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Aspergillus flavus (A. flavus) is one of the most important model environmental fungi which can produce a potent toxin and carcinogen known as aflatoxin. Aflatoxin contamination causes massive agricultural economic loss and a critical human health issue each year. Although a functional vacuole has been highlighted for its fundamental importance in fungal virulence, the molecular mechanisms of the vacuole in regulating the virulence of A. flavus remain largely unknown. Here, we identified a novel vacuole-related protein in A. flavus, the ortholog of phosphatidylinositol-3-phosphate-5-kinase (Fab1) in Saccharomyces cerevisiae. This kinase was located at the vacuolar membrane, and loss of fab1 function was found to affect the growth, conidia and sclerotial development, cellular acidification and metal ion homeostasis, aflatoxin production and pathogenicity of A. flavus. Further functional analysis revealed that Fab1 was required to maintain the vacuole size and cell morphology. Additional quantitative proteomic analysis suggested that Fab1 was likely to play an important role in maintaining vacuolar/cellular homeostasis, with vacuolar dysregulation upon fab1 deletion leading to impaired aflatoxin synthesis in this fungus. Together, these results provide insight into the molecular mechanisms by which this pathogen produces aflatoxin and mediates its pathogenicity, and may facilitate dissection of the vacuole-mediated regulatory network in A. flavus.

Cancer is a serious threat to human health, and there is an urgent need to develop new treatment methods to overcome it. Organelle targeting therapy, as a highly effective and less toxic side effect treatment strategy, has great research significance and development prospects. Being an essential organelle, the Golgi apparatus plays a particularly major role in the growth of cancer cells. Acting as an indispensable and highly expressed antioxidant in cancer cells, glutathione (GSH) also contributes greatly during the Golgi oxidative stress. Therefore, it counts for much to track the changes of GSH concentration in Golgi for monitoring the occurrence and development of tumor cells, and exploring Golgi-targeted therapy is also extremely important for effective treatment of cancer. In this work, we designed and synthesized a simple Golgi-targeting fluorescent probe GT-GSH for accurately detecting GSH. The probe GT-GSH reacting with GSH decomposes toxic substances to Golgi, thereby killing cancer cells. At the same time, the ratiometric fluorescent probe can detect the concentration changes of GSH in Golgi stress with high sensitivity and selectivity in living cells. Therefore, such a GSH-responsive fluorescent probe with a Golgi-targeted therapy effect gives a new method for accurate treatment of cancer.

Inconsistent findings on the association between urine albumin‐to‐creatinine ratio (UACR) and risk of hypertension have been reported. This meta‐analysis sought to evaluate the association between the elevated level of UACR within the normal range and incident hypertension in the general population. We comprehensively searched PubMed and Embase databases until July 31, 2020. All longitudinal observational studies that assessed the association of elevated baseline level of UACR within the normal range with incident hypertension in the general population were included. The predictive value was estimated by pooling risk ratio (RR) with 95% confidence intervals (CI) for the highest versus the lowest category of UACR level. Nine articles (10 studies) involving 27 771 individuals were identified and analyzed. When compared with the lowest category of UACR, individuals with the highest UACR had a 1.75‐fold (RR 1.75; 95% CI 1.47–2.09; p

Esophageal squamous cell carcinoma (ESCC) is a major type of esophageal cancer. The prognosis of patients with ESCC remains poor because of the high morbidity and mortality of the disease. One strategy for drug discovery for ESCC treatment or prevention is screening FDA-approved drugs. In the present study, we found that the antitussive agent cloperastine can inhibit the proliferation of ESCC cells. However, the underlying mechanism was unclear. To determine the mechanism of this inhibitory effect, we performed proteomic analysis using KYSE150 cells treated with cloperastine and DMSO. The results identified several down-regulated signaling pathways included those of three key proteins (NADH dehydrogenase [ubiquinone] 1 alpha subcomplex 1, NADH ubiquinone oxidoreductase subunit S5, and cytochrome C oxidase subunit 6B1) involved in oxidative phosphorylation. Meanwhile, we observed that oxidative phosphorylation in mitochondria was inhibited by the drug. Importantly, cloperastine suppressed ESCC growth in a xenograft mouse model in vivo. Our findings revealed that cloperastine inhibits the proliferation of ESCC in vivo and in vitro by suppressing mitochondrial oxidative phosphorylation.

Introduction Arenaria kansuensis Maxim. (AKM) is one of the most valued medicinal and edible herbs widely used in Qinghai-Tibet Plateau and there is also a large number of AKM bioactive constituents for health benefits of human beings. However, few works have referred to phytochemical content, fingerprint analysis and quality control of AKM. Therefore, the establishment of validated analytical methods is urgently needed for fingerprint comparison and quantitative analysis of AKM multicomponent. Objectives To determine quantitatively and compare the phytochemical constituents of AKM located at different areas. Methodology The chemical constituents in AKM samples were separated, identified, and quantified by high-performance liquid chromatography (HPLC) with a diode array detector. The discrimination and separation models for the chemical constituents were developed by chemometric analysis. Results The flavones and β-carboline alkaloids were rich in AKM herbs, and the overall pattern of phytochemical profiles was the same, while the significant differences were detected in the total flavonoids, total β-carboline alkaloids and individual contents, especially the predominant compounds such as tricin and arenarine B. This demonstrated that ecogeographical origin gave an important impact on phytochemical compositions which could be considered as reliable parameters for classifying the AKM resources. Moreover, the contents of AKM constituents were higher in July and/or August than other months of the year, and there were no significant differences in the main phytochemical contents between cultivated and wild AKM herbs. Conclusion This study could provide credible data and method for geographical origin trace, comprehensive evaluation and further utilization of AKM resources.

Background Non-small cell lung cancers (NSCLC) account for most cases of lung cancer. More effort is needed to research new drug and combination therapies for this disease. An anthraquinone derivative, emodin shows anticancer potency. We hypothesis that emodin suppresses lung cancer cells through hyaluronan (HA) synthase 2-HA-CD44/receptor for hyaluronic acid-mediated motility (RHAMM) interaction-dependent signaling pathway mediated cell cycle regulation. Methods We tested the effect of emodin on viability, apoptosis, and HA secretion of 5 NSCLC cell lines. We used NSCLC cells A549 for two rounds of knockdown study: (1) knocking down either the synthases (HAS2 and HAS3) or the receptors (CD44 and RHAMM); (2) knocking down either HAS2 or HAS3. Then determined the effect of emodin on viability, HA secretion, cell cycle, and expression of cyclin proteins. Results Emodin suppressed viability and HA secretion of all 5 NSCLC cell lines except for HA secretion of H460. Emodin had a slight apoptosis induction effect on all cell lines and was not different among cell lines. The knockdown of either the synthases or the receptors blocked emodin effects on viability while the knockdown of HAS2 block emodin effects but not HAS3. Emodin increased cells in the G1/G0 phase, and decreased cells in the S and G2/M phase by down-regulating cyclin A and B and up-regulating cyclin C, D, and E. HAS2 knockdown blocked the effects of emodin on the cell cycle. Conclusions This study demonstrated that emodin regulates the cell cycle of NSCLC cells through the HAS2-HA-CD44/RHAMM interaction-dependent signaling pathway.

Immune response initiation and regulation require activation of dendritic cells (DCs). However, the mechanism by which ferritin, a carrier for immunogen, induces DCs maturation remains unclear. Recombinant ferritin nanoparticle (RFNp), were prepared through the baculovirus expression vector system, formed spherical and hollow cage-liked proteins with a diameter of approximately 12.17 ± 0.87 nm. They induced bone marrow-derived DC (BMDC) maturation via surface molecules up-regulation of (MHC II, CD80, CD86 and CD40), increased pro-inflammatory cytokines production (IL-6, IL-12, TNF-α, and IFN-γ), and decreased antigen capturing capacity. They positively regulated IκBα and NF-κB (p65) phosphorylation, and facilitate NF-κB (p65) translocation into mature BMDCs nuclei. Following pre-treatment of RFNp-treated BMDCs with TLR4 and NF-κB (p65) inhibitors, respectively, surface molecule expression, pro-inflammatory cytokines production, and IκBα and NF-κB (p65) activities were suppressed. RFNp-treated BMDCs can also facilitate T-cell proliferation and differentiation into Th1 and Th2. RFNps induced DCs maturation lends the potential application of RFNps as carrier platforms in DC-based vaccine.

A coupled-spiral interferometer is a compact photonic component employing a continuous coupling between the arms of the spiral. Strong resonances occur when phase matching between the arms is achieved. In this work, we present an integrated silicon nitride organic-hybrid laser which is based on such a coupled-spiral interferometer resonator. Optical excitation is achieved with a 450 nm laser diode. The emission wavelength of the organic-hybrid laser is at 613 nm in transverse-magnetic-like polarization. As the coherent light is generated and directly emitted into a single-mode optical waveguide on the photonic chip elaborate coupling of laser light from an external source can be avoided.

Metal halide perovskites are promising light-emitting materials for applications such as wearable lighting devices and flat panel displays because of their high photoluminescence efficiency, high color purity, and facile solution processability. However, the intrinsic ambient instability and crystal friability issues have fundamentally hindered the practical applications of perovskites. Here, we solve this problem through a liquid to liquid self-encapsulation inkjet-printing technique. Perovskite inks are directly inkjet-printed into the liquid polydimethylsiloxane (PDMS) precursor to in situ form the self-encapsulation perovskite single-crystal-embedded PDMS structure. We show that the space-confined effect of the liquid PDMS precursor can significantly retard the perovskite crystallization process and promote the embedded growth of perovskite single crystals in PDMS. Benefiting from the sealing function of PDMS, the printed perovskite single crystals show excellent ambient stability and flexibility. Furthermore, we demonstrate that wafer-scale air-stable and flexible perovskite fluorescent patterns can be produced in PDMS by direct inkjet printing, which is cost-effective and free of complex microfabrication processes. This method provides a facile approach to scalable fabrication of air-stable and wearable perovskite fluorescent patterns, which will be of great significance for potential application in perovskite light-emitting diode display.

Thioridazine (THIO) is a phenothiazine derivative that is mainly used for the treatment of psychotic disorders. However, cardiac arrhythmias especially QT interval prolongation associated with the application of this compound have received serious attention after its introduction into clinical practice, and the mechanisms underlying the cardiotoxicity induced by THIO have not been well defined. The present study was aimed at exploring the long-term effects of THIO on the hERG and L-type calcium channels, both of which are relevant to the development of QT prolongation. The hERG current (IhERG) and the calcium current (ICa‐L) were measured by patch clamp techniques. Protein levels were analyzed by Western blot, and channel-chaperone interactions were determined by coimmunoprecipitation. Reactive oxygen species (ROS) were determined by flow cytometry and laser scanning confocal microscopy. Our results demonstrated that THIO induced hERG channel deficiency but did not alter channel kinetics. THIO promoted ROS production and stimulated endoplasmic reticulum (ER) stress and the related proteins. The ROS scavenger N-acetyl cysteine (NAC) significantly attenuated hERG reduction induced by THIO and abolished the upregulation of ER stress marker proteins. Meanwhile, THIO increased the degradation of hERG channels via disrupting hERG-Hsp70 interactions. The disordered hERG proteins were degraded in proteasomes after ubiquitin modification. On the other hand, THIO increased ICa‐L density and intracellular Ca2+ ([Ca2+]i) in neonatal rat ventricular cardiomyocytes (NRVMs). The specific CaMKII inhibitor KN-93 attenuated the intracellular Ca2+ overload, indicating that ROS-mediated CaMKII activation promoted calcium channel activation induced by THIO. Optical mapping analysis demonstrated the slowing effects of THIO on cardiac repolarization in mouse hearts. THIO significantly prolonged APD50 and APD90 and increased the incidence of early afterdepolarizations (EADs). In human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), THIO also resulted in APD prolongation. In conclusion, dysfunction of hERG channel proteins and activation of L-type calcium channels via ROS production might be the ionic mechanisms for QT prolongation induced by THIO.

The design of electrodes with simultaneously high compaction density, developed porosity, and structural stability has always been a challenge so as to meet the demand of high volumetric performance lithium ion storage devices. In this paper, we demonstrate a new compositing method for hollow carbon “room” loading of Fe3O4 nanoparticles (HCR@Fe3O4) with the assistance of Na2CO3 salt crystal templates. The as-obtained HCR@Fe3O4 composites have a massive compaction density (1.79 g cm−3), abundant multimodal pores (1.26 cm3 g−1), and a large content of Fe3O4 (64.2 wt%), which leads to excellent volumetric capacitive performance. More importantly, the unique compositing model not only provides a fast transmission channel for Li+ but also alleviates the mechanical strain efficiently through the cavity between the Fe3O4 nanoparticles and the carbon wall. When evaluated as an anode of lithium ion batteries, the resultant HCR@Fe3O4 electrode exhibits a remarkable volumetric capacity of 2044 mA h cm−3 at 0.2 A g−1 and a stable cycle life of 828 mA h cm−3 after 1000 cycles at 5 A g−1. The assembled HCR@Fe3O4//AC lithium ion hybrid capacitor device exhibits a high energy density of 173 W h L−1 at a power density of 190 W L−1, demonstrating its high-level integrated volumetric density/power density.

Background: The human ether-a-go-go-related gene (hERG) potassium channel is the rapidly activating component of cardiac delayed rectifier potassium current (IKr), which is a crucial determinant of cardiac repolarization. The reduction of hERG current is commonly believed to cause Long QT Syndrome (LQTs). Probucol, a cholesterol-lowering drug, induces LQTs by inhibiting the expression of the hERG channel. Unfortunately, there is currently no effective therapeutic method to rescue probucol-induced LQTs. Methods: Patch-clamp recording techniques were used to detect the action potential duration (APD) and current of hERG. Western blot was performed to measure the expression levels of proteins. Results: In this study, we demonstrated that 1 μM matrine and oxymatrine could rescue the hERG current and hERG surface expression inhibited by probucol. In addition, matrine and oxymatrine significantly shortened the prolonged action potential duration induced by probucol in neonatal cardiac myocytes. We proposed a novel mechanism underlying the probucol induced decrease in the expression of transcription factor Specificity protein 1 (Sp1), which is an established transactivator of the hERG gene. We also demonstrated that matrine and oxymatrine were able to upregulate Sp1 expression which may be one of the possible mechanisms by which matrine and oxymatrine rescued probucol-induced hERG channel deficiency. Conclusion: Our current results demonstrate that matrine and oxymatrine could rescue probucol-induced hERG deficiency in vitro, which may lead to potentially effective therapeutic drugs for treating acquired LQT2 by probucol in the future.

As emerging woody oil crops, the tree peony seeds recently have been attracting great attention for their metabolites and bioactivities. In this research, the phytochemical profiles of the seed coats of tree peonies from different production regions were investigated systematically. Twelve phytochemicals were separated and prepared, mainly belonging to stilbenes. A great variation in stilbene content was detected in the three Paeonia plants, and Paeonia ostii seed coats (POSC) had significantly higher contents of the stilbene compounds than other species. There were nineteen significant correlations between ecogeographical factors and the predominant compounds. A clear discrimination among the species was observed in their HPLC fingerprint and chemometric analysis. Furthermore, POSC extracts could significantly reduce the starch mediated PBG (postprandial blood glucose) levels in normal/diabetic mice. Meanwhile, in vitro enzyme tests revealed that the predominant compounds, suffruticosol B and ampelopsin D, could effectively and competitively inhibit α-glucosidase, indicating that POSC could be a natural source of hypoglycemics in the food and drug fields.

Background: Esophageal squamous cell carcinoma (ESCC) is a high recurrence rate of upper-digestive cancer with a low 5-year survival rate. Therefore, there is an urgent need for effective chemopreventive drugs that can extend the survival rate of patients. Through screening of FDA-approved drugs, dasabuvir was found to suppress ESCC proliferation. Methods: Cell number count assay was used to screen for drugs with inhibitory effect on ESCC cells and detect the inhibitory effect of dasabuvir on proliferation of ESCC cells KYSE150 and KYE450. Phosphoproteomics and proteomics were used to investigate the mechanism of dasabuvir inhibiting ESCC. In vitro kinase assay was used to verify the inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) activation by ROCK1 by dasabuvir. The PDX model was used to test the inhibitory effect of dasabuvir on ESCC in vivo.Results: In this study, we found that dasabuvir is a novel inhibitor of Rho-associated protein kinase 1 (ROCK1). Dasabuvir inhibited the growth of the KYSE150 and KYSE450 ESCC cell lines in a time and dose-dependent manner and arrested cell cycle at the G0/G1 phase. The antitumor activity was validated in vivo using a patient-derived xenograft tumor model in mice. Dasabuvir inhibited the activation of ERK1/2 by ROCK1 and downregulated cyclin-dependent kinase 4 (CDK4) and cyclin D1 expression. Conclusions: These results provide the first evidence that dasabuvir serves as a ROCK1 inhibitor, suppresses ESCC growth in vivo and in vitro, and arrests the cell cycle through the ROCK1/ERK signaling pathway.

Deoxynivalenol (DON) is one of the most common mycotoxins in animal feed worldwide and causes significant threats to the animal health. Increased use of plant ingredients in aquaculture feeds increased the risk of mycotoxin contamination. To evaluate the effects of dietary deoxynivalenol (DON) on growth performance, immune response and intestinal health of turbot and the mitigation efficacy of yeast cell wall extract (YCWE) toward DON, nine isonitrogenous and isolipidic diets were formulated: Diet 1 (control): No DON added; Diets 2–5 or Diets 6–9: 0.5 or 3.0 mg added DON/kg diet + 0%, 0.1%, 0.2%, or 0.4% YCWE, respectively. Results showed that Diet 6 (3 mg/kg DON, 0% YCWE) significantly decreased weight gain, specific growth rate and feed efficiency ratio of fish and reduced immunoglobulin M and complement 4 concentrations in serum. Fish fed Diet 6 presented morphological alterations, lower activity of superoxide dismutase, catalase and total antioxidant capacity but higher malondialdehyde content, lower claudin-4 and occludin expression but higher interleukin-1β expression in intestine. Besides, Diet 6 decreased the abundance of potential helpful bacteria but increased the abundance of potential pathogens in intestine. While, dietary YCWE, especially Diet 8 (3 mg/kg DON, 0.2% YCWE) and 9 (3 mg/kg DON, 0.4% YCWE), markedly improved growth performance and immune response and enhanced the intestinal health of turbot. In conclusion, dietary YCWE could mitigate the toxic effects induced by DON in turbot, and could be used as an effective strategy to control DON contamination in fish feed.

This trial was conducted to investigate the effect of mannose oligosaccharides (MOS) on the growth performance, antioxidation, immunity and disease resistance of Vibro Parahemolyticus in juvenile abalone Haliotis discus hannai Ino. Four formulated diets were produced to contain 0.00 g/kg, 0.40 g/kg, 0.80 g/kg and 1.60 g/kg Actigen®, with functional ingredients of MOS, respectively. Accordingly, the experimental diets were named as A0, A4, A8 and A16. After 120-days feeding trial, the best growth performance was observed in A8 group (P 0.05) and there was no significant difference in A0, A4 and A16 groups. With the increase of dietary MOS, the activity of the total antioxidant capacity in hepatopancreas is increasingly elevated (P 0.05) while no significant difference was observed on activity of glutathione S-transferase (P 0.05). The activities of superoxide dismutase and glutathione peroxidase were firstly increased and then decreased, with the highest values in A8 group (P 0.05). Immune-related parameters were significantly affected by dietary MOS inclusion. Specifically, the activities of alkaline phosphatase and acid phosphatase in hepatopancreas and serum of abalone fed diets containing MOS were significantly higher than those of control A0 group (P 0.05). Moreover, the highest values of both enzymes were observed in hepatopancreas of A8 group but in serum of A16 group, respectively. The lysozyme activities in hepatopancreas and serum of A4 group were significantly higher than those of other groups (P 0.05) and there was no significant difference in A0, A8 and A16 groups (P 0.05). The activities of cytophagy and respiratory burst in serum of abalone were not significantly affected by dietary MOS content (P 0.05). The mRNA levels of focal adhesion kinase and integrin-linked kinase were gradually elevated with the increase of dietary MOS, with the highest value recorded in A16 group (P 0.05). The gene expression of caspse-3 in A8 group was dramatically higher than those of other groups (P 0.05) and there was no significant difference in A0, A4 and A16 groups (P 0.05). The mRNA level of nuclear factor-κB was not significantly affected by dietary MOS (P 0.05). During 56 h of V. Parahemolyticus challenge period, the accumulated mortality rate of abalone fed diets containing MOS were significantly lower than that of control A0 group in each time point (P 0.05). Overall, the lowest rate was happened in A8 group (P 0.05). In conclusion, MOS inclusion in diet has obviously positive effect on growth, immunity and disease resistance capability of abalone, with the optimal level of Actigen® at 0.80 g/kg in diet.

Summary Lightweight and mechanically flexible photovoltaics enable roll-to-roll processing, which improves their potential for low-cost mass production. However, the lack of highly conductive and transparent flexible electrodes still causes reduced efficiency relative to solar cells formed on rigid substrates. Here, we demonstrate an electrode that reduces this performance gap in perovskite solar cells (PSCs) by regulating the phase separation of a conducting polymer network using a fluorosurfactant dopant. This network electrode simultaneously offers high conductivity (>4,000 S/cm), improved transmittance (over 80% from 400 to 900 nm), and high mechanical endurance. PSCs with this electrode achieve stabilized power conversion efficiencies of 19.0% and 10.9% at aperture areas of 0.1 cm 2 and 25 cm 2 , respectively, which is comparable to control devices on rigid substrates. This electrode further shows promise as the top electrode in semi-transparent PSCs, which show a stabilized efficiency of 12.5% at 30.6% average visible transmittance. Each of these cells exhibits strong mechanical stability, retaining 80% at 25 cm 2 , 85% at 0.1 cm 2 , and 90% for semi-transparent devices of their original efficiency after 5,000 bending cycles at a curvature radius of 3 mm.

The contaminantsin environment generally do not exist alone and possess different physical and chemical properties, their environmental behavior and mechanism of action in environment are more complicated. Montmorillonite was employed as adsorbent to remove tetracycline (TC) and sulfamethoxazole (SMZ) respectively and simultaneously under batch kinetic and different solution conditions. As the contaminant present singly, it only had a good effect to TC removal. The experimental data were well fitted to pseudo-second-order kinetic model, and the adsorption behavior followed the Langmuir isotherm indicated that TC adsorption was a monolayer coverage and charge-limited adsorption process. In addition, the TC molecular arrangement in the interlayer were analyzed experimentally and through simulation. While the contaminants co-exist, not only TC but also SMZ was removed effectively. SMZ adsorption mechanism were investigated through adsorption equilibrium experiment, characterization and molecular dynamics simulation. Experiment data showed that the best agreement was obtained with the Freundlich model and the adsorption mechanism was proved that SMZ was trapped by hydrophobic interaction.

Phytophthora nicotianae is a phytopathogenic oomycete with a wide host range and worldwide distribution. Rapid detection and diagnosis at the early stages of disease development are important for the effective control of P. nicotianae. In this study, we designed a simple and rapid loop‐mediated isothermal amplification (LAMP)‐based detection method for P. nicotianae. We tested three DNA extraction methods and selected the Kaneka Easy DNA Extraction Kit version 2, which is rapid and robust for LAMP‐based detection. The designed primers were tested using mycelial DNA from 35 species (81 isolates) of Phytophthora, 12 species (12 isolates) of Pythium, one isolate of Phytopythium and one isolate each from seven other soil‐borne pathogens. All of the 42 P. nicotianae isolates were detected by these primers, and no other isolates gave positive results. Three isolates were tested for the sensitivity of the reaction, and the lowest amounts of template DNA that could be detected were 10 fg for two isolates and 1 fg for the third. The target was detected within 25 min in all tested samples, including DNA extracted from both inoculated and naturally infected plants. In contrast, PCR assays with P. nicotianae‐specific primers failed or showed weakened detection in several samples. Thus, we found that the rapid DNA extraction and LAMP assay methods developed in this study can be used to detect P. nicotianae with high sensitivity, specificity and stability.

The objective of this study is to extract crude polysaccharide from Enteromorpha prolifera, investigate its structure and convert it into high-quality liquid oil by deoxy-liquefaction. This liquid oil was compared with that directly obtained from Enteromorpha prolifera raw material via elemental, FTIR and GC–MS analyses. The relative nitrogen content of the crude polysaccharide oil (0.97%) was much lower than that of Enteromorpha prolifera oil (4.85%), which can be attributed to the deproteinization process during the extraction of crude polysaccharide. Meanwhile, the crude polysaccharide oil featured high quality such as low oxygen (4.35%) and high calorific value (44.26 MJ/kg). The deoxy-liquefaction technique may be an effective way to convert crude polysaccharide into high-quality liquid fuel.

Soil potential nitrification rate (PNR) and diversity of ammonia-oxidizing microbes were investigated in spiked soils with Cu and Sulfadiazine (SDZ). An obvious decrease of PNR was observed with the increase of Cu and SDZ concentrations in the soil. Real-time fluorescence quota PCR result showed that AOA and AOB were slightly stimulated at the gene level in both contaminated soils. Sequential analysis indicated that 200 mg kg−1 Cu could improve AOA diversity but reduce AOB diversity, but 5 mg kg−1 SDZ caused a decrease of both AOA and AOB diversity. Microbial community’s analysis also found that 200 mg kg−1 Cu and 5 mg kg−1 SDZ had different influence on the populations of AOA and AOB. It could be concluded that Cu and SDZ might have a different ecological effect mechanism on soil potential nitrification and ammonia-oxidizing microbial communities.

Sulfidation has been regarded as a primary transformation and detoxification process for silver nanoparticles (AgNPs). However, considering the high stability of silver sulfide (Ag2S) and its potential persistence in the environment, it is imperative to evaluate how sulfidation impacts the long-term effect of AgNPs. The model bacterium Escherichia coli was exposed to 0.02 mg L−1 Ag2S-coated AgNPs (s-AgNPs) for more than 100 subcultures (>200 days), and both phenotypic and genotypic changes were monitored. The transcriptomic results showed that even though no discernable effect could be detected at this concentration in 48 h, chronic exposure induced a significant stress response due to respiration disturbance. The intracellular stress induced notable upregulation of multidrug-resistant genes; thus, the bacteria showed decreased susceptibility to various antibiotics. A variety of mutations in genes related to SOS response, DNA repair and oxidative stress indicated genetic instability driven by oxidative stress. Interestingly, although sulfidation considerably hindered Ag+ dissolution, after chronic exposure, the cells still developed observable tolerance to both Ag+ and s-AgNPs, as indicated by a change of approximately 2-fold in the minimal inhibitory concentration, which was ascribed to the overexpression of copper efflux transporters. Collectively, sulfidation may effectively decrease acute toxicity; however, the chronic effects of sulfided AgNPs, such as accumulative changes in physiological characteristics, the development of silver tolerance and the triggering of pathogenic evolution, may cast a shadow on the role of sulfidation as an antidote.

To investigate responses difference of soil potential nitrification rates (PNR) to heavy metals and antibiotics, batch toxicity experiments of Cu and sulfadiazine (SDZ) were conducted in four typical soils which were collected from different locations of China. Toxic differences of Cu and SDZ to soil PNR were evaluated based on their values of EC20 and EC50 calculated with logistic model. It was found that soil nitrification was a good indicator of Cu contamination in soils except for paddy soil. For SDZ, their ECX values were significantly higher than its concentration level (0.002 ~ 0.760 mg·kg-1) in soils. Thus, it was concluded that soil nitrification might be more sensitive to Cu than SDZ in field soil. The further Pearson correlation analysis indicated that the response of soil PNR to Cu and SDZ contamination were significantly related with soil PNR0 and pH.

Background Esophageal squamous cell carcinoma (ESCC) accounts for 90% of esophageal cancer and has a high mortality rate worldwide. The clinical treatment of ESCC is mainly surgical resection. The five-year survival rate of ESCC patients in developing countries is less than 20%. Therefore, identifying new and effective drugs that can prevent the occurrence and recurrence of ESCC is clinically significant. Here, daurisoline, a bis-benzylisoquinoline alkaloid, was found to have an anticancer effect on ESCC. Methods We investigated the effects of daurisoline on ESCC cell growth and proliferation using ESCC cell lines (KYSE150 and KYSE450 cells) and tumor growth in an ESCC patient-derived xenograft model. Phosphoproteomics was used to identify changes in protein phosphorylation after daurisoline treatment. Molecular docking simulation, pull down assay and amino acid mutation experiments were conducted to determine the target proteins and specific amino acid binding sites of daurisoline. In vitro kinase assay was used to determine the effect of daurisoline on protein phosphorylation. The correlation between MEK1/2 and ERK1/2 expression levels in ESCC was analyzed using TCGA database. Results In vitro experiments showed that daurisoline inhibited the proliferation and anchorage-independent growth of ESCC cells. In vivo experiments indicated that daurisoline significantly inhibited tumor growth. Phosphoproteomics analysis revealed that daurisoline reduced ERK1/2 phosphorylation. A pull down assay showed that daurisoline could bind to MEK1/2. In vitro kinase assay confirmed that daurisoline inhibited the biological functions of MEK1/2. We observed a significant correlation between MEK1 and ERK2 in ESCC from the TCGA database. Conclusion Daurisoline is a MEK1/2 inhibitor that suppressed ESCC growth in vitro and in vivo.

Bioinspired dynamic structural color has great potential for use in dynamic displays, sensors, cryptography, and camouflage. However, it is quite rare for artificial structural color devices to withstand thousands of cycles. Male hummingbird's crowns and gorgets are brightly colored, demonstrating frequent color switching that is induced by regulating the orientation of the feathers through movement of skin or joints. Inspired by this unique structural color modulation, we demonstrate a flexible, mechanically triggered color switchable sheet based on a photonic crystal (PhC)-coated polydimethylsiloxane (PDMS) kirigami (PhC-PDMS kirigami) made by laser cutting. Finite element modeling (FEM) simulation reveals that the thickness of PDMS kirigami and the chamfer at the incision induced by laser cutting both dominate the out-of-plane deformation through in-plane stretching. The bioinspired PhC-PDMS kirigami shows precisely programmable structural color and keeps the color very well after recycling over 10 000 times. This bioinspired PhC-PDMS kirigami also shows excellent viewability even in bright sunlight, high readability, robust functionality, technical flexibility, and mechanical durability, which are readily exploitable for applications, such as chromic mechanical monitors for the sports industry or for medical applications, wearable camouflage, and security systems.

To address drug resistance caused by ALK kinase mutations, a series of novel 2,4-diarylaminopyrimidine (DAAP) analogues were designed by incorporating 1H-benzo[d]imidazol motif onto the maternal framework. All compounds were efficiently synthesized and antiproliferative activities against Karpas299, H2228 and A549 cell lines were evaluated by MTT assay. Delightly, the most promising derivative H-11 was detected with IC50 values of 0.016 μM and 0.099 μM against ALK- positive Karpas299 and H2228 cells. Meanwhile, H-11 displayed encouraging enzymatic inhibitory potency with IC50 values of 2.7 nM, 3.8 nM and 5.7 nM toward ALKWT, ALKL1196M and ALKG1202R, respectively. Ultimately, the binding modes of optimal H-11 with ALK wild-type and mutants were ideally established which further confirmed the structural basis in accordance with the SARs analysis.

As an alternative to triclosan (TCS), the widespread use of silver nanoparticles (AgNPs) in daily products shows genuine potential. However, information regarding whether AgNPs are substantially better than TCS in their potential disruption of the gut microbiome and health effects is lacking. Using a simulator of the human intestinal microbial ecosystem (SHIME), we systemically compared the effects of TCS and AgNPs (at 1 μg/L and 30 μg/L) on the human gut microbiome in terms of changes in gut homeostasis, microbial community structure, antibiotic resistance profiles and abundances of opportunistic pathogens. Generally, TCS exerted more severe effects than AgNPs on gut disturbances (i.e., decreased production of short-chain fatty acids, increased contents of ammonium and total bile acids, and increased β-glucosidase activities) in a dose-dependent manner, whereas no clear dose effect was observed for the AgNP treatment because of potential nanoparticle transformation. The more serious effect of TCS than AgNPs on the microbiota composition was indicated by the dynamic increase in the Firmicutes/Bacteroidetes ratio determined using 16S rDNA sequencing. Metagenomic analyses revealed a more pronounced effect of TCS than AgNPs on the selection and dissemination of multiple resistance genes to antibiotics, TCS, and even Ag via the enrichment of genes encoding efflux pumps and mobile genetic elements. Consequently, the overgrowth of opportunistic pathogens was observed upon TCS exposure due to an imbalanced microbiome, in contrast to a slight increase in the abundance of some beneficial bacteria (i.e., Bifidobacterium) induced by the AgNP treatment. In conclusion, from the perspective of effects on gut health, AgNPs may prevail over TCS to some extent. However, the stress and potential selection of Ag resistance indicates the need for targeted surveillance of AgNP commercialization for daily use.

Aims The preservation of pancreatic beta-cell function is crucial for the treatment of type 2 diabetes. Inhibition of class I histone deacetylase (HDAC) has been proved to protect beta-cells from palmitate- or cytokine-induced apoptosis and increase insulin secretion. However, the underlying molecular mechanism is unclear. Main methods Rat islets were isolated for insulin secretion, real-time PCR, RNA- sequencing, ChIP-PCR, and oxygen consumption rate analysis after treated with the HDAC1 and HDAC3 inhibitor MS-275. Key findings MS-275 pretreatment significantly potentiated insulin secretion from rat islets. RNA-sequencing revealed that multiple signaling pathways were involved in MS-275-regulated islet function. Cacna1g and Adcy1 in calcium and cAMP signaling pathways were up-regulated in MS-275-treated islets, which was validated by real-time PCR. The expressions of the two genes displayed a similar increase in islets isolated from mice treated with MS-275. Knockdown of HDAC1 elevated Cacna1g and Adcy1 expressions in islets. ChIP-sequencing analysis showed that the pan-HDAC inhibitor sodium butyrate increased H3K27 acetylation level in the upstream region of Adcy1 and the promoter region of Cacna1g. ChIP-PCR revealed a similar result in MS-275-treated rat islets. However, MS-275 had minor effect on glucose-induced oxygen consumption rate in rat islets. Unlike glucose, MS-275 did not alter the expressions of glucose-sensitive genes such as Glut2 and Gck, but elevated intracellular Ca2+ concentration in beta-cells. Significance Our findings support the notion that MS-275-potentiated insulin secretion is involved in calcium and cAMP signaling-mediated gene expressions independent of glucose oxidation. Therefore, HDAC inhibition may serve as a therapeutic strategy for type 2 diabetes.

CD47, an immune checkpoint receptor frequently unregulated in various blood and solid tumors, interacts with ligand SIPRα on innate immune cells, and conveys a “do not eat me” signal to inhibit macrophage-mediated tumor phagocytosis. This makes CD47 a valuable target for cancer immunotherapy. However, the therapeutic utility of CD47-SIRPα blockade monoclonal antibodies is largely compromised due to significant red blood cell (RBCs) toxicities and fast target-mediated clearance as a result of extensive expression of CD47 on normal cells. To overcome these limitations and further improve therapeutic efficacy, we designed IBI322, a CD47/PD-L1 bispecific antibody which attenuated CD47 activity in monovalent binding and blocked PD-L1 activity in bivalent binding. IBI322 selectively bound to CD47+PD-L1+ tumor cells, effectively inhibited CD47-SIRPα signal and triggered strong tumor cell phagocytosis in vitro, but only with minimal impact on CD47 single positive cells such as human RBCs. In addition, as a dual blocker of innate and adaptive immune checkpoints, IBI322 effectively accumulated in PD-L1-positive tumors and demonstrated synergistic activity in inducing complete tumor regression in vivo. Furthermore, IBI322 showed only marginal RBCs depletion and was well tolerated in non-human primates (NHP) after repeated weekly injections, suggesting a sufficient therapeutic window in future clinical development of IBI322 for cancer treatment.

In recent years, synthetic biology develops rapidly, the purpose of which is to create beneficial products or organisms with special functions. Genetic circuits are dynamic regulating systems of organisms controlling their own life processes. According to specific rules and grammar, synthetic biologists try to design artificial genetic circuits to achieve their goals. In our research, we designed grammar rules on basis of the context-free grammar, imported a part library which we acquired from IGEM database and then we processed, and constructed a genetic circuit for expressing TetR in GenoCAD, which is a free web-based application for synthetic biology. Finally, we generated a plasmid map on the PlasMapper, and we can see the concrete information of the plasmid. We creatively designed the genetic circuit to express the TetR. The work provides a new dynamic regulating system for synthetic biology. We think the genetic circuit will help us predict the biological regulator process.

In this study, an efficient heterojunction photocatalyst, g-C3N4/ZnO (CNZn), was successfully produced by coupling graphitic carbon nitride (g-C3N4) with hierarchical zinc oxide nanoparticles (ZnO) using a facile wet-chemical strategy. Electron microscope results showed that CNZn is characterized by a unique three-dimensional flower-like porous architecture. The physicochemical properties of the synthesized photocatalysts were determined by using energy dispersive X-ray spectroscopy, fourier transform infrared spectra and X-ray powder diffractometry. The photocatalytic properties of the prepared catalysts were evaluated based on their photodegradation of methylene blue (MB) under ultraviolet (UV) and solar irradiation. The results indicated that the CNZn composite exhibited superior photocatalytic properties compared with pristine g-C3N4 and ZnO alone, which could be ascribed to the effective establishment of heterojunctions between g-C3N4 and ZnO. It was also found that the catalytic activity of the CNZn composite can be further enhanced by modifying reaction parameters including the illumination source, catalyst dosage and solution pH. Meanwhile, trapping experiments of reactive species suggested that holes and superoxide radicals played a major role in promoting the MB photodegradation. This study could shed light for the construction of high-performing photocatalysts.

The Lower Silurian marine shale gas in South China has great potential. In order to study the influence factors of methane adsorption capacity of the marine shale in Sangzhi block, six samples from...

Broadband plasmonic absorbers are essential components for photovoltaic, photothermal, and light-emitting devices. They are often made by lithographic processes that impart out-of-plane surface features with subwavelength dimensions to metallic films. However, lithographic subwavelength patterning of inexpensive plasmonic ceramics, such as TiN, is challenging because of high-temperature processing and the chemical robustness of these materials. In this work, we show that layer-by-layer assembly (LbL) of TiN plasmonic nanoparticles with polyelectrolytes results in spontaneous formation of out-of-plane topography with subwavelength dimensions. The columnar morphology of these corrugated coatings and their plasmonic functionality results in broadband absorption capabilities exemplified by 90% of the light from the ultraviolet to infrared parts of the spectrum being absorbed. The method is applicable to large, flexible, and conformal surfaces with complex geometry. It is also fast, scalable, and environmental...

3.5 mol% Yb 2 O 3 stabilized zirconia (YbSZ) doped with 10 mol% TiO 2 (Ti-YbSZ) was produced, and its hot corrosion behavior exposed to Na 2 SO 4 + V 2 O 5 molten salt was investigated. The as-fabricated ceramic mainly consists of metastable tetragonal (t′) phase. When exposed to the molten salt at 700 °C, 800 °C, 900 °C and 1000 °C for 2 h and 10 h, YbVO 4 and m-ZrO 2 formed as corrosion products due to chemical reactions between the ceramics and the salt. Ti 4+ in Ti-YbSZ solid solution keeps stable during the hot corrosion tests, which acts as a stabilizer for ZrO 2 , preventing total decomposition of the t′ phase. After the hot corrosion tests, Ti-YbSZ has an apparently lower m phase content than Y 2 O 3 doped Zirconia and YbSZ, indicative of better corrosion resistance. The hot corrosion mechanism of Ti-YbSZ is proposed based on Lewis acid-base rule, phase diagrams and thermodynamics.

Hot corrosion behavior of Ba 2 REAlO 5 (RE = Dy, Er, Yb) ceramics exposed to V 2 O 5 molten salt at 900 °C and 1000 °C was investigated, providing a better understanding of their corrosion resistance as promising thermal barrier coatings. Obvious surface reactions occurred forming continuous, dense reaction layers on the top surfaces of the samples, the types of corrosion products being temperature and time independent. After heat treatment for 4 h and 20 h in V 2 O 5 salt at the two temperatures, the corrosion products consisted of REVO 4 , Ba 2 REV 3 O 11 and BaAl 2 O 4 (RE = Dy, Er, Yb). Prolonged heat treatment and elevated temperature promoted the growth of Ba 2 REV 3 O 11 and REVO 4 grains. The reaction layer had a positive function on suppressing further penetration of the molten salt. The mechanism by which the corrosion reaction occurs is proposed based on Lewis acid-base rule, phase diagrams and thermodynamics.

Calcium-magnesium-alumina-silicate (CMAS) has posed enormous threat to thermal barrier coatings (TBCs). In this study, a series of newly developed TBC ceramics, BaLn 2 Ti 3 O 10 (Ln=La, Nd), are found to have high resistance to the penetration of molten CMAS at 1250 °C. The formation of a continuous, dense crystalline layer, mainly composed of apatite and CaTiO 3 phases, on the sample surfaces contributed to this desirable attribute. The accumulation of Ba in the molten CMAS triggered the crystallization of the melt, leading to the formation of many BaAl 2 Si 2 O 8 celsian crystals above the crystalline layer, which could reduce the mobility of the molten CMAS. The mechanisms by which the CMAS attacks BaLn 2 Ti 3 O 10 samples are discussed. The results indicate that Ba is an effective element for altering CMAS composition, and doping Ba in TBCs might be an attractive way of mitigating CMAS attack.

Nanostructured 30 mol% LaPO 4 doped Gd 2 Zr 2 O 7 (Gd 2 Zr 2 O 7 -LaPO 4 ) thermal barrier coatings (TBCs) were produced by air plasma spraying (APS). The coatings consist of Gd 2 Zr 2 O 7 and LaPO 4 phases, with desirable chemical composition and obvious nanozones embedded in the coating microstructure. Calcium-magnesium-alumina- silicate (CMAS) corrosion tests were carried out at 1250 °C for 1–8 h to study the corrosion resistance of the coatings. Results indicated that the nanostructured Gd 2 Zr 2 O 7 -LaPO 4 TBCs reveals high resistance to penetration by the CMAS melt. During corrosion tests, an impervious crystalline reaction layer consisting of Gd-La-P apatite, anorthite, spinel and tetragonal ZrO 2 phases forms on the coating surfaces. The layer is stable at high temperatures and has significant effect on preventing further infiltration of the molten CMAS into the coatings. Furthermore, the porous nanozones could gather the penetrated molten CMAS like as an absorbent, which benefits the CMAS resistance of the coatings.

Nowadays, environmental pollution is a big problem. Metal organic frameworks (MOFs) provide a novel strategy for exhaust gases adsorption and toxic pollutants removal. We proposed a facile and versatile method to prepare a highly efficient three dimensional MOF–sponge by coating MOF crystals on polyurethane sponge surface, mimicking the porous structure of the marine animal, sponge. Owing to combination of the spatial structure of the commercial sponge and the excellent adsorption capacity of MOF coatings, the MOF–sponge possessed good permeability and high dynamic adsorption capacity. Dynamic adsorption ability of the prepared Cu3(BTC)2–sponge was demonstrated by flowing gas-mixtures of NH3/N2 and an aquatic solution of Rhodamine B through it, with a capacity of 101.6 mg g−1 and 8.8 mg g−1 for NH3 and Rhodamine B, respectively.

Flexible reduced graphene oxide (rGO) sheets are being considered for applications in portable electrical devices and flexible energy storage systems. However, the poor mechanical properties and electrical conductivities of rGO sheets are limiting factors for the development of such devices. Here we use MXene (M) nanosheets to functionalize graphene oxide platelets through Ti-O-C covalent bonding to obtain MrGO sheets. A MrGO sheet was crosslinked by a conjugated molecule (1-aminopyrene-disuccinimidyl suberate, AD). The incorporation of MXene nanosheets and AD molecules reduces the voids within the graphene sheet and improves the alignment of graphene platelets, resulting in much higher compactness and high toughness. In situ Raman spectroscopy and molecular dynamics simulations reveal the synergistic interfacial interaction mechanisms of Ti-O-C covalent bonding, sliding of MXene nanosheets, and π-π bridging. Furthermore, a supercapacitor based on our super-tough MXene-functionalized graphene sheets provides a combination of energy and power densities that are high for flexible supercapacitors., Poor mechanical properties of reduced graphene oxide sheets hinder development of flexible energy storage systems. MXene functionalised graphene oxide with Ti-O-C bonding and additional crosslinking is here reported to dramatically increase toughness for flexible supercapacitors.

Ferritin is an attractive vector for the delivery of drug molecules and antigen proteins because of its unique structural and biochemical features. In this study, recombinant ferritin from Helicobacter pylori was expressed in the soluble form employing the baculovirus expression system. The optimum conditions for producing recombinant ferritin comprised MOI 5 of rBV-ferritin for 96 h of infection. The recombinant ferritin was purified by Ni Sepharose™ 6 Fast Flow, with a purity and yield of 92.5% and 11.25 mg/L, respectively. In addition, the recombinant ferritin showed a multimeric structure under non-denaturing conditions, as well as self-assembled spherical cage architecture with a diameter of approximately 12 nm. Dot-ELISA results suggested that the His-tag at the N-terminus likely existed on the surface of the recombinant ferritin. Recombinant ferritin was produced by the baculovirus expression system, which has the potential to display exogenous proteins, and may aid in the delivery of drugs for disease prevention and treatment.

We report several PECVD silicon nitride photonic building blocks required for the implementation of a CMOS-compatible photonic integrated circuit technology platform operating in the 850 nm and 600 nm wavelength domain. In particular, for the 850 nm wavelength region we discuss a low-loss broadband 1x2 power splitter and a loop mirror. In the 600 nm wavelength region, we present new results on an optically pumped integrated dye-doped polymer laser that couples its light directly into a silicon nitride waveguide. Moreover, we discuss design considerations for a waveguide based gas sensing concept detecting target gas specific absorption changes in a thin dye-doped polymer cladding layer.

The major concern regarding the biocide triclosan (TCS) stems from its potential coselection for antibiotic resistance. However, environmental impacts are often investigated using high concentrations and acute exposure, while predicted releases are typified by chronic low concentrations. Moreover, little information is available regarding the reversibility of TCS and derived antibiotic resistance with diminishing TCS usage. Here, the model Gram-negative bacterium Escherichia coli was exposed to 0.01 mg/L TCS continuously for more than 100 generations. The adapted cells gained considerable resistance to TCS as indicated by a significant increase in the minimal inhibitory concentration (MIC50) from 0.034 to 0.581 mg/L. This adaptive evolution was attributed to overexpression and mutation of target genes (i.e., fabI) as evidenced by transcriptomic and genomic analyses. However, only mild tolerance to various antibiotics was observed, possibly due to reduced membrane permeability and biofilm formation. After TCS exposure ceased, the adapted cells showed persistent resistance to TCS due to inheritable genetic mutations, whereas their antibiotic tolerance declined over time. Our results suggest that extensive use of TCS may promote the evolution and persistence of TCS-resistant bacterial pathogens. A quantitative definition of the conditions under which TCS selects for multidrug resistance in the environment is crucially needed.

Longan (Dimocarpus longan Lour.) pericarp, the main by-product of aril and pulp processing, is abundant in phenolic compounds and worthy of further utilization. The present work firstly reported HPLC analysis and in vitro antioxidant evaluation of longan (cv. Shixia) pericarp-derived phenolics (LPPs), the purified longan pericarp extract (LPE), as well as their cytotoxic effect on lung cancer cell line, A549. The results indicated that the purified LPE had significant amounts of phenolics, with content of 57.8 &plusmn, 0.6 mg of gallic acid equivalents per gram of dry longan pericarp (mg GAE&middot, g&minus, 1 DLP), which consisted of six phenolic compounds (A&ndash, F), including protocatechuic acid (A), isoscopoletin (B), quercetin (C), ellagic acid (D), corilagin (E), and proanthocyanidins C1 (F). Antioxidant assays showed that LPPs (10 &mu, M) and LPE (1.0 mg&middot, mL&minus, 1) had certain antioxidant activities, in which corilagin (E) possessed the best DPPH radical scavenging rate 71.8 &plusmn, 0.5% and &bull, OH inhibition rate 75.9 &plusmn, 0.3%, and protocatechuic acid (A) exhibited the strongest Fe2+ chelating ability 36.4 &plusmn, 0.7%. In vitro cytotoxic tests suggested that LPPs had different effect on A549 cell line, in which corilagin (E) exhibited potent cytotoxicity with an IC50 value of 28.8 &plusmn, 1.2 &mu, M. These findings were further confirmed by cell staining experiments.

Coherent light sources are a key component for photonic integrated circuits. Organic solid-state lasers can be monolithically integrated and are highly cost-effective. We report silicon nitride organic hybrid laser designs pumped with a laser diode.