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Biological redox molecules play essential regulatory roles in diverse cellular processes. In particular, abnormal levels of redox signaling molecules are related to the progression of several diseases. Therefore, redox-responsive polymeric nanomaterials appear as competent candidates for disease-targeting drug delivery systems. In the past decades, considerable works have been done to develop polymeric nanomaterials showing controlled release in response to reactive oxygen species, glutathione or both. To further advance this research field, two new redox-responsive polymeric nanomaterials are described in this dissertation. In chapter 1, hydrogen peroxide-responsive polycaprolactone nanoparticles are reported. By exploiting an intramolecular cyclization strategy, polycaprolactone that contains pendant arylboronic ester motifs shows fast hydrogen peroxide-induced degradation. Nanoparticles formulated from this polycaprolactone exhibit high sensitivity to disease relevant levels of hydrogen peroxide. In chapter 2, a hydrogen sulfide-responsive nanogel is introduced. Cholesteryl groups were conjugated on dextran via hydrogen sulfide-responsive linkers to yield amphiphilic polysaccharides that can self-assemble to form nanogels in aqueous solutions. This work presents the first hydrogen sulfide-responsive nanogel that shows hydrogen sulfide-induced swelling behavior and controlled payload release.

Wearable pressure sensors have drawn significant attention because of their extensive applications in motion detection, tactile sensing, and health monitoring. However, the complex manufacturing process and high cost of active materials make low-cost, large-scale production elusive. In this work, we report a flexible piezoresistive pressure sensor assembled with two 3D laser-induced graphene (LIG) foam electrodes on a polyimide thin film from a simple laser scribing process in the ambient environment. The design of the air gap between the two foam electrodes allows the sensor to showcase a low limit of detection of 0.274 Pa, which provides favorable sensing performance in motion detection and wrist pulse monitoring. The addition of spherical MoS2 nanoparticles between the two foam electrodes further enhances the sensitivity to 88 kPa−1 and increases the sensing range to significantly outperform the previous literature reports. The demonstrated LIG pressure sensors also exhibit fast response/recovery rates and excellent durability/repeatability.

Surface layer proteins (SLPs) are crystalline arrays in the outermost layer of cell envelope in many archaea and bacteria. SLPs subunits have the ability to reassemble on the surface of lipid layers. In this work, the SLP from Lactobacillus acidophilus ATCC 4356 was extracted and reassembled on the surface of positively charged liposomes composed of dipalmitoyl phosphatidylcholine, cholesterol and octadecylamine. Zeta potentials and particle size were determined to describe the adsorption process of SLP on liposomes. The liposomes completely coated with SLP were observed by transmission electron microscope. To investigate the stabilizing effects of SLP on liposomes, carboxyfluorescein (CF) was encapsulated and its leakage was determined as an evaluation index. The results showed that the L. acidophilus ATCC 4356 SLP significantly (P < 0.05) increased the stability of the liposomes in the course of thermal challenge. Furthermore, SLP was able to reduce the aggregation of liposomes in serum. Storage stability of liposomes was performed at 25 °C, 4 °C and -20 °C for 90 days. And the SLP-coated liposomes released less CF than the control liposomes during storage at the three evaluated temperatures. Our findings extended the application field of Lactobacillus SLPs and introduced a novel nanocarrier system with good chemical stability.

Escherichia coli and Salmonella are common pathogenic bacteria in human intestine, which can infect epithelial cells and cause diseases. Adhesion to intestinal tissue is the first step of pathogen infection. This work was to investigate the protective function of surface layer protein (SLP) from Lactobacillus casei fb05 against the harmful effects of E. coli and Salmonella on intestinal tissue (collagen and HT-29 cells). The SLP of L. casei fb05 was identified by transmission electron microscopy and SDS-PAGE. The purified SLP could reduce the adhesion of E. coli and Salmonella to collagen and HT-29 cells as observed by light microscope. The flow cytometry results showed that the L. casei fb05 SLP decreased the two pathogens-induced apoptosis of HT-29 cells by about 45%–49%. In addition, the activation of caspase-9 and caspase-3 caused by the two pathogens was significantly declined by the interference of the L. casei fb05 SLP. All the findings demonstrated that the L. casei fb05 SLP could decrease the deleterious effects of E. coli and Salmonella on intestinal tract in two ways: reducing pathogen adhesion and inhibiting pathogen-induced apoptosis. The potential of L. casei fb05 SLP in the treatment of intestinal diseases might be explored in this work.

In the process of nickel-based alloy machining, chips are easy to bond on the tool surface, which weaken the tool performance and make the tool wear. Therefore, it is very important to study the mechanism of tool bond wear in the process of nickel-based superalloy machining. In order to reflect the wear process of the tool from the perspective of micro cutting, the molecular dynamics simulation model for cutting Ni–Fe-Cr-Co–Cu nickel-based alloy with SiC tool was established. The Morse potential functions between the tool and workpiece are calculated, and the simulation results are analyzed visually. It is found that the bond wear is the main wear form of tool in the process of cutting nickel-based alloy, and the wear processes are divided into three stages: contact, adhesion and shedding. The stress and strain in the cutting area are calculated and it is found that the bond occurs when the tool-workpiece extrusion is strong. Through the calculation of radial distribution function and formation energy, it is found that Ni-Si compound is formed on the tool surface, and the newly generated Ni-Si compound reduces the tool performance compared with the silicon carbide structure. This study provides a more complete microscopic explanation of the tool wear mechanism, which is helpful to find a method to prolong tool life.

Redox-responsive polymeric nanomaterials (PNMs) have been attractive research targets for drug delivery systems because disturbed levels of redox molecules are associated with the progression of various diseases. To enable PNMs to target biorelevant redox molecules, including reactive oxygen species (ROS), glutathione (GSH) and hydrogen sulfide (H2S), appropriate responsive moieties have to be installed within the polymer structure. Upon application of redox stimuli, redox-responsive PNMs undergo structural changes to release encapsulated payloads. Chalcogen ether, thioketal and arylboronic ester have been widely incorporated into the structure of ROS-responsive PNMs. While disulfide is commonly utilized in GSH-responsive PNMs, azide is a newly explored responsive motif targeting H2S selectively. Diselenide, on the other hand, is a group susceptible to both oxidative and reducing conditions and therefore it has been exploited in dual redox-responsive PNMs. Here, we review PNMs, mainly reported in the last four years, that contain these redox-responsive moieties for controlled payload release.

We demonstrate luminescent solar concentrators (LSCs) based on colloidal silicon quantum dots (SiQDs) as UV-selective fluorophores and coupled with front-facing silicon photovoltaic cells for the solar window application. The visibly transparent LSC composed of a thin layer of liquid SiQD suspension sandwiched between two thin glass slabs constitutes the windowpane, while strips of silicon photovoltaic cells with their front surfaces adhering to the LSC rear surface form the window frame. Furthermore, the LSC perimeter is surrounded by reflecting mirrors for preventing the fluorescence from leaking out through the edges. The SiQDs dispersed in 1-octadecene selectively absorb UV light and re-emit red fluorescence with quantum efficiency about 40%. Owing to the negligible overlap between the absorbance and photoluminescence spectra, the reabsorption effect is insignificant. The front-facing silicon photovoltaic strips located at the window frame can produce electricity by harvesting not only solar radiation but also the SiQD-generated fluorescence propagating from the windowpane. For the SiQD-LSC with the total light absorbing area equal to 12 cm × 12 cm and the reflecting mirrors tilted 45°, an overall power conversion efficiency of 2.47% under simulated sunlight can be obtained of which about 6% is contributed by the SiQD fluorescence. Meanwhile, the SiQD-LSC retains high spectral quality with average visible transmission and color rendering index through the windowpane equal to 86% and 94, respectively.

Hydrogen sulfide (H2S) is a signaling molecule whose overexpression is identified in various cancers. Despite the flourishing research of H2S-responsive nanomaterials, the development of H2S-respon...

Peripheral blood mononuclear cells are widely used as source material for anticancer immunotherapies. The conventional cryopreservation method for peripheral blood mononuclear cells is time-consuming and expansive, which involves controlled rate freezing followed by storage in liquid nitrogen. Instead, the convenient uncontrolled rate freezing cryopreservation method had been reported successfully in peripheral blood hematopoietic stem cells and peripheral blood progenitor cells. Therefore, we hypothesized that uncontrolled rate freezing cooling method maybe also applied to peripheral blood mononuclear cells cryopreservation. In this study, we evaluated the performance of uncontrolled rate freezing and controlled rate freezing cooling methods through cell recovery rate, viability, differentiation potential into cytokine-induced killer cells and the cellular properties of the cultured cytokine-induced killer cells. The results showed similar post-thaw viability and recovery rate in both controlled rate freezing and uncontrolled rate freezing cryopreserved peripheral blood mononuclear cells. Importantly, the uncontrolled rate freezing cryopreserved peripheral blood mononuclear cells exhibited higher growth ratio and earlier cell clustering during ex-vivo cytokine-induced killer cell culture than the controlled rate freezing ones. These two groups of expanded cytokine-induced killer cells also exhibited similar effector cell subset ratio and tumoricidal activity. In general, the performance of cryopreserved peripheral blood mononuclear cells using uncontrolled rate freezing cooling method, with the commercial cryoprotective agent CellBanker 2, was equal or better than the controlled rate freezing method. Our study implied that the combined use of cryoprotective agent CellBanker 2 and uncontrolled rate freezing could be a convenient cryopreservation method for peripheral blood mononuclear cells.

By using a bifunctional organic ligand 4,4′-(1 H-1,2,4-triazol-1-yl)methylene-bis(benzonic acid) (H2tmb) which features both triazol and carboxylate groups, two new coordination polymers (CPs) {[Co...

Oxygen-consuming fuel tank inerting technology is a novel technology with a simple structure and a high efficiency for tank explosion suppression based on flameless catalytic combustion. To...

Cleavage of carbon–carbon bonds has been found in some important industrial processes, for example, petroleum cracking, and has inspired development of numerous synthetic methods. However, nonpolar unstrained C(aryl)–C(aryl) bonds remain one of the toughest bonds to be activated. As a detailed study of a fundamental reaction mode, here a full story is described about our development of a Ru-catalyzed reductive cleavage of unstrained C(aryl)–C(aryl) bonds. A wide range of biaryl compounds that contain directing groups (DGs) at 2,2′ positions can serve as effective substrates. Various heterocycles, such as pyridine, quinoline, pyrimidine, and pyrazole, can be employed as DGs. Besides hydrogen gas, other reagents, such as Hantzsch ester, silanes, and alcohols, can be employed as terminal reductants. The reaction is pH neutral and free of oxidants; thus a number of functional groups are tolerated. Notably, a one-pot C–C activation/C–C coupling has been realized. Computational and experimental mechanistic studies indicate that the reaction involves a ruthenium(II) monohydride-mediated C(aryl)–C(aryl) activation and the resting state of the catalyst is a η(4)-coordinated ruthenium(II) dichloride complex, which could inspire development of other transformations based on this reaction mode.

Chemotherapy resistance is an important problem for clinical therapy of osteosarcoma (OS). The potential effects of histone deacetylases (HDACs) on OS chemoresistance are studied. The expression of HDACs in OS cells resistance to doxorubicin (Dox) and cisplatin (CDDP) is checked. Among 11 members of HDACs, levels of HDAC6 are significantly upregulated in OS cells resistance to Dox and CDDP. Inhibition of HDAC6 via its specific inhibitor ACY1215 restores chemosensitivity of OS-resistant cells. Further, HDAC6 directly binds with estrogen-related receptors alpha (ERRα) to regulate its acetylation and protein stability. Inhibition of ERRα further strengthens ACY1215-increased chemosensitivity of OS-resistant cells. Mechanistically, K129 acetylation is the key residue for HDAC6-regulated protein levels of ERRα. Collectively, we find that ERRα contributes to HDAC6-induced chemoresistance of OS cells. Inhibition of HDAC6/ERRα axis might be a potential approach to overcome chemoresistance and improve therapy efficiency for OS treatment. 1. HDAC6 was significantly upregulated in Dox and CDDP resistant OS cells; 2. Inhibition of HDAC6 can restore chemosensitivity of OS cells; 3. HDAC6 binds with ERRα at K129 to decrease its acetylation and increase protein stability; 4. ERRα contributes to HDAC6-induced chemoresistance of OS cells.

Circular FOXM1 (circFOXM1) has been demonstrated to participate in the initiation and development of cancers, including prostate cancer (PCa). However, there is no relevant information on the regulation of PCa by circFOXM1. The RNA level of circFOXM1 was detected by qRT-PCR in PCa tissues and cells. The protein expression was performed by western blot and immunohistochemistry assay. Cell proliferation was examined by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide, colony formation and flow cytometry assays. The abilities of cell migration and invasion were determined by transwell assay. The relationship between circFOXM1 and miR-515-5p or ADAM10 was predicted by starBaseV2.0 online database, and identified by dual-luciferase reporter assay or RNA pull-down assay. The effects of circFOXM1 silencing and ADAM10 knockdown on PCa growth in vivo were evaluated by in-vivo tumor formation assay. As a result, we found that circFOXM1 and ADAM10 expression were upregulated in PCa tissues and cells. Functional analysis showed that circFOXM1 silencing repressed proliferation, migration and invasion, and induced cell cycle arrest, whereas these effects were partly reversed by miR-515-5p inhibitor. Additionally, circFOXM1 directly sponged miR-515-5p, and miR-515-5p bound to ADAM10. ADAM10 absence also repressed PCa process. Furthermore, in-vivo tumor formation assay revealed that both circFOXM1 silencing and ADAM10 knockdown repressed tumor growth in vivo. Thus, we came a conclusion that circFOXM1 contributed to PCa progression via regulating miR-515-5p/ADAM10 axis. These results may provide a theoretical basis for further studying the progression of PCa.

Dolomite diagenesis is a key issue in the evolution of dolomite reservoirs. Hence, lower Paleozoic carbonate samples from the Bonan Low Uplift are analyzed. Data collected from thin sections, cathodoluminescence, X-ray diffraction, major and trace elements, rare earth elements, isotopes, and other experimental work to determine the types, diagenetic environment, and fluid characteristics of dolomite, are used to determine its genesis. Three main dolomite types are identified: D1 with a very good original structure, D2 without an original structure, and D3 with a poorly preserved original structure. The concentrations of many geochemical indicators follow the order of D1>D2>D3. The ratios of MnO to TiO2 in both D2 and D3 are >0.5, and the Rb concentration of D2 is greater than that of D3. δCe shows that D1 and D2 are partially oxidized, while D3 is not. The D1, D2, and D3 diagenetic temperatures are 49.28, 54.96, and 50.23°C, respectively. The order degrees of D1 and D2 are 0.56 and 0.75, respectively, while that of D3 ranges widely. Comprehensive data show that D1 originated from evaporative dolomitization in the syndiagenetic period, and the diagenetic fluid was sea-sourced fluid mixed with terrestrial fluids. D2 was generated by seepage reflux dolomitization, which occurred in the penecontemporaneous-shallow burial period, and its high-salinity diagenetic fluid is inherited from sea-sourced fluids, with the participation of pore fluids. D3 was formed in shallow burial dolomitization, and its diagenetic fluid inherited from sea-sourced fluids and pore fluids is characterized by low salinity.

A simple and effective approach is demonstrated to fabricate tough metallosupramolecular hydrogel films of poly(acrylic acid) by one-pot photopolymerization of the precursor solution in the presence of Zr4+ ions that form coordination complexes with the carboxyl groups and serve as the physical crosslinks of the matrix. Both as-prepared and equilibrated hydrogel films are transparent, tough, and stable over a wide range of temperature, ionic strength, and pH. The thickness of the films can be easily tailored with minimum value of ≈7 μm. Owing to the fast polymerization and gelation process, kirigami structures can be facilely encoded to the gel films by photolithographic polymerization, affording versatile functions such as additional stretchability and better compliance of the planar films to encapsulate objects with sophisticated geometries that are important for the design of soft electronics. By stencil printing of liquid metal on the hydrogel film with a kirigami structure, the integrated soft electronics shows good compliance to cover curved surfaces and high sensitivity to monitor human motions. Furthermore, this strategy is applied to diverse natural and synthetic macromolecules containing carboxyl groups to develop tough hydrogel films, which will open opportunities for the applications of hydrogel films in biomedical and engineering fields.

BackgroundThere have been reports of increasing azole resistance in Candida tropicalis, especially in the Asia-Pacific region. Here we report on the epidemiology and antifungal susceptibility of C. tropicalis causing invasive candidiasis in China, from a 9-year surveillance study.MethodsFrom August 2009 to July 2018, C. tropicalis isolates (n = 3702) were collected from 87 hospitals across China. Species identification was carried out by mass spectrometry or rDNA sequencing. Antifungal susceptibility was determined by Clinical and Laboratory Standards Institute disk diffusion (CHIF-NET10–14, n = 1510) or Sensititre YeastOne (CHIF-NET15–18, n = 2192) methods.ResultsOverall, 22.2% (823/3702) of the isolates were resistant to fluconazole, with 90.4% (744/823) being cross-resistant to voriconazole. In addition, 16.9 (370/2192) and 71.7% (1572/2192) of the isolates were of non-wild-type phenotype to itraconazole and posaconazole, respectively. Over the 9 years of surveillance, the fluconazole resistance rate continued to increase, rising from 5.7 (7/122) to 31.8% (236/741), while that for voriconazole was almost the same, rising from 5.7 (7/122) to 29.1% (216/741), with no significant statistical differences across the geographic regions. However, significant difference in fluconazole resistance rate was noted between isolates cultured from blood (27.2%, 489/1799) and those from non-blood (17.6%, 334/1903) specimens (P-value < 0.05), and amongst isolates collected from medical wards (28.1%, 312/1110) versus intensive care units (19.6%, 214/1092) and surgical wards (17.9%, 194/1086) (Bonferroni adjusted P-value < 0.05). Although echinocandin resistance remained low (0.8%, 18/2192) during the surveillance period, it was observed in most administrative regions, and one-third (6/18) of these isolates were simultaneously resistant to fluconazole.ConclusionThe continual decrease in the rate of azole susceptibility among C. tropicalis strains has become a nationwide challenge in China, and the emergence of multi-drug resistance could pose further threats. These phenomena call for effective efforts in future interventions.

A new design strategy through the synergy of Mo(VI)–Mo(V) intervalence charge transfer and π(radical)–π(radical/cation) interactions is proposed to obtain semiconductors with photoresponsive ranges covering the whole UV–SWIR (ultraviolet–shortwave near-infrared; ca. 250–3000 nm) region. With this strategy, a viologen-based molybdate semiconductor with a UV–SWIR photoresponsive range was obtained through UV/X-ray irradiation or thermal annealing. The thermally annealed semiconductor has the highest conversion and the best photocurrent response in the range of 355–2400 nm.

Rogressive deconstruction of filament actin (F-actin) in hippocampal neurons in the epileptic brain have been associated with epileptogenesis. Previous clinical studies suggest that glucocorticoids treatment plays beneficial roles in refractory epilepsy. Glucocorticoids treatment affects dendritic spine morphology by regulating local glucocorticoid receptors and F-actin cytoskeleton dynamics. However, how glucocorticoids regulate epileptogenesis by controlling F-actin cytoskeleton is not clear yet. Here we study the function of glucocorticoids in epileptogenesis by examining F-actin abundance, hippocampal neuron number, and synaptic markers in pilocarpine-induced epileptic mice in the presence or absence of dexamethasone (DEX) treatment. We found that spontaneous seizure duration was significantly reduced; F-actin damage in hippocampal subfields was remarkably attenuated; loss of pyramidal cells was dramatically decreased; more intact synaptic structures indicated by pre- and postsynaptic markers were preserved in multiple hippocampal regions after DEX treatment. However, the number of ZNT3 positive particles in the molecular layer in the hippocampus of pilocarpine epileptic mice was not altered after DEX treatment. Although not sufficient to cease epileptogenesis, our results suggest that dexamethasone treatment ameliorates the damage of epileptic brain by stabilizing F-actin cytoskeleton in the pilocarpine epileptic mice.

Chemical vapor transport deposition (CVTD) is an effective method for preparing large tungsten coatings for space thermionic reactors. In this study, a high-density, high-work-function polycrystalline tungsten coating was prepared using a WCl6 transport agent in a concentric tube-type closed transport system. The relationship between the kinetics and the microstructures of the CVTD polycrystalline tungsten coating at the substrate temperature of 1593 K-1793 K and system pressure of 15.93 Pa-106.8 Pa was studied, which provided a basis for the preparation of high-quality tungsten coatings. At a low temperature or a low pressure, the activation energy was approximately 2 kJ/mol, the deposition rate was almost independent of the temperature changes, and the control mechanism was mass transport limited. The tungsten coating had nodules on the surface with pores in the grain boundaries and grew preferentially along . At a high temperature and a high pressure, the apparent activation energy was approximately 90 kJ/mol, the value of order was approximately 1, and the control mechanism in this process range was surface limited. The tungsten coating exhibited a hexagonal pyramidal structure, and the growth direction was preferred along . The average work function of the tungsten coating prepared at a temperature of 1673 K and a system pressure of 106.80 Pa was as high as 5.20 eV.

Herein, the preparation of numerous bismuth oxychloride/bismuth oxybromide/bismuth oxyiodide/graphene oxide (BiOxCly/BiOmBrn/BiOpIq/GO) composites is reported. A facile hydrothermal method was employed to synthesize these photocatalysts, which had various GO contents. A total of 10 bismuth-oxyhalide composites were isolated and characterized using FE–SEM, XRD, FE–TEM, UV–Vis–DRS, FT–IR, EPR, HR–XPS, PL, and BET. The photocatalytic efficiencies of these 10 bismuth-oxyhalide composites were measured under visible-light irradiation by estimating the concentration of 2-hydroxybenzoic acid (HBA) degradation. The findings indicated that the rate constant order of the HBA degradations was BiOCl/BiOBr/BiOI/GO > Bi3O4Cl/Bi3O4Br/Bi4O5I2/GO > Bi12O17Cl2/Bi3O4Cl/Bi12O17Br2/ Bi7O9I3/GO > Bi12O17Cl2/BiOBr/BiOI/GO > Bi12O17Cl2/Bi12O17Br2/Bi7O9I3/Bi5O7I/GO > Bi3O4Cl/BiOBr/Bi3O4Br/Bi4O5I2 > Bi3O4Cl/BiOBr/BiOI > BiOCl/BiOBr/BiOI > Bi12O17Cl2/Bi5O7Br/Bi5O7I > GO. A maximum rate constant of 0.191 h−1 was reached for BiOCl/BiOBr/BiOI/GO, providing photocatalytic efficiency that was eight times higher than that of composite BiOCl/BiOBr/BiOI. We also proposed a photocatalytic mechanism demonstrating that O2 −, h±, OH, and 1O2 are all essential for HBA degradation.

Kaempferol is a kind of bioflavonoid exerts diverse pharmacological activities, including anti-apoptotic and anti-inflammatory activities. Kaempferol has been recognized as an effective agent for alleviating the clinical symptoms of osteoarthritis (OA). This study aimed to provide evidence that Kaempferol has potential in the management of OA. Lipopolysaccharide (LPS) stimulation induced a significant cell death and inflammatory injury in ATDC5 cells, as evidenced by the decreased cell viability, the induced apoptosis, the activated caspase-3, and the excessive production of IL-6, IL-8 and TNF-α. Precondition of cells with Kaempferol prevented apoptosis and the release of proinflammatory cytokines triggered by LPS. miR-146a was down-regulated by Kaempferol treatment, and Decorin was up-regulated by miR-146a overexpression. Consistently, both silence of miR-146a and Decorin exhibited Kaempferol-like effects towards ATDC5 cells stimulated by LPS. Moreover, Decorin silence activated PI3K/AKT/mTOR signaling pathway. In rat model of OA, the expression of miR-146a and Decorin in cartilage tissues was repressed by Kaempferol. Also, the activated PI3K/AKT/mTOR signaling pathway in OA animal model was enhanced by Kaempferol administration. These data suggested that Kaempferol exerted potential anti-OA effects through down-regulation of miR-146a, and thus repressing the expression of Decorin.

In this study, we compared three commercially available and two widely used CPAs for their ability of cryopreserving PBMCs. Similar survival (81.0%) and recovery rate (73.7%) were observed among cells using these five CPAs. However, all the cryopreserved PBMCs exhibited a significantly lower survival rate when compared with the fresh samples (94.3%). We further evaluated effector cell subpopulation and tumoricidal activity of PBMC-derived cytokine-induced killing (CIK) cells and natural killing (NK) cells. Similar and high survival (CIK: 88.6%; NK: 87.5%) and recovery (CIK: 99.5%; NK: 99.7%) rates were detected in CIK and NK cells prepared from cryopreserved PBMCs using the five CPAs. The CD3+CD56+ effector percentage (27.3%) of cryopreserved PBMC-derived CIK cells using the five different CPAs and their tumoricidal activities on melanoma CHL-1 cells (45.7%) and bladder cancer cell line T-24 (44.7%) were similar but significantly lower than those of the fresh PBMC-derived controls (effector: 30.7%; CHL-1: 84.2%; T-24: 82.2%). Cryopreserved PBMC-derived NK cells also exhibited similar tumoricidal activities (CHL-1: 73.8%; T-24: 71.9%) but was significantly lower than that of the fresh control group. We were not able to identify a specific CPA that performed superior than others in PBMC cryopreservation.

Two Cu(II) complexes of the non-steroidal anti-inflammatory drug Naproxen were synthesized, characterized and evaluated for anti-inflammatory, analgesic, ulcerogenic and urease inhibition activities. The complex 1 [Cu(nap)2(H2O)3]·H2O was reported previously, and the crystal structure of complex 2 [Cu(nap)2(dap)(H2O)] (nap = Naproxen, dap = 1,3-diaminopropane) was confirmed by X-ray diffraction crystallography. The anti-inflammatory and ulcerogenic study showed that the compounds 1 and 2 were the promising anti-inflammatory agents and demonstrated significant gastric tolerance when compared with Naproxen, especially for complex 1 with the edema inhibition of 93.6% after 3 h, and ulcer index of 15 ± 2. Analgesic and urease inhibition assay showed that complex 2 was a potent urease inhibitor with the IC50 value of 1.69 ± 0.08 μM and pain inhibition value of 65%. As effective urease inhibitors, molecular docking study was performed to investigate the binding mode of the complexes with urease.

The repair of peripheral nerve injury is still a great challenge in clinic. Autologous nerve transplantation is the gold standard for the treatment of long-distance peripheral nerve defects, but this method remains associated with high morbidity of the donor site and lack of matching donor. In this study, a novel chitosan scaffold (CS) loaded with control-released basic fibroblast growth factor (bFGF) was used to repair 20 mm sciatic nerve defects in adult rat. The ultrastructure of bFGF-CS was observed by scanning electron microscope. The tensile tester and nano-indentation were used to evaluate its mechanical properties. Cholera toxin B-subunit (CTB) tracing, sciatic nerve function index, electromyography, immunofluorescence staining of regenerated nerve and motor endplate were used to evaluate the regeneration of sciatic nerve in rats. The results showed that the structure and mechanical properties of bFGF-CS was beneficial to the regeneration of sciatic nerve. At 12 weeks after operation, bFGF-CS facilitated sciatic nerve regeneration in rat. CTB successfully crossed the sciatic nerve defect area to reach the cell body of sciatic nerve. The motor endplate was reconstructed, thus promoting the behavioral recovery. These findings suggest that the bFGF-CS provides an effective means of repairing 20 mm sciatic nerve defects and shows great potential for clinical application.

The beneficial effects of 5-aminolevulinic acid (ALA) on abiotic stress have been demonstrated in several plant species. However, little is known about the signal transduction pathways triggered by ALA in the photooxidative stress response. In this study, we investigated the effects of ALA on methyl viologen (MV)-induced photooxidative stress tolerance in detached pear leaves (Pyrus ussuriensis). Furthermore, we also examined the involvement of NADPH oxidase (RBOH)-mediated H2O2 as a signaling molecule in ALA-induced photooxidative stress tolerance. Our results showed that exogenous ALA alleviated the observed decreases in chlorophyll content and maximum potential photosystem II efficiency under MV-induced stress. Exogenous ALA also effectively reduced MV-induced oxidative damage and enhanced the activities of antioxidative enzymes (SOD and CAT). In situ determination of reactive oxygen species revealed that ALA induced H2O2 production in the pear leaves. Importantly, ALA-induced tolerance was abolished by an RBOH inhibitor. Further investigation revealed that the transient overexpression of RBOHF in tobacco leaves alleviated MV-induced damage by enhancing the activities of SOD and CAT. This study provides new insights into the mechanisms by which ALA improves photooxidative tolerance in pear leaves.

Background:Apoptosis of photoreceptor cells and oxidative stress of RPE in age-related macular degeneration (AMD) could be promoted by photopic oxidative stress. In our study we are aim to study the protective effect of chrysanthemum extract on light damaged retina of mice.Methods:In vitro, ARPE-19 cells are incubated and divided into four groups: the control, the light damaged, the low and high dose-chrysanthemum extract groups. The last three groups were dropped in zero, low and high concentration of chrysanthemum extract separately before exposing to light. Cellular viability and Reactive Oxygen Species(ROS) production were measured by MTT and immunofluorescence. In vivo, C57BL/6J mice were divided into four groups as above mentioned. Low and high concentration of chrysanthemum extract were given by continuous intragastric administration before being exposed to white light. Retinal function was evaluated by electroretinogram. Optical coherence tomography and Fluorescein fundus angiography were used to observe the morphology and vessels. HE staining and TUNEL immunofluorescence for presenting morphology and apoptosis of isolated retina.Results:Viability of ARPE-19 cells decreased and ROS production increased after the light damaged. However, treatment with chrysanthemum extract, viability improved and ROS declined. After light injury, dysfunctional retina, destroyed morphology and increased apoptosis rate were observed in mice especially in RPE and photoreceptor layer. Treatment with chrysanthemum extract, retina function improved as well as structure of RPE and photoreceptor layers. Rate of apoptosis decreased via the raised concentration of anti-oxidative enzyme superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px). Conclusions:Preventive administration of chrysanthemum extract reduces the oxidative-stress induced by light damage, which indicating Chrysanthemum have a potential of preventive measure for AMD.

Gas/particle (G/P) partition quotients of semi-volatile organic compounds (SVOCs) for bulk air have been widely discussed in experimental and theoretical contexts, but research on size-resolved G/P partition quotients (KPi) are scarce and limited in scope. To investigate G/P partition behavior of polybrominated diphenyl ethers (PBDEs) for size-segregated particles in the atmosphere, 396 individual size-segregated particulate samples (36 batches × 11 size-ranges), and 108 pairs of concurrent gaseous and bulk particulate samples were collected in Harbin, China. A steady-state equation based on bulk particles is derived to determine G/P partition quotients of PBDEs for size-segregated particles, which depends on the organic matter contents of size-segregated particles (fOMi). This equation can well predict KPi with knowledge of bulk partition quotient (KPS), ambient temperature, and fOMi, the results of which match well with monitoring data in Harbin and other published data collected in Shanghai and Guangzhou of China and Thessaloniki of Greece, and remedies a defect of over-estimate KPi for high-brominated PBDEs by the previous equation. In particular, the new equation contributes to obtaining the PBDEs concentrations in all atmospheric phase from partial phase, then provides a credible path to evaluate healthy exposure dose from the airborne PBDEs, by co-utilization with exposure models.

We synthesized an oxidation-responsive polycaprolactone (O-PCL) bearing pendant arylboronic esters as H2O2-responsive motifs. H2O2 induces fast depolymerization of O-PCL within days. Nanoparticles formulated from O-PCL disintegrate and release payload in response to concentrations of H2O2 (50 μM) that are relevant to human disease.

Aims The beneficial effects of cannabinoid type 2 receptor (CB2R) activation have been verified in various tissue repair processes. Our recent study revealed CB2R activation promotes myogenesis partly through Nrf2 signaling in a mouse skeletal muscle ischemia-reperfusion (IR) injury model. Other relevant mechanisms need to be further elucidated. Macrophages orchestrate tissue regeneration mainly by changing their phenotype and function. The aim of this study was to investigate the role of CB2R in IR-induced skeletal muscle regeneration, focusing on its impact on macrophage polarization and the consequences on myogenesis. Main methods The effects of CB2R on skeletal muscle regeneration, and the macrophage infiltration and M1/M2 polarization were tested with the IR injury model in wild type (WT) and CB2R knockout (CB2R-KO) mice. The effect of CB2R on peritoneal macrophage polarization, and its impact on the myoblasts differentiation was evaluated by co-culture experiments in vitro. Key findings The present study revealed the myofiber regeneration was hindered in the CB2R-KO mice. The infiltration of M1 macrophages and relevant markers' protein expression were enhanced in the CB2R-KO mice, while that of M2 macrophages was decreased compared with the WT mice. The in vitro studies further demonstrated that the absence of CB2R promoted M1 polarization while inhibited M2 polarization. The promoted M1 polarization and retarded M2 polarization in CB2R-KO macrophages hindered myoblasts differentiation. Significance Overall, these results suggested CB2R plays a beneficial effect on skeletal muscle regeneration partly by regulating macrophage M1/M2 polarization after IR injury in mice.

A quantitative method was established to determine the well-known endocrine disruptor bisphenol A (BPA) in barreled drinking water. Samples were pretreated by solid phase extraction (SPE), and then analyzed by liquid chromatography-mass spectrometry (LC-MS). Working standard solutions were obtained by pretreatment of a series of aqueous standard solutions over the concentration range of 122.9-1190.7 ng L

Three kinds of Pt-Cu bimetallic catalysts (Cu/Pt (111), Pt/Cu/Pt (111), and Pt4Cu5/Pt (111)) have been researched employing density functional theory (DFT) calculation, using dehydrogenation of cyclohexene to benzene as a probe reaction. The adsorption energies are basically in the sequence: Pt4Cu5/Pt (111) > Cu/Pt (111) ≈ Pt/Cu/Pt (111). The key step is C6H9 → C6H8 on Cu/Pt (111) (0.85 eV) and Pt/Cu/Pt (111) (0.87 eV). On Pt4Cu5/Pt (111), the key step is C6H7 → C6H6 (1.17 eV). The selectivity for gas phase benzene is in the order of Cu/Pt(111) > Pt/Cu/Pt(111) > Pt4Cu5/Pt(111), according to the energy difference between the barrier of benzene dehydrogenated to phenyl and benzene desorption. The co-adsorbed hydrogen atoms lead to improved selectivity for gas phase benzene on Cu/Pt (111) and Pt/Cu/Pt (111), by making benzene desorption easy but dehydrogenation difficult. However, the barrier of benzene dehydrogenation decreases with the increase of H coverage on the Pt4Cu5/Pt (111) due to obvious destabilized benzene, and thus the effect on Pt4Cu5/Pt (111) is closely related to the concentration of surface H. Attributed to thermodynamic stability, high activity, and selectivity for gas benzene, the Pt/Cu/Pt (111) structure is suggested as reasonable dehydrogenation catalyst, and the dehydrogenation process on Pt/Cu/Pt(111) has been further studied by microkinetic modeling. A volcano-like relationship is found between the adsorption of cyclohexene and the TOF (turnover frequency) of gas phase benzene. Secondly, two apparent activation energies are obtained: 0.77 eV (250~350 K) and 0.45 eV (350~650 K), implying the RDS (rate-determined step) changes with temperature.

Programmed deformations are widespread in nature, providing elegant paradigms to design self-morphing materials with promising applications in biomedical devices, flexible electronics, soft robotics, etc. In this emerging field, hydrogels are an ideal material to investigate the deformation principle and the structure-deformation relationship. One crucial step is to construct heterogeneous structures in a facile yet effective way. Herein, we provide a focus review on different deformation modes and corresponding structural features of hydrogels. Photolithography is a versatile approach to control the outer shape of the hydrogel and spatial distribution of the component in the hydrogel, endowing the patterned hydrogels with programmed internal stress and thus controllable deformations. Specifically, cooperative deformations take place in periodically patterned hydrogels with in-plane gradients, and multiple morphing structures are formed in one patterned hydrogel using selective preswelling to direct the buckling of each unit. The structural control strategy and deformation principles should be applicable to other materials with broad applications in diverse areas.

Three chiral metal–organic coordination polymers (CCPs) [Co(L)(bimb)] (1), [Cd(L)(bimb)] (2), [Zn(L)(bimb)] (3), (L = (R)-4-(4-(1-carboxyethoxy)phenoxy)-3-nitrobenzoic acid; bimb = 4,4′-bis((1H-imidazol-1-yl)methyl)-1,1′-biphenyl) have been successfully obtained via solvothermal reactions. The isomorphic 2D sq1 type network structures of CCPs 1–3 were determined by single-crystal X-ray diffraction analysis and further characterized by elemental analyses, IR, PXRD, TGA and circular dichroism (CD) spectra. Crystallized in chiral space group, CCPs 1–3 exhibit obvious Cotton effects in CD spectra and are proved to be second-harmonic generation (SHG) active. CCPs 1–3 also exhibit luminescence properties, the intensities of which could be affected by some metal cations, especially Fe3+. The Fe3+ sensing and photo catalytic properties toward methylene blue (MB) were also studied.

Zanamivir (ZA) and guanidino-oseltamivir carboxylic acid (GOC) are very potent inhibitors against influenza neuraminidase (NA). The guanidinium moiety plays an important role in NA binding; however, its polar cationic nature also hinders the use of ZA and GOC from oral administration. In this study, we investigated the use of ZA and GOC acylguanidine derivatives as possible orally available prodrugs. The acylguanidine derivatives were prepared by coupling with either n-octanoic acid or (S)-naproxen. The lipophilic acyl substituents were verified to improve cell permeability, and may also improve the bioavailability of acylguanidine compounds. In comparison, the acylguanidines bearing linear octanoyl chain showed better NA inhibitory activity and higher hydrolysis rate than the corresponding derivatives having bulky branched naproxen moiety. Our molecular docking experiments revealed that the straight octanoyl chain could extend to the 150-cavity and 430-cavity of NA to gain extra hydrophobic interactions. Mice receiving the ZA octanoylguanidine derivative survived from influenza infection better than those treated with ZA, whereas the GOC octanoylguanidine derivative could be orally administrated to treat mice with efficacy equal to oseltamivir. Our present study demonstrates that incorporation of appropriate lipophilic acyl substituents to the polar guanidine group of ZA and GOC is a feasible approach to develop oral drugs for influenza therapy.

Backgrounds Chronic inflammation in retinal pigment epithelial (RPE) cells is related to the pathogenesis of retinal inflammatory blind causing diseases such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). Nepetin, a natural flavonoid compound, has shown potent anti-inflammatory activities but has not been studied on ocular resident cells yet. Here, we assess the ability of Nepetin to alleviate the inflammatory responses of ARPE-19 cells induced by interleukin (IL)-1β. Methods The secretion and mRNA expression of inflammatory cytokines IL-6, IL-8 and monocyte chemoattractant protein-1 (MCP-1) induced by IL-1β are measured by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR) respectively. To clarify the underlying action mechanism, we examine the effect of Nepetin on activation of nuclear factor of kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways using Western blot. Results Nepetin can significantly decrease the three inflammatory mediators at both protein and mRNA level in a dose-dependent manner. Western blot results show that Nepetin can decrease the nuclear translocation of p65 through suppressing phosphorylation of inhibitor of nuclear factor kappa B (IκB) and IκB kinase (IKK). Also, Nepetin can decrease the phosphorylation of extracellular signal-regulated kinases (ERK) 1/2, c-Jun N-terminal kinase (JNK) and p38 MAPK. Conclusions Taken together, Nepetin abolishes IL-1β-induced IL-6, IL-8 and MCP-1 secretion and mRNA expression by repressing the activation of NF-κB and MAPKs. These results indicate that Nepetin shows potential to be used for prevention and treatment of inflammatory retinal diseases or as a lead compound.

A Co(0)-catalyzed intramolecular alkyne/benzocyclobutenone coupling through C–C cleavage of benzocyclobutenones is described. Co2(CO)8/P[3, 5-(CF3)2C6H3]3 was discovered to be an effective metal/ligand combination, which exhibits complementary catalytic activity to the previously established rhodium catalyst. In particular, the C8-substituted substrates failed in the Rh system, but succeeded with the Co catalysis. Experimental and computational studies show that the initially formed tetrahedral dicobalt-alkyne complex undergoes C1–C2 activation via oxidative addition with Co(0), followed by migratory insertion and reductive elimination to give the β-naphthol products.

COP1/SPA1 complex in Arabidopsis inhibits photomorphogenesis through the ubiquitination of multiple photo-responsive transcription factors in darkness, but such inhibiting function of COP1/SPA1 complex would be suppressed by cryptochromes in blue light. Extensive studies have been conducted on these mechanisms in Arabidopsis whereas little attention has been focused on whether another branch of land plants bryophyte utilizes this blue-light regulatory pathway. To study this problem, we conducted a study in the liverwort Marchantia polymorpha and obtained a MpSPA knock-out mutant, in which Mpspa exhibits the phenotype of an increased percentage of individuals with asymmetrical thallus growth, similar to MpCRY knock-out mutant. We also verified interactions of MpSPA with MpCRY (in a blue light-independent way) and with MpCOP1. Concomitantly, both MpSPA and MpCOP1 could interact with MpHY5, and MpSPA can promote MpCOP1 to ubiquitinate MpHY5 but MpCRY does not regulate the ubiquitination of MpHY5 by MpCOP1/MpSPA complex. These data suggest that COP1/SPA ubiquitinating HY5 is conserved in Marchantia polymorpha, but dissimilar to CRY in Arabidopsis, MpCRY is not an inhibitor of this process under blue light.

(Imido)vanadium(V) dichloride complexes containing 2-(2′-benzimidazolyl)-6-methylpyridine ligand (L) of type V(NR)Cl2(L) [R = 1-adamantyl (Ad, 1), C6H5 (2), and 2,6-Me2C6H3 (3)] have been prepared, and their structures were determined by X-ray crystallography as distorted trigonal bipyramidal structures around vanadium. Reactions with ethylene using 1–3 in the presence of methylaluminoxane (MAO) afforded a mixture of oligomer and polymers, and the compositions were affected by the imido ligand employed. By contrast, 1–3 exhibited remarkable catalytic activities for ethylene polymerization in the presence of Me2AlCl; the phenylimido complex (2) exhibited the highest activity [80 100 kg-PE/mol-V·h turn over frequency (TOF, 2 850 000 h–1, 792 s–1)]. The ethylene copolymerizations with norbornene afforded ultrahigh-molecular-weight copolymers with uniform molecular weight distributions and compositions [e.g., Mn = 1.71–2.66 × 106, Mw/Mn = 2.27–2.53]. On the basis of V nuclear magnetic resonance (51V NMR), electron spin resonance, and V K-edge X-ray absorption near-edge structure (XANES) spectra of the catalyst solution, the observed difference in the catalyst performance in the presence of (between) MAO and Me2AlCl cocatalyst should be due to the formation of different catalytically active species with different oxidation states. Apparent changes in the oxidation state were observed in the (especially in the NMR and XANES) spectra upon addition of Me2AlCl, whereas no significant changes in the spectra were observed in presence of MAO.

Background: Because Pertuzumab hasn't been approved in China until 2020y, trastuzumab has been standard neoadjuvant treatment for HER2-positive breast cancer. But we don't know which is the optimal chemotherapy with or without anthracyclines in the trastuzumab-based HER2-blockade. We designed this clinical trial to compare efficacy and safety between anthracycline and carboplatin in combination with docetaxel and trastuzumab as neoadjuvant therapy. Methods: From Apr, 2013 to Apr, 2019, 124 patients were enrolled. 60 patients were randomly assigned to the ATH-TH group and 64 to the TCH group. The treatment plan is showed as following, 1. TCH group: Trastuzumab(8mg/kg loading dose followed by 6mg/kg maintenance dose on day 1 every 3 weeks) combined with carboplatin(AUC=6 on day1 every 3 weeks) and docetaxel (75mg/m2 d1 every 3 weeks), total 6 cycles ; 2. ATH-TH group: Trastuzumab combined with doxorubicin( 50mg/m2 on day1 every 3 weeks) and docetaxel (75mg/m2 d1 every 3 weeks) after 4 cycles, followed by Trastuzumab plus docetaxel (75mg/m2 d1 every 3 weeks) 4 cycles. Primary endpoint was pCR(ypT0/is/ypN0). Second endpoints included safety, event-free and overall survial (EFS and OS). This trial is registered with ClinicalTrials.gov, number NCT 02510781.Results: Baseline Patients’ characteristics were well balanced between ATH-TH group and TCH group: median age 49y/48y, hormone receptor positive 51.7% vs 46.9%, II stage 60.0% VS 64.0%, III stage 33.3% VS 32.8%. The pCR rate was no significant difference(P=0.457) in ATH-TH 56.7%(95% CI:43.8%-69.6% ) and TCH group 50.0% ( 95% CI :37.4%-62.6%) .In hormone positive subgroup, the pCR rate was 36.7% ( 95% CI:18.4%-55.0% )for TCH group, and 51.6% (95% CI:33.0%-70.2%) for ATH-TH group (P=0.24). In hormone negative subgroup, the pCR rate was 61.8% (95% CI:44.6%-79.0% )for TCH group, and 62.1% ( 95% CI:43.3%-80.9%) for ATH-TH group (P=0.98). The most common adverse events were hematologic toxicities. ATH-TH group had higher 3/4 grade leukocyte decrease rates than TCH group ( 86.7% VS 43.8%, p Citation Format: Tao Wang, Jin-Mei Zhou, Xiao-Peng Hao, Hui-Qaing Zhang, Shao-Hua Zhang, Li Bian, Ze-Fei Jiang. A randomized, opened, phase II trial assessing the efficacy and safety of ATH-TH(doxorubicin/docetaxel/trastuzumab followed by docetaxel/trastuzumab) versus TCH(docetaxel/carboplatin/trastuzumab) as neoadjuvant treatment in HER2-positive breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-14.

Electrocatalytic conversion of short-chain hydrocarbons is a promising alternative route of traditional heterogeneous catalytic conversion, due to the advantages of ease in selectivity tuning by electrode potential, effective utilization of renewable electricity and reducing CO2 emission. In this study, we investigated electrochemical conversion of ethane on Pt single crystal electrodes (Pt(S)[n(1 0 0) × (1 1 0)] and Pt(S)[n(1 0 0) × (1 1 1)] step surfaces) for the first time through the combination of cyclic voltammetry (CV) and in situ FTIR spectroscopy (In situ FTIRS). The results revealed that the reactivity of ethane conversion is highly sensitive to the surface structure of Pt, and the highest reactivity is achieved on Pt(1 0 0) surface. The introduction of step sites on (1 0 0) terrace will dramatically decrease the activity. Cyclic voltammogram of ethane oxidation on Pt(1 0 0) shows three oxidative peaks in positive-going potential scan and one oxidative peak in negative-going potential scan. In the potential range from 0.25 to 0.55 V, ethane can be dissociated to form mainly bridge-bonded CO, which can be further oxidized to CO2 at high potentials. The other promising pathway is without C C breaking, resulting in valuable products such as acetic acid and acetaldehyde at a relatively low potential of 0.50 V. At a potential over 0.60 V, bridge-bonded acetate was detected by in situ FTIR spectroscopy. Based on the experiment results, a possible reaction mechanism for the electrocatalytic conversion of ethane on Pt(1 0 0) was proposed.

Purpose The ocular surface is considered an important route for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. The expression level of the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) is vital for viral infection. However, the regulation of ACE2 expression on the ocular surface is still unknown. We aimed to determine the change in ACE2 expression in inflamed corneal epithelium and explore potential drugs to reduce the expression of ACE2 on the ocular surface. Methods The expression of the SARS-CoV-2 receptors ACE2 and TMPRSS2 in human corneal epithelial cells (HCECs) was examined by qPCR and Western blotting. The altered expression of ACE2 in inflammatory corneal epithelium was evaluated in TNFα- and IL-1β-stimulated HCECs and inflamed mouse corneal epithelium, and the effect of resveratrol on ACE2 expression in HCECs was detected by immunofluorescence and Western blot analysis. Results ACE2 and TMPRSS2 are expressed on the human corneal epithelial cells. ACE2 expression is upregulated in HCECs by stimulation with TNFα and IL-1β and inflamed mouse corneas, including dry eye and alkali-burned corneas. In addition, resveratrol attenuates the increased expression of ACE2 induced by TNFα in HCECs. Conclusions This study demonstrates that ACE2 is highly expressed in HCECs and can be upregulated by stimulation with inflammatory cytokines and inflamed mouse corneal epithelium. Resveratrol may be able to reduce the increased expression of ACE2 on the inflammatory ocular surface. Our work suggests that patients with an inflammatory ocular surface may display higher ACE2 expression, which increases the risk of SARS-CoV-2 infection.

Objectives Vascular calcification is a dysfunction of the vasculature. Recent findings indicate that fibroblast growth factor21 (FGF21), a protector of the cardiovascular system, is related to the mineral deposition of bone and enhances the osteogenic activity of bone morphogenic protein (BMP)-2. In this study, we explored whether FGF21 suppresses vascular calcification. Methods A calcifying model was established by culturing primary rat vascular aortic smooth muscle cells (VSMCs) in a beta-glycerophosphate (BGP)-containing calcifying medium for 14 days. In addition, recombinant human FGF21 was applied to protect against VSMC calcification. Results In the presence of BGP, the expression levels of osteoblastic genes, including alkaline phosphatase (ALP), BMP-2 and runt-related transcription factor (RUNX)-2, were significantly upregulated on day 3, an effect that was maintained through day 14 (P < 0.001). A concomitant increase in ALP protein expression was observed through day 9 (P < 0.05). The incubation of VSMCs with calcifying medium for 14 days increased ALP activity (P < 0.05) and led to the formation of visible calcium nodules over the course of the protocol. β-klotho expression was unaltered in BGP-induced VSMCs for the 14-day culture period. The culturing of VSMCs with calcifying medium led to opposing trends in the expression of FGFRs, namely, an increase in FGFR1 and FGFR4 mRNA levels (P < 0.001) and a decrease in FGFR2 and FGFR3 mRNA levels (P < 0.01). Reduced mineral deposition, in combination with decreased ALP activity (P < 0.001) and ALP protein expression (P < 0.001), was noted in VSMCs treated with varying doses of FGF21 and BGP in a dose-dependent manner. In addition, FGF21 downregulated osteoblastic-promoting gene expression, including ALP (P < 0.001), BMP-2 (P < 0.001) and RUNX-2 (P < 0.001). Furthermore, FGF21 enhanced β-klotho expression (P < 0.05) and increased FGFR1 and FGFR3 mRNA levels (P < 0.001). FGFR-1 inhibitor SU5402 blocked partial inhibition of FGF21 on the expression of BMP-2 (P < 0.001) and RUNX-2 (P < 0.05). Furthermore, FGF21 suppressed the phosphorylation of P38, while P38 inhibitor, SB203580, attenuated the downregulation of RUNX-2 (P < 0.05). Conclusions These data demonstrate FGF21 attenuates VSMC calcification in vitro via an FGF21/FGFR1/3/β-klotho/P38MAPK/RUNX-2 signalling pathway.

A novel actinomycete strain, designated XHU 5301T, was isolated from a hypersaline habitat, China. The strain was aerobic, Gram-stain positive and the optimum NaCl concentration for growth was 7-9% (w/v). Phylogenetic analysis based on an almost-complete 16S rRNA gene sequence of strain XHU 5301T showed that the organism was most closely related to Glycomyces halotolerans TRM 40137T (96.0%). The whole-cell sugar pattern consisted of glucose and galactose. The predominant menaquinone was MK-10(H4), MK-10(H2), and MK-9(H4). The major fatty acids were anteiso-C15: 0, iso-C15: 0, iso-C16: 0, and methyl-C19: 0. The polar lipids consist of diphosphatidylglycerol, phosphatidylglycerol, and one unknown phospholipid. The G+C content of the genomic DNA was 72.5 mol %. The novel species Glycomyces xinjiangensis sp. nov. was proposed, with strain XHU 5301T (=CCTCC AA 2016043T =KCTC 39689T) as the type strain of Glycomyces xinjiangensis.