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Xuanfeibaidu Formula (XFBD) is a Chinese medicine used in the clinical treatment of coronavirus disease 2019 (COVID-19) patients. Although XFBD has exhibited significant therapeutic efficacy in clinical practice, its underlying pharmacological mechanism remains unclear. Here, we combine a comprehensive research approach that includes network pharmacology, transcriptomics, and bioassays in multiple model systems to investigate the pharmacological mechanism of XFBD and its bioactive substances. High-resolution mass spectrometry was combined with molecular networking to profile the major active substances in XFBD. A total of 154 compounds were identified or tentatively characterized, including flavonoids, terpenes, carboxylic acids, and other types of constituents. Based on the chemical composition of XFBD, a network pharmacology-based analysis identified inflammation-related pathways as primary targets. Thus, we examined the anti-inflammation activity of XFBD in a lipopolysaccharide-induced acute inflammation mice model. XFBD significantly alleviated pulmonary inflammation and decreased the level of serum proinflammatory cytokines. Transcriptomic profiling suggested that genes related to macrophage function were differently expressed after XFBD treatment. Consequently, the effects of XFBD on macrophage activation and mobilization were investigated in a macrophage cell line and a zebrafish wounding model. XFBD exerts strong inhibitory effects on both macrophage activation and migration. Moreover, through multimodal screening, we further identified the major components and compounds from the different herbs of XFBD that mediate its anti-inflammation function. Active components from XFBD, including Polygoni cuspidati Rhizoma, Phragmitis Rhizoma, and Citri grandis Exocarpium rubrum, were then found to strongly downregulate macrophage activation, and polydatin, isoliquiritin, and acteoside were identified as active compounds. Components of Artemisiae annuae Herba and Ephedrae Herba were found to substantially inhibit endogenous macrophage migration, while the presence of ephedrine, atractylenolide, and kaempferol was attributed to these effects. In summary, our study explores the pharmacological mechanism and effective components of XFBD in inflammation regulation via multimodal approaches, and thereby provides a biological illustration of the clinical efficacy of XFBD.

Higher manganese silicide (HMS) is a P-type medium temperature thermoelectric (TE) material, which has attracted widespread attention over the past few decades due to its remarkable mechanical properties, excellent chemical and thermal stability, as well as the non-toxicity, abundance and competitive price. The peak power factor (PF) of HMS is as high as ∼1.50 × 10−3 W m−1 K−2 because of its intrinsic high electrical conductivity and Seebeck coefficient. However, the thermal conductivity of HMS is also high, resulting in relatively low zT values. Introducing nano-dispersion in the matrix is one of the most effective methods to enhance the TE properties via reducing the lattice thermal conductivity significantly without drastic changes on the other parameters. In this study, CsPbBr3 QDs with uniform size were synthesized and introduced into HMS bulks. The PF (at 823 K) was enhanced to 1.71 × 10−3 W m−1 K−2, which is improved 14.0% approximately compared with that of pure HMS owing to the combined effect of element doping and energy filtering. The lattice thermal conductivity (at 823 K) decreased from 2.56 W m−1 K−1 to 1.99 W m−1 K−1 synchronously (∼22.0%) due to the intensive phonon scattering caused by Cs doping, and the embedding of Pb riched CsPbBr3 QDs and Pb QDs. A maximum zT value of 0.57 (823 K) is achieved in CsPbBr3 QDs/HMS composites, which is 36.0% higher than that of pure HMS. Predictably, for other TE materials, it is also feasible to improve the TE properties via introducing metastable quantum dots.

In this study, a series of poly (butylene succinate) (PBSU)/gelatin composites were prepared by electrospinning. The morphology, physicochemical analysis, biomechanical properties, biocompatibility, and biodegradability of the materials were evaluated. The results showed that the ultimate tensile stress of the vascular PBSU/gelatin grafts at (95/5), (90/10), (85/15), and (80/20) was (4.17 ± 0.54) MPa, (3.81 ± 0.44) MPa, 2.94 ± 0.69 MPa and 2.11 ± 0.72 MPa respectively, and the burst pressure was (282.7 ± 22.3) kPa, (295.3 ± 3.9) kPa, (306.8 ± 13.9) kPa and (307.6 ± 9.0) kPa respectively, which met the requirements of tissue-engineered blood vessels. Furthermore, the addition of gelatin improved the hydrophilicity and degradation properties of PBSU, thus enhancing cell adhesion and promoting the inward growth of vascular smooth muscle cells. In summary, the research in this paper provides a useful reference for the preparation and optimization of vascular scaffolds.

Xiexin decoctions (XXDs) display beneficial anti-inflammatory and anti-diabetic effects, which raises interests on this group of formulae for broad clinical applications. However, there was no report about systematic analysis of XXDs to elucidate the constitution of chemical components, which hampers further investigations on the therapeutic values of XXDs. In this work, crude herbs were extracted and prepared to obtain the XXDs for systemic analysis on their chemical compositions, according to the information described in the ancient Zhang Zhongjing's herbal formulae. LC-MS analysis of five XXDs was carried out to facilitate recognition of the source herbs for compounds in the mixture. A total number of 93 compounds were identified through our methods and their chemical classes encompassed five major groups, including protoberberine alkaloids, flavonoids, stilbenes, anthraquinones and saponins. Our current work provided important information about material basis for pharmacological studies on XXDs and would help shed light on relationships between chemical compositions and therapeutic effects.

Element doping and nano-inclusion embedding are effective approaches to enhance the electrical conductivities and decrease the lattice thermal conductivities of thermoelectric (TE) materials, respectively. However, the intrinsic low electrical thermal conductivities and high electrical properties are severely sacrificed, and the final figure of merit (ZT) is usually restricted. In this study, Ag doping and Pt quantum dot (QD) embedding were synchronously achieved via embedding Ag/Pt alloy QDs into the higher manganese silicides to avoid the conventional single-element doping strategy. The power factor (at 823 K) was enhanced from 1.57 × 10−3 W m−1 K−2 to 1.82 × 10−3 W m−1 K−2 (∼16%) due to the ∼18% increase in carrier concentration that was derived from the Ag doping effect. Simultaneously, the lattice thermal conductivity (at 823 K) decreased from 2.65 W m−1 K−1–1.92 W m−1 K−1 (∼28%) because of the broadband phonon scattering effect that resulted from the residual Pt QDs inclusions. Synthetically, the optimal ZT value increased by ∼52% from 0.42 to 0.64 at 823 K. This study demonstrated that incorporating metastable alloy QDs to obtain element doping and nano-inclusion embedding effects is a novel and feasible means to enhance the ZT value of HMS. This method is also possibly applicable to other alloy QD/TE composites.

A binder-free structure is beneficial for effective electron transport in electrocatalysts. Although metallic carbides have been well demonstrated as a kind of efficient electrocatalysts in the hydrogen evolution reaction (HER), a binder-free film of metal carbides has rarely been developed. In addition, the role of surface molybdenum oxide during HER has not been assessed, and is easily formed on the surface of molybdenum carbides due to air exposure. Here we show the convenient and scalable growth of a binder-free film of porous molybdenum carbide (Mo1.98C1.02) on the surface of carbon fiber paper. The nanoparticles of molybdenum carbide showed a clean surface. The resultant structure exhibited prominent catalytic activity in HER, reaching a current density of 10 mA cm−2 in alkaline solution at an overpotential of 47 mV, while that in acidic electrolyte occurred at an overpotential of 63 mV. The binder-free film of porous molybdenum carbide could sustain its activity in long-term HER. Comparative experiments showed that the superb performance of the binder-free film of porous molybdenum carbide was correlated with its binder-free structure, in situ removal of surface oxide, and the optimal amount of residual carbon in the film.

Discovering efficient and low CO selectivity non-noble heterogeneous catalysts toward formic acid (FA) dehydrogenation is vital for H2 energy systems. As a heating temperature is required to activate this reaction, the strategy of coupling a FA dehydrogenation reactor with a photothermal system possesses great potential for industrial applications. Herein, a sophisticated catalyst, a Mo1.98C1.02 porous film supported on carbon fiber paper, is demonstrated, with the advantages of a porous nanostructure, small nanoparticles and a carbon-supported structure simultaneously. The composite exhibits prominent thermal catalytic FA dehydrogenation, with a CO-free H2 generation rate of 0.79 L g−1 h−1 at 100 °C. Density functional theory calculations show that the formate route (*OCHOH → *OCOH + 1/2H2 → *OCO + 1/2H2 → CO2) is the minimum energy path for H2 and CO2 formation. Besides, a photothermal device was designed based on Bi2Te3/Cu, which can absorb and convert 1 kW m−2 irradiation into a high temperature of 240 °C, due to the high sunlight absorption, low heat conduction and low heat irradiation. Thus, a sunlight-driven thermal catalytic system was designed based on this device, with a H2 generation rate of 1.07 L g−1 h−1 under 0.25 kW m−2. This value is about two orders of magnitude faster than that of photocatalytic FA decomposition over reported non-precious photocatalysts. These results demonstrate that FA dehydrogenation can be realized under weak solar irradiation with the assistance of photothermal systems, facilitating industrial applications.

Sunlight driven formic acid decomposition has great potential to supply high-purity H2 without consuming fossil fuel-derived energy. However, a trace amount of CO invariably exists in the obtained H2 and the H2 production rate is always lower than 278 mmol g−1 h−1. Here, we found that high quality MoS2 grown on graphene decorated on Ni foam (Ni/G/MoS2) was active and stable for H2 production from thermocatalytic formic acid decomposition without CO presentation and first principles calculation confirmed that the perfect surface terminating sulfur of MoS2 changed the reaction path of intermediates, thus inhibiting the production of CO. Furthermore, a reaction device constructed with Cu2Se can heat catalysts to 120 and 260 °C under 0.25 kW m−2 and 1 kW m−2 (1 Sun) of irradiation, respectively. By using the system of the Cu2Se based reaction device and Ni/G/MoS2, a CO free H2 production rate of 982 mmol g−1 h−1 was achieved under 0.6 Sun of irradiation, 3.5 times higher than the previous record of photocatalytic formic acid decomposition. Therefore, this work provides a new viewpoint for large scale CO free H2 production in a sustainable and green way.

Discovering efficient and promising non-noble catalysts toward the alkaline hydrogen evolution reaction (HER) is vital for a clean energy system. Here, we design an efficient alkaline HER electroca...

Objective To explore the effect of kartogenin (KGN) on proliferation and chondrogenic differentiation of human umbilical cord mesenchymal stem cells (hUCMSC) in vitro, and the synergistic effects of KGN and transforming growth factor (TGF)‐β3 on hUCMSC. Methods Human umbilical cord mesenchymal stem cells were isolated and cultured. Then the differentiation properties were identified by flow cytometry analysis. HUCMSC were divided into four groups: control group, KGN group, TGF‐β3 group, and TK group (with TGF‐β3 and KGN added into the medium simultaneously). Cells in all groups were induced for 21 days using the suspension ball culture method. Hematoxylin and eosin, immunofluorescence, and Alcian blue staining were used to analyze chondrogenic differentiation. Real‐time reverse transcriptase polymerase chain reaction was performed to investigate genes associated with chondrogenic differentiation. Result Hematoxylin and eosin staining showed that cells in the TGF‐β3 group and the TK group had formed cartilage‐like tissue after 21 days of culture. The results of immunofluorescence and Alcian blue staining showed that compared with the control group, cells in the KGN and TGF‐β3 groups demonstrated increased secretion of aggrecan after 21 days of culture. In addition, cells in the group combining KGN with TGF‐β3 (5.587 ± 0.27, P

With the shortage of energy and the development of technology, self-powered devices are promptly needed and aroused much concern in the world. However, restricted to the working principle, external biases are usually needed to get high longitudinal photocurrent responses for the current prototype devices. Here, the lateral photovoltaic effect (LPE) is first introduced to study the lateral photocurrent (LPC) responses in the Cu(In,Ga)Se2 (CIGS) heterostructure. It is found that the CIGS heterojunction can be developed to both an LPC-based self-powered position-sensitive detector (PSD) and photodetector. This PSD shows ultralarge LPC responses in a wide spectral range with a position sensitivity of up to 4.66 mA/mm (at 532 nm) and can work in different contact distances as large as 10.2 mm with excellent linearities. Moreover, the LPC responses can be considerably improved by modulating the thickness of the indium tin oxides (ITOs) layer, which can be mainly attributed to the ITO thickness-dependent external quantum efficiency of the CIGS devices. For the photodetector, the responsivity reaches up to 0.197 A/W but exhibits a nearly reverse laser power- and contact distance-dependent changing tendency with the position sensitivity due to their different definitions.

Introduction Chronic trauma repair is an important issue affecting people's healthy lives. Thermo-sensitive hydrogel is injectable in situ and can be used to treat large-area wounds. In addition, antioxidants play important roles in promoting wound repair. Methods The purpose of this research was to prepare a novel thermo-sensitive hydrogel-poly(N-isopropyl-acrylamide)/poly(γ-glutamic acid) (PP) loaded with superoxide dismutase (SOD) to improve the effect for trauma treatment. The micromorphology of the hydrogel was observed by scanning electron microscope and the physical properties were measured. The biocompatibility of hydrogel was evaluated by MTT experiment, and the effect of hydrogel on skin wound healing was evaluated by in vivo histological staining. Results Gelling behavior and differential scanning calorimeter outcomes showed that the PP hydrogels possessed thermo-sensitivity at physiological temperature and the phase transformation temperature was 28.2°C. The high swelling rate and good water retention were conducive to wound healing. The activity of SOD in vitro was up to 85% at 10 h, which was advantageous to eliminate the superoxide anion. MTT assay revealed that this hydrogel possessed good biocompatibility. Dressings of PP loaded with SOD (SOD-PP) had a higher wound closure rate than other treatments in vivo in diabetic rat model. Discussion The SOD-PP thermo-sensitive hydrogels can effectively promote wound healing and have good application prospects for wound repair.

Aging is a universal property of multicellular organisms. Although some tree species can live for centuries or millennia, the molecular and metabolic mechanisms underlying their longevity are unclear. To address this, we investigated age-related changes in the vascular cambium from 15- to 667-y-old Ginkgo biloba trees. The ring width decreased sharply during the first 100 to 200 y, with only a slight change after 200 y of age, accompanied by decreasing numbers of cambial cell layers. In contrast, average basal area increment (BAI) continuously increased with aging, showing that the lateral meristem can retain indeterminacy in old trees. The indole-3-acetic acid (IAA) concentration in cambial cells decreased with age, whereas the content of abscisic acid (ABA) increased significantly. In addition, cell division-, cell expansion-, and differentiation-related genes exhibited significantly lower expression in old trees, especially miR166 and HD-ZIP III interaction networks involved in cambial activity. Disease resistance-associated genes retained high expression in old trees, along with genes associated with synthesis of preformed protective secondary metabolites. Comprehensive evaluation of the expression of genes related to autophagy, senescence, and age-related miRNAs, together with analysis of leaf photosynthetic efficiencies and seed germination rates, demonstrated that the old trees are still in a healthy, mature state, and senescence is not manifested at the whole-plant level. Taken together, our results reveal that long-lived trees have evolved compensatory mechanisms to maintain a balance between growth and aging processes. This involves continued cambial divisions, high expression of resistance-associated genes, and continued synthetic capacity of preformed protective secondary metabolites.

Hydrogen generation from water-gas shift (WGS) reaction requires the import of secondary energy, making it unsuitable for large scale applications. Herein, we present a new scalable system consisting of new photothermal device and catalysts that can produce hydrogen via the WGS reaction with zero additional energy import. The new photothermal device based on a chromium film can completely absorb sunlight, fully convert sunlight to heat energy and localize the heat energy synergistically, which makes a high temperature of 305 °C under one standard sunlight irradiation. The catalysts are scalable CuOx/ZnO/Al2O3 nanosheets (2D CuZnAl) with high WGS activity, which were synthesized via the surfactant effect of boric acid. The 2D CuZnAl could be heated to 297 °C under one standard solar irradiation with the new photothermal device. This new system shows a hydrogen production rate of 192.33 mmol g−1 h−1 under one standard sunlight irradiation, 402 times to that of the current record of the one sunlight-driven WGS reaction. Moreover, this new system could be amplified to industrial scale with 4.2 m2 of irradiated area and was able to generate 6.60 m3 of hydrogen from the WGS reaction solely driven by outdoor sunlight in the daytime of spring as well as realized a zero emission of CO2 with the help of a greenhouse agriculture. This study introduces a scalable, highly efficient zero CO2 emission and stable route of outdoor sunlight-driven hydrogen generation from the WGS reaction.

Exploring efficient and economical electrocatalysts for the alkaline hydrogen evolution reaction (HER) is of great importance for the ever-broader applications of hydrogen energy. Tungsten oxides have been long expected to be promising acidic HER electrocatalysts, whereas the poor intrinsic stability in an alkaline electrolyte and inferior electrical conductivity hamper their application in the alkaline HER. Herein, we design a hierarchical electrocatalyst, Ni loaded on N-doped carbon shell coated oxygen-vacancy-rich WOx nanowires. The composite shows an overpotential of 67 mV at 20 mA cm−2 and 164 mV at 100 mA cm−2 in 1 M KOH, which is highly comparable to that of the commercial Pt/C catalyst. It also shows long-term electrochemical durability over 20 h. The excellent HER performance of the electrocatalyst is attributed to the synergetic catalytic effects between the highly dispersed Ni nanoparticles and the N-doped carbon-encapsulated WOx nanowires with rich oxygen vacancies, as well as the carbon shell endowing enhanced chemical stability.

Hydrogels have been extensively favored as drug and cell carriers for the repair of knee cartilage defects. Recruiting mesenchymal stem cells (MSCs) in situ to the defect region could reduce the risk of contamination during cell delivery, which is a highly promising strategy to enhance cartilage repair. Here, a cell-free cartilage tissue engineering (TE) system was developed by applying an injectable chitosan/silk fibroin hydrogel. The hydrogel system could release first stromal cell-derived factor-1 (SDF-1) and then kartogenin (KGN) in a unique sequential drug release mode, which could spatiotemporally promote the recruitment and chondrogenic differentiation of MSCs. This system showed good performance when formulated with SDF-1 (200 ng/mL) and PLGA microspheres loaded with KGN (10 μΜ). The results showed that the hydrogel had good injectability and a reticular porous structure. The microspheres were distributed uniformly in the hydrogel and permitted the sequential release of SDF-1 and KGN. The results of in vitro experiments showed that the hydrogel system had good cytocompatibility and promoted the migration and differentiation of MSCs into chondrocytes. In vivo experiments on articular cartilage defects in rabbits showed that the cell-free hydrogel system was beneficial for cartilage regeneration. Therefore, the composite hydrogel system shows potential for application in cell-free cartilage TE. Schematic illustration of functional injectable hydrogel system for cartilage regeneration. (1) Preparation of hydrogel with the function for spatiotemporal releasing SDF-1 and KGN; (2) Spatiotemporal regulation of MSCs recruitment and chondrogenic differentiation by hydrogel in vitro; (3) Implantation of hydrogel and cartilage regeneration.

Polyhydroxyalkanoate (PHA), a class of biopolyester synthesized by various bacteria, is considered as an alternative to petroleum-based plastics because of its excellent physochemical and material properties. Pseudomonas putida KT2440 can produce medium-chain-length PHA (mcl-PHA) from glucose, fatty acid and glycerol, and its whole-genome sequences and cellular metabolic networks have been intensively researched. In this study, we aim to improve the PHA yield of P. putida KT2440 using a novel promoter engineering-based strategy. Unlike previous studies, endogenous strong promoters screening from P. putida KT2440 instead of synthetic or exogenous promoters was applied to the optimization of PHA biosynthesis pathway. Based on RNA-seq and promoter prediction, 30 putative strong promoters from P. putida KT2440 were identified. Subsequently, the strengths of these promoters were characterized by reporter gene assays. Furthermore, each of 10 strong promoters screened by transcriptional level and GFP fluorescence was independently inserted into upstream of PHA synthase gene (phaC1) on chromosome. As a result, the transcriptional levels of the phaC1 and phaC2 genes in almost all of the promoter-substituted strains were improved, and the relative PHA yields of the three promoter-substituted strains KTU-P1C1, KTU-P46C1 and KTU-P51C1 were improved obviously, reaching 30.62 wt%, 33.24 wt% and 33.29 wt% [the ratio of PHA weight to cell dry weight (CDW)], respectively. By further deletion of the glucose dehydrogenase gene in KTU-P1C1, KTU-P46C1 and KTU-P51C1, the relative PHA yield of the resulting mutant strain KTU-P46C1-∆gcd increased by 5.29% from 33.24% to 38.53%. Finally, by inserting P46 into upstream of pyruvate dehydrogenase gene in the genome of KTU-P46C1-∆gcd, the relative PHA yield and CDW of the resulting strain KTU-P46C1A-∆gcd reached nearly 42 wt% and 4.06 g/l, respectively, which increased by 90% and 40%, respectively, compared with the starting strain KTU. In particular, the absolute PHA yield of KTU-P46C1A-∆gcd reached 1.7 g/l, with a 165% improvement compared with the strain KTU. Herein, we report the highest PHA yield obtained by P. putida KT2440 in shake-flask fermentation to date. We demonstrate for the first time the effectiveness of endogenous strong promoters for improving the PHA yield and biomass of P. putida KT2440. More importantly, our findings highlight great potential of this strategy for enhanced production of secondary metabolites and heterologous proteins in P. putida KT2440.

Salmonella should be absence in pharmaceutical preparations and foods according to regulations in many countries. Up to now, rapidly detecting Salmonella at 1 CFU·[10 g (mL) ]-1 in pharmaceutical preparation or 1 CFU·[25 g (mL)] -1 in food samples is still a challenge. Herein, we present an aptamer-based surface-enhanced Raman spectroscopy (SERS) method for rapidly detecting Salmonella Enteritidis by using a handheld Raman instrument. The aptamer could specifically recognize S. Enteritidis, and 4-MBA self-assembled on the surface of Au@Ag NPs was used as a Raman reporter molecule. The method was validated to be high specific with no interference from other five pathogenic bacteria. It could identify S. Enteritidis contaminant at ∼1 CFU·(10 g)-1 spiked level in a real sample (Wenxin granule, a botanical drug) after 6 h of enrichment. The detection time was much shorter than that of the methods (more than 54∼96 h) in the standards of pharmaceutical preparations and foods. In addition, the method could quantitatively determinate S. Enteritidis with satisfactory results. The SERS peak intensities of 4-MBA at 1072 cm-1 showed a good linear correlation (R2 =0.9873) with the logarithms of S. Enteritidis concentrations ranging from 4.17×102 to 1.39×107 CFU·mL-1. T-test result (P=0.425) revealed that there was no significant difference between the determination results obtained by the SERS method and the plate counting method. Therefore, the study indicated that the method was practical and reliable, and it could be a promising alternative for on-site detection of S. Enteritidis.

Antimony selenide (Sb2Se3) nanorod arrays along the [001] orientation are known to transfer photogenerated carriers rapidly due to the strongly anisotropic one‐dimensional crystal structure. With advanced light‐trapping structures, the Sb2Se3 nanorod array‐based solar cells have excellent broad spectral response properties, and higher short‐circuit current density than the conventional planar structured thin film solar cells. However, the interface engineering for the Sb2Se3 nanorod array‐based solar cell is more crucial to increase the performance, because it is challenging to coat a compact buffer layer with perfect coverage to form a uniform heterojunction interface due to its large surface area and length–diameter ratio. In this work, an intermeshing In2S3 nanosheet‐CdS composite as the buffer layer, compactly coating on the Sb2Se3 nanorod surface is constructed. The application of In2S3‐CdS composite buffers build a gradient conduction band energy configuration in the Sb2Se3/buffer heterojunction interface, which reduces the interface recombination and enhances the transfer and collection of photogenerated electrons. The energy‐level regulation minimizes the open‐circuit voltage deficit at the interfaces of buffer/Sb2Se3 and buffer/ZnO layers in the Sb2Se3 solar cells. Consequently, the Sb2Se3 nanorod array solar cell based on In2S3‐CdS composite buffers achieves an efficiency of as high as 9.19% with a V OC of 461 mV., An intermeshing In2S3 nanosheet‐CdS composite buffer layer is constructed and applied in Sb2Se3 nanorod array solar cells, which build a gradient conduction band energy configuration in the Sb2Se3/buffer heterojunction interface. The champion cell based on In2S3‐CdS composite buffers achieves a PCE of 9.19% with an V OC of as high as 461 mV.

Aim: Host remolding with scaffolds degradation and rapid formation of a complete endothelium, are prospective solutions for improving performance of small diameter vascular grafts. Materials & methods: For this purpose, microfibrous polycaprolactone (PCL)/gelatin scaffolds were prepared by electrospinning and subsequently functionalized with heparin and organoselenium-immobilized polyethyleneimine for nitric oxide generation through layer-by-layer self-assembly. Results: Our results showed that modified PCL/gelatin grafts had strong catalytic nitric oxide generation capacity and facilitated the enhanced attachment of endothelial cells, compared with control scaffold groups. Meanwhile, the modified grafts exhibited good hemocombatility, rapid endothelialization and smooth muscle cell regeneration. Conclusion: Modification of biodegradable scaffolds, proposed in this work, could enhance biological functions of vascular grafts and provides new strategies for the construction of small diameter vascular grafts.

For the photovoltaic effect (PE), the surface potential is suggested to be an adverse factor, and researchers usually try to increase the thickness of the conductive layer or the number of strip electrodes to avoid it. However, the potential can still not be eliminated. More importantly, the huge cost has to be paid, and the photovoltaic performances are largely reduced. While the drawback of potential in PE may become excellent merit in lateral PE (LPE) due to their different working mechanisms. Moreover, the decreasing thickness of the conductive layer may be inversely used as an efficient method to modulate the LPE performances. In this paper, the indium tin oxide (ITO) conductive layer thickness-dependent LPE responses are well studied in the copper indium gallium selenide (CIGS) heterostructure. The LPE response is significantly improved with ITO thickness decreasing from 150 to 10 nm, and the thickness-dependent enhancement is strongly dependent on the illumination intensity, especially in high illumination intensities, a nonmonotonic thickness dependence is obtained. In addition, it is found that the heterostructure exhibits an ultrafast response speed of ~14.5 $\mu$ s/~15.0 $\mu$ s, and what is more, the response time nearly remains constant without depending on the ITO thickness.

Summary Poly‐γ‐glutamic acid (γ‐PGA) is a biocompatible and biodegradable polypeptide with wide‐ranging applications in foods, cosmetics, medicine, agriculture and wastewater treatment. Bacillus amyloliquefaciens LL3 can produce γ‐PGA from sucrose that can be obtained easily from sugarcane and sugar beet. In our previous work, it was found that low intracellular glutamate concentration was the limiting factor for γ‐PGA production by LL3. In this study, the γ‐PGA synthesis by strain LL3 was enhanced by chromosomally engineering its glutamate metabolism‐relevant networks. First, the downstream metabolic pathways were partly blocked by deleting fadR, lysC, aspB, pckA, proAB, rocG and gudB. The resulting strain NK‐A6 synthesized 4.84 g l−1 γ‐PGA, with a 31.5% increase compared with strain LL3. Second, a strong promoter PC 2up was inserted into the upstream of icd gene, to generate strain NK‐A7, which further led to a 33.5% improvement in the γ‐PGA titre, achieving 6.46 g l−1. The NADPH level was improved by regulating the expression of pgi and gndA. Third, metabolic evolution was carried out to generate strain NK‐A9E, which showed a comparable γ‐PGA titre with strain NK‐A7. Finally, the srf and itu operons were deleted respectively, from the original strains NK‐A7 and NK‐A9E. The resulting strain NK‐A11 exhibited the highest γ‐PGA titre (7.53 g l−1), with a 2.05‐fold improvement compared with LL3. The results demonstrated that the approaches described here efficiently enhanced γ‐PGA production in B. amyloliquefaciens fermentation.

Background Iturins, which belong to antibiotic cyclic lipopeptides mainly produced by Bacillus sp., have the potential for application in biomedicine and biocontrol because of their hemolytic and antifungal properties. Bacillus amyloliquefaciens LL3, isolated previously by our lab, possesses a complete iturin A biosynthetic pathway as shown by genomic analysis. Nevertheless, iturin A could not be synthesized by strain LL3, possibly resulting from low transcription level of the itu operon. Results In this work, enhanced transcription of the iturin A biosynthetic genes was implemented by inserting a strong constitutive promoter C2up into upstream of the itu operon, leading to the production of iturin A with a titer of 37.35 mg l−1. Liquid chromatography-mass spectrometry analyses demonstrated that the strain produced four iturin A homologs with molecular ion peaks at m/z 1044, 1058, 1072 and 1086 corresponding to [C14 + 2H]2+, [C15 + 2H]2+, [C16 + 2H]2+ and [C17 + 2H]2+. The iturin A extract exhibited strong inhibitory activity against several common plant pathogens. The yield of iturin A was improved to 99.73 mg l−1 by the optimization of the fermentation conditions using a response surface methodology. Furthermore, the yield of iturin A was increased to 113.1 mg l−1 by overexpression of a pleiotropic regulator DegQ. Conclusions To our knowledge, this is the first report on simultaneous production of four iturin A homologs (C14–C17) by a Bacillus strain. In addition, this study suggests that metabolic engineering in combination with culture conditions optimization may be a feasible method for enhanced production of bacterial secondary metabolites. Electronic supplementary material The online version of this article (10.1186/s12934-019-1121-1) contains supplementary material, which is available to authorized users.

Polyhydroxyalkanoates (PHAs) can be produced by microorganisms from renewable resources and are regarded as promising bioplastics to replace petroleum-based plastics. A medium-chain-length PHAs (mcl-PHA)-producing strain Pseudomonas mendocina NK-01 was isolated previously by our lab and its whole-genome sequence is currently available. Morphology engineering of manipulating cell morphology-related genes has been applied for enhanced accumulation of the intracellular biopolymer short-chain-length PHAs (scl-PHA). However, it has not yet been reported to improve the yield of mcl-PHA by morphology engineering so far. In this work, several well-characterized cell morphology-related genes, including the cell fission ring (Z-ring) location genes minCD, peptidoglycan degradation gene nlpD, actin-like cytoskeleton protein gene mreB, Z-ring formation gene ftsZ, and FtsZ inhibitor gene sulA, were intensively investigated for their impacts on the cell morphology and mcl-PHA accumulation by gene knockout and overexpression in P. mendocina NKU, a upp knockout mutant of P. mendocina NK-01. For a minCD knockout mutant P. mendocina NKU-∆minCD, the average cell length was obviously increased and the mcl-PHA production was improved. However, the nlpD knockout mutant had a shorter cell length and lower mcl-PHA yield compared with P. mendocina NKU. Overexpression of mreB in P. mendocina NKU resulted in spherical cells. When ftsZ was overexpressed in P. mendocina NKU, the cell division was accelerated and the mcl-PHA titer was improved. Furthermore, mreB, ftsZ, or sulA was overexpressed in P. mendocina NKU-∆minCD. Consequently, the mcl-PHA titers were all increased compared with P. mendocina NKU-∆minCD carrying the empty vector. The multiple fission pattern was finally achieved in ftsZ-overexpressing NKU-∆minCD. In this work, improved production of mcl-PHA in P. mendocina NK-01 has been achieved by morphology engineering. This work provides an alternative strategy to enhance mcl-PHA accumulation in mcl-PHA-producing strains.

Although solar-driven water evaporation has made extraordinary progress for fresh water generation, great challenges still remain in the mass production of photothermal materials, such as low efficiency and stability, for solar-driven highly corrosive water evaporation. The commercial black sponge has the merits of full sunlight absorbability and robust corrosion resistance. Herein, we treated the commercial black sponge with nitric acid to make it superhydrophilic for efficient water evaporation from not only seawater but also corrosive solutions. The superhydrophilic sponge demonstrates a seawater evaporation rate of 2.72 kg m−2 h−1 under simulated 1 sun irradiation, 7.7 times higher than that of the corresponding pure seawater evaporation and exceeding most of the photothermal materials. More importantly, the superhydrophilic sponge displays photothermal water evaporation performances in 0.5 M H2SO4 and 1 M NaOH with stable 2.53 and 2.22 kg m−2 h−1 water evaporation rates, respectively, exhibiting the record water evaporation rates from highly corrosive solutions. We found that the superhydrophilicity of commercial sponges led to a decrease in the latent heat of water evaporation from 2444 to 1081 kJ kg−1, thereby boosting the water evaporation rate. Therefore, superhydrophilic black sponges have great potential for wide industrial applications such as seawater desalination, salt production, brine management and water purification on a large scale.

Background Inflammatory bowel diseases (IBD) are chronic relapsing intestinal inflammations with increasing global incidence, and new drug development remains in urgent demand for IBD management. To identify effective traditional Chinese medicine (TCM) formulae and compounds in IBD treatment, we innovatively combined the techniques of knowledge mining, high-content screening and high-resolution mass spectrometry, to conduct a systematic screening in Zhongjing formulae, which is a large collection of TCM prescriptions with most abundant clinical evidences. Methods Using Word2vec-based text learning, the correlations between 248 Zhongjing formulae and IBD typical symptoms were analyzed. Next, from the top three formulae with predicted relationship with IBD, TCM fractions were prepared and screened on a transgenic zebrafish IBD model for their therapeutic effects. Subsequently, the chemical compositions of the fraction hits were analyzed by mass spectrometry, and the major compounds were further studied for their anti-IBD effects and potential mechanisms. Results Through knowledge mining, Peach Blossom Decoction, Pulsatilla Decoction, and Gegen Qinlian Decoction were predicted to be the three Zhongjing formulae mostly related to symptoms typical of IBD. Seventy-four fractions were prepared from the three formulae and screened in TNBS-induced zebrafish IBD model by high-content analysis, with the inhibition on the intestinal neutrophil accumulation and ROS level quantified as the screening criteria. Six herbal fractions showed significant effects on both pathological processes, which were subsequently analyzed by mass spectrometry to determine their chemical composition. Based on the major compounds identified by mass spectrometry, a second-round screen was conducted and six compounds (palmatine, daidzin, oroxyloside, chlorogenic acid, baicalin, aesculin) showed strong inhibitory effects on the intestinal inflammation phenotypes. The expression of multiple inflammatory factors, including il1β, clcx8a, mmp and tnfα, were increased in TNBS-treated fish, which were variously inhibited by the compounds, with aesculin showing the most potent effects. Moreover, aesculin and daidzin also upregulated e-cadherin’s expression. Conclusion Taken together, we demonstrated the regulatory effects of several TCM formulae and their active compounds in the treatment of IBD, through a highly efficient research strategy, which can be applied in the discovery of effective TCM formulae and components in other diseases. Graphic abstract

Background Metastasis and invasion are crucial in determining the mortality of cervical carcinoma (CC) patients. The epithelial–mesenchymal transition (EMT) is now a universal explanation for the mechanisms of tumor metastasis. Α-chimeric protein (α-chimaerin, CHN1) plays an important role in the regulation of signal transduction and development. However, the molecular regulatory relationships between CHN1 and CC progression in relation to EMT have not yet been identified. Methods The expression of CHN1 in CC tissues, adjacent tissues, and lymph node metastases from CC patients was detected by immunohistochemistry. Upregulation and knockdown of CHN1 were achieved by transfection of CC cells. The effect of CHN1 on cell proliferation was determined by CCK-8 and plate clone formation assays. Changes in migration and invasion capabilities were evaluated using scratch migration and transwell invasion assays. The effect of CHN1 overexpression and interference on xenograft tumor growth was determined by tumor weight and pathological analyses. The expression of EMT-related mRNAs was measured by qRT-PCR in transfected CC cells. EMT-related proteins and Akt/GSK-3β/Snail signaling pathway-related proteins were also evaluated by western blotting. Results CHN1 was overexpressed in CC tissues and was associated with lymph node metastasis and low survival in CC patients. Overexpression of CHN1 promoted cell proliferation, migration, and invasion in CC cells. In contrast, silencing of CHN1 inhibited these phenomena. Overexpression of CHN1 promoted tumor formation in an in vivo xenograft tumor mouse model, with increased tumor volumes and weights. In addition, CHN1 induced the expression of EMT-related transcription factors, accompanied by the decreased expression of epithelial markers and increased expression of mesenchymal markers. The Akt/GSK-3β/Snail signaling pathway was activated by overexpression of CHN1 in vitro, and activation of this pathway was inhibited by the signaling pathway inhibitor LY294002. Conclusion These results suggest that CHN1 promotes the development and progression of cervical carcinoma via the Akt/GSK-3β/Snail pathway by inducing EMT.

Hypertrophic scar, a common skin disorder typically caused by deep burns or scald were usually treated via surgical resection, laser irradiation, and drugs. However, all the approaches were always companied with complications and devastatingly subjected to relapse, which indicated the urgently need of an effective treatment method. In this project, a new hydrogel composed of Poly (γ-glutamic acid) (γ-PGA), Chitooligo-saccharide, and Papain was developed via crosslinker (EDC&NHS), and characterized with good porously three-dimensional network structure, good water absorption, and mechanical properties. Besides, G/C/P hydrogel facilitated cell adhesion and inhibited excessive proliferation of fibroblasts, which indicated the potential of in vivo application. After applied onto skin wound healing in vivo on a rabbit ear skin wound model, G/C/P hydrogel inhibited excessive collagen deposition and the generation of hyperplastic scars effectively during wound healing. The hydrogel described here provide a new platform for regeneration field and hold great promise for solving serious skin disorder.

Saccharification, the conversion of cellulose to sugar for fermentation-based biofuels, remains problematic for lignocellulosic feedstocks such as wood. Genetic modifications to reduce the amount or change the structure of lignin can improve saccharification efficiency but often result in dwarf plants. Here, we report that overexpression of Pag-MIR408 in hybrid poplar results in a near doubling saccharification efficiency, with no requirement for acid-pretreatment, increased accessibility of secondary cell walls to fungal cellulase and scaffoldin cellulose-binding modules, accompanied by enhanced photosynthesis, and increased number of cambium zone layers, xylem width and vessel diameter. Conversely, Pag-MIR408 loss-of-function plants by CRISPR/Cas9 showed decreased cell wall accessibility. Moreover, miR408 targets LACCASE 19/25, leading to delayed lignification, and modestly reduced lignin content, S/G ratio, as well as the degree of lignin polymerization. This study provides a unique insight into enhanced saccharification efficiency altered wood structure through modulation of the balance between secondary development and lignification.

Botanical drugs hold great potential to prevent and treat complex diseases. Quality control is essential in ensuring the safety, efficacy, and therapeutic consistency of these drug products. The quality of a botanical drug product can be assessed using a variety of analytical methods based on criteria that judge the identity, strength, purity, and potency. However, most of these methods are developed on separate analytical platforms, and few approaches are available for in-process monitoring of multiple quality properties in a non-destructive manner. Here, we present a hyperspectral imaging-based strategy for online measurement of physical, chemical, and biological properties of botanical drugs using artificial intelligence algorithms. An end-to-end convolutional neural network (CNN) model was established to accurately determine phytochemicals and bioactivities based on the spectra. Besides, a new dual-scale anomaly (DSA) detection algorithm was proposed for visible particle inspection based on the images. The strategy was exemplified on Shuxuening Injection, a Ginkgo biloba-derived drug used in the treatment of cerebrovascular and cardiovascular diseases. Four quality metrics of the injection, including total flavonol, total ginkgolides, antioxidant activity, and anticoagulant activity, were successfully predicted by the CNN model with validation R2 of 0.922, 0.921, 0.880, and 0.913 respectively, showing better performance than the other models. Unqualified samples with visible particles could be detected by DSA with a low false alarm rate of 9.38 %. Chromaticity results indicated that the inter-company variations of color were significant, while intra-company variations were relatively small. This demonstrates a real application of integrating hyperspectral imaging with artificial intelligence to provide a rapid, accurate, and non-destructive approach for process analysis of botanical drugs.

Background Genome reduction and metabolic engineering have emerged as intensive research hotspots for constructing the promising functional chassis and various microbial cell factories. Surfactin, a lipopeptide-type biosurfactant with broad spectrum antibiotic activity, has wide application prospects in anticancer therapy, biocontrol and bioremediation. Bacillus amyloliquefaciens LL3, previously isolated by our lab, contains an intact srfA operon in the genome for surfactin biosynthesis. Results In this study, a genome-reduced strain GR167 lacking ~ 4.18% of the B. amyloliquefaciens LL3 genome was constructed by deleting some unnecessary genomic regions. Compared with the strain NK-1 (LL3 derivative, ΔuppΔpMC1), GR167 exhibited faster growth rate, higher transformation efficiency, increased intracellular reducing power level and higher heterologous protein expression capacity. Furthermore, the chassis strain GR167 was engineered for enhanced surfactin production. Firstly, the iturin and fengycin biosynthetic gene clusters were deleted from GR167 to generate GR167ID. Subsequently, two promoters PRsuc and PRtpxi from LL3 were obtained by RNA-seq and promoter strength characterization, and then they were individually substituted for the native srfA promoter in GR167ID to generate GR167IDS and GR167IDT. The best mutant GR167IDS showed a 678-fold improvement in the transcriptional level of the srfA operon relative to GR167ID, and it produced 311.35 mg/L surfactin, with a 10.4-fold increase relative to GR167. Conclusions The genome-reduced strain GR167 was advantageous over the parental strain in several industrially relevant physiological traits assessed and it was highlighted as a chassis strain for further genetic modification. In future studies, further reduction of the LL3 genome can be expected to create high-performance chassis for synthetic biology applications.

In the chemical industry, reactors are typically designed and filled with supported catalyst particles. However, the intrinsic problems associated with the internal/external diffusion effect and catalyst separation/loss in these traditional reactors can be very challenging to mitigate. To address these issues, herein, an active metal sintered membrane reactor anchored with Pt atoms was successfully developed, and applied into continuous, liquid-phase, hydrogenation processes. The catalyzing reactions transpired on the active sites that were fastened onto the surface of the reactor's microchannels. As a result, the mass transfer at the gas–liquid–solid three-phase was greatly enhanced, and an incredibly high reaction efficiency was obtained. The novel, active reactor demonstrated a superior catalytic performance and stability to nitrobenzene (NB) hydrogenation at 120 °C and 0.5 MPa H2, which enabled an aniline (ANI) yield of 19.28 molANI h−1 L−1. This work opens a new window for the design of high-performance gas–liquid–solid reactor toward multiphase catalytic reactions.

Ginkgo biloba L. leaf (GBL) is one of the most commonly used medicinal plants in the world. Phenolic acids with biological activities have a relatively high content in G. biloba leaf extracts (GBE); therefore they are of great significance for the quality control of GBL, GBE and its preparations. However, there have been few studies focused on their analysis. In this work, 12 phenolic acids, including 11 phenolic acid glycosides, were identified by liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (LC-Q-TOF/MS). Then, a method combining enzymolysis with HPLC was established for quantification of phenolic acid glycosides. It was found that the aglycones of phenolic acid glycosides mainly comprised five phenolic acids: 2,4,6-trihydroxybenzoic acid, protocatechuic acid, p-hydroxybenzoic acid, vanillic acid and p-coumaric acid. The quantitative method was validated, and the correlation coefficient (0.9993-0.9999), recovery (≥88.4%), repeatability (≤0.8%), and inter-day precision (≤5.5%) were satisfactory. Finally, the contents of glycosides of five phenolic acids in GBL, GBE and GBE injection from different sources were determined by the developed method. The method was accurate, repeatable and practicable, which could be helpful for the quantification of phenolic acid glycosides in other products containing GBL or GBE.

Jie-Geng-Tang (JGT), a traditional formula, is employed in the treatment of sore throat and cough and comprises Platycodonis Radix and Glycyrrhizae Radix et Rhizoma in the ratio 1 : 2. Our previous study demonstrated that JGT protected mice from S. aureus-induced acute lung injury (ALI). Five constituents of JGT showed antibacterial activities against S. aureus in vitro. However, the potential effective constituents of JGT in vivo were still unclear. In this study, the chemical constituents of JGT were identified by liquid chromatography with quadrupole time-of-flight spectrometry (LC-Q-TOF-MS). A total of 96 constituents were identified or assumed, including seven organic acids, 45 flavonoids, 36 triterpene saponins, and eight compounds of other types. The structures of 31 of the constituents were confirmed by comparing them with corresponding authentic standards. Moreover, 15 prototypes and 49 metabolites were deduced in the serums of mice, 24 prototypes and 47 metabolites were deduced in the lungs of mice after the oral administration of JGT. Three types of constituents, namely organic acids, flavonoids, and triterpene saponins, could be absorbed into the blood. Moreover, flavonoids and triterpene saponins were more likely distributed in the lung than in the blood. To the best of our knowledge, this is the first report on the systematic metabolites profile of JGT in vivo. The results reported were beneficial to the elucidation of the effective material basis of JGT.

Pseudomonas mendocina NK-01 previously isolated by our lab is able to accumulate medium-chain-length polyhydroxyalkanoate (mcl-PHA) intracellularly and secrete alginate oligosaccharide (AO) to the extracellular milieu. The present study aimed at investigating whether improved production of mcl-PHA and AO by P. mendocina can be accomplished by genome reduction. In this study, 14 large genomic fragments accounting for 7.7% of the genome of P. mendocina NK-01 were sequentially deleted to generate a series of genome-reduced strains by an upp-based markerless knockout method. As a result, the intracellular ATP/ADP ratio of the strain NKU421 with the largest deletion improved by 11 times compared to NK-01. More importantly, the mcl-PHA and AO yields of NKU421 increased by 114.8% and 27.8%, respectively. Enhancing mcl-PHA and AO production by NKU421 may be attributed to improved transcriptional levels of PHA synthase genes and AO secretion-related genes. The present study suggests that rational reduction of bacterial genome is a feasible approach to construct an optimal chassis for enhanced production of bacterial metabolites. In the future, further reduction of the NKU421 genome can be expected to create high-performance chassis for the development of microbial cell factories.

Thrombosis and neointimal hyperplasia are the main causes for the failure of small diameter vascular grafts, and a complete and functional endothelium is essential in preventing these problems. Therefore, grafts that could be endothelialized rapidly are highly desirable. This study constructed a vascular graft with catalytic nitric oxide (NO) generation and promoted endothelial cell (EC) adhesion for rapid in situ endothelialization, and examined the in vivo performance of an NO-generating vascular graft for the first time. A macroporous electrospun polycaprolactone (PCL) graft was prepared and modified via layer-by-layer self-assembly. Organoselenium immobilized polyethyleneimine was loaded onto the graft for in situ catalytic NO generation, while hyaluronic acid was grafted with an EC specific peptide Arg–Glu–Asp–Val and deposited to promote EC adhesion. This dual-modified material generated a strong and sustained flow of NO from S-nitrosoglutathione and significantly enhanced EC adhesion in vitro. In a co-culture experiment of ECs and smooth muscle cells (SMCs), this material promoted the adhesion of ECs and increased the EC/SMC ratio. After implantation in rats, the modified grafts showed a remarkably promoted endothelialization compared to PCL ones with an endothelium coverage of 89% versus 55% after 4 weeks, and the ECs on modified grafts were better organized in a pattern similar to that of the native vessel. The results indicated that the combination of catalytic NO generation and promoted EC adhesion proposed in this work may be a promising method for rapid endothelialization of small diameter vascular grafts.

Saccharides are the major constituents of many herbs, and they are often utilized as quality indicators of many botanical drugs, such as Chinese medicines. A method for the rapid determination of saccharides in the in-process extract solutions is beneficial for process monitoring and ensuring consistency in the quality of the end-products during the manufacturing of Chinese medicines. In this work, a method based on Raman spectroscopy and a competitive adaptive reweighted sampling-partial least squares (CARS-PLS) model was established for the rapid quantification of saccharides. The accuracy and precision of this method were confirmed by employing one monosaccharide (glucose), one oligosaccharide (maltotriose), and two polysaccharides (Codonopsis radix polysaccharides and Polygonati rhizome polysaccharides) as reference substances. The determined results correlated well with the reference values of the four substances with the coefficient of determination of prediction (Rp2) ≥ 0.9939 and the root-mean-square error of prediction (RMSEP) ≤ 1.1052 mg/mL. Then, the method was applied to monitoring the simulated extraction process for Wenxin granule manufacture using total saccharides as a quality indicator. The CARS-PLS model exhibited satisfactory fitting and predictive capability, with Rp2 and RMSEP values of 0.9743 and 1.4931 mg/mL, respectively. Our work demonstrated that Raman spectroscopy coupled with chemometrics can offer a reliable and nondestructive alternative for the determination of different types of saccharides, in addition to being useful for real-time monitoring of the extraction process during the manufacturing of Wenxin granules. The presented approach is expected to be applicable to other Chinese medicines.

s Ethnopharmacological relevance Induced vascular growth in the myocardium has been widely acknowledged as a promising intervention strategy for patients with ischemic coronary artery disease. Yet despite long-term efforts on gene, protein or cell-based pro-angiogenic therapies, the clinical translation remains challenging. Noticeably, multiple medicinal herbs have long-term documented effects in promoting blood circulation. Salvia miltiorrhiza and Ligusticum stratum are two representative traditional Chinese medicine herbs with suggested roles in enhancing organ blood supply, and Guanxinning Tablet (GXNT), a botanical drug which is formulated with these two herbs, exhibited significant efficacy against angina pectoris in clinical practices. Aim of the study This study aimed to examine the pro-angiogenic activity of GXNT and its major components, as well as to explore their pharmacological mechanism in promoting angiogenesis. Materials and methods In vitro, the pro-angiogenic effects of GXNT and its major components were examined on human umbilical vein endothelial cells by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), scratch assay, and endothelial cell tube formation assay. In vivo, the pro-angiogenic effects were examined on the ponatinib-induced angiogenesis defective zebrafish model. The active compounds were identified through phenotype-based screening in zebrafish, and their pharmacological mechanism was explored in both in vitro and in vivo models by immunofluorescent staining, cell cycle analysis, quantitative PCR and whole embryo in-situ hybridization. Results We demonstrated strong pro-angiogenic effects of GXNT in both human umbilical vein endothelial cells and zebrafish model. Moreover, through phenotype-based screening in zebrafish for active compounds, pro-angiogenic effects was discovered for salvianolic acid B (Sal B), a major component of Salvia miltiorrhiza, and its activity was further enhanced when co-administered with ferulic acid (FA), which is contained in Ligusticum stratum. On the cellular level, Sal B and FA cotreatment increased endothelial cell proliferation of sprouting arterial intersomitic vessels in zebrafish, as well as largely restored G1-S cell cycle progression and cyclin D1 expression in angiogenic defective HUVECs. Through quantitative transcriptional analysis, increased expression of vegfr2 (kdr, kdrl) and vegfr1 was detected after GXNT or SalB/FA treatment, together with upregulated transcription of their ligands including vegf-a, vegf-b, and pgfb. Bevacizumab, an anti-human VEGF-A monoclonal antibody, was able to significantly, but not completely, block the pro-angiogenic effects of GXNT or SalB/FA, suggesting their multi-targeting properties. Conclusions In conclusion, from a traditional Chinese medicine with effects in enhancing blood circulation, we demonstrated the synergistic pro-angiogenic effects of Sal B and FA via both in vitro and in vivo models, which function at least partially through regulating the expression of VEGF receptors and ligands. Future studies are warranted to further elaborate the molecular interaction between these two compounds and the key regulators in the process of neovascularization.

The bioinert characteristic of polycaprolactone (PCL) remains a major defect when using PCL-based materials as small-diameter vascular grafts for implantation in vivo. To improve the hydrophilicity, cytocompatibility, and biodegradation of PCL vascular grafts, we constructed hybrid vascular grafts from electrospun PCL/gelatin. The PCL/gelatin hybrid vascular graft was further functionalized with the addition of heparin, to improve hemocompatibility. This study investigated the performance of heparin-loaded PCL/gelatin hybrid vascular grafts in vivo. Our results showed that the combination of gelatin and PCL was an effective approach to overcome each individual component's shortcomings, in the context of vascular graft generation. Furthermore, by loading heparin onto the grafts, thrombosis, which could be otherwise induced by gelatin, was prevented. Overall, our electrospun heparin-loaded PCL/gelatin vascular grafts promoted endothelialization and regulated smooth muscle regeneration. The data presented here show PCL/gelatin and heparin-loaded vascular grafts as an effective biomaterial candidate for the generation of artificial small-diameter vascular grafts. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2040-2049, 2019.

Background Effectiveness of a flow-based treatment device using riboflavin photochemistry was demonstrated by cytopathic effect method using indicator viruses. However, inactivation efficacy against real blood-borne viruses needs to be evaluated, especially at nucleic acid level. Material and Methods Special plasma samples with varying concentrations of blood-borne virus were selected using a strict blood selection procedure and were treated with device treatment (DT). Nucleic acid test (NAT) using polymerase chain reaction fluorescence method was used to detect virus copies. Results The NAT value of 4325 in plasma with high Hepatitis B Virus (HBV) concentrations decreased to 1330 with DT. After 100-fold dilution, the NAT value was below the NAT detection limits with DT compared with 23.0 that without DT. The NAT value of 61.9 in plasma with medium HBV concentrations decreased to 37.8 with DT, and after 10-fold dilution, the NAT value was below the NAT detection limits with DT compared with below 20 that without DT. The Ct values of plasma with low concentrations of blood-borne viruses were below the NAT detection limits with DT. Conclusion There was a dose effect with DT which was effective in blood-borne viruses damaging nucleic acids to a level below the NAT detection limits.

In our study, the mechanical properties and degradability of vascular grafts made from poly(e-caprolactone) (PCL) and poly(lactic-co-glycolic acid) (PLGA) at different ratios were investigated. The results showed that the electrospun PCL/PLGA grafts possess good mechanical properties and biodegradability. The tensile and burst strength of the scaffolds met the demands of vascular grafts. In vitro degradation tests indicated that the degradation rate of the materials increased with the percentage of PLGA, and in vivo tests showed that increasing the amount of PLGA is an effective way to promote cell infiltration. Particularly, the electrospun PCL/PLGA blended scaffold with 10% PLGA exhibited a balance of mechanical and degradation properties, making it a promising tissue engineering material for vascular grafts.

Oxygen-functionalized graphene is active for oxygen evolution reaction (OER). However, the high costs, complex instruments and pollution risks in the synthesis process make oxygen-functionalized graphene difficult to be industrialized. The microwave reaction has originally been used to remove the oxygen groups on graphene structures. In this work, the microwave reaction is reversed to decorate oxygen groups on graphene from carbon cloth, by solely using a household microwave oven. After microwave treatment, the carbon cloth shows greatly improved OER performance with a much lower overpotential of 417 mV, in comparison with the pristine carbon cloth (627 mV), due to the decoration of oxygen groups on graphene, a higher electron conductivity and a higher specific surface area. Meanwhile, an overpotential of 542 mV at 10 mA cm−2 is obtained in an acidic electrolyte, which is one of the best values for non-precious OER catalysts in acidic media. This work provides a facile, green and economic method for producing functionalized carbon catalysts for OER.

Polyamines (PAs) participate in many plant growth and developmental processes, including fruit ripening. However, it is not clear whether PAs play a role in the ripening of strawberry (Fragaria ananassa), a model nonclimacteric plant. Here, we found that the content of the PA spermine (Spm) increased more sharply after the onset of fruit coloration than did that of the PAs putrescine (Put) or spermidine (Spd). Spm dominance in ripe fruit resulted from abundant transcripts of a strawberry S-adenosyl-l-Met decarboxylase gene (FaSAMDC), which encodes an enzyme that generates a residue needed for PA biosynthesis. Exogenous Spm and Spd promoted fruit coloration, while exogenous Put and a SAMDC inhibitor inhibited coloration. Based on transcriptome data, up- and down-regulation of FaSAMDC expression promoted and inhibited ripening, respectively, which coincided with changes in several physiological parameters and their corresponding gene transcripts, including firmness, anthocyanin content, sugar content, polyamine content, auxin (indole-3-acetic acid [IAA]) content, abscisic acid (ABA) content, and ethylene emission. Using isothermal titration calorimetry, we found that FaSAMDC also had a high enzymatic activity with a Kd of 1.7 × 10-3 m In conclusion, PAs, especially Spm, regulate strawberry fruit ripening in an ABA-dominated, IAA-participating, and ethylene-coordinated manner, and FaSAMDC plays an important role in ripening.

Small-diameter (