations were elucidated by analysis of spectroscopic data. Fourteen compounds with ester chains significantly decreased PCSK9 protein level in medium of HepG2 cells, especially for compounds 14 and 29 (5 µM) with inhibition rates of 69.0% and 72.8%, respectively. Compound 14 in HepG2 cells was evaluated via DiI-LDL uptake assays and found to increase LDL uptake by upregulating LDLR mRNA and protein level. Meanwhile, 14 decreased the secretion of PCSK9 protein in medium and downregulated intracellular PCSK9 protein and mRNA level. The discovery of these natural small molecule compounds provides a novel structure basis for design PCSK9 regulators, making them a promising lead for development of new lipid-lowering agents.

Isolation and characterization of intestinal bacteria associated with cellulose degradation in grasshoppers (Orthoptera).

Insect gut bacteria play an essential role in the nutritional metabolism, growth, and development of insects. Grasshoppers (Orthoptera) are cellulose-rich plant-feeding pests. Although the biological potential of grasshopper gut microorganisms to assist cellulose decomposition is well established, microbial resources for efficient degradation of cellulose biomass are still scarce and need to be developed. In this study, we used selective media to isolate cellulose-degrading bacteria from the intestines of Atractomorpha sinensis, Trilophidia annulata, Sphingonotus mongolicus, and Calliptamus abbreviatus. Phylogenetic analysis based on the maximum likelihood method using 16S rDNA sequencing sequences to identify bacteria revealed the isolation of 11 strains belonging to 3 genera, including Klebsiella, Aeromonas, and Bacillus. The degradability of the isolates to cellulose was then determined by the DNS colorimetric method, and the results showed that Bacillus had the highest degradation rate. The elucidation of microbial cellulose degradation capacity in grasshoppers not only contributes to the understanding of multiple plant-insect-microbe interactions, but also provides a valuable microbial resource for solving the biomass conversion of cellulose species problem.

Heterodyne detection of backscattering for whispering-gallery-mode sensors.

Whispering-gallery-mode (WGM) microcavities have shown significant applications in nanoparticle sensing for environmental monitoring and biological analysis. However, the enhancement of detection resolution often calls for active cavities or elaborate structural designs, leading to an increase of fabrication complexity and cost. Herein, heterodyne amplification is implemented in WGM microsensors based on backscattering detection mechanism. By interfering with an exotic reference laser, the reflecting light backscattered by perturbation targets can be strongly enlarged, yielding an easy-to-resolve and consequently sensitive microsensor. The dependence of detection laser frequency has also been characterized with the assistance of optothermal dynamics. We show that exploiting heterodyne interferometry boosts the detection of weak signals in microresonator systems and provides a fertile ground for optical microsensor development.

Color-detuning-dynamics-based quantum sensing with dressed states driving.

Exploring quantum technology to precisely measure physical quantities is a meaningful task for practical scientific researches. Here, we propose a novel quantum sensing model based on color detuning dynamics with dressed states driving (DSD) in stimulated Raman adiabatic passage. The model is valid for sensing different physical quantities, such as magnetic field, mass, rotation and so on. For different sensors, the used systems can range from macroscopic scale, e.g. optomechanical systems, to microscopic nanoscale, e.g. solid spin systems. The dynamics of color detuning of DSD passage indicates the sensitivity of sensors can be enhanced by tuning system with more adiabatic or accelerated processes in different color detuning regimes. To show application examples, we apply our approach to build optomechanical mass sensor and solid spin magnetometer with practical parameters.

Demonstration of Yb3+-doped and Er3+/Yb3+-codoped on-chip microsphere lasers.

Rare-earth-doped on-chip microlasers are of great significance in both fundamental research and engineering. To the best of our knowledge, this is the first report of Yb3+-doped and Er3+/Yb3+-codoped on-chip microsphere lasers fabricated via sol-gel synthesis. Laser emissions were observed in a band around 1040 nm in both Yb3+-doped and Er3+/Yb3+-codoped resonators pumped at 980 nm and had measured ultralow thresholds of 5.2 µW and 0.6 µW, respectively. Both single-mode and multi-mode emissions were recorded around 1040 nm in these lasers. Single-mode and two-mode emissions were obtained at 1550 nm in the Er3+/Yb3+-codoped lasers when pumped at 980 nm and 1460 nm, respectively. Furthermore, quality factors induced by different loss mechanisms in the microsphere lasers are theoretically estimated. These resonators are expected to contribute to the high-density integration of on-chip silica-based microlasers.

Scalable higher-order exceptional surface with passive resonators.

The sensitivity of perturbation sensing can be effectively enhanced with higher-order exceptional points due to the nonlinear response to frequency splitting. However, experimental implementation is challenging since all the parameters need to be precisely prepared. The emergence of an exceptional surface (ES) improves the robustness of the system to the external environment, while maintaining the same sensitivity. Here, we propose, to our knowledge, the first scalable protocol for realizing a photonic high-order ES with passive resonators. By adding one or more additional passive resonators in the low-order ES photonic system, the three- or arbitrary N-order ES is constructed and proved to be easily realized in experiment. We show that the sensitivity is enhanced and the experimental demonstration is more resilient against fabrication errors. The additional phase-modulation effect is also investigated.

Phase-controlled dual-wavelength resonance in a self-coupling whispering-gallery-mode microcavity.

We report a novel, to the best of our knowledge, way to achieve phase-controlled dual-wavelength resonance based on whispering-gallery-mode (WGM) microcavities experimentally. With the help of a feedback waveguide, not only two optical pathways but also a unidirectional coupling between counter-propagating waves are formed, which is the requirement of all-optical analogues of electromagnetically induced transparency and Autler-Townes splitting. By adjusting the accumulating phase introduced from the fiber waveguide, we observe the signal lineshape changes from symmetric to asymmetric, i.e., the resonant transmission and extinction ratio of two splitting modes can be controlled, which brings a new degree of freedom to the WGM resonator system. These results may boost the development of quantum state control and pave the way for reconfiguring devices such as narrow-band filters.

α-Glucosidase inhibitory triterpenoids from Euonymus fortunei.

α-Glucosidase plays an important role in catalyzing the hydrolytic cleavage of disaccharides into monosaccharides. In this study, a phytochemical investigation of the potential α-glucosidase inhibitory fraction from the aerial parts of Euonymus fortunei led to the isolation and identification of two new tetracyclic triterpenoids, fortunenones A and B (1-2), together with 11 known triterpenoids (3-13). Fortunenones A and B are rare C32 triterpenoids possessing a 24,24-dimethyl group. The partial isolated compounds were evaluated their effects on α-glucosidase, of which echinochlorin D (5), lupenone (7), wilforlide B (12), and wilforlide A (13) exhibited remarkable inhibitory effects with the half inhibitory concentration ranged from 207.2 × 10-6 M to 388.3 × 10-6 M compared with the positive control, acarbose. An enzyme kinetics analysis by Lineweaver-Burk plots revealed that the inhibition types of the four active compounds were all mixed inhibition. Molecular docking further revealed that hydrophobic interactions and hydrogen bonds play an important role in the inhibition of α-glucosidase activity. Our results demonstrate the potential of E. fortunei extract and its constituents to inhibit α-glucosidase.

Manipulation of optomechanically induced transparency and absorption by indirectly coupling to an auxiliary cavity mode.

We theoretically study the optomechanically induced transparency (OMIT) and absorption (OMIA) phenomena in a single microcavity optomechanical system, assisted by an indirectly coupled auxiliary cavity mode. We show that the interference effect between the two optical modes plays an important role and can be used to control the multiple-pathway induced destructive or constructive interference effect. The three-pathway interference could induce an absorption dip within the transparent window in the red sideband driving regime, while we can switch back and forth between OMIT and OMIA with the four-pathway interference. The conversion between the transparency peak and absorption dip can be achieved by tuning the relative amplitude and phase of the multiple light paths interference. Our system proposes a new platform to realize multiple pathways induced transparency and absorption in a single microcavity and a feasible way for realizing all-optical information processing.

Identification of Transient Receptor Potential Vanilloid 3 Antagonists from Achillea alpina L. and Separation by Liquid-Liquid-Refining Extraction and High-Speed Counter-Current Chromatography.

Bioassay-guided fractionation of the ethanol extract of whole herbs of Achillea alpina led to the isolation of isochlorogenic acids A and B as transient receptor potential vanilloid 3 (TRPV3) channel antagonists by using a calcium fluorescent assay. The structures were identified by spectroscopic analysis and the inhibitory activities of isochlorogenic acids A and B were confirmed by whole-cell patch clamp recordings of human embryonic kidney 293 (HEK293) cells expressing human TRPV3. Molecular docking results revealed that these two compounds reside in the same active pocket of human TRPV3 channel protein with lower binding energy than the agonist 2-aminoethoxydiphenyl borate (2-APB). High-speed counter-current chromatography (HSCCC) coupled with a liquid-liquid extraction approach was successfully established for the separation of isochlorogenic acids A and B from the whole herbs of A. alpina. Ethyl acetate and n-hexane-ethyl acetate-water (3:3:4 and 1:5:4, v/v/v) were selected as liquid-liquid extraction solvent systems to remove high- and low-polarity impurities in the mixture. Sixty g of ethanol extract was refined by solvent partition to yield 1.7 g of the enriched fraction, of which 480 mg in turn obtained 52.5 mg of isochlorogenic acid B (purity 98.3%) and 37.6 mg isochlorogenic acid A (purity 96.2%) after HSCCC with n-hexane-ethyl acetate-water containing 1% acetic acid (1:4:8, v/v/v).

Differentiation of sow and mouse ovarian granulosa cells exposed to zearalenone in vitro using RNA-seq gene expression.

Zearalenone (ZEA), a natural contaminant found in feed, has been shown to have a negative impact on domestic animal reproduction, particularly in pigs. There are species-specific differences in the ZEA-induced toxicity pattern. Here, we investigated the different biological effects of ZEA exposure on porcine and mouse granulosa cells, using RNA-seq analysis. We treated murine and porcine granulosa cells with 10 µM and 30 µM ZEA during 72 h of culturing, in vitro. The results showed that 10 µM ZEA exposure significantly altered mitosis associated genes in porcine granulosa cells, while the same treatment significantly altered the steroidogenesis associated genes in mouse granulosa cells. Exposure to 30 µM ZEA resulted in significantly up-regulated expression of inflammatory related genes in porcine granulosa cells as well as the cancer related genes in mouse granulosa cells. Similarly, 30 µM ZEA exposure significantly decreased the expression of tumor suppressor factors in the mouse granulosa cells. Furthermore, immunofluorescence, RT-qPCR as well as western-blot analysis verified the different expression of related genes in ZEA exposed porcine and mouse granulosa cells. Collectively, these results illustrate the presence of species differences with regards to ZEA effects between porcine and mouse ovarian granulosa cells, in vitro.

Fabrication of a microtoroidal resonator with picometer precise resonant wavelength.

Fabricating an optical microresonator with precise resonant wavelength is of significant importance for fundamental research and practical applications. Here, we develop an effective method to fabricate ultra-high Q microtoroid with picometer-precise resonant wavelength. Our method adds a tuning reflow process, using low-power CO2 laser pulses, to the traditional fabrication process. It can tailor resonant wavelength to a red or blue direction by choosing a proper laser power. Also, this shift can be controlled by the exposure time. Meanwhile, quality factor remains nearly unchanged during this tailoring process. Our method can greatly reduce the difficulties of experiments where precise resonances are required.

Insulin regulates primordial-follicle assembly in vitro by affecting germ-cell apoptosis and elevating oestrogen.

Insulin is a protein secreted by pancreatic ß-cells, which plays an important role in the regulation of ovarian function. However, the specific molecular mechanism of its function remains largely unknown. This study aimed to assess the effect of insulin on mouse folliculogenesis using an in vitro ovary-culture model. The results demonstrated that insulin promoted the proliferation of ovarian granulosa cells in vitro, and thereby accelerated the progress of folliculogenesis (the percentage of oocytes in cysts declined from 42.6% to 29.3%); however, the percentage of apoptotic oocytes increased after insulin treatment. Further investigation indicated that apoptosis occurred mainly in germ-cell cysts. After 3 days of insulin treatment, oestrogen in the culture medium of mouse ovaries significantly increased (P<0.01), while the lower dose of oestrogen promoted primordial-follicle assembly in vitro. In conclusion, insulin promoted folliculogenesis by facilitating germ-cell apoptosis within the cysts and upregulating oestrogen levels.

Exposure to diethylhexyl phthalate (DEHP) results in a heritable modification of imprint genes DNA methylation in mouse oocytes.

Diethylhexyl phthalate (DEHP) is an estrogen-like compound widely used as a plasticizer in commercial products and is present in medical devices, and common household items. It is considered an endocrine disruptor since studies on experimental animals clearly show that exposure to DEHP can alter epigenetics of germ cells. This study was designed to assess the effects of DEHP on DNA methylation of imprinting genes in germ cells from fetal and adult mouse. Pregnant mice were treated with DEHP at doses of 0 and 40 µg DEHP/kg body weight/day from 0.5 to 18.5 day post coitum. The data revealed DEHP exposure significantly reduced the percentage of methylated CpG sites in Igf2r and Peg3 differentially methylated regions (DMRs) in primordial germ cells from female and male fetal mouse, particularly, in the oocytes of 21 dpp mice (F1), which were produced by the pregnant micetreated with DEHP. More surprisingly, the modification of the DNA methylation of imprinted genes in F1 mouse oocytes was heritable to F2 offspring which exhibit lower percentages of methylated CpG sites in imprinted genes DMRs. In conclusion, DEHP exposure can affect the DNA methylation of imprinting genes not only in fetal mouse germ cells and growing oocytes, but also in offspring's oocytes.

Cloning and in vitro function analysis of codon-optimized FatI gene.

Currently, n-3 polyunsaturated fatty acids (n-3 PUFAs) have attracted great attention because of their biological significance to organisms. In addition, PUFAs show an obvious impact on prevention and treatment of various diseases. Because n-3 PUFAs cannot be endogenously synthesized by mammals, mammals have to rely on a dietary supplement for sufficient supply. The finding and application of the fatty acid dehydrogenase I (FatI) gene are expected to change the current situation because it can convert n-6 polyunsaturated fatty acids (n-6 PUFAs) to n-3 PUFAs. Meanwhile, the gradual maturation of transgenic technology makes it possible to produce transgenic animals that can synthesize n-3 PUFAs by themselves. In this study, the DNA coding sequence of FatI was synthesized by a chemical method after codon optimization according to the mammal's codon bias. The synthesized DNA sequence was introduced into Boer goat fetal fibroblasts by the constructed recombinant eukaryotic expression vector pcDNA3.1(+)-FatI. Boer goat fetal fibroblasts were transfected by electroporation, and the stable transfected cell lines were obtained by G418 selection. Genomic DNA PCR and Southern blot were applied to verify that the foreign gene FatI was integrated into the genome of the Boer goat fibroblasts. RT-PCR results showed the expression of FatI gene at the mRNA level. The fatty acid profile of cells carrying the FatI gene revealed an increase in total n-3 PUFAs (from 0.61 to 0.95), but a decrease in n-6 PUFAs (from 10.34 to 9.85), resulting in a remarkable increase in the n-3:n-6 ratio (from 0.059 to 0.096). The n-3:n-6 ratio had a 63.49 percent increase, which is a precursor of the response of n-3 desaturase activity of the FatI gene. The study may provide a practical tool for producing transgenic animals that can produce n-3 PUFAs by themselves, and we hope that the application will lay the foundation for animals producing n-3 PUFAs, which will benefit human nutrition and wellness.

Anti-senescence effect of FatI gene in goat somatic cells.

The fatty acid dehydrogenase I (FatI) is able to express in mammalian cells and convert n-6 polyunsaturated fatty acids (PUFAs) to n-3 PUFAs. n-3 PUFA is an important component of the cell membrane and plays an important role in the prevention and control of a variety of human diseases. However, n-3 PUFAs cannot be endogenously synthesized by mammals because they lack the dehydrogenase that converts n-6 to n-3 PUFA. For the time being, gradually matured transgenic technology makes it possible to produce transgenic animals that are able to synthesize n-3 PUFAs by themselves. However, the transgenic technology itself may bring negative impacts. In this study, the eukaryotic expression vector pcDNA3.1-FatI was introduced into the genome of Boer goat fetal fibroblasts cultured in vitro, and the influence of biological characteristics of the fetal fibroblast was studied via overexpression of FatI. The results showed that the proliferation and apoptosis of cultured fetal fibroblast were not affected significantly by the overexpression of FatI using BrdU and TUNEL staining methods, respectively. Moreover, the overexpression of FatI significantly inhibited the senescence of somatic cells compared with enhanced green fluorescent protein (EGFP) transgenic cells (P < 0.01). Quantitative PCR revealed that the mRNA expression of P16 and P53 in the FatI transgenic cell group was significantly lower than that in the EGFP transgenic cell group (P < 0.01). In conclusion, the senescence of goat somatic cells was inhibited by the overexpression of the FatI gene.

MnS-BaS Heterostructures as Effective Catalysts for Oxygen Reduction Reaction.

The inadequate electrical conductivity of metal sulfides, along with their tendency to agglomerate, has hindered their use in energy storage and catalysis. The construction of a heterojunction can ameliorate these deficiencies to some extent. In this paper, MnS-BaS heterojunction catalysts were prepared by a hydrothermal method, which is a simple and inexpensive process. The MnS-BaS heterojunction catalysts exhibited superior performance owing to the strong synergistic interaction between MnS and BaS. Density functional theory (DFT) calculations reveal strong interactions at the heterojunction interface and significant electron transfer between MnS and BaS, which further modulates the electronic structure of Mn. The elevation of the center of the d-band enhances the adsorption of oxygen and oxygen-containing intermediates on the catalyst, thus promoting the oxygen reduction reaction (ORR). The practical application of MnS-BaS catalysts was tested by assembling zinc-air batteries. This study provides a rational strategy for designing transition metal catalysts that are efficient and low cost.

Amide alkaloids and neolignans from Piper hongkongense and their inhibitory activities of PCSK9 expression.

Four undescribed amide alkaloids hongkongensines A-C and 1-(1-oxo-6-hydroxy-2E,4E-dodecadienyl)-piperidine, five known amide alkaloids, and three known neolignans were isolated from the aerial part of Piper hongkongense. The planar structures of these compounds were determined by detailed analyses of HR-ESI-MS and NMR data. The absolute configurations of hongkongensines A-C were elucidated by single-crystal X-ray diffraction analysis and ECD calculations. Moreover, the inhibitory activities of PCSK9 expression in vitro for all compounds were assessed by PCSK9 AlphaLISA screening. Kadsurenone (10) displayed a significant inhibitory activity at 5 µM with an inhibition rate of 51.98%, compared with 55.55% of berberine (BBR 5 µM).

Novel Jatrophane Diterpenoids from Euphorbia esula Promotes Lipid Clearance by Transcriptional Regulation of PCSK9.

PCSK9 has been recognized as an efficient target for hyperlipidemia and related cardiovascular/cerebrovascular diseases. However, PCSK9 inhibitors in the clinic are all biological products, and no small molecules are available yet. In the current work, we discovered that the crude extract of Euphorbia esula (E. esula) promoted LDL uptake in vitro and then obtained 8 new and 12 known jatrophane diterpenoids by activity-guided isolation. After summarized their structure-activity relationship of PCSK9 inhibition, we selected compound 11 (C11) with potent activity and high abundance to investigate its mechanism and in vivo efficacy. Mechanistically, C11 bound with HNF1α to influence its nuclear distribution and subsequently inhibit PCSK9 transcription, thereby enhancing LDLR and promoting LDL uptake. Moreover, C11 demonstrated obvious lipid-lowering activity in HFD mouse model. In conclusion, we first revealed the novel application of E. esula in the discovery of a lipid-lowering candidate and highlighted the potential of C11 in the treatment of hyperlipidemia.