Coordinated regulation of BACH1 and mitochondrial metabolism through tumor-targeted self-assembled nanoparticles for effective triple negative breast cancer combination therapy

The poor prognosis of triple negative breast cancer(TNBC)results from a lack of approved targeted therapies coupled with aggressive proliferation and metastasis,which is associated with high recurrence and short overall survival.Here we developed a strategy by employing tumor-targeted selfassembled nanoparticles to coordinately regulate BACH1(BTB domain and CNC homology 1)and mitochondrial metabolism.The BACH1 inhibitor hemin and mitochondria function inhibitor berberine derivative(BD)were used to prepare nanoparticles(BH NPs)followed by the modification of chondroitin sulfate(CS)on the surface of BH NPs to achieve tumor targeting(CS/BH NPs).CS/BH NPs were found to be able to inhibit tumor migration and invasion by significantly decreasing the amounts of tumor cell metabolites,glycolysis and metastasis-associated proteins,which were related to the inhibition of BACH1 function.Meanwhile,decreased mitochondrial membrane potential,activated caspase 3/9 and increased ROS production demonstrated coordinated regulation of BACH1 and mitochondrial metabolism.In a xenograft mice model of breast cancer,CS/BH NPs significantly inhibited tumor growth and metastasis due to the synergetic effect of hemin and BD without showing obvious toxicities for major organs.In sum,the results of efficacy and safety experiments suggest potential clinical significance of the prepared self-assembled CS/BH nanoparticles for the treatment of TNBC.

Effects of water and salt coordinated regulation at the different growth stages on water consumption and yield of tomato

The objective of this study was to explore the effects of different degrees of water and salt stress on the actual water consumption and soil salt accumulation of tomatoes and the salt tolerance characteristics of tomatoes under brackish water combined with regulated deficit irrigation mode.The greenhouse pot experiment was used to set three influencing factors,the irrigation water salinity S1 was 1.1 g/L(local shallow groundwater),S2 was 2.0 g/L,and S3 was 4.0 g/L,respectively,and different degrees of water deficit(W1 ranged from 65%-75%Field Capacity(FC),W2 ranged from 55%-65%FC,W3 ranged from 45%-55%FC)and seedling stage(T1),blossoming and bearing fruits stage(T2)and mature picking stage(T3).The response of fresh fruit weight,stems and leaves weight,yield and water use efficiency of tomato under water and salt stress were monitored and analyzed.The results showed the coordinated regulation of water and salt can significantly reduce the electrical conductivity of the 0-30 cm soil of the tomato root system.The higher the salinity of irrigation water,the better the salt control effects of the coordinated regulation of water and salt;the coordinated regulation of water and salt at different growth stages had significant effects on the weight of fresh tomato fruits,the weight of stems and leaves and the yield.The salinity of irrigation water was in inverse proportion to the yield of tomatoes;In S1 treatment irrigation(irrigation water salinity was 1.1 g/L)under the mildly regulated deficit in the seedling stage(irrigation water was 55%-65%of the field water capacity)can effectively reduce the irrigation water volume during the whole growth stage while ensuring that there was no significant reduction in yield.The research results provided a scientific and reliable theoretical basis for the increase of local tomato production,the improvement of water use efficiency and the formulation of suitable irrigation patterns.

2D CoOOH Sheet-Encapsulated Ni2P into Tubular Arrays Realizing 1000 mA cm^-2-Level-Current-Density Hydrogen Evolution Over 100 h in Neutral Water

Water electrolysis at high current density(1000 mA cm-2 level)with excellent durability especially in neutral electrolyte is the pivotal issue for green hydrogen from experiment to industrialization.In addition to the high intrinsic activity determined by the electronic structure,electrocatalysts are also required to be capable of fast mass transfer(electrolyte recharge and bubble overflow)and high mechanical stability.Herein,the 2D CoOOH sheet-encapsulated Ni2P into tubular arrays electrocatalytic system was proposed and realized 1000 mA cm-2-levelcurrent-density hydrogen evolution over 100 h in neutral water.In designed catalysts,2D stack structure as an adaptive material can buffer the shock of electrolyte convection,hydrogen bubble rupture,and evolution through the release of stress,which insure the long cycle stability.Meanwhile,the rich porosity between stacked units contributed the good infiltration of electrolyte and slippage of hydrogen bubbles,guaranteeing electrolyte fast recharge and bubble evolution at the high-current catalysis.Beyond that,the electron structure modulation induced by interfacial charge transfer is also beneficial to enhance the intrinsic activity.Profoundly,the multiscale coordinated regulation will provide a guide to design high-efficiency industrial electrocatalysts.

ARF2 coordinates with PLETHORAs and PINs to orchestrate ABA-mediated root meristem activity in Arabidopsis

Multiple hormones, including abscisic acid（ABA） and auxin, regulate cell division and differentiation of Arabidopsis root meristems. AUXIN RESPONSE FACTOR2（ARF2） functions as a negative regulator of ABA responses, as seed germination and primary root growth of arf2 mutants are hypersensitive to ABA. In this study, we found that ABA treatment reduced the expression levels of the PIN-FORMEDs（PIN） auxin efflux carriers, PIN1, PIN3,PIN4, and PIN7, to a greater extent in the root meristems of arf2-101 mutant than in the wild type. Also, arf2-101 pin1 and arf2-101 pin4 double mutants show less ABA-induced inhibition of root meristem activity than the arf2-101 mutants. Furthermore, ARF2 positively mediates the transcripts of transcription factor PLETHORA 1（PLT1）gene but negatively mediates PLT2 at protein level in root meristems. Using a dexamethasone（DEX）-inducible transgenic line, Pro35S：PLT2-GR, we showed that PLT2 greatly promotes cell division and completely inhibits cell differentiation in root meristems of the arf2-101 mutant once PLT2 is induced by DEX, which can be partially reversed by ABA treatment, suggesting that ABA regulates root meristem activity in both ARF2-dependent and independent pathways. Our results uncover a complex regulatory architecture in which ARF2 coordinates with PLTs and PINs to orchestrate ABA-mediated regulation of root meristem activity in Arabidopsis.

Tuned single atom coordination structures mediated by polarization force and sulfur anions for photovoltaics

Impeding high temperature sintering is challengeable for synthesis of carbon-supported single-atom catalysts (C-SACs), which requires high-cost precursor and strictly-controlled procedures. Herein, by virtue of the ultrastrong polarity of salt melts, sintering of metal atoms is effectively suppressed. Meanwhile, doping with inorganic sulfur anions not only produces sufficient anchoring sites to achieve high loading of atomically dispersed Co up to 13.85 wt.%, but also enables their electronic and geometric structures to be well tuned. When served as a cathode catalyst in dye-sensitized solar cells, the C-SAC with Co-N4-S2 moieties exhibits high activity towards the iodide reduction reaction (IRR), achieving a higher power conversion efficiency than that of conventional Pt counterpart. Density function theory (DFT) calculations revealed that the superior IRR activity was ascribed to the unique structure of Co-N4-S2 moieties with lower reaction barriers and moderate binding energy of iodine on the Co center, which was beneficial to I2 dissociation.