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In recent years, the repurposing of conventional and chemotherapeutic drugs is recognized as an alternative strategy for health care. The main purpose of this study is to strengthen the application of non‐oncological drug metformin on breast cancer treatment in the perspective of epigenetics. In the present study, metformin was found to inhibit cell proliferation, promote apoptosis and induce cell cycle arrest in breast cancer cells at a dose‐dependent manner. In addition, metformin treatment elevated acH3K9 abundance and decreased acH3K18 level. The expression of lncRNA MALAT1, HOTAIR, DICER1‐AS1, LINC01121 and TUG1 was up‐regulated by metformin treatment. In metformin‐treated cells, MALAT1 knock‐down increased the Bax/Bcl2 ratio and enhanced p21 but decreased cyclin B1 expression. The expression of Beclin1, VDAC1, LC3‐II, CHOP and Bip was promoted in the cells received combinatorial treatment of metformin and MALAT1 knock‐down. The reduced phosphorylation of c‐Myc was further decreased in the metformin‐treated cells in combination with MALAT1 knock‐down than metformin treatment alone. Taken together, these results provide a promising repurposed strategy for metformin on cancer treatment by modulating epigenetic modifiers.

Xylanase releases xylo-oligosaccharides from dietary xylan, which stimulate the growth of the gut bacteria lactobacilli. Many lactobacilli adhere to dietary fibers, which may facilitate the assimilation of xylo-oligosaccharides and help them gain competence in the gut, but the underlying mechanisms remain elusive. Herein we report, from the highly abundant transcripts of

Summary The static PN junction is the foundation of integrated circuits. Herein, we pioneer a high current density generation by mechanically moving N-type semiconductor over P-type semiconductor, named as the dynamic PN junction. The establishment and destruction of the depletion layer causes the redistribution and rebounding of diffusing carriers by the built-in field, similar to a capacitive charge/discharge process of PN junction capacitance during the movement. Through inserting dielectric layer at the interface of the dynamic PN junction, output voltage can be improved and designed numerically according to the energy level difference between the valence band of semiconductor and conduction band of dielectric layer. Especially, the dynamic MoS2/AlN/Si generator with open-circuit voltage of 5.1 V, short-circuit current density of 112.0 A/m2, power density of 130.0 W/m2, and power-conversion efficiency of 32.5% has been achieved, which can light up light-emitting diode timely and directly. This generator can continuously work for 1 h, demonstrating its great potential applications., Graphical Abstract, Highlights • High current density direct-current generator based on dynamic PN junctions • Dynamic equilibrium between establishment and destruction of the depletion layer • Capacitive discharge of PN junction capacitance caused by hot carriers rebounding • Enhance and design voltage numerically by inserting dielectric layer at the interface, Electrical Engineering; Energy Materials; Mechanical Engineering; Tribology

Summary Although perovskite has been widely explored in optoelectronic devices, it has been rarely explored as a Schottky junction. Here, we demonstrate a light- and mechanical-energy co-harvesting generator based on a dynamic metal/perovskite Schottky junction. In dark conditions, by moving Al over perovskite film (conductivity: 70.0 S/cm), output voltage and current density of −0.70 V and −41.1 A/m2, respectively, are achieved. As defects eliminate the photo-generated carriers in the static metal/perovskite junction under light illumination, the photoresponse is negligible. Strikingly, the output current of dynamic metal/perovskite junction under light illumination is enhanced by 3-fold compared with the dynamic junction in the dark condition. This nonlinear photo-enhanced effect is proposed as a result of strong interaction between the photo-generated and bound back carriers in the dynamic Schottky junction as well as the high light-absorption coefficient of perovskite. A flexible Al/perovskite generator has been demonstrated as a wearable energy-harvesting device.

Acid mine drainage (AMD) from abandoned coal mines can lead to serious environmental problems due to its low pH and high concentrations of potentially toxic elements. In this study, soil pH, sulfur (S) content, and arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), lead (Pb), nickel (Ni), zinc (Zn), iron (Fe), manganese (Mn), and mercury (Hg) concentrations were measured in 27 surface soil samples from areas in which coal-mining activities ceased nine years previously in Youyu Catchment, Guizhou Province, China. The soil was acidic, with a mean pH of 5.28. Cadmium was the only element with a mean concentration higher than the national soil quality standard. As, Cd, Cu, Ni, Zn, Mn, Cr, and Fe concentrations were all higher than the background values in Guizhou Province. This was especially true for the Cd, Cu, and Fe concentrations, which were 1.69, 1.95, and 12.18 times their respective background values. The geoaccumulation index of Cd and Fe was present at unpolluted to moderately polluted and heavily polluted levels, respectively, indicating higher pollution levels than for the other elements in the study area. Spatially, significantly high Fe and S concentrations, as well as extremely low pH values, were found in the soils of the AMD sites, however, sites where tributaries merged with the Youyu River (TM) had the highest Cd pollution level. Iron originated mainly from non-point sources (e.g., AMD and coal gangues), while AMD and agricultural activity were the predominant sources of Cd. The results of an eco-risk assessment indicated that Cd levels presented a moderate potential ecological risk, while the other elements all posed a low risk. For the TM sites, the highest eco-risk was for Cd, with levels that could be harmful for aquatic organisms in the wet season, and may endanger human health via the food chain.

Magnesium, the second most predominant intracellular cation, plays a crucial role in many physiological functions; magnesium-based biomaterials have been widely used in clinical application. In a variety of cancer types, the high intracellular concentration of magnesium contributes to cancer initiation and progression. Therefore, we initiated this study to investigate the likelihood of confounding magnesium with cancer therapy. In this study, the anti-tumor activity of magnesium and underlying mechanisms were assessed in bladder cancer both in vitro and in vivo. The results indicated that the proliferation of bladder cancer cells was inhibited by treatment with a high concentration of MgCl2 or MgSO4. The apoptosis, G0/G1 cell cycle arrest, autophagy, and ER stress were promoted following treatment with MgCl2. However, the migratory ability of MgCl2 treated cells was similar to that of control cells, as revealed by the trans-well assay. Besides, no significant difference was observed in the proportion of CD44 or CD133 positive cells between the control and MgCl2 treated cells. Thus, to improve the therapeutic effect of magnesium, VPA was used to treat cancer cells in combination with MgCl2. As expected, combination treatment with MgCl2 and VPA could markedly reduce proliferation, migration, and in vivo tumorigenicity of UC3 cells. Moreover, the Wnt signaling was down-regulated, and ERK signaling was activated in the cells treated with combination treatment. In conclusion, the accurate utilization of MgCl2 in targeting autophagy might be beneficial in cancer therapy. Although further studies are warranted, the combination treatment of MgCl2 with VPA is an effective strategy to improve the outcome of chemotherapy.

As the fast development of internet of things (IoTs), distributed sensors have been frequently used and the small and portable power sources are highly demanded. However, the present portable power source such as lithium battery has low capacity and need to be replaced or recharged frequently. A portable power source which can continuously generate electrical power in situ will be an idea solution. Herein, we demonstrate a wind driven semiconductor electricity generator based on a dynamic Schottky junction, which can output a continuous direct current with an average value of 4.4 mA (the maximum value of 8.4 mA) over 360 seconds. Compared with the previous metal/semiconductor generator, the output current is one thousand times higher. Furthermore, this wind driven generator has been explored to function as a turn counter due to its stable output and also to drive a graphene ultraviolet photodetector, which shows a responsivity of 35.8 A/W under the 365 nm ultraviolet light. Our research provides a feasible method to achieve wind power generation and power supply for distributed sensors in the future.

Searching for light and miniaturized functional device structures for sustainable energy gathering from the environment is the focus of energy society with the development of the internet of things. The proposal of a dynamic heterojunction-based direct current generator builds up new platforms for developing in situ energy. However, the requirement of different semiconductors in dynamic heterojunction is too complex to wide applications, generating energy loss for crystal structure mismatch. Herein, dynamic homojunction generators are explored, with the same semiconductor and majority carrier type. Systematic experiments reveal that the majority of carrier directional separation originates from the breaking symmetry between carrier distribution, leading to the rebounding effect of carriers by the interfacial electric field. Strikingly, NN Si homojunction with different Fermi levels can also output the electricity with higher current density than PP/PN homojunction, attributing to higher carrier mobility. The current density is as high as 214.0 A/m 2 , and internal impedance is as low as 3.6 k Ω , matching well with the impedance of electron components. Furthermore, the N-i-N structure is explored, whose output voltage can be further improved to 1.3 V in the case of the N-Si/Al 2 O 3 /N-Si structure, attributing to the enhanced interfacial barrier. This approach provides a simple and feasible way of converting low-frequency disordered mechanical motion into electricity.

The present paper describes how to use coordination between neighbouring intersections in order to improve the performance of urban traffic controllers. Both the local MPC (LMPC) introduced in the companion paper (Hao et al., 2018) and the coordinated MPC (CMPC) introduced in this paper use the urban cell transmission model (UCTM) (Hao et al., 2018) in order to predict the average delay of vehicles in the upstream links of each intersection, for different scenarios of switching times of the traffic lights at that intersection. The feedback controller selects the next switching times of the traffic light corresponding to the shortest predicted average delay. While the local MPC (Hao et al., 2018) only uses local measurements of traffic in the links connected to the intersection in comparing the performance of different scenarios, the CMPC approach improves the accuracy of the performance predictions by allowing a control agent to exchange information about planned switching times with control agents at all neighbouring intersections. Compared to local MPC the offline information on average flow rates from neighbouring intersections is replaced in coordinated MPC by additional online information on when the neighbouring intersections plan to send vehicles to the intersection under control. To achieve good coordination planned switching times should not change too often, hence a cost for changing planned schedules from one decision time to the next decision time is added to the cost function. In order to improve the stability properties of CMPC a prediction of the sum of squared queue sizes is used whenever some downstream queues of an intersection become too long. Only scenarios that decrease this sum of squares of local queues are considered for possible implementation. This stabilization criterion is shown experimentally to further improve the performance of our controller. In particular it leads to a significant reduction of the queues that build up at the edges of the traffic region under control. We compare via simulation the average delay of vehicles travelling on a simple 4 by 4 Manhattan grid, for traffic lights with pre-timed control, traffic lights using the local MPC controller (Hao et al., 2018), and coordinated MPC (with and without the stabilizing condition). These simulations show that the proposed CMPC achieves a significant reduction in delay for different traffic conditions in comparison to these other strategies.

This paper is the first in a series of reports presenting a framework for the hierarchical design of feedback controllers for traffic lights in urban networks. The goal of the research is to develop an easy to understand methodology for designing model based feedback controllers that use the current state estimate in order to select the next switching times of traffic lights. In this paper we introduce an extension of the cell transmission model that describes with sufficient accuracy the major causes of delay for urban traffic. We show that this model is computationally fast enough such that it can be used in a model predictive controller that decides for each intersection, taking into account the vehicle density as estimated along all links connected to the intersection, what switching time minimizes the local delay for all vehicles over a prediction horizon of a few minutes. The implementation of this local MPC only requires local online measurements and local model information (unlike the coordinated MPC, to be introduced in the next paper in this series, that takes into account interactions between neighbouring intersections). We study the performance of the proposed local MPC via simulation on a simple 4 by 4 Manhattan grid, comparing its delay with an efficiently tuned pretimed control for the traffic lights, and with traffic lights controlled according to the max pressure rule. These simulations show that the proposed local MPC controller achieves a significant reduction in delay for various traffic conditions.

A type of broadband (325−980 nm) self-powered photodetector based on graphene/GaAs van der Waals heterojunction is reported. By simply spinning a layer of Ag nano-particles (Ag NPs) onto graphene/GaAs heterostructure, the responsivity and detectivity of our devices for the whole spectrum range are enhanced significantly. The maximum photocurrent responsivity of 210 mA W−1 (increased by 38%) and detectivity of 2.98 × 1013 Jones (increased by 202%) are achieved at 405 nm, which is about two or three orders of magnitude larger than other graphene based self-powered photodetectors. The mechanism of the improvement originates from the overlap the depletion region of graphene/GaAs heterostructure, the surface plasmon enhanced light field region below the surface and the light absorption region of the GaAs layer. The external quantum efficiency (EQE) measurement, transient photoluminescence (PL) test and the comparative theoretical simulation show that the surface plasmon enhancement should only be applicable for graphene/direct band gap semiconductor heterostructure, where the semiconductor should have a high optical absorption coefficient. The obtained high performance broadband photodetector with excellent detectivity is a promising candidate for many important optoelectronic applications, such as ultrasensitive image sensor in charge coupled displayer field, which requires colour sensors not only with high photo responsivity but also in a wide spectral range.

The observation of regional evaporative fraction (EF) over a heterogeneous area is crucial to surface energy balance modeling and satellite-based evapotranspiration (ET) validation over complex areas. However, regional EF observations are often lacking or not directly acquired because the sparse distribution and inadequate spatial representativeness of ground measurements cannot represent the region's heterogeneity in landscape and land-surface processes. The UAV-based eddy-covariance (EC) system can be used to observe the regional EF at large areas. UAV-based EC measurements were performed in December 2020 at around 90 m above the ground level over Yancheng coastal wetland, which included 7 flights for comparison with ground EC measurements and 4 flights for investigating the regional EF. The results of comparison showed that the sensible and latent heat fluxes from UAV were consistent with those measured from the ground, with the R2 of 0.84, RMSE of 15.7 W/m2, bias of 50.7 W/m2 for sensible heat flux, and the R2 of 0.77, RMSE of 13.1 W/m2, bias of -3.67 W/m2 for latent heat flux. Then, 53 flux observations were obtained from the 4 regional flights after applying a quality filter. A footprint model in conjunction with a high-resolution land cover map were used to determine the fluxes contribution source areas and to determine the accumulated footprint weight of the various land cover classes within the footprint areas. Thirdly, a multiple linear regression model was used to dis-aggregate the observed fluxes into component land-cover-class-specific fluxes, and to resolve the EF of each land cover class. The dis-aggregation results revealed that cropland had the highest EF (0.69 ± 0.11), followed by Spartina alterniflora (0.3 ± 0.11) and Phragmites australis (0.27 ± 0.09). Lastly, the EF of Phragmites australis was compared with ground measurement and had a relative error of 2.9%, demonstrating that the UAV-based EC system provided a reliable observation of regional EF.

Enzymatic treatment is an attractive method for mycotoxin detoxification, which ideally prefers the use of one or a few enzymes. However, this is challenged by the diverse structures and co-contamination of multiple mycotoxins in food and feed. Lignin-degrading fungi have been discovered to detoxify organics including mycotoxins. Manganese peroxidase (MnP) is a major enzyme responsible for lignin oxidative depolymerization in such fungi. Here, we demonstrate that eight MnPs from different lignocellulose-degrading fungi (five from Irpex lacteus, one from Phanerochaete chrysosporium, one from Ceriporiopsis subvermispora, and another from Nematoloma frowardii) could all degrade four major mycotoxins (aflatoxin B1, AFB1, zearalenone, ZEN, deoxynivalenol, DON, fumonisin B1, FB1) only in the presence of a dicarboxylic acid malonate, in which free radicals play an important role. The I. lacteus and C. subvermispora MnPs behaved similarly in mycotoxins transformation, outperforming the P. chrysosporium and N. frowardii MnPs. The large evolutionary diversity of these MnPs suggests that mycotoxin degradation tends to be a common feature shared by MnPs. MnP can, therefore, serve as a candidate enzyme for the degradation of multiple mycotoxins in food and feed if careful surveillance of the residual toxicity of degradation products is properly carried out.

Additional file 4. Primers used in this study.

Table S1. Primers used in this study. Figure S1. Sequencing the ura5 gene of QM9414, C5 expressing Cas9 intracellularly, and the C5-derived transformants. (DOCX 1220 kb)

Static heterojunction-based electronic devices have been widely applied because carrier dynamic processes between semiconductors can be designed through band gap engineering. Herein, we demonstrate a tunable direct-current generator based on the dynamic heterojunction, whose mechanism is based on breaking the symmetry of drift and diffusion currents and rebounding hot carrier transport in dynamic heterojunctions. Furthermore, the output voltage can be delicately adjusted and enhanced with the interface energy level engineering of inserting dielectric layers. Under the ultrahigh interface electric field, hot electrons will still transfer across the interface through the tunneling and hopping effect. In particular, the intrinsic anisotropy of black phosphorus arising from the lattice structure produces extraordinary electronic, transport, and mechanical properties exploited in our dynamic heterojunction generator. Herein, the voltage of 6.1 V, current density of 124.0 A/m 2 , power density of 201.0 W/m 2 , and energy-conversion efficiency of 31.4% have been achieved based on the dynamic black phosphorus/AlN/Si heterojunction, which can be used to directly and synchronously light up light-emitting diodes. This direct-current generator has the potential to convert ubiquitous mechanical energy into electric energy and is a promising candidate for novel portable and miniaturized power sources in the in situ energy acquisition field.

What influences Chinese agricultural eco-efficiency (AEE)? Taking the underlying technology heterogeneity into account, we proposed an analytical framework which combines meta-frontier analysis and a non-separable hybrid model with undesirable output (Meta-Hybrid-U). The general aim of this study is to apply the proposed framework to measure the AEE in 30 provinces in China from 1997 to 2015 under the group-frontier and meta-frontier. The dimensions of management and technology were used for the deconstruction of the agricultural eco-inefficiency (AEI) of various provinces. The Dagum Gini coefficient method was used for decomposition of regional differences in the AEE in China. Three main results were found. First, the mean AEE of all Chinese provinces under the meta-frontier is low, and there is much room for improvement. Secondly, at the national level, the AEI is caused by both the management inefficiency (MI) and technology gap inefficiency (TGI). At the regional level, the AEI in eastern China is wholly caused by the MI, while the AEI in the central and western regions is caused by both the MI and TGI. Finally, during the studied period, there is an increasing trend for the overall Gini coefficient of the AEE in China. The regional differences in the AEE in China are mainly due to the inter-regional differences and the intensity of transvariation. The paper also includes some suggestions for policies to improve China’s AEE and to reduce the inter-regional differences in China’s AEE.

Background CRISPR/Cas9 has wide application potentials in a variety of biological species including Trichoderma reesei, a filamentous fungus workhorse for cellulase production. However, expression of Cas9 heterologously in the host cell could be time-consuming and sometimes even troublesome. Results We tested two gene disruption methods in T. reesei using CRISPR/Cas9 in this study. The intracellularly expressed Cas9 led to unexpected off-target gene disruption in T. reesei QM9414, favoring inserting 9- or 12-bp at 70- and 100-bp downstream of the targeted ura5. An alternative method was, therefore, established by assembling Cas9 and gRNA in vitro, followed by transformation of the ribonucleoprotein complex with a plasmid containing the pyr4 marker gene into T. reesei TU-6. When the gRNA targeting cbh1 was used, eight among the twenty seven transformants were found to lose the ability to express CBH1, indicative of successful cbh1 disruption through genome editing. Large DNA fragments including the co-transformed plasmid, chromosomal genes, or a mixture of these nucleotides, were inserted in the disrupted cbh1 locus. Conclusions Direct transformation of Cas9/gRNA complex into the cell is a fast means to disrupt a gene in T. reesei and may find wide applications in strain improvement and functional genomics study. Electronic supplementary material The online version of this article (10.1186/s12896-018-0498-y) contains supplementary material, which is available to authorized users.

Traditionally, Schottky diodes are used statically in the electronic information industry while dynamic or moving Schottky diode-based applications are rarely explored. Herein, a novel Schottky diode named "moving Schottky diode generator" is designed, which can convert mechanical energy into electrical energy by means of lateral movement between the graphene/metal film and semiconductor. The mechanism is based on the built-in electric field separation of the diffusing carriers in moving Schottky diode. A current-density output up of 40.0 A m-2 is achieved through minimizing the contact distance between metal and semiconductor, which is 100-1000 times higher than former piezoelectric and triboelectric nanogenerators. The power density and power conversion efficiency of the heterostructure-based generator can reach 5.25 W m-2 and 20.8%, which can be further enhanced by Schottky junction interface design. Moreover, the graphene film/semiconductor moving Schottky diode-based generator behaves better flexibility and stability, which does not show obvious degradation after 10 000 times of running, indicating its great potential in the usage of portable energy source. This moving Schottky diode direct-current generator can light up a blue light-emitting diode and a flexible graphene wristband is demonstrated for wearable energy source.

Peptide aptamers – artificial short peptides with specific binding affinity for target molecules – can be used to interfere with protein functions and protein–protein interactions in plant cells. Therefore, peptide aptamers have emerged as a new, powerful tool with high efficiency and specificity and wide applications in functional genomics and plant biotechnology.

Additional file 1. Observation of representative T. reesei strains expressing DsRed by naked eyes. The culture medium is MM-lactose plus agar.

Cellulase and mannanase are both important enzyme additives in animal feeds. Expressing the two enzymes simultaneously within one microbial host could potentially lead to cost reductions in the feeding of animals. For this purpose, we codon-optimized the Aspergillus niger Man5A gene to the codon-usage bias of Trichoderma reesei. By comparing the free energies and the local structures of the nucleotide sequences, one optimized sequence was finally selected and transformed into the T. reesei pyridine-auxotrophic strain TU-6. The codon-optimized gene was expressed to a higher level than the original one. Further expressing the codon-optimized gene in a mutated T. reesei strain through fed-batch cultivation resulted in coproduction of cellulase and mannanase up to 1376 U·mL

The overloaded energy cost has become the main concern of the now fast developing society, which make novel energy devices with high power density of critical importance to the sustainable development of human society. Herein, a dynamic Schottky diode based generator with ultrahigh power density of 1262.0 W m−2 for sliding Fe tip on rough p‐type silicon is reported. Intriguingly, the increased surface states after rough treatment lead to an extremely enhanced current density up to 2.7 × 105 A m−2, as the charged surface states can effectively accelerate the carriers through large atomic electric field, while the reflecting directions are regulated by the built‐in electric field of the Schottky barrier. This research provides an open avenue for utilizing the surface states in semiconductors in a subversive way, which can co‐utilize the atomic electric field and built‐in electric field to harvest energy from the mechanical movements, especially for achieving an ultrahigh current density power source.

By combining the surface plasmon enhancement technique with gating effect, a tunable blue lighting emitting diode (LED) based on graphene/Ag nanoparticles (NPs)-polymethyl methacrylate (PMMA)/graphene/p-GaN heterostructure has been achieved. The surface plasmon enhancement is introduced through spin-coating Ag nanoparticles on graphene/p-GaN heterostructure while the gating effect is demonstrated through a graphene/PMMA/graphene sandwich structure, where the top graphene layer acts as the gate electrode. Compared with initial graphene/p-GaN heterostructure LEDs, the electroluminescence (EL) emission intensity of Ag NPs/graphene/p-GaN heterostructure LEDs has been largely enhanced, attributing to the surface plasmon resonance (SPR) of Ag nanoparticles. The EL emission intensity of graphene/Ag NPs-PMMA/graphene/p-GaN heterostructure LEDs can further be gate-tunable effectively through exerting a static voltage between the sandwich structure, which tunes the Fermi level of graphene contacting with p-GaN. These results indicate that through sophisticated design, graphene/Ag NPs-PMMA/graphene/p-GaN heterostructure LEDs can be a potential candidate for many essential electronic and optoelectronic applications.