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Angiogenesis inhibitors targeting the VEGF signaling pathway are developed into drugs for the treatment of vaious diseases, such as cancer, rheumatoid arthritis, and age-related macular degeneration. Recent studies have revealed that oleanolic acid (OA), a natural pentacyclic triterpenoid, inhibited the VEGF/VEGFR2 signaling pathway and angiogenesis in HUVECs, which may represent an attractive VEGF inhibitor. In this paper, rational structural modification towards OA was performed in order to improve its inhibitory effects aganist VEGF and anti-angiogenesis potential. As a result, a series of novel OA derivatives, possessing α,β-unsaturated ketone system in ring A and amide functional group at C-28, were prepared and evaluated for cytotoxicity and their ability to inhibit VEGF-induced abnormal proliferation of HUVECs. The results showed that two promising derivatives, OA-1 and OA-16, exhibited no in vitro cytotoxicity against HUVECs but showed more potent inhibitory activity against VEGF-induced proliferation and angiogenesis in HUVECs, compared with OA. The results of Western blot indicated that OA-1 and OA-16 inhibited VEGF-induced VEGFR2 activation. Furthermore, small interfering RNA experiments were performed to confirm that both compounds inhibited VEGF-induced angiogenesis via VEGFR2. Thus, the present study resulted in the discovery of new promising OA-inspired VEGF inhibitors, which can serve as potential lead compounds for the treatment of angiogenesis-related diseases.

A kind of organic/inorganic composite material composed of waterborne polyurethane and sepiolite was prepared in this work. Sepiolite was organically modified by three kinds of silane coupling agents, and then compounded with waterborne polyurethane through layer-by-layer method in order to prepare composite materials. X-ray diffraction (XRD) and Fourier transform infrared (FTIR) show the crystal and chemistry structure of sepiolite samples, and confirmed the preparation of organic sepiolite. Scanning electron microscope (SEM) and energy dispersive X-ray spectroscopy (EDS) showed the surface microstructure and elemental content of sepiolite and organic sepiolite, and was consistent with the XRD results. Transmission electron microscope (TEM) examination of waterborne polyurethane composites surfaces showed that sepiolite particles were regularly dispersed in the waterborne polyurethane matrix. Thermal resistance of waterborne polyurethane composites was determined by thermogravimetry analyzer (TG) and derivative thermogravimetry analyzer (DTG), differential scanning calorimetry (DSC), gas chromatography (GC), and mass chromatography (MS). Mechanical behavior was examined by tensile strength tester, showed higher break strength than that of the control waterborne polyurethane. Therefore, organically modified sepiolite was considered to be a kind of wonderful inorganic material that could be used to improve the thermal stability and mechanical property of polymer.

Purpose To evaluate the effects of manganese superoxide dismutase (Mn-SOD) from thermophilic bacterium HB27 (name as Tt-SOD) on chemical cystitis. Methods Control and experimental rats were infused by intravesical saline or hydrochloric acid (HCl) on the first day of the experiments. Saline, sodium hyaluronate (SH) or Tt-SOD were infused intravesically once a day for three consequent days. On the fifth day, the rats were weighted and sacrificed following a pain threshold test. The bladder was harvested for histological and biochemical analyses. Results Tt-SOD could reduce the bladder index, infiltration of inflammatory cells in tissues, serum inflammatory factors and SOD levels, mRNA expression of inflammatory factors in tissues, and increase perineal mechanical pain threshold and serum MDA and ROS levels in HCl-induced chemical cystitis. Furthermore, Tt-SOD alleviated inflammation and oxidative stress by the negative regulation of the NF-κB p65 and p38 MAPK signaling pathway. Conclusions Intravesical instillation of Tt-SOD provides protective effects against HCl-induced cystitis.

With the development of coal chemical industry, large amounts of naphthalene and n-butene are produced, and converting them into high value-added products through alkylation has gained particular importance and interest. In this work, liquid coordination complexes (LCCs) were used as acid catalysts for the first time in the naphthalene alkylation reaction under mild conditions to obtain multi-butylnaphthalenes with high yield. Various reaction conditions were thoroughly investigated. The LCC consisting of urea and AlCl3 showed excellent catalytic performance under optimal reaction conditions, giving 100% conversion of naphthalene and 99.66% selectivity towards multi-butylnaphthalenes. Combining the catalyst properties and catalytic results, a plausible reaction mechanism was proposed. The lubricating properties of the synthesized products were investigated for their potential application as lubricating base oils. The synthesized multi-butylnaphthalenes showed comparable physicochemical properties and tribological performances as the commercial cycloalkyl base oil.

STUDY QUESTIONIs the protein l-arginine methyltransferase 3 (PRMT3)/asymmetrical dimethylarginine (ADMA)/nitric oxide (NO) pathway involved in the development of recurrent miscarriage (RM), and what is the potential mechanism?SUMMARY ANSWERElevated levels of PRMT3 and ADMA inhibit NO formation in the decidua, thereby impairing the functions of trophoblast cells at the maternal–foetal interface.WHAT IS KNOWN ALREADYDecreased NO bioavailability is associated with RM. ADMA, an endogenous inhibitor of nitric oxide synthase (NOS), is derived from the methylation of protein arginine residues by PRMTs and serves as a predictor of mortality in critical illness.STUDY DESIGN, SIZE, DURATIONA total of 145 women with RM and 149 healthy women undergoing elective termination of an early normal pregnancy were enrolled. Ninety-six female CBA/J, 24 male DBA/2 and 24 male BALB/c mice were included. CBA/J × DBA/2 matings represent the abortion group, while CBA/J × BALB/c matings represent the normal control group. The CBA/J pregnant mice were then categorised into four groups: (i) normal + vehicle group (n = 28), (ii) abortion + vehicle group (n = 28), (iii) normal + SGC707 (a PRMT3 inhibitor) group (n = 20) and (iv) abortion + SGC707 group (n = 20). All injections were made intraperitoneally on Days 0.5, 3.5 and 6.5 of pregnancy. Decidual tissues were collected on Days 8.5, 9.5 and 10.5 of gestation. The embryo resorption rates were calculated on Day 9.5 and Day 10.5 of gestation.PARTICIPANTS/MATERIALS, SETTING, METHODSNO concentration, ADMA content, NOS activity, expression levels of NOS and PRMTs in decidual tissues were determined using conventional assay kits or western blotting. PRMT3 expression was further analysed in decidual stromal cells, macrophages and natural killer cells. A co-culture system between decidual macrophages (DMs) and HTR-8/SVneo trophoblasts was constructed to study the roles of the PRMT3/ADMA/NO signalling pathway. Trophoblast apoptosis was analysed via Annexin V-fluorescein isothiocyanate/propidium iodide staining. CBA/J × DBA/2 mouse models were used to investigate the effects of SGC707 on embryo resorption rates.MAIN RESULTS AND THE ROLE OF CHANCEOur results show that NO concentration and NOS activity were decreased, but ADMA content and PRMT3 expression were increased in the decidua of RM patients. Moreover, compared with the normal control subjects, PRMT3 expression was significantly up-regulated in the macrophages but not in the natural killer cells or stromal cells of the decidua from RM patients. The inhibition of PRMT3 results in a significant decrease in ADMA accumulation and an increase in NO concentration in macrophages. When co-cultured with DMs, which were treated with SGC707 and ADMA, trophoblast apoptosis was suppressed and induced, respectively. In vivo experiments revealed that the administration of SGC707 reduced the embryo resorption rate of CBA/J × DBA/2 mice.LIMITATIONS, REASONS FOR CAUTIONAll sets of experiments were not performed with the same samples. The main reason is that each tissue needs to be reserved for clinical diagnosis and only a small piece of each tissue can be cut and collected for this study.WIDER IMPLICATIONS OF THE FINDINGSOur results indicate that the PRMT3/ADMA/NO pathway is a potential marker and target for the clinical diagnosis and therapy of RM.STUDY FUNDING/COMPETING INTEREST(S)This study was supported by the National Key Research and Development Program of China (2017YFC1001401), National Natural Science Foundation of China (81730039, 82071653, 81671460, 81971384 and 82171657) and Shanghai Municipal Medical and Health Discipline Construction Projects (2017ZZ02015). The authors have declared no conflict of interest.TRIAL REGISTRATION NUMBERN/A.

Conjugated organic radical polymers with stable radical features are difficult to design because the π conjugation in the polymer backbones makes the radicals readily delocalize and tend to undergo covalent bonding processes. In this work, we report an electronic isolation strategy to design stable porous radical polymers by homocoupling reaction from a meta-position active monomer. The meta linkage ensures less conjugation in the polymer skeletons, localizes the resonant radicals, and prevents them from recombination. The resulting porous radical polymer exhibits exceptional radical characters with ultralow band gap of 0.68 eV, strong yet extended UV/Vis-NIR absorption up to 1800 nm, and high spin density. The above features make the polymer very promising in the photothermal conversion with record-high photothermal temperature increment of ≈∼240 °C and striking solar-driven water evaporation efficiency of 96.8 %. Our results demonstrate the feasibility of electronic isolation of radicals for producing outstanding photothermal materials.

Cosmic rays, γ-rays, and X-ray-driven reactions on interstellar grains have been the main focus in understanding the extraterrestrial synthesis of complex organic molecules. Herein, using temperature-programmed desorption and X-ray photoelectron spectroscopy, we report for the first time X-ray-induced CO2 production from a CO-covered rutile TiO2(110) surface at 110 K, in addition to X-ray-induced CO desorption. The X-ray-induced CO2 production was found to follow a Mars and van Krevelen (MvK) mechanism via the reaction between adsorbed CO and surface lattice oxygen of TiO2. Defects of TiO2 suppress the X-ray-induced CO2 production but promote the X-ray-induced CO desorption. These findings suggest a novel X-ray-induced CO-to-CO2 reaction on oxide surfaces at cryogenic temperature likely occurring in the interstellar medium and also warn us to keep in mind the possibility of X-rays inducing chemical reactions during structural characterizations of oxides with X-ray-involved techniques.

Yi-Hui Liu,1 Yan Guo,2 Hong Xu,1 Hui Feng,1 Dong-Ya Chen1 1Department of Digestive Hepatology, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang, 310003, People’s Republic of China; 2Department of Gastroenterology, Hangzhou Third Hospital, Hangzhou, Zhejiang, 310009, People’s Republic of ChinaCorrespondence: Yi-Hui LiuDepartment of Digestive Hepatology, Hangzhou Red Cross Hospital, No. 208 of Huancheng East Road, Xiacheng District, Hangzhou, Zhejiang, 310003, People’s Republic of ChinaTel +8613588227972Email yhl_123drsea@163.comObjective: To observe the effect of non-alcoholic simple fatty liver disease on drug-induced liver injury caused by tuberculosis.Methods: We retrospectively analyzed the incidence, characteristics, and risk factors of antituberculosis drug-induced liver injury in 104 patients with initial treatment of tuberculosis complicated with non-alcoholic simple fatty liver disease. The patients were divided into two groups according to whether there was liver injury or not. The differences in age, gender, body mass index (BMI), cholesterol, and triglycerides were studied between the two groups.Results: Among the 104 patients with initial treatment of tuberculosis complicated with non-alcoholic fatty liver disease, 24 (23%) patients developed a drug-induced liver injury. The remaining 80 (77%) patients did not develop drug-induced liver injury (χ2 = 60.308, P < 0.05). In the liver injury group, there were 20 cases of mild liver injury, two cases of moderate liver injury, two cases of severe liver injury, 22 cases of hepatocellular injury, two cases of cholestasis, and no cases of mixed liver injury. The time of abnormal liver function in antituberculosis treatment was 16.42 ± 9.18 days from the beginning of the antituberculosis treatment. There were no significant differences in gender, age, BMI, or triglyceride between the liver injury group and the non-liver injury group (χ2 = 2.063, t = 0.179, t = 0.703, t = 1.12, P > 0.05 in all), but there were significant differences in cholesterol (t = 3.08, P < 0.05). By logistic regression analysis, cholesterol was a high-risk factor for liver injury.Conclusion: Non-alcoholic simple fatty liver disease may increase the risk of antituberculosis drug-induced liver injury.Keywords: non-alcoholic simple fatty liver disease, antituberculosis drugs, drug-induced liver injury

Chlorin e6 (Ce6) is a promising photosensitizer for tumor photodynamic therapy (PDT). However, the efficacy of Ce6 PDT is limited by Ce6's poor water solubility, rapid blood clearance, and inadequate accumulation in the tumor tissue. This problem is tackled in this work, wherein functionalized superparamagnetic iron oxide nanoparticles (IO-NPs) were used as carriers to deliver Ce6 to melanoma. The IO-NPs were coated with polyglycerol (PG) to afford good aqueous solubility. The chemotherapeutic agent doxorubicin (DOX) was attached to the PG coating via the hydrazone bond to afford affinity to the cell membrane and thereby promote the cell uptake. The hydrophobic nature of DOX also induced the aggregation of IO-NPs to form nanoclusters. Ce6 was then loaded onto the IO nanoclusters through physical adsorption and coordination with surface iron atoms, yielding the final composites IO-PG-DOX-Ce6. In vitro experiments showed that IO-PG-DOX-Ce6 markedly increased Ce6 uptake in mouse melanoma cells, leading to much-enhanced photocytotoxicity characterized by intensified reactive oxygen species production, loss of viability, DNA damage, and stimulation of tumor cell immunogenicity. In vivo experiments corroborated the in vitro findings and demonstrated prolonged blood clearance of IO-PG-DOX-Ce6. Importantly, IO-PG-DOX-Ce6 markedly increased the Ce6 distribution and retention in mouse subcutaneous melanoma grafts and significantly improved the efficacy of Ce6-mediated PDT. No apparent vital organ damage was observed at the same time. In conclusion, the IO-PG-DOX NPs provide a simple and safe delivery platform for efficient tumor enrichment of Ce6, thereby enhancing antimelanoma PDT.

This work describes a base-mediated borylsilylation of benzylic ammonium salts to synthesize geminal silylboronates bearing benzylic proton under mild reaction conditions. Deaminative silylation of aryl ammonium salts was also achieved in the presence of LiOtBu. This strategy which is featured with high efficiency, mild reaction conditions, and good functional group tolerance provides efficient routes for late-stage functionalization of amines.

Uncontrollable leakage has significant effects on the safety of fractured rock mass, and microbially induced carbonate precipitation (MICP) is an effective way to control the seepage. In this study, four sets of seepage experiments are conducted on transparent rock-like specimens containing MICP filled single cracks to investigate the effects of bacterial concentration, crack inclination angle, crack roughness, and crack opening on fracture permeability. The experimental results show that calcium carbonate precipitation is produced when Sporosarcina pasteurii and cementing fluid are injected into the cracks, which can seal the cracks and reduce the permeability of the cracks. Moreover, the calcium carbonate produced by Sporosarcina pasteurii increases with increasing bacterial concentration. Furthermore, the fracture permeability of the MICP filled crack increases first and then decreases with increasing inclination, roughness, and opening of cracks. The experimental results provide a better understanding of the influence of different construction conditions on fracture permeability when the MICP technology is applied in rock engineering.

The coordination between a ligand and a metal is a spontaneous and uncontrollable process. In this Article, we successfully observe the formation of metal coordination in a triphenylamine-functionalized salicylaldehyde Schiff base with a copper(II) ion. The ligand TPA-Py first reacts with Cu2+ in a stepwise process to afford the dynamic complex TPA-Py@Cu2+ ([ligand]:[Cu2+] = 1:1), which further reacts with an extra copper(II) ion to afford 2TPA-Py@4Cu2+ with the following stepwise (or cumulative) stability constants: K1 = 4.0694 × 103 and K2 = 1.0761 × 106, respectively. The entire metal coordination process can be visualized, and the coordination mode of the probe toward copper was further evaluated by ultraviolet-visible/fluorescence spectra, single-crystal X-ray diffraction, density functional theory calculations, high-resolution mass spectra, and nuclear magnetic resonance spectroscopic titrations. Compound TPA-Py exhibited excellent sensitivity and specificity toward copper(II) ions in THF/water media with a low limit of detection of 2.687 × 10-7 mol L-1. In addition, TPI-An-Py can be applied to the detection of Cu2+ in real samples with satisfactory recoveries in the range of 100-112% in lake water and 98-101% in tap water. This Article not only reports an excellent fluorescence probe for copper(II) ion detection but also presents an instance for more fully understanding the metal coordination process.

Pol μ is capable of performing gap-filling repair synthesis in the nonhomologous end joining (NHEJ) pathway. Together with DNA ligase, misincorporation of dGTP opposite the templating T by Pol μ results in a promutagenic T:G mispair, leading to genomic instability. Here, crystal structures and kinetics of Pol μ substituting dGTP for dATP on gapped DNA substrates containing templating T were determined and compared. Pol μ is highly mutagenic on a 2-nt gapped DNA substrate, with T:dGTP base pairing at the 3ʹ end of the gap. Two residues (Lys438 and Gln441) interact with T:dGTP and fine tune the active site microenvironments. The in-crystal misincorporation reaction of Pol μ revealed an unexpected second dGTP in the active site, suggesting its potential mutagenic role among human X family polymerases in NHEJ., Pol μ performs gap-filling repair synthesis in the nonhomologous end joining (NHEJ) pathway. Here the authors provide crystal structures and kinetics of human Pol μ to reveal insights into the molecular mechanism of Pol μ during the process of dGTP misincorporation.

The most significant challenge in designing wound dressings is to mimic the tissue microenvironment because of the pro-regenerative structural and functional properties of skin. Herein, we developed a type of bionic extracellular matrix (ECM) hydrogels based on thiol-modified poly (γ-glutamic acid) (γ-PGA-SH) and oxidized hyaluronic acid (HA-CHO). The rapid and reversible thiol-aldehyde addition reaction of thiols in γ-PGA-SH and aldehyde groups in HA-CHO provided hydrogels with a dynamic covalent network and endowed them with properties of adaptability and self-healing capability, which are conducive for initial wound coverage and for prolonging the lifespan of the dressing. Interestingly, these hydrogels also showed typical viscoelastic characteristics similar to those of natural ECM, degradation property in vitro and in vivo, and free radical scavenging capability. In addition, the gelation time, rheological behavior, mechanical property, porous structure, and degradation process of the hydrogels could be tuned by adjusting polymer content. Furthermore, the ECM-inspired hydrogels significantly enhanced the wound healing process in vivo in a full-thickness skin defect model compared to those by commercial dressing (Tegaderm™) by facilitating angiogenesis and promoting collagen deposition. The successful application of the multifunctional hydrogel as an antioxidant wound dressing for wound treatment significantly exhibited its great application potential for biomedical areas. STATEMENT OF SIGNIFICANCE: The application of tissue engineering techniques to repair full-thickness skin wounds remains a great challenge in clinical trials. Among the recent approaches used for wound healing, in situ forming injectable hydrogels have gained much attention, and few of them have shown satisfactory overall performance, such as integration into the wound bed, biodegradability, immunocompatibility, vascularization, and recapitulation of the structure and function of skin. In the present study, we designed a simple and convenient in situ forming injectable adaptable self-healing hydrogels with biodegradability and antioxidative properties, which could substantially improve wound healing quality at an affordable cost. The hydrogel-based wound dressing is expected to solve the abovementioned problems and help in promoting cutaneous wound healing.

Alzheimer's disease (AD) is a devastating brain disorder characterized by neurofibrillary tangles and amyloid plaques. Inhibiting Tau protein and amyloid-beta (Aβ) production or removing these molecules is considered potential therapeutic strategies for AD. Genipin is an aglycone and is isolated from the extract of Gardenia jasminoides Ellis fruit. In this study, the effect and molecular mechanisms of genipin on the inhibition of Tau aggregation and Aβ generation were investigated. The results showed that genipin bound to Tau and protected against heparin-induced Tau fibril formation. Moreover, genipin suppressed Tau phosphorylation probably by downregulating the expression of CDK5 and GSK-3β, and activated mTOR-dependent autophagy via the SIRT1/LKB1/AMPK signaling pathway in Tau-overexpressing cells. In addition, genipin decreased Aβ production by inhibiting BACE1 expression through the PERK/eIF2α signaling pathway in N2a/SweAPP cells. These data indicated that genipin could effectively lead to a significant reduction of phosphorylated Tau level and Aβ generation in vitro, suggesting that genipin might be developed into an effective therapeutic complement or a potential nutraceutical for preventing AD.

Graphic Abstract Alkylbenzenes have a wide range of uses and are the most demanded aromatic chemicals. The finite petroleum resources compels the development of production of alkylbenzenes by non-petroleum routes. One-pass selective conversion of benzene and syngas to alkylbenzenes is a promising alternative coal chemical engineering route, yet it still faces challenge to industrialized applications owing to low conversion of benzene and syngas. Here we presented a Cu–ZnO–Al2O3/ZSM-5 bifunctional catalyst which realizes one-pass conversion of benzene and syngas to alkylbenzenes with high efficiency. This bifunctional catalyst exhibited high benzene conversion (benzene conversion of 50.7%), CO conversion (CO conversion of 55.0%) and C7&C8 aromatics total yield (C7&C8 total yield of 45.0%). Characterizations and catalytic performance evaluations revealed that ZSM-5 with well-regulated acidity, as a vital part of this Cu–ZnO–Al2O3/ZSM-5 bifunctional catalyst, substantially contributed to its performance for the alkylbenzenes one-pass synthesis from benzene and syngas due to depress methanol-to-olefins (MTO) reaction. Furthermore, matching of the mass ratio of two active components in the dual-function catalyst and the temperature of methanol synthesis with benzene alkylation reactions can effectively depress the formation of unwanted by-products and guarantee the high performance of tandem reactions. Supplementary Information The online version contains supplementary material available at 10.1007/s10562-021-03617-5.

Objectives This study was designed to evaluate the pharmacological activity and therapeutic mechanism of Xiaojin Pills (XJW) on lung cancer. Methods Mice were orally administered with Xiaojin Pills for 21 days. Tumour samples were collected to evaluate the antilung cancer effect, and blood samples were collected to identify differential metabolites with metabolomics. Through the analysis of network pharmacology, the active ingredients and targets related to XJW therapy for lung cancer were filtered. Key findings Different expression of seven metabolites related to seven pathways, including Arachidonic acid metabolism, Citrate cycle, tryptophan metabolism, glyoxylate and dicarboxylate metabolism, arginine and proline metabolism, primary bile acid biosynthesis and nicotinate and nicotinamide metabolism, were demonstrated to explain the efficacy of XJW in the treatment of lung cancer. Furthermore, a total of 19 active ingredients (ursolic acid, α-thujone, pelargonidin, succinic acid, boswellic acid, muscone, daidzein, xanthorrhizol, isoeugenol, oleic acid, β-caryophyllene, vanillin, β-sitosterol, lupeol, palmitic acid, eugenol, methylbutenol, β-elemene and quercetin) acted directly on 9 targets (CAT, PTGS2, PTGS1, CTH, ABTA, ALT1, ME2, AGXT and AGXT 2) and regulated 3 out of 7 metabolites (3-Hydroxyanthranilic acid, Pyruvate and Prostaglandin G2). Conclusions Through metabolomics and network pharmacology analyses, this study demonstrated that the major metabolites of XJW in treating lung cancer were regulated by multitarget and multicomponent interaction network.

Upgrading of the biomass-derived levulinic acid (LA) with the activation of carbonyl functional groups is a pivotal reaction in converting biomass into high-value-added products. Herein, we reporte...

Fe-N compounds with excellent electrocatalytic oxygen reduction activity are considered to be one of the most promising non-precious metal materials for fuel cells. Fe-N compounds with excellent electrocatalytic oxygen reduction activity are considered to be one of the most promising non-precious metal materials for fuel cells, which focuses on the Fe-N4 single-atom catalysts and the iron nitride materials (such as Fe2N and Fe3N). A hybridized catalyst having a hierarchical porous structure with regular macropores could enable the desired mass transfer efficiency in the catalytic process. In this study, we have constructed a new type of hybrid catalyst having iron and iron-nitrogen alloy nanoparticles (Fe-N austenite, termed as Fe-NA) embedded in the three-dimensional ordered macroporous N-doped carbon (3DOM Fe/Fe-NA@NC) by direct pyrolysis of single-source dicyandiamide-based iron metal-organic frameworks. The as-synthesized composites preserve the hierarchical porous carbon framework with ordered macropores and high specific surface area, incorporating the uniformly dispersed iron/iron-nitrogen austenite nanoparticles. Thereby, the striking architectural configuration embedded with highly active catalytic species delivers a superior oxygen reduction activity with a half-wave potential of 0.88 V and a subsequent superior Zn-air battery performance with high open-circuit voltage and continuous stability as compared to those using a commercial 20% Pt/C catalyst.

Adenomyosis is associated with dysmenorrhea, infertility, and lesional fibrosis. The pathogenesis of adenomyosis is still unclear. Plasminogen activator inhibitor 1 (PAI-1) plays important roles in pathological activities like tumor metastasis and endometriosis. Our objective was to investigate the expression and localization of PAI-1 in eutopic and ectopic endometrium with adenomyosis and in endometrium without adenomyosis. We also sought to determine the relationship between PAI-1 immunoreactivity and the severity of dysmenorrhea and the extent of lesional fibrosis in adenomyosis. PAI-1 expression was significantly higher in the ectopic endometrium of patients with adenomyosis than in both the eutopic endometrium of patients with adenomyosis and the endometrium of controls. Ectopic PAI-1 expression correlated positively with dysmenorrhea visual analog scale (VAS) scores and the extent of lesional fibrosis in adenomyosis. High PAI-1 expression increased the likelihood of moderate to severe dysmenorrhea in adenomyosis. These results suggest that PAI-1 is involved in the adenomyosis-associated dysmenorrhea and lesional fibrosis, which provide a potential target in treating symptomatic adenomyosis. Supplementary Information The online version contains supplementary material available at 10.1007/s43032-021-00513-6.

Low-temperature corrosion of the system and external input make it difficult to avoid the entering Fe ions in the supercritical reactor. Fe ions crystallize into particles in supercritical water and deposit on the surface of the reactor, causing safety threats and economic losses. In this paper, research on the Fe ion deposition process, from crystallization, to oxide particle formulation and to completely adhering to the wall surface, is reviewed. The literature mainly includes theoretical and experimental research on the nucleation and growth process of Fe oxide particles in a supercritical water (SCW) environment, particle movement and experimental observation methods in trans-critical turbulence, and the effects of Derjaguin-Landau-Verwey-Overbeek (DLVO) and collisions considered in the process of particle attachment. The particle deposition process involves particle formation, particle movement and surface adhesion. These three dynamic processes have cross-influencing factors that include geometric factors (the size of the particles themselves, the roughness of the wall), hydrodynamic factors (turbulence and transcritical conditions), and environmental parameters (temperature, pH). Independent research on dynamic processes is no longer suitable. The review aims to clarify the mechanism of three dynamic processes and their roles in the particle deposition process so that they can be comprehensively considered in the study of particle deposition in actual operating systems in the future.

It is difficult to recycle photocatalysts for water purification when they are in aqueous suspension. Cellulose aerogels with porous structure and biodegradability are promising carriers for photocatalysts that can be used to solve many environmental problems. In this study, a 3D recyclable g-C3N4@cellulose aerogel for photocatalytic degradation of pollutants was synthesized using a facile chemical cross-linking method. g-C3N4@cellulose aerogel (30% loading) exhibited excellent photocatalytic activity up to 99.0% degradation. In addition, the g-C3N4@cellulose aerogel exhibited high recyclability and structural stability while the photocatalytic efficiency is not significantly reduced in cycling tests. The photocatalyst was optimized using high temperature calcination, resulting in 95.35 m2 g−1 actual surface determined from Brunner–Emmet–Teller measurements. Therefore, aggregation of the photocatalyst can be avoided by the cellulose aerogel support whilst the photocatalytic property remained as efficient as its powder form. Such composites may become attractive material for practical applications.

The safety concern on lithium-ion batteries hampers the widely application of electric vehicles. Separator is crucial to battery safety, as its mechanical failure may trigger drastic reactions between cathode and anode. Though the separator is soaked in nonaqueous electrolyte in the state-of-the-art lithium-ion batteries, its dimensional stability, which is one of the important indications for mechanical reliability, is generally tested in a dry state. In this study, the thermal and mechanical properties of dry polyolefin separators, as well as the separators soaking with different electrolytes, are carefully investigated at elevated temperatures. The thermal shrinkage of the polyolefin separators is obviously enhanced by the solvents, and lithium salts (LiPF6, LiFSI, or LiTFSI) get the separator involved into decomposition. Significantly, the mechanical strength of the polyolefin separator declines 73.8% in the soaked state at even a relatively low operation temperature (60 °C). This work provides an instructive and supplementary approach for separator evaluation, as well as an understanding of battery failure due to the performance degradation of electrolyte-soaked separators.

Piper crocatum Ruiz & Pav. (P. crocatum), a traditional medicinal plant, has been shown to possess various pharmacological activities, including anticancer activity, antioxidant activity, antibacterial activity, anti-hyperglycemic activity, anti-allergic inflammatory activity and others. To identify the potential anti-allergic inflammatory effective constituents of P. crocatum, 13 single compounds were isolated from the methanol extract of P. crocatum leaves, and their structures were identified by contrasting their NMR spectroscopic data and previously published papers. First, the anti-allergic inflammatory activities of these single compounds were examined by accessing immune function related biomarkers such as nitric oxide (NO) and β-hexosaminidase. We found that the methanol extract and catechaldehyde (compound 1) potently suppressed NO production. Additionally, Western blot analysis showed that P. crocatum methanol extract and compound 1 suppressed the production of NO by reducing inducible nitric oxide synthase (iNOS) expression in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Consistent with these observations, P. crocatum methanol extract and compound 1 remarkably decreased β-hexosaminidase release from RBL-2H3 cells stimulated with 2,4-dinitrophenylated bovine serum albumin (DNP-BSA)-specific immunoglobulin E (IgE) antibodies. Furthermore, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay indicated that P. crocatum methanol extract and compound 1 exhibited no cytotoxicity to RAW264.7 and RBL-2H3 cells. Based on these findings, compound 1 is suggested as an active anti-allergic inflammatory component of P. crocatum.

Herein, a highly active Mott–Schottky nanocatalyst with tunable Schottky barrier was constructed by embedding Co nanoparticles (NPs) into phosphorus-doped graphitic carbon nitrides (PxCN) for the enhanced dehydrogenation of ammonia-borane (AB). Analyses show that P doping can efficiently decrease the work function of g-C3N4 and elevate the conduction band edge potential; thus, P doping offers a simple approach to tune the Schottky barrier of Co/PxCN by varying the doping amount of P atoms. Upon rationally tuning the Schottky barrier from 0.60 to 0.78 eV, the obtained photocatalyst with the molar composition Co/P3.59CN showed a remarkable TOF (total turnover frequency) value of 67.09 mol H2 per mol metal per min for the dehydrogenation of AB under visible light at 298 K, which, to the best of our knowledge, is one of the highest values reported to date for non-noble metal-based monometallic catalysts and is even comparable to those of some noble metal catalysts. This study opens a new prospect for the rational design and preparation of metal/g-C3N4 nanocatalysts with tunable Schottky barriers and provides a simple way to elevate the catalytic activity of these nanocatalysts.

Context Icariin has attracted increasing attention because of its wide variety of pharmacological effects. Objective This study investigates whether icariin could promote fracture healing in young and old rats and its mechanisms. Materials and methods A Wistar rat model for the tibia fracture in relatively young and old rats, respectively, was established. The rats were divided into four groups: model group, L-icariin (50 mg/kg icariin), M-icariin (100 mg/kg icariin) and H-icariin (200 mg/kg icariin), and intragastric administration of icariin was performed for 10 days or 20 days. In addition, isolated and cultured rat bone mesenchymal stem cells (rBMSCs) from young and old rats were cultured with 5% and 20% of icariin-containing serum, respectively, then cell viability and alkaline phosphatase (ALP) activity were measured. Results Icariin administration induced the expression of Runx2, Osterix, BMP-2, p-Smad5 and osteocalcin secretion (young rats: model: 2.50 ± 0.71; L-icariin: 10.10 ± 1.55; M-icariin: 24.95 ± 2.19; H-icariin: 36.80 ± 2.26; old rats: model: 1.55 ± 0.49; L-icariin:6.55 ± 0.50; M-icariin: 15.00 ± 0.85; H-icariin:20.50 ± 2.27) at the fracture site, and increased the levels of bone formation markers (OC, BAP, NTX-1 and CTX-1) in a dose-dependent manner. In vitro, icariin treatment promoted rBMSC viability, increased ALP activity and the expression of BMP-2/Smad5/Runx2 pathway proteins. Discussion and conclusions Icariin may accelerate fracture healing by activating the BMP-2/Smad5/Runx2 pathway in relatively young and old rats. The research on the mechanism of icariin to promote fracture healing can provide a theoretical basis for the clinical application and promotion of icariin.

A tetraphenylethylene-based covalent organic framework (TTPE-COF) with a rhomboid-shaped framework is constructed by a Schiff base reaction. Due to its porous structure and high surface area (681.27 m2 g−1), the TTPE-COF will be a meritorious adsorbent for gas storage (CO2 of 485.89 mg g−1 at 45 bar/318 K) and volatile organic compound (VOC) capture (benzene of 5.80 mmol g−1 and toluene of 5.20 mmol g−1 at 293 K). Furthermore, the TTPE-COF has good selectivity and detection effect for Fe3+, and the detection limit (LOD) of Fe3+ is 3.07 μM. The TTPE-COF has potential applications in adsorbents and fluorescent sensors.

A new tetrapyrazole-modified tetraphenylethene (TPE) ligand L was designed and found to display “turn-on” fluorescence when it combines with Ag+ ions in dilute solution by restricting intramolecular rotation of TPE. A series of Ag complexes 1–7 were obtained, and they exhibit excellent fluorescence properties in the solid state. Compared with PF6−, the silver complex with the CF3SO3− anion can further enhance its fluorescence due to the transformation of its structure from Ag2L (2) to Ag4L2 (3). As zero-dimensional complexes, 1 and 3 have excellent piezochromic properties with a color change from blue to green. Furthermore, structural changes of 1 and 3 to the corresponding three-dimensional frameworks 4 and 5 occur upon immersing in ethanol. In addition, 1 can act as a potential fluorescent probe for sensing nitrile compounds.

Lignin, a carbon-rich biopolymer, has great application potentials in the field of biomaterial manufacture. However, lignin produced from separation process is a heterogeneous polymer with low functionality, which largely limits its application. In this case, a simple and green approach was proposed to fractionate tetrahydrofurfuryl alcohol lignin with different acetone concentrations to produce homogeneous lignin having high antioxidant capacity. Lignin dissolved in 60% acetone solution was stirred for 1 h at room temperature and water was gradually added to precipitate and to obtain fractions with a high purity. The molecular weight distribution, structural characteristics and thermal stability of lignin before and after fractionation were extensively studied by using various methods (nuclear magnetic resonance techniques, thermogravimetric analysis, etc.). At the lowest acetone concentration, the molecular weight of lignin was 1490 g/mol, the polydispersity index was as low as 1.16, and the total phenolic hydroxyl content reached 3.3 mmol/g. Results showed that lignin samples had strong antioxidant activity as compared to commercial antioxidant butylated hydroxytoluene. This study indicated that separation with acetone/water system is meaningful approach to prepare homogeneous lignin with excellent functionality.

A novel 3D MOF [(Zn4O)(H2O)2(TPA)2]·8DMA (1) (H3TPA = 4,4′,4′′-nitrilotrisbenzoic acid; DMA = N,N-dimethylacetamide) with tetragonal nanochannels has been rationally obtained under solvothermal conditions using the fluorescent ligand H3TPA. MOF 1 demonstrates a unique (3,6)-connected network with nanosized square channels, displaying strong blue emission. Interestingly, 1 can be used as a fluorescent probe, which can detect nitroaromatic explosives efficiently and selectively via fluorescence quenching phenomena. As the number of –NO2 groups increase, fluorescence quenching becomes more obvious, which is maybe because the energy transfer from the electron-donating framework to electron-withdrawing nitroaromatic analytes becomes greater. Notably, the sensor is particularly sensitive to picric acid (PA), showing complete fluorescence quenching at a PA concentration as low as 30 ppm. MOF 1 can be recycled in the detection of nitroaromatic explosives with excellent recyclability. Additionally, the photo-induced electron transfer mechanism was validated through theoretical calculations for the fluorescence quenching.

AIE fluorophores have been developed as bioimaging probes due to their strong brightness at high concentration and increase of the photostability to promote highly recognizable cellular signaling. However, conventional AIE fluorescent probes for bioimaging just solely lighten the cells or tissues, suffering from the limitation of satisfying the requirement of disease diagnosis. Herein, we report an AIE-active bioprobe (TPP-Tba) for linear fluorescence response and qualitative detection of hydrogen peroxide (H2O2) and viscosity with a wide detection range and a low detection limit. TPP-Tba displays an impressive ability of distinguishing normal cells and pathological cells. Furthermore, fatty liver tissue can also be efficiently distinguished from normal liver tissue, attributed to the great H2O2 and viscosity dual-response as well as the specific targeting to mitochondria by TPP-Tba. Given the high sensitivity for H2O2 and viscosity, great biocompatibility, high specificity to mitochondria, and impressive ability of distinguishing normal tissue and pathological tissue, we envisage that this novel TPP-Tba probe would open a new window for designing novel bioprobes for disease diagnosis.

Aiming at recyclable catalyst carriers, porous cellulose macrospheres from wood pulp dissolved in an alkaline urea system were regenerated by simple injection regeneration. After solvent exchange, porous cellulose macrospheres (CMs) with a high specific surface area of 325.3 m2 g−1 were obtained by lyophilization, and CuS nanoparticles (CuS NPs) were coated on CMs by in situ growth in the liquid phase to achieve CuS-supported CM macrospheres (CuS@CM). The results indicated that the CuS@CM biocatalyst was successfully prepared with an average diameter of approximately 1.2 mm. In addition, CuS@CM was further used as a heterogeneous catalyst for the catalytic degradation of methylene blue (MB) and methyl orange (MO) model dyes during the oxidation of hydrogen peroxide (H2O2). In the presence of low doses of H2O2, the degradation rate of MB reached 94.8% within 10 min, showing high catalytic activity under neutral and alkaline conditions. After five cycles, 90.1% of the original catalytic activity was still retained, indicating that the prepared CuS@CM composite possessed excellent catalytic activity and reusability.

Cerebral ischemia-reperfusion (CIR) is a common feature of ischemic stroke and is a major cause of disability and death among stroke patients worldwide. Phyllanthin, a lignin polyphenol, is known for its varied biological properties, although its protective effects against CIR have not been reported. We evaluated the neuroprotective property of phyllanthin against CIR as well as the involvement of the AMP-activated protein kinase/nuclear factor erythroid 2-related factor 2 (AMPK/Nrf2) and nuclear factor kappa B (NF-κB) signaling pathways. Experimental animals were divided into five groups: controls (sham-operated), CIR-induced by middle cerebral artery occlusion (MCAO), and CIR-induced and administered phyllanthin at 2.5, 5, and 10 mg/kg, respectively. We investigated neurological functions, various signaling genes, and inflammatory clues. The results of in vitro assays demonstrated that phyllanthin assertively improved cellular functions through abrogation of the Nrf2 pathway. In vivo, CIR rats demonstrated neurological function deficits, while ischemic severity was evidenced by the activation of neuroinflammatory cytokines and tissue oxidative stress. Moreover, the expression of apoptosis markers such as Bax, B-cell lymphoma (Bcl-2), caspase-3, COX-2, PGE2, and LOX-1 abruptly increased. Phyllanthin prevented brain dysfunction and cerebral edema, and protected brain integrity. Conversely, it improved antioxidative enzyme activity, abrogated inflammatory cytokines, and increased IL-10 in chemokines. Also, phyllanthin significantly reduced Nrf2 and AMPK levels, with reduced expression of NF-κB indicating that cross-talk between the NF-kB and Nrf2 pathways is activated in CIR. Phyllanthin rescues the ischemic brain by regulating cellular signaling, which supports its use for complications like CIR and associated injury.

P2X7 receptor (P2X7R) and NLRP3 cooperatively participate in inflammation and hepatocyte damage during hepatic injury induced by lipopolysaccharides (LPS). High-mobility group box 1 (HMGB1) released from immune cells in response to such stimuli plays a vital role in mediating inflammation via TLR4 and the receptor for advanced glycation end products (RAGE), a receptor for HMGB1. However, the correlation among P2X7R, RAGE and TLR4 in regulating the release of HMGB1 has not been elucidated. Increasing the number of daily foods is found to be beneficial for hepatocyte damage in septic hepatic injury. Hence, we investigated the effects of luteolin, a natural flavonoid mainly existing in vegetables and fruits, on liver injury, focusing on how luteolin participates in hepatitis based on the P2X7R-RAGE-TLR4 axis by regulating the release of HMGB1. The results demonstrated that the indicators of hepatic injury such as increased ALT, AST in the serum and infiltration of immune cells were attenuated after luteolin treatment in LPS-induced mice. Luteolin could also suppress the production and release of HMGB1 and the activation of caspase 1 both in LPS-induced mice and LPS/ATP-stimulated HepG2 cells. Collectively, luteolin reversed LPS-induced hepatic injury, especially inflammation, likely by regulating the release of HMGB1 through the P2X7R-RAGE-TLR4 axis.

We have realized a B(C6F5)3-catalyzed three-component tandem reaction of naphthoquinone, indole and maleimide, which has broad adaptability of substrates and good compatibility of functional groups, and synthesized 33 examples. After photophysical characterization, we found that parts of these compounds have excellent photophysical properties, the value of relative quantum yield is up to 0.98, and surprisingly, compound 4j has the ability to selectively recognize alkali carbonates.

C42H38N4O7, triclinic, P 1 ‾ $P\bar{1}$ (no. 2), a = 11.8563(6) Å, b = 12.6263(6) Å, c = 13.4492(6) Å, α = 113.563(2)°, β = 96.740(2)°, γ = 104.429(2)°, V = 1733.07(15) Å3, Z = 2, R gt (F) = 0.0470, wR ref (F 2) = 0.1248, T = 301.72 K.

This work developed a sensitive electrochemiluminescence (ECL) biosensor based on a cyclometalated iridium(III) complex ((bt)2Irbza), which was synthesized for the first time. Annihilation, reductive-oxidative, and oxidative-reductive ECL behaviors of (bt)2Irbza were investigated, respectively. The oxidative-reductive ECL intensity was the strongest compared with the other two, which showed 16.7 times relative ECL efficiency compared with commercial [Ru(bpy)3]2+ under the same experimental conditions. Therefore, an ECL biosensing system with (bt)2Irbza as the anodic luminophore was established for miRNA detection based on a closed bipolar electrode (BPE). Combined with both steric hindrance and catalytic effects induced by hemin/G-quadruplex in the cathodic reservoir of BPE that changed the Faraday current of the cathode and thus mediated the ECL intensity of (bt)2Irbza in the anode of BPE, the ECL sensor stated an ultrahigh sensitivity for microRNA (miRNA-122) analysis with a detection limit of 82 aM.

Background: Icariin has been shown to enhance bone formation. Objective: The present study aimed to investigate whether icariin also promotes bone fracture healing and its mechanisms. Methods: First, we isolated and cultured rat bone marrow stromal cells (rBMSCs) with icariincontaining serum at various concentrations (0%, 2.5%, 5% and 10%) and then measured alkaline phosphatase (ALP) activity and the expression of Core-binding factor, alpha 1 (Cbfα1), bone morphogenetic protein-2 (BMP-2) and bone morphogenetic protein-4 (BMP-4) in the rBMSCs. Second, we established a model of fracture healing in rats and performed gavage treatment for 20 days. Then, we detected bone biochemical markers (ELISA kits) in the serum, fracture healing (digital radiography, DR), and osteocalcin expression (immunohistochemistry). Results: Icariin treatment increased ALP activity and induced the expression of Cbfα1, BMP-2 and BMP-4 in rBMSCs in a dose-dependent manner. In addition, Icariin increased the serum levels of osteocalcin (OC), bone-specific alkaline phosphatase (BAP), N-terminal telopeptides of type I collagen (NTX-1), C-terminal telopeptide of type I collagen (CTX-1) and tartrate-resistant acid phosphatase 5b (TRACP-5b); promoted osteocalcin secretion at the fracture site; and accelerated fracture healing. Conclusions: Icariin can promote the levels of bone-formation markers, accelerate fracture healing, and activate the WNT1/β-catenin osteogenic signaling pathway.

AIMS The purpose of this study is to examine the safety and efficacy of eltrombopag as first-line treatment for thrombocytopenia among paediatric patients after haematopoietic stem cell transplantation (HSCT). METHODS Forty-three childhood patients with thrombocytopenia after HSCT who received eltrombopag were retrospectively analysed. RESULT Eltrombopag was began at the median of 27 days after HSCT and lasted for 24 days. Thirty-five children responded to eltrombopag therapy, and the cumulative platelet recovery rate was 88.9%. The cumulative incidence of platelet recovery was lower (83.9 vs 100%; P = .035) in patients with decreased numbers of megakaryocytes before starting eltrombopag than in those with normal. Factors associated with a significantly elevated response to eltrobopag from univariate analysis were donor type. Results from the multiple regression analysis found that weight (hazard ratio [HR] = 0.7, 95% confidence interval [CI] 0.5-0.9, P = .022), platelet engraftment time (HR = 1.0, 95%CI 1.0-1.0, P = .012) and bone marrow megakaryocytes (HR = 8.0, 95%CI 1.5-43.3, P = .016) before starting eltrombopag were the independent risk factors. Based on Youden's index algorithm in the receiver-operating characteristic curve, the optimal cut-off value of the maintenance dose of eltrombopag in predicting nonresponders was 4 mg/kg. The area under the receiver-operating characteristic curve was 0.923 with sensitivity of 97.8%, specificity of 87.9%, positive predictive value of 72.3%, and negative predictive value of 92%. None of the paediatric patients stopped using eltrombopag due to side effect or intolerability. CONCLUSION Eltrombopag is effective and safe in paediatric patients with thrombocytopenia after HSCT. The number of megakaryocytes in bone marrow before eltrombopag treatment may serve as a predictor of the response to eltrombopag. We recommend that the maintenance dose of eltrombopag should not exceed 4 mg/kg/d.

In order to increase the utilization rate of drug carried by microneedles and reduce waste, a two-step casting method was proposed to fabricate tip-loaded dissolving microneedles in this paper. The tip-loaded dissolving microneedles, also named layered microneedles, was consisted of two layers. The tip layer of the microneedles carried model drug, while the backing layer was fabricated with pure dissolving material. Polyvinyl alcohol, polyvinylpyrrolidone and hyaluronic acid were used as the base materials to fabricate the dissolving layers of the microneedle patches. Rhodamine B was chosen as the model drug to show the layered structure of tip-loaded microneedles. The material formulation and fabricating conditions of the tip-loaded dissolving microneedles and their transdermal insulin delivery efficiency were systematically studied. Nanoindentation testing showed that the tips of all three kinds of dissolving microneedles can bear the maximum loading of 50 mN with no damages, indicated sufficient mechanical strength for smooth skin puncturing as the minimum pressure required was 10 mN only. Moreover, our fabricated tip-loaded dissolving microneedles can greatly reduce the drug waste cause by unused backing layer in normal microneedles and realize a 30% enhancement of drug delivery efficiency after puncture treatment.

Commercial lithium-ion batteries still undergo safety concerns due to using perilous and flammable liquid electrolytes that are prone to fire and leakage issues. Meanwhile, the development of high energy density lithium-metal batteries with conventional liquid electrolytes has also encountered bottlenecks because of the growth of lithium-dendrites and parasitic reactions. Therefore, the use of flammable liquid electrolytes in lithium batteries is the main obstacle to be overcome, and at the same time, the contradiction between high energy density and high safety for practical applications needs to be addressed. Currently, solid polymer electrolyte has been considered as a promising solution, and hence solid polymer-based lithium batteries have attracted much attention due to their high safety compared to their counterparts. However, its low ionic conductivity, poor mechanical properties, and insufficient cycle life restrict their practical applications. At present, there are fewer comprehensive reviews available on lithium batteries based on polymer electrolyte systems, so it is substantial worthy of summarizing the existing literature and timely apprises of incessantly improving strategies of this field. This review summarizes the ion transfer mechanism and performance requirements of polymer electrolytes for lithium batteries, the classification and design of polymer electrolytes, and the essential principles and characterization for electrode/electrolyte interface construction and the research of composite electrolyte. Finally, the current status and development prospects of polymer electrolytes are briefly summarized and discussed, enabling a foundation for the wide application of solid polymer electrolyte-based batteries.

Exopolysaccharide (EPS) plays an important role in plant growth-promoting bacteria (PGPB)-mediated enhancement of plant abiotic stress resistance. In this study, it is found that EPS from Pantoea alhagi NX-11 foliar sprayed at 20, 50, and 100 ppm could significantly enhance drought resistance of rice seedlings. The fresh weight and relative water content of EPS sprayed were increased. In addition, malondialdehyde content reduced while total chlorophyll, proline and soluble sugar content, prominent enhanced. Meanwhile, the antioxidant enzymes, CAT, POD and SOD, were also significantly increased. The drought resistance of rice was most pronounced at the 50 ppm EPS dose. For the sake of commercializing the gram-negative EPS-producing PGPB which were difficult to preserve, it is vital to improve the EPS yield. First, the carbon source, nitrogen source and inorganic salt were optimized. Subsequently, the effect of three oxygen vectors, which could increase the efficiency of oxygen mass transfer, on EPS yield was studied by response surface methodology. The maximum EPS yield (19.27 g/L) was obtained, which is 51.7% higher than the initial yield of 12.7 g/L. Overall, it may provide a new way for the industrialization of PGPB to increase the yield of EPS.

HSCs (hepatic stellate cells) contribute to the excessive extracellular matrix (ECM) deposition, inflammatory pathways and crucial cell-cell interactions in hepatic disease leading to fibrosis. P2x7R is considered a potential orchestrater in liver fibrosis. For this reason, this work explored the role of P2x7R in liver fibrosis and the mechanism by which P2x7R in macrophages promotes fibrogenesis. In a model of liver fibrosis induced by administration of thioacetamide (TAA), inhibition of P2x7R with its selective inhibitor A438079 reversed TAA-induced liver damage and fibrosis. The mechanism was linked to inhibition of P2x7R-NLRP3 inflammasome activation and thereby infiltration of macrophages and neutrophils into the liver. This result indicated that the P2x7R-TLR4-NLRP3 axis is involved in the process of TGF-β-mediated ECM deposition in HSCs. Ectopic overexpression of P2x7R lowered the threshold of extracellular matrix (ECM) deposition and maintained HSCs in an activated state. The culture medium of THP-1 macrophages stimulated by LPS/ATP aggravated ECM deposition in HSCs by activating P2x7R. Additionally, IL-1β secreted by LPS / ATP activated macrophages amplified fibrosis. These data indicate that P2x7R plays a key regulative role in the activation and maintenance of HSCs promoted by macrophages. Thus, pharmacological inhibition of P2x7R could be a potential therapeutic mechanism to treat human liver fibrosis.

Background N-Acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a short peptide with an anti-silicosis effect. However, the short biological half-life and low plasma concentration of Ac-SDKP hamper discovery of specific targets in organisms and reduce the anti-silicosis effect. A novel peptide, Ac-SDK (biotin) proline, termed "Ac-B", with anti-fibrotic properties was synthesized. Methods Ac-B was detected quantitatively by high-performance liquid chromatography. Phagocytosis of Ac-B by the alveolar epithelial cell line A549 was investigated by confocal laser scanning microscopy and flow cytometry. To further elucidate the cellular-uptake mechanism of Ac-B, chemical inhibitors of specific uptake pathways were used. After stimulation with transforming growth factor-β1, the effects of Ac-B on expression of the myofibroblast marker vimentin and accumulation of collagen type I in A549 cells were analyzed by Western blotting. Sirius Red staining and immunohistochemical analyses of the effect of Ac-B on expression of α-smooth muscle actin (SMA) in a rat model of silicosis were undertaken. Results Ac-B had good traceability during the uptake, entry, and distribution in cells. Ac-B treatment prevented an increase in α-SMA expression in vivo and in vitro and was superior to that of Ac-SDKP. Caveolae-mediated uptake of Ac-B by A549 cells led to achieving anti-epithelial-mesenchymal transformation (EMT) effects. Conclusion Ac-B had an anti-fibrotic effect and could be a promising agent for the fibrosis observed in silicosis in the future.

Electrically conducting elastomer composites are indispensable in the development of flexible, wearable and soft electronic products. The continuous fabrication of highly electrically conductive polymeric composites at large scale remains a technical challenge due to the lack of control of the dispersion and orientation of the conductive fillers, interfacial interaction and filler-filler network stability in the polymer matrices. Herein, an innovative design was investigated by combining a continuous compression molding and curing through a flexible roller enabled continuous process. This approach forced the alignment of short carbon fibers (SCF) along the rolling direction in a polydimethylsiloxane (PDMS) matrix due to the deformation of the flexible roller, and effectively condensed the conductive SCF network in PDMS, The distance among SCFs can be further reduced with the rolling cycles which is ascribed to a spatial confining-forced network assembly. With a rolling cycle of 20, dual electrical conducting percolation thresholds reached at 0.1 wt% and 0.5 wt% of SCF, respectively. A maximum electrical conductivity of 44.1 S/m was achieved with a SCF loading of 4 wt%. A fiber contact model was proposed to predict the electrical conductivity of the composites. The PDMS/SCF composites were tested for conductive electrodes and flexible pressure sensors. The present work provides a facile method for continuous fabrication of conductive elastomeric composites, with potential for continuous fabrication of thermosetting composites.