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Introduction Abnormal extravillous trophoblast (EVT) function is closely related to preeclampsia (PE) and may be caused by inadequate autophagy, apoptosis, and senescence. Cyclosporin A (CsA) is an effective immunosuppressant that has been reported to stimulate autophagy and exert benign biological effects on EVTs. Therefore, we hypothesized that CsA may display therapeutic efficacy against PE by activating autophagy. Methods We established the nitro- l -arginine methyl ester ( l -NAME)-induced preeclamptic mice model and a hypoxia‐reoxygenation (H/R) model in vitro. The effects of CsA on autophagy were evaluated by western blotting (WB). The effects of CsA on apoptosis were analyzed by Hematoxylin-eosin (H&E) staining, cell apoptosis assay and WB. Senescence‐associated β‐galactosidase (SA‐β‐gal) staining, RT-qPCR and WB were used to examine the senescence level. RT-qPCR were used to detect the senescence-associated secretory phenotype (SASP) level. DCFH-DA fluorescent probe, dihydroethidium (DHE) staining and mitochondrial membrane potential (ΔΨm) were used to detect senescence-associated mitochondrial dysfunction (SAMD). Results CsA alleviated PE-like symptoms and reduced placental necrosis and senescence in mice injected with l -NAME. CsA ameliorated placental SASP and SAMD level induced by l -NAME. CsA also upregulated the expression of autophagic proteins in mouse placentas disrupted using l -NAME. In vitro, we found that CsA reversed H/R-induced apoptosis and senescence, as well as decreasing SASP and SAMD levels and upregulating autophagic proteins levels. Notably, 3-methyladenine (3-MA), an early phase inhibitor of autophagosome formation, abolished the protective effects of CsA against H/R. Discussion CsA may display some therapeutic effects against PE by activating autophagy in vivo and in vitro.

Introduction Advanced oxidation protein products (AOPPs), which are novel markers of oxidant-mediated protein damage, are prevalent in numerous diseases. We previously demonstrated that AOPPs act as a new class of pathogenic mediators in preeclampsia by causing trophoblast damage and dysfunction. Herein, we explored whether AOPPs could regulate the Nrf-2/ARE/HO-1 anti-oxidative pathway to facilitate the progression of preeclampsia. Methods To investigate the pathophysiology of preeclampsia, we evaluated the effects of AOPPs on trophoblast damage, apoptotic proteins, and Nrf-2/ARE/HO-1 anti-oxidative pathway expression, as well as their underlying mechanisms. Results AOPPs directly increased the expression of apoptotic proteins and significantly inhibited the expression of Nrf-2/ARE/HO-1 pathway in trophoblasts. Nrf-2 silencing aggravated the AOPPs-induced cell apoptosis in vitro by activating p53 and caspase cascade, whereas Nrf-2 overexpression had the opposite effect. Moreover, Nrf-2 exerted cytoprotective effects by increasing HO-1. Discussion These findings suggest that AOPPs induce trophoblast apoptosis by triggering p53 and caspase activation via inhibition of the Nrf-2/ARE/HO-1 anti-oxidative pathway. Hence, Nrf-2/ARE/HO-1 pathway activation plays a protective role in AOPPs-induced cell apoptosis; thus, holding potential as a therapeutic target against preeclampsia.

In the free-cutting field, Bi-bearing steel is widely concerned because it supplies the parts for instruments. This work aims to explore the forms of Bi particles existing in 1215MS steel and to detect the effect of Bi on the grain size and thermal expansion performance of steel by heat treatment and thermal expansion experiments with a thermal expansion instrument and a box type electric resistance furnace. Results show that both co-existence of the Bi-MnS inclusions and the isolated Bi particles merely existed in the austenite grain boundary of steel. The higher Bi content in steel is helpful to refine the austenite grain size of as-cast steel. When the austenite grain sizes were in the range of 0~5 μm, the normalized frequency of grains in 0, 130, 240 and 760 ppm Bi content steels was 0.014~0.042, while the normalized frequency in 1200 and 2300 ppm Bi content steels was 0.45 and 0.23, respectively. With adding Bi to steel, the net elongation curves of the Bi-bearing steels showed the upward convex peaks in cooling process. Liquid Bi inhibited the volume shrinkage of heated steel, showing the abnormal expansion phenomenon of Bi.

BACKGROUND Glycogen storage disease type Ib (GSD-Ib) is a glycogen metabolism disorder that leads to the manifestations of inflammatory bowel disease (IBD), especially Crohn’s disease (CD)-like colitis. Although biological agents are effective for treating CD, their application in the treatment of GSD-Ib with CD-like colitis has been rarely reported. CASE SUMMARY A 13-year-old Han male was diagnosed with GSD-Ib with CD. The patient was treated with granulocyte colony-stimulating factor. When he had symptoms of CD-like colitis, he was continuously pumped with enteral nutrition and administered oral mesalazine for 2 wk; however, the symptoms did not improve significantly. Hence, infliximab (IFX) was administered. Hitherto, the patient has been followed up for 1 year, and no clinical manifestations have been observed. After 6 mo of treatment (fifth IFX treatment), the disease activity index and all inflammatory indexes decreased, and a review of the colonoscopy data showed that the ulcers appeared smooth. CONCLUSION In this study, the patient was successfully treated with IFX. In cases of GSD-Ib, IBD should be highly considered.

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Acid treated kaolinites (KA) were successively loaded with Zr and Fe, Ni or Co component to control the product distribution and upgrade the tar quality in coal pyrolysis. The structure of the resultant catalysts was characterized and their catalytic performance in the pyrolysis of demineralized low-rank coal and benzyl phenyl ether (BPE), a model compound containing Cal-O bridge bond, were investigated. Results show that the introducing of Zr into the KA can enlarge the hysteresis loop due to the stacking of ZrO2 particles. The acidities, especially the strong ones, increase as the Zr content is below 8 wt% (KA-8Z). When adding Fe, Ni or Co metals into the KA-8Z, the number of Bronsted acid sites obviously decreases, but Lewis acid sites increase. The maximum BPE conversion of 94.0% occurs for the KA-8Z, further metal-loaded sample promotes the cleavage of Cal-O bond in BPE and the formation of active H radicals from CH3OH, leading to the increase of BPE conversion. Besides, remarkable enhancement of target monomeric aromatics is observed for the Fe, Ni and Co-loaded samples. Compared with the pyrolysis without catalyst, the tar yield as well as pitch content decrease over the KA-8Z and its metal-modified catalysts. Wherein, Ni-KA-8Z has the highest activity for tar upgrading, leading to the largest increase in the contents of light oil and phenol oil. In-situ pyrolysis by time-of-flight mass spectrometry reveals the enhanced dissociation of weak covalent bonds linked in the coal skeleton over the KA-8Z and Fe, Ni and Co-modified catalysts, resulting in a decrease in the peak temperature for product release. A marked increase in phenols and diphenols confirms a promoted dissociation of ether bond in coal.

Recent evidence suggests that melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs), a neuronal class regulating non-image forming (NIF) vision and generally thought to be injury resistant, are dysfunctional in certain neurodegenerative diseases. Although disrupted NIF visual functions have been reported in patients and animals with diabetes, it remains controversial whether ipRGCs exhibit remodeling during diabetes and if so, whether such remodeling is variable among ipRGC subtypes. Here, we demonstrate that survival, soma-dendritic profiles, and melanopsin-based functional activity of M1 ipRGCs were unaltered in streptozotocin-induced 3-month diabetic mice. Such resistance remained at 6 months after streptozotocin administration. In contrast, M2/M3 ipRGCs underwent significant remodeling in diabetic mice, manifested by enlarged somata and increased dendritic branching complexity. Consistent with the unaltered melanopsin levels, the sensitivity of melanopsin-based activity was unchanged in surviving M2 cells, but their response gain displayed a compensatory enhancement. Meanwhile, the pupillary light reflex, a NIF visual function controlled by M2 cells, was found to be impaired in diabetic animals. The resistance of M1 cells might be attributed to the adjacency of their dendrites to capillaries, which makes them less disturbed by the impaired retinal blood supply at the early stage of diabetes.

Phosphorescent metal complexes are a new kind of multifunctional antitumor compounds that can integrate imaging and antitumor functions in a single molecule. In this minireview, we summarize the recent research progress in this field, concentrating on the theranostic applications of phosphorescent iridium(iii), ruthenium(ii) and rhenium(i) complexes. The molecular design that affords these complexes with tumour- or subcellular organelle-targeting properties is elucidated. The potential of these complexes to induce and monitor the dynamic behavior of subcellular organelles and the changes in microenvironment during the process of therapy is demonstrated. Moreover, the potential and advantages of applying new technologies, such as super-resolution imaging and phosphorescence lifetime imaging, are also described. Finally, the challenges faced in the development of novel theranostic metallo-anticancer complexes for possible clinical translation are proposed., The recent development in phosphorescent iridium, ruthenium and rhenium complexes as theranostic anticancer agents is summarized.

A mild and selective Cp*Ir(III)- and Cp*Rh(III)-catalyzed direct C(sp2)–H amination of arenes and three types of nitrene precursor reagents is reported, with the assistance of a thioether directing group. This redox-neutral protocol proceeds under mild reaction conditions, has a broad substrate scope and high functional-group compatibility and generates the desired aminated products in moderate to excellent yields. The reaction represents the first example of a thioether-directed Cp*Ir(III)- and Cp*Rh(III)-catalyzed C(sp2)–H direct amination reaction. Moreover, azide compounds were employed as a diverse and robust aminating reagent for the first time in a thioether-directed C–H functionalization reaction.

Backgrounds Preeclampsia (PE) is characterized as placental vascular disturbance and excessive secretion of soluble fms-like tyrosine kinase 1 (sFlt-1) into the maternal circulation. Trimethylamine N-oxide (TMAO, a gut microbe-derived metabolite) is strongly associated with various cardiovascular and cerebrovascular diseases. Recently, we observe that higher maternal circulating TMAO and sFlt-1 in patients with PE. The aims of the present study are to explore the effects of TMAO on placental sFlt-1 production and the underlying mechanism in human placenta. Methods Human placental explants, human placental primary trophoblasts and the extravillous trophoblasts (EVT) cell line (HRT-8/SVneo) were exposured to various concentrations of TMAO (100, 150, 300, and 600 μM). The mRNA expression and protein secretion of sFlt-1 in placental explants, primary trophoblasts and HRT-8/SVneo cells were determined with qPCR and ELISA, respectively. The levels of intracellular reactive oxygen species (ROS) production in primary trophoblasts and HRT-8/SVneo cells were measured by peroxide-sensitive fluorescent probe dichlorofluorescein diacetate. Results Exposure of placental explants, primary trophoblasts and HRT-8/SVneo cells to TMAO significantly enhanced sFlt-1 at both mRNA and protein levels in a dose dependent manner. Moreover, inhibition of NADPH oxidase with apocynin significantly attenuated TMAO-induced ROS production in primary trophoblasts and HRT-8/SVneo, and suppressed sFlt-1 secretion in placental explants, primary trophoblasts and HRT-8/SVneo. Conclusions Our findings indicated the NADPH oxidase dependent ROS pathway played a critical role in mediating TMAO-induced sFlt-1 generation in human placenta. TMAO may become a potential novel target for pharmacological or dietary interventions to reduce the risk of developing PE.

A serials of modified kaolinites were prepared by calcination and further acid treatment and characterized by in-situ XRD, N2 adsorption, NH3-TPD, Py-IR and 27Al MAS-NMR. And their catalytic performance in pyrolysis of methanol/benzyl phenyl ether (MeOH-BPE), a model compound of low-rank coal, were investigated at 400 °C in a fixed-bed reactor to explore the correlation between the structure of modified samples and their catalytic performances. The results show that calcination temperature above 500 °C causes the collapse of kaolinite structure. Further acid leaching facilitates the formation of micropores and mesopores. The calcination of kaolinite leads to the transformation of six-coordinate Al atoms (AlVI) into four and five coordinate species (AlIV and AlV), while the subsequent acid treatment increases the contents of AlIV and AlVI and removes AlV. Total acid sites exhibit a first increase and then decrease tendency with the raising calcination temperature. In the presence of the modified kaolinites, BPE conversion significantly enhances and reaches the highest value of 91.41% over K-A-700 prepared by calcination at 700 °C of kaolinite and further acid leaching. Besides, the maximum content of phenol and toluene is also achieved due to the highest acid sites and AlIV content of K-A-700, which favors the generation of ·H, thus resulting in an obvious inhibition of bibenzyl formation but a significant increase of 2-benzylphenol. In-situ pyrolysis by time-of-flight mass spectrometry suggests that the cleavage of Cal-O bond of BPE to form phenol radicals and benzyl radicals is the primary way, while insufficient ·H results in the formation of dominant product of 2-benzylphenol.

Comprehensive and in-depth understanding of the molecular structure of low-rank coals is the basis for clean and efficient utilization. The detailed molecular structure of sequential thermal dissolution (TD) extracts from a subbituminous coal was characterized using a high-resolution mass spectrometry run in a tandem MS method, in-source collision-activated dissociation. Cyclohexane and toluene TD extracts released compounds with less oxygen and more nitrogen atoms located on aromatic cores compared to ethanol and isopropanol TD extracts. Archipelago-structured compounds presented in asphaltenes were also observed in compounds from toluene TD extract. Principle component analysis, a multivariate statistical method, was introduced to mine molecular characteristics of the TD extracts. TD yield and relative abundance of CH class (without heteroatom) became the key point to determine the clustering pattern for whole molecules and aromatic cores, respectively.

Poor crystalline MoS2 was synthesised by a novel two-step hydrothermal method, including aging and hydrothermal stages. The structures were characterised by different analytical methods such as X-ray diffraction (XRD), Brunauer–Emmett–Teller, field emission scanning electron microscopy, transmission electron microscopy and X-ray photoelectron spectroscopy (XPS). The synthesised products were typical mesoporous materials with a high specific surface area (273 m2/g). XRD and XPS displayed that the products were poor crystalline MoS2 mixed with metal Mo and Mo4+/(Mo + Mo4+) was 72.6%. The electron microscopy results showed that the products were uniform bent nanosheets with150 nm diameter and 3–5 layers. Furthermore, the product displayed excellent hydrodesulphurisation performance of dibenzothiophene (DBT) and the DBT conversion reached 87.3%. Compared with the one-step hydrothermal method, the two-step one was able to shorten the reaction time by 12 h, create more active sites and affect crystalline, composition, specific surface area and morphology of products.

A hybrid palladium catalyst assembled from a chiral phosphoric acid (CPA) and thioamide enables a highly efficient and enantioselective β-C(sp3 )-H functionalization of thioamides (up to 99 % yield, 97 % ee). A kinetic resolution of unsymmetrical thioamides by intermolecular C(sp3 )-H arylation can be achieved with high s-factors. Mechanistic investigations have revealed that stereocontrol is achieved by embedding the substrate in a robust chiral cavity defined by the bulky CPA and a neutral thioamide ligand.

G-quadruplexes form folded structures because of tandem repeats of guanine sequences in DNA or RNA. They adopt a variety of conformations, depending on many factors, including the type of loops and cations, the nucleotide strand number, and the main strand polarity of the G-quadruplex. Meanwhile, the different conformations of G-quadruplexes have certain influences on their biological functions, such as the inhibition of transcription, translation, and DNA replication. In addition, G-quadruplex binding proteins also affect the structure and function of G-quadruplexes. Some chemically synthesized G-quadruplex sequences have been shown to have biological activities. For example, bimolecular G-quadruplexes of AS1411 act as targets of exogenous drugs that inhibit the proliferation of malignant tumours. G-quadruplexes are also used as vehicles to deliver nanoparticles. Thus, it is important to identify the factors that influence G-quadruplex structures and maintain the stability of G-quadruplexes. Herein, we mainly discuss the factors influencing G-quadruplexes and the synthetic G-quadruplex, AS1411. SIGNIFICANCE OF THE STUDY: This review summarizes the factors that influence G-quadruplexes and the functions of the synthetic G-quadruplex, AS1411. It also discusses the use of G-quadruplexes for drug delivery in tumour therapy.

Background The inflammation and oxidative stress (OS) have been considered crucial components of the pathogenesis of depression. Edaravone (EDA), a free radical scavenger, processes strong biological activities including antioxidant, anti-inflammatory and neuroprotective properties. However, its role and potential molecular mechanisms in depression remain unclear. The present study aimed to investigate the antidepressant activity of EDA and its underlying mechanisms. Methods A chronic social defeat stress (CSDS) depression model was performed to explore whether EDA could produce antidepressant effects. Behaviors tests were carried out to examine depressive, anxiety-like and cognitive behaviors including social interaction (SI) test, sucrose preference test (SPT), open field test (OFT), elevated plus maze (EPM), novel object recognition (NOR), tail suspension test (TST) and forced swim test (FST). Hippocampal and medial prefrontal cortex (mPFC) tissues were collected for Nissl staining, immunofluorescence, targeted energy metabolomics analysis, enzyme-linked immunosorbent assay (ELISA), measurement of MDA, SOD, GSH, GSH-PX, T-AOC and transmission electron microscopy (TEM). Western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) detected the Sirt1/Nrf2/HO-1/Gpx4 signaling pathway. EX527, a Sirt1 inhibitor and ML385, a Nrf2 inhibitor were injected intraperitoneally 30 min before EDA injection daily. Knockdown experiments were performed to determine the effects of Gpx4 on CSDS mice with EDA treatment by an adeno-associated virus (AAV) vector containing miRNAi (Gpx4)–EGFP infusion. Results The administrated of EDA dramatically ameliorated CSDS-induced depressive and anxiety-like behaviors. In addition, EDA notably attenuated neuronal loss, microglial activation, astrocyte dysfunction, oxidative stress damage, energy metabolism and pro-inflammatory cytokines activation in the hippocampus (Hip) and mPFC of CSDS-induced mice. Further examination indicated that the application of EDA after the CSDS model significantly increased the protein expressions of Sirt1, Nrf2, HO-1 and Gpx4 in the Hip. EX527 abolished the antidepressant effect of EDA as well as the protein levels of Nrf2, HO-1 and Gpx4. Similarly, ML385 reversed the antidepressant and anxiolytic effects of EDA via decreased expressions of HO-1 and Gpx4. In addition, Gpx4 knockdown in CSDS mice abolished EDA-generated efficacy on depressive and anxiety-like behaviors. Conclusion These findings suggest that EDA possesses potent antidepressant and anxiolytic properties through Sirt1/Nrf2/HO-1/Gpx4 axis and Gpx4-mediated ferroptosis may play a key role in this effect.

A highly efficient iridium(III)-catalyzed arylation coupling of sulfoxonium ylides with arylboronic acids to generate α-aryl ketones has been established for the first time. This protocol proceeded under redox-neutral conditions with a wide substrate scope (56 examples, up to 98% yield), high functional group compatibility, easily accessible starting materials and suitability for late-stage modification of structurally complex drug compounds. Further synthetic applications and elaboration of the product were also accomplished.

In this study, a series of CoCeOx catalysts were prepared by template, solid-state grinding with cobalt sulfate or cobalt acetate as the precursor and the oil bath method for catalytic reduction of...

CaO needs to show high activity to be used as Ca-sorbent and slagging agent. Hydration activity is an important characteristic to evaluate the activity of CaO. In this study, carbide slag from polyvinyl chloride (PVC) industry was utilized as precursor for preparing high activity CaO. The roles of crystallite grain, average pore diameter (APD) and volume fraction of pore

The effects of nickel salts with different anions as the additive on structure and pyrolysis behavior of Hefeng coal were studied by using a thermogravimetric analyzer (TGA) and a fixed-bed reactor. Four Ni2+ salts (Ni(NO3)2, NiCl2, NiSO4 and Ni(C2H3O2)2) with the same mass ratio of Ni2+ to coal being 0.01 were impregnated in demineralized coal (DC), separately. Elemental analysis, FTIR, SEM, simulated distillation and GC–MS were adopted to characterize the structural characteristics of char and the quality of tar. The ion exchange reaction between Ni2+ and hydrogen-containing functional groups in coal occurs, and the surface of Ni-loaded coal samples becomes rough. The anion of nickel salts obviously influences the coal pyrolysis. The total weight loss decreases while the peak intensity of CH4 obviously increases for NiSO4-loaded DC sample. The char yield of all Ni-loaded coal samples increases but the hydrogen content in all char decreases compared with that in DC-Char. The addition of NiCl2 inhibits the evolution of volatiles, resulting in a 19.73% decrease compared with DC. The addition of NiSO4 results in a 4.33% increase of tar yield although gas yield decreases 22.35% owning to the inhibition of CO production. Part of nickel species could be reduced to metal Ni by the produced char and/or reductive gases during coal pyrolysis, but reduction temperature is different for various Ni species. In comparison with other nickel salts, NiSO4 plays a major role to affect the volatile release. Under the influence of these metal species, the percentage of light components in all of the tar increases, especially a 27.32% increase for NiSO4. GC–MS analysis exhibited that long chain alkanes account for about 70% of the tar, while Ni(C2H3O2)2 and NiSO4 could promote the cracking of long chain alkanes. The highest fraction and yield of light tar reveal that NiSO4 is in favor of tar upgrading. This work provides a potential route to control products distribution and tar quality of coal pyrolysis by using appropriated catalyst precursor.

A single genome gives rise to diverse tissues through complex epigenomic mechanisms, including N6-methyladenosine (m6A), a widespread RNA modification that is implicated in many biological processes. Here, to explore the global landscape of m6A in human tissues, we generated 21 whole-transcriptome m6A methylomes across major fetal tissues using m6A sequencing. These data reveal dynamic m6A methylation, identify large numbers of tissue differential m6A modifications and indicate that m6A is positively correlated with gene expression homeostasis. We also report m6A methylomes of long intergenic non-coding RNA (lincRNA), finding that enhancer lincRNAs are enriched for m6A. Tissue m6A regions are often enriched for single nucleotide polymorphisms that are associated with the expression of quantitative traits and complex traits including common diseases, which may potentially affect m6A modifications. Finally, we find that m6A modifications preferentially occupy genes with CpG-rich promoters, features of which regulate RNA transcript m6A. Our data indicate that m6A is widely regulated by human genetic variation and promoters, suggesting a broad involvement of m6A in human development and disease.

CaO-containing carbon pellets (CCCP) was prepared by mixing carbide slag (Ca(OH)2) and powdered char to produce CaC2, achieving the recycling of carbide slag during CaC2 production process. The thermal strength of CCCP was the focus of most attention when employing arc furnaces as reactors for CaC2 production in industry. To improve the thermal strength of CCCP, H3PO4 was used as a binder in this study. The results indicated that Ca3(PO4)2 reacted by H3PO4 and Ca(OH)2 could help refine the average particle sizes of CaO, resulted in a relatively uniform pore diameter distribution of CCCP with low porosity, therefore improving the thermal strength of CCCP. When H3PO4 content was more than 8 wt%, some over-sintering and melting structure for CaO particles appear, and thus resulting in the decrease in thermal strength of CCCP. The experimental results show that CCCP with 3% H3PO4 has the best thermal strength at 1100 °C. The non-isothermal shrinkage kinetics of CCCP indicated that the addition of 3% H3PO4 reduced the apparent activation energy of sintering reactions and accelerated the sintering of CaO particles in CCCP. Furthermore, the addition of H3PO4 has a positive effect on the formation of CaO sintered necks, enhancing the strength of CCCP.

Preeclampsia (PE) is a life-threatening disease of pregnant women associated with severe hypertension, proteinuria, or multi-organ injuries. Mitochondrial-mediated placental oxidative stress plays a key role in the pathogenesis of PE. However, the underlying mechanism remains to be revealed. Here, we identify Rnd3, a small Rho GTPase, regulating placental mitochondrial reactive oxygen species (ROS). We showed that Rnd3 is down-regulated in primary trophoblasts isolated from PE patients. Loss of Rnd3 in trophoblasts resulted in excessive ROS generation, cell apoptosis, mitochondrial injury, and proton leakage from the respiratory chain. Moreover, Rnd3 overexpression partially rescues the mitochondrial defects and oxidative stress in human PE primary trophoblasts. Rnd3 physically interacts with the peroxisome proliferators-activated receptor γ (PPARγ) and promotes the PPARγ-mitochondrial uncoupling protein 2 (UCP2) cascade. Forced expression of PPARγ rescues deficiency of Rnd3-mediated mitochondrial dysfunction. We conclude that Rnd3 acts as a novel protective factor in placental mitochondria through PPARγ-UCP2 signaling and highlight that downregulation of Rnd3 is a potential factor involved in PE pathogenesis.

Herein, we report a neutral iridium complex, [Ir(4-(2-pyridinyl)benzaldehyde)2(acetylacetone)] (Ir-ER), with viscosity-responsive phosphorescent emission intensity and lifetime. Quantitative measurement by two-photon phosphorescent lifetime imaging shows that the viscosity of ER increases significantly in the process of erastin-induced ferroptosis. Our work provides an effective strategy for quantitative measurement of the micro-environmental alternations of subcellular organelles during a specific cell death process.

We show for the first time that the neuropeptide orexin modulates pupillary light response, a non-image-forming visual function, in mice of either sex. Intravitreal injection of the orexin receptor (OXR) antagonist TCS1102 and orexin-A reduced and enhanced pupillary constriction in response to light, respectively. Orexin-A activated OX1Rs on M2-type intrinsically photosensitive retinal ganglion cells (M2 cells), and caused membrane depolarization of these cells by modulating inward rectifier potassium channels and nonselective cation channels, thus resulting in an increase in intrinsic excitability. The increased intrinsic excitability could account for the orexin-A-evoked increase in spontaneous discharges and light-induced spiking rates of M2 cells, leading to an intensification of pupillary constriction. Orexin-A did not alter the light response of M1 cells, which could be because of no or weak expression of OX1Rs on them, as revealed by RNAscopein situhybridization. In sum, orexin-A is likely to decrease the pupil size of mice by influencing M2 cells, thereby improving visual performance in awake mice via enhancing the focal depth of the eye's refractive system.SIGNIFICANCE STATEMENTThis study reveals the role of the neuropeptide orexin in mouse pupillary light response, a non-image-forming visual function. Intravitreal orexin-A administration intensifies light-induced pupillary constriction via increasing the excitability of M2 intrinsically photosensitive retinal ganglion cells by activating the orexin receptor subtype OX1R. Modulation of inward rectifier potassium channels and nonselective cation channels were both involved in the ionic mechanisms underlying such intensification. Orexin could improve visual performance in awake mice by reducing the pupil size and thereby enhancing the focal depth of the eye's refractive system.

Background: Fibrosis is an important histological change occurring in preeclamptic placentas, and might depends on the excess deposition of collagen I. However, the role of fibrotic placentas and collagen I in the pathogenesis of preeclampsia remains unclear. Methods: Collagen deposition and the expression of Collagen I in human placentas were analysed by Masson staining, Sirius red staining and western blotting. The role of collagen I in preeclampsia pathogenesis was studied in C57BL/6 mice.HTR-8/SVneo cells were used to investigate the mechanisms underlying the effects of collagen I in trophoblasts by transcriptome sequencing and pharmacological agonists. Finding: Human preeclamptic placentas exhibited a higher degree of fibrosis in stem villi and terminal villi than normal placentas, and were characterized by collagen I deposition. In vivo, a single injection of collagen I on gestational day 0.5 led to an increase in systolic pressure of pregnant mice from gestational day 4.5 -17.5, to a decrease in weight and number of viable embryos, and to enhanced placental collagen I expression, and degree of fibrosis compared with control mice. In vitro, collagen I attenuated the proliferation and invasion of HTR-8SV/neo cells. This effect could be reversed by treatment with agonist s of ERK and β-catenin. Transcriptome sequencing demonstrated that pathways related to cell proliferation and invasion were significantly downregulated in HTR-8/SVneo cells. Interpretation: Collagen I induced preeclampsia-like symptoms by suppressing the proliferation and invasion of trophoblasts through inhibition of the ERK phosphorylation and WNT/β-catenin signalling pathways. Funding: National Natural Science Foundation of China and Guangdong Province. Declaration of Interest: The authors declare no conflicts of interest. Ethical Approval: The collection of placentas was approved by the Ethics Committee of Nanfang Hospital（NFEC-2017-055）. All participants gave written consent prior to donating their placenta.

Correlated spontaneous activity in the developing retina (termed &ldquo, retinal waves&rdquo, ) plays an instructive role in refining neural circuits of the visual system. Depolarizing (ON) and hyperpolarizing (OFF) starburst amacrine cells (SACs) initiate and propagate cholinergic retinal waves. Where cholinergic retinal waves stop, SACs are thought to be driven by glutamatergic retinal waves initiated by ON-bipolar cells. However, the properties and function of cholinergic and glutamatergic waves in ON- and OFF-SACs still remain poorly understood. In the present work, we performed whole-cell patch-clamp recordings and Ca2+ imaging from genetically labeled ON- and OFF-SACs in mouse flat-mount retinas. We found that both SAC subtypes exhibited spontaneous rhythmic depolarization during cholinergic and glutamatergic waves. Interestingly, ON-SACs had wave-induced action potentials (APs) in an age-dependent manner, but OFF-SACs did not. Simultaneous Ca2+ imaging and patch-clamp recordings demonstrated that, during a cholinergic wave, APs of an ON-SAC appeared to promote the dendritic release of acetylcholine onto neighboring ON- and OFF-SACs, which enhances their Ca2+ transients. These results advance the understanding of the cellular mechanisms underlying correlated spontaneous activity in the developing retina.

Basing on the simplest hydrothermal system containing deionized water, hexa-ammonium molybdate, and thiourea, hydrothermal mechanism on preparation of MoS2 was studied by DFT calculation. Hydrothermal process was divided into four steps which covered ionization equilibrium, the hydrolysis of CS(NH2)2, the formation of intermediates, and the formation of MoS2. Ionization equilibrium occurs at normal condition and determines the existence of Mo in the form of molybdic acid. Thiourea hydrolysis is rate-determining step in the process of hydrothermal which contains 10 elementary reactions. The formation of intermediates includes hydrogen transfer, dehydration, and vulcanization three steps which contain 18 elementary reactions, and the energy barrier of vulcanization is the highest. The formation of MoS2 is divided into two steps, the first step is that MoO(OH)(SH)3.H2O reacts with MoO (SH)4.H2O to form layer MoS2, and the second step is a very fast process that can affect the morphology of the products.

Aims Numerous studies suggest that excessive maternal inflammation and defective extravillous trophoblast (EVT) invasion could contribute to the development of preeclampsia (PE), but the underlying mechanism remains unclear. Some evidence suggests that CyPA is elevated in PE. This research aims to investigate the effect of recombinant human CyPA on trophoblast migration and invasion both in vitro and in vivo. Materials and methods We detected the expression and localization of CyPA in human placenta and explored the effects of CyPA on cell migration and invasion on HTR8/SVneo cell. Additionally, the expression levels of matrix metalloproteinase (MMP)-2/9 and molecules in the p38/ERK/JNK signaling pathway were detected. We established a mouse model by injecting pregnant mice with recombinant human CyPA and measured blood pressure, albumin/creatinine ratio, fetal and placenta weight of mice. Moreover, we examined the placental histology and MMP-2/9 and p38/ERK/JNK expression. Key findings Our results showed that CyPA inhibited the migration and invasion of HTR8/SVneo cells in a dose-dependent manner, decreasing the expression of matrix metalloproteinase (MMP)-2/9 and molecules in the p38/ERK/JNK signaling pathway. Silencing CyPA could reverse the above effects. Moreover, CyPA could induce PE-like features in pregnant mice and disrupt the structure of the mouse placenta by reducing the junctional zone area. CyPA attenuated the trophoblast invasiveness in mice placenta by downregulating MMP-2/9 expression and p38/ERK/JNK pathway activity. Significance We proposed that CyPA could inhibit trophoblast migration and invasion both in vitro and in vivo, which was involved in PE development.

A degradative solvent extraction at around 350°C for low-rank coal or biomass wastes upgrading and fractionation was proposed in our previous work. The extraction yield of low-rank coal is relatively lower than that of biomass. In this work the blends of low-rank coal and biomass were treated by this method at 350°C to investigate the interaction between them. The results showed that the yields and elemental compositions of the extracts obtained from the blends were slight different to the calculated results, which were calculated by assuming that there was no interaction between the coal and biomass. The slight promotion of yield was judged to be caused by the catalytic action of the minerals in the coal for thermal decomposition of biomass. It was worth to note that the elemental composition, molecular weight distribution, chemical structure, thermal decomposition behavior and thermoplastic behavior of the extracts obtained from low-rank coal, biomass and their blend, were rather similar to each other, independent of the properties of the raw feedstocks. Overall, the interaction between low-rank coal and biomass during the extraction was not significant. On the other hand, the proposed degradative solvent extraction method was fit not only by single low-rank coal and biomass but also by their blends to produce the product having similar physicochemical properties. This implied that an industrial system of degradative solvent extraction can use coal, biomass or their blends as feedstock at the same time without modification or adjustment.

Purpose Experimental access to specific cell subtypes is essential for deciphering the complexity of retinal networks. Here, we characterized the selective labeling, caused by ectopic transgene expression, of two atypical retinal neurons in the ChAT-Channelrhodopsin-2 (ChR2)-EYFP mouse. Methods Retinal sections and flat-mounts were prepared for double-staining immunohistochemistry with antibodies against EYFP and various neuronal markers. Sagittal/coronal brain slices were made to visualize EYFP signals in central nuclei. Whole-cell recordings were conducted to test the functionality of ChR2. Results Two populations of EYFP-positive retinal cells were observed. The inner nuclear layer (INL)-located one (type I cell) distributed regularly throughout the entire retina, whereas the ganglion cell layer (GCL)-residing one (type II cell) was restricted ventrally. None of them was cholinergic, as evidenced by the complete absence of ChAT immunoreactivity. Type I cells were immunolabeled by the amacrine marker syntaxin. However, the vast majority of them were neither positive to GABA/GAD65, nor to GlyT1/glycine, suggesting that they were non-GABAergic non-glycinergic amacrine cells (nGnG ACs), which was confirmed by double-labeling with the nGnG AC marker PPP1R17. Type II cells were immunopositive to melanopsin, but not to Brn3a or Brn3b. They possessed dendrites stratifying in the outermost inner plexiform layer (IPL) and axons projecting to the suprachiasmatic nucleus (SCN) rather than the olivary pretectal nucleus (OPN), suggesting that they belonged to a Brn3b-negative subset of M1-type intrinsically photosensitive retinal ganglion cells (ipRGCs). Glutamatergic transmission-independent photocurrents were elicited in EYFP-positive cells, indicating the functional expression of ChR2. Conclusions The ChAT-ChR2-EYFP retina exhibits ectopic, but functional, transgene expression in nGnG ACs and SCN-innervating M1 ipRGCs, thus providing an ideal tool to achieve efficient labeling and optogenetic manipulation of these cells.

Fruit abscission is largely governed by carbohydrate supply, and carbohydrate shortage intensifies fruit abscission. Understanding cues from the starving fruit that activate the abscission zone (AZ) is an intriguing research subject and important for control fruit abscission. In this study, starvation stress generated by girdling and defoliating the bearing shoots was used to explore the cues from the starving fruit that triggers abscission in longan. The starving fruit abscised quickly within 5 days. However, removing the starving fruit induced even faster AZ activation with greater ethylene production in the pedicel. Abscission of the defruited pedicel was strongly suppressed by IAA, slightly by ethylene action inhibitor, silver thiosulfate (STS), but not by GA3 or zeatin. Both IAA and ABA concentrations in the starving fruit and the pedicel were significantly reduced compared with the control. IAA exudation from the starving fruit was significantly lower, while IAA oxidase activity in the fruit was higher. The activity of plasma membrane H+-ATPase (PM H+-ATPase) in the fruit and the pedicel was not significantly affected by carbohydrate starvation, while that of PM Ca2+-ATPase in both organs was significantly reduced by starvation. The results suggested that the starving fruit seems not send abscission-promoting signal e.g. ABA or ethylene, but sends weakened abscission-suppressing signal, IAA, to the AZ. The weakened capacity of starving fruit to export IAA is related to increase in IAA deactivation and reduction in PM Ca2+-ATPase activity. The reduced IAA in the AZ leads to increased sensitivity to ethylene synthesized in situ in the pedicel, which activates the AZ under starvation.

An unusual hybrid palladium catalyst containing an anionic chiral CoIII complex and a chiral phosphoramidite ligand shows a high capacity for catalyzing asymmetric thioamide-directed C(sp3 )-H arylation and delivers excellent yield and enantioselectivity (up to 99 % yield, 99 % ee). Significant synergy between the chiral ligand and the anion in terms of stereochemical control was observed. Mechanistic investigations have revealed both the nature of the C-H activation and the origin of the enantioselectivity.

Dayan lignite (DL) was subjected to thermal dissolution sequentially with cyclohexane, acetone and methanol to obtain three filtrates. The filtrates were characterized by Fourier transform infrared spectroscopy, gas chromatography/mass spectrometry (GC/MS), and time-of-flight mass spectrometry (TOF-MS) equipped with atmospheric pressure photoionization (APPI), electrospray ionization (ESI) or direct analysis in real time (DART) to understand the structural features of DL. Aliphatic hydrocarbons, furans and alcohols were enriched in the filtrate of cyclohexane, acetone and methanol, respectively, according to the data of GC/MS. One ring aromatics was also identified by GC/MS as major species in the three filtrates. Both GC/MS and APPI-MS can well analyze compounds with low polarity, but APPI-TOF-MS in this work successfully characterized polycyclic aromatics and extended the measurement range (molecular weight and ring size) of GC/MS. ESI-TOF-MS is suitable to analyze polar compounds in coal. Data from ESI-TOF-MS indicated that heteroatom compounds including non-aromatics and aromatics with 1-2 rings are the major polar components in DL. As an ambient MS ionization method, DART shortened the analysis time without sample pretreatment and more aromatics over 4 rings were identified by DART-TOF-MS. Characterization of the complex coal filtrates with multiple mass spectrometers provided a full view of the molecular information of DL.

Orexin-A, -B play a crucial role in arousal and feeding by activating two G-protein-coupled receptors: orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R). Orexins, along with orexin receptors, are expressed in retinal neurons, and they have been shown to differentially modulate excitatory AMPA receptors of amacrine and ganglion cells in the inner retina. In this work we report that orexin-B modulates the activity of rod bipolar cells (RBCs) located in the outer retina of rat. Intravitreal injection of orexin-B increased the amplitude of the scotopic electroretinographic b-wave, a reflection of RBC activity, recorded in vivo. Patch clamp recordings in rat retinal slices showed that orexin-B did not change glutamatergic excitatory component of the RBC response driven by photoreceptors. Effects of orexin-B on GABA receptor-mediated synaptic transmission of RBCs were then examined. In retinal slice preparations orexin-B suppressed GABA receptor-mediated inhibitory postsynaptic currents of RBCs in the inner plexiform layer. Furthermore, using whole-cell recordings in isolated RBCs it was shown that orexin-B suppressed GABAC receptor-, but not GABAA receptor-, mediated currents of the RBCs, an effect that was blocked by OX1R and OX2R antagonists. The orexin-B-induced inhibition of GABAC currents was likely mediated by a Gi/o/PC-PLC/Ca2+-independent PKC signaling pathway, as such inhibition was absent when each step of the above-pathway was blocked with GDP-β-S/pertussis toxin (for Gi/o), D609 (for PLC), bisindolylmaleimide IV (for PKC)/rottlerin (for PKCδ), respectively. The orexin-B-induced potentiation of RBC activity may improve visual acuity and contrast sensitivity of the animal during the dark period (wake phase).

Objective Intracellular protein fibroblast growth factor 13 (FGF13) is highly expressed in human placenta, although its biological function remains unexplored. The aims of this study were to investigate the expression of FGF13 in placentae with early-onset preeclampsia (PE) and the associated mechanisms in the pathophysiology of PE. Methods The expression levels of FGF13 in placentae obtained from patients with early-onset PE and normal pregnancies were assessed using immunofluorescent staining, Western blot assays and quantitative PCR. We knocked down FGF13 in trophoblast cell lines BeWo and HTR8/SVneo, and analyzed cell permeability. Clinical trophoblast cell-cell junctions were identified by cytokeratin 7 (CK7) immunofluorescent staining of human placental sections. The expressions of FGF13 were manipulated in BeWo and HTR8/SVneo cell lines, and the expressions of E-cadherin were quantified by reverse transcription followed by quantitative PCR, Western blot assays and immunofluorescent staining. The expressions of FGF13 and E-cadherin were further confirmed in the isolated human primary trophoblasts. Results Downregulation of FGF13 along with trophoblast disarrangement were found in human placentae with early-onset PE. In trophoblast cell lines decreased FGF13 expression resulted in increased cell permeability and decreased E-cadherin expression. The FGF13 insufficiency-mediated loss of E-cadherin was further confirmed in the human villous trophoblasts isolated from PE patients. Conclusion FGF13 was downregulated in human placentae with early-onset PE. FGF13 played an important role in maintaining placental trophoblast permeability via the modulation of E-cadherin.

Direct coal liquefaction (DCL) can be highly promoted by catalysts due to the acceleration of hydrogen activation. There are two pathways of activation for H2 during the process of DCL. One is that H2 dissolves in the liquid phase and then transfers to coal after splitting (molecular hydrogen), and the other is dissolved H2 is hydrogenated with solvent and then transferred from solvent to coal (transfer hydrogen). In addition, hydrogen in the solvent molecules can be supplied to coal (solvent hydrogen). The effects of two catalysts, Fe2O3 and MoS2, on the activation of molecular hydrogen, transfer hydrogen, and solvent hydrogen during DCL were investigated. Herein, we conducted a series of experiments, including DCL with H2-decalin, DCL with N2-tetralin, tetralin dehydrogenation, naphthalene hydrogenation, and DCL with H2-tetralin. The catalyst and products were characterized by XRD, GC, GC-MS, 1H NMR and TG. Quantum chemistry reveals the catalyst effect on hydrogen activation. The catalytic performance and different hydrogen consumption reveal that the Fe2O3 catalyst primarily activates molecular hydrogen, and MoS2 activates all three kinds of hydrogen. This work not only reveals the catalyst effect on hydrogen activation but also gives light to the design of an appropriate and effective catalyst for DCLs.

G-triplexes have recently been identified as a new kind of DNA structures. They perhaps possess specific biological and chemical functions similar as identified G-quadruplex but can be formed by shorter G-rich sequences with only three G-tracts. However, until now, limited G-triplexes sequences have been reported, which might be due to the fact that their stability is one of the biggest concerns during their functional studies and application research. Herein, we found a G-rich sequence (5'-TGGGTAGGGCGGG-3') which can form a stable G-triplex (Tm ∼ 60 °C) at room temperature. The stable G-triplex can combine with thioflavin T and function as an efficient fluorescence light-up probe. Comparing with the traditional G-quadruplex based probe, this triplex based probe was easy to be controlled and excited. Finally, the probe was successfully applied into constructing a label-free molecular beacon for miRNA detection. Taking advantage of these abilities of the G-triplex based fluorescent probe, the challenges faced during designing G-rich sequences based fluorescent biosensors can be efficiently solved. These findings provide important information for the future application of G-triplex.

In this paper, a novel process for integrating lignite pyrolysis volatiles upgrading with methane dry reforming (MDR) was carried out over Ni-Ce bimetallic catalysts in a fixed-bed reactor. The effects of Ni-xCe/Y catalysts on CH4/CO2 conversions, products distributions and tar compositions were investigated. The results indicated that the Ni-Ce bimetallic catalysts could significantly decrease coke deposit and obviously improve tar components, especially for light aromatics (LAs). The Ni-7Ce/Y catalyst exhibited better catalytic performance in pyrolysis volatiles upgrading in the respects of high light tar yield, selectivity to LAs, the resistance of coke deposition and the removal of heteroatoms in tar. The resultant high-quality tar could be attributed to the moderate acidity with suitable ratio of Bronsted/Lewis acid sites, better dispersion and strong interaction of Ni and Ce species on supports. The 2H NMR and GC–MS results confirmed that methane dry reforming participated in the tar formation, especially aromatic rings. This work could provide more insights into catalytic upgrading of lignite pyrolysis volatiles and sufficient utilization of CH4/CO2 greenhouse gases.

Ectopic transgene expression in the retina has been reported in various transgenic mice, indicating the importance of characterizing retinal phenotypes. We examined transgene expression in the VGAT-ChR2-EYFP mouse retina by fluorescent immunohistochemistry and electrophysiology, with special emphasis on enhanced yellow fluorescent protein (EYFP) localization in retinal neuronal subtypes identified by specific markers. Strong EYFP signals were detected in both the inner and outer plexiform layers. In addition, the ChR2-EYFP fusion protein was also expressed in somata of the great majority of inhibitory interneurons, including horizontal cells and GABAergic and glycinergic amacrine cells. However, a small population of amacrine cells residing in the ganglion cell layer were not labeled by EYFP, and a part of them were cholinergic ones. In contrast, no EYFP signal was detected in the somata of retinal excitatory neurons: photoreceptors, bipolar and ganglion cells, as well as Müller glial cells. When glutamatergic transmission was blocked, bright blue light stimulation elicited inward photocurrents from amacrine cells, as well as post-synaptic inhibitory currents from ganglion cells, suggesting a functional ChR2 expression. The VGAT-ChR2-EYFP mouse therefore could be a useful animal model for dissecting retinal microcircuits when targeted labeling and/or optogenetic manipulation of retinal inhibitory neurons are required.

Purpose In the industrialized production of mushrooms usually only one flush of fruitbody is harvested, so that nutrients and energy in the substrate is not fully exploited. In this study, the spent Pleurotus eryngii substrate was recycled for the cultivation of Agrocybe chaxingu under ambient temperature. Method Six formulae were tested: (1) Control: 98% spent substrate, 1% sucrose, 1% lime; (2) Control + 10% wheat bran; (3) Control + 20% wheat bran; (4) Control + 10% T. molitor feces; (5) Control + 20% T. molitor feces; (6) Control + 10% wheat bran + 10% T. molitor feces. Results Two flushes of fruitbody were harvested, the control substrate resulted in a biological efficiency of 40.42%; the formulae with supplementation of 10% wheat bran, 20% wheat bran and 10% T. molitor feces significantly increased biological efficiency to 52.50, 54.61 and 51.56%, respectively, and supplementation of 20% T. molitor feces, or 10% wheat bran plus 10% feces further significantly increased biological efficiency to 62.95 and 61.10%, respectively. All supplemented substrates had significantly higher cellulose and laccase activity than the Control (cellulase 0.10 U/g; laccase 41.00 U/g), which were 10% wheat bran (0.15 U/g; 72.67 U/g), 10% T. molitor feces (0.17 U/g; 98.33 U/g), 20% wheat bran (0.22 U/g; 76.00 U/g), 20% T. molitor feces (0.27 U/g; 87.00 U/g), 10% wheat bran plus 10% T. molitor feces (0.25 U/g; 97.67 U/g), respectively. Conclusion Spent Pleurotus eryngii substrate was promising for cultivation of Agrocybe chaxingu, especially when supplemented with 20% T. molitor feces, or with 10% T. molitor feces plus 10% wheat bran.

Micro-arc oxidation coatings were fabricated on 7E04 aluminum drillpipes materials in Na 2 SiO 3 -NaOH electrolyte system containing 3.0 g/L SiC particles at different current density (1, 5, 10, 15 and 20 A/dm 2 ). The oxidation voltage, coating thickness, surface morphologies, surface micro-hardness, phase composition and potentiodynamic polarization curves of the MAO coatings were investigated. The results showed that the oxidation voltage increased and the coatings thickened with the increment of current density. The coating surface morphologies got coarser gradually which led to the reduction of the surface micro-hardness. The phase composition of the coatings consisted of SiO 2 because of the oxidation of SiC particles and the corrosion resistance of the coatings increased slightly.

DNA polymorphism exerts a fascination on a large scientific community. Without crystallographic structural data, clarification of the binding modes between G-quadruplex (G4) and ligand (complex) is a challenging job. In the present work, three porphyrin compounds with different flexible carbon chains (arms) were designed, synthesized and characterized. Their binding, folding and stabilizing abilities to human telomeric G4 DNA structures were comparatively researched. Positive charges at the end of the flexible carbon chains seem to be favorable for the DNA-porphyrin interactions, which were evidenced by the spectral results and further confirmed by the molecular docking calculations. Biological function analysis demonstrated that these porphyrins show no substantial inhibition to Hela, A549 and BEL 7402 cancer cell lines under dark while exhibit broad inhibition under visible light. This significantly enhanced photocytotoxicity relative to the dark control is an essential property of photochemotherapeutic agents. The feature of the flexible arms emerges as critical influencing factors in the cell photocytotoxicity. Moreover, an ROS-mediated mitochondrial dysfunction pathway was suggested for the cell apoptosis induced by these flexible-armed porphyrins. It is found that the porphyrins with positive charges located at the end of the flexible arms represent an exciting opportunity for photochemotherapeutic anti-cancer drug design.

Patrinia scabiosaefolia Fisch. (PSF), a well-known traditional Chinese medicine, has been demonstrated to show therapeutic effects on inflammatory bowel disease. In this study, a rapid and sensitive method using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) was developed for identification of the major constituents in PSF. The separation analysis was performed on Waters Acquity UPLC system, and the accurate mass of molecules and their fragment ions were determined by Q-TOF-MS. Thirty-one constituents, including triterpenoids, iridoids, flavonoids, and organic acids were detected and tentatively deduced on the basis of their element compositions, tandem mass spectrometry (MS/MS) data, and relevant literatures. Twelve constituents were discovered for the first time in PSF. The results demonstrated that hederagenin-type and oleanolic acid-type saponins were the main constituents of PSF. Our work provides a certain foundation for further quantitation of ma...

Introduction Sepsis can cause decreased diaphragmatic contractility. Intracellular calcium as a second messenger is central to diaphragmatic contractility. However, changes in intracellular calcium concentration ([Ca2+]) and the distribution and co-localization of relevant calcium channels [dihydropyridine receptors, (DHPRα1s) and ryanodine receptors (RyR1)] remain unclear during sepsis. In this study we investigated the effect of changed intracellular [Ca2+] and expression and distribution of DHPRα1s and RyR1 on diaphragm function during sepsis. Methods We measured diaphragm contractility and isolated diaphragm muscle cells in a rat model of sepsis. The distribution and co-localization of DHPRα1s and RyR1 were determined using immunohistochemistry and immunofluorescence, whereas intracellular [Ca2+] was measured by confocal microscopy and fluorescence spectrophotometry. Results Septic rat diaphragm contractility, expression of DHPRα1s and RyR1, and intracellular [Ca2+] were significantly decreased in the rat sepsis model compared with controls. Discussion Decreased intracellular [Ca2+] coincides with diaphragmatic contractility and decreased expression of DHPRα1s and RyR1 in sepsis. Muscle Nerve 56: 1128–1136, 2017

To analyze the amino acids (AA) and acyl carnitine (AC) profiles in dry blood spot (DBS) specimens of low birth weight (LBW), preterm birth (PTB), and small for gestational age (SGA), and to compare the concentration difference of AA and AC with those without above.This is a retrospectively study. Eight thousand nine hundred and seventy-nine uncomplicated pregnant newborns were enrolled into the study. DBS were collected on the third day of life, and concentrations of 11 types of AA, free carnitine and 30 types of AC were detected by using high-performance liquid chromatography tandem mass spectrometry (HPLC-MS). Shapiro-Wilk test and Kruskal-Wallis rank test were applied in statistical analysis.Concentrations of most AA and AC in infants born in SGA were significantly higher than those in non-SGA group, while lower in LBW and PTB groups than those in non-LBW and non-PTB groups (p 0.05).The difference of concentration of AA and AC in the subgroups suggested there may be a dysutilization of AA and AC in SGA, but an inborn insufficient of AA and AC in LBW and PTB neonates.

Tripterygium hypoglaucum(Levl.) Hutch (THH) shows well clinical effect on rheumatoid arthritis (RA), but the active ingredients and molecular mechanisms remain unclear. This work was designed to explore these issues by network pharmacology. Compounds from THH were gathered by retrieving literatures. Compound-related and RA-related genes were identified using databases, and the overlapping genes were identified by Venn diagram. The active ingredients and genes of THH against RA were confirmed by dissecting interactions between overlapping genes and compounds using Cytoscape. SystemsDock website was used to further verify the combining degree of key genes with active ingredients. Pathway enrichment analysis was performed to decipher the mechanisms of THH against RA by Database for Annotation, Visualization and Integrated Discovery. A total of 123 compounds were collected, and 110 compounds-related and 1871 RA-related genes were identified, including 64 overlapping genes. The target genes and active ingredients of THH against RA comprised 64 genes and 17 compounds, the focus of which was PTGS2, triptolide, and celastrol. SystemsDock website indicated that the combing degree of PTGS2 with triptolide or celastrol was very good. The mechanisms of THH against RA were linked to 31 signaling pathways, and the key mechanism was related to inhibition of inflammation response through inactivating TNF and NF-kappa B signaling pathways. This work firstly explored the active ingredients and mechanisms of THH against RA by network pharmacology and provided evidence to support clinical effects of THH on RA.