pH-responsive size-adjustable liposomes induce apoptosis of fibroblasts and macrophages for rheumatoid arthritis treatment.

In rheumatoid arthritis (RA), macrophages infiltrate joints, while fibroblast-like synovial cells proliferate abnormally, forming a barrier against drug delivery, which hinders effective drug delivery to joint focus. Here we firstly designed a pH-responsive size-adjustable nanoparticle, composed by methotrexate (MTX)-human serum albumin (HSA) complex coating with pH-responsive liposome (Lipo/MTX-HSA) for delivering drugs specifically to inflamed joints in acidic environments. We showed in vitro that the nanoparticles can induce mitochondrial dysfunction, promote apoptosis of fibroblast-like synoviocytes and macrophages, further reduce the secretion of inflammatory factors (TNF-α, IL-1ß, MMP-9), and regulate the inflammatory microenvironment. We also demonstrated similar effects in a rat model of arthritis, in which Lipo/MTX-HSA accumulated in arthritic joints, and at low pH, liposome phospholipid bilayer cleavage released small-sized MTX-HSA, which effectively reduced the number of fibroblast-synoviocytes and macrophages in joints, alleviated joint inflammation, and repaired bone erosion. These findings suggest that microenvironment-responsive size-adjustable nanoparticles show promise as a treatment against rheumatoid arthritis. STATEMENT OF SIGNIFICANCE: Abnormal proliferation of fibroblast synoviocytes poses a physical barrier to effective nanoparticle delivery. We designed size-adjustable nano-delivery systems by preparing liposomes with cholesterol hemisuccinate (CHEM), which were subsequently loaded with small-sized albumin nanoparticles encapsulating the cytotoxic drug MTX (MTX-HSA), termed Lipo/MTX-HSA. Upon tail vein injection, Lipo/MTX-HSA could be aggregated at the site of inflammation via the ELVIS effect in the inflamed joint microenvironment. Specifically, intracellular acidic pH-triggered dissociation of liposomes promoted the release of MTX-HSA, which was further targeted to fibroblasts or across fibroblasts to macrophages to exert anti-inflammatory effects. The results showed that liposomes with adjustable particle size achieved efficient drug delivery, penetration and retention in joint sites; the strategy exerted significant anti-inflammatory effects in the treatment of rheumatoid arthritis by inducing mitochondrial dysfunction to promote apoptosis in fibrosynoviocytes and macrophages.

Advances in Nanodelivery Systems Based on Metabolism Reprogramming Strategies for Enhanced Tumor Therapy.

Tumor development and metastasis are closely related to the complexity of the metabolism network. Recently, metabolism reprogramming strategies have attracted much attention in tumor metabolism therapy. Although there is preliminary success of metabolism therapy agents, their therapeutic effects have been restricted by the effective reaching of the tumor sites of drugs. Nanodelivery systems with unique physical properties and elaborate designs can specifically deliver to the tumors. In this review, we first summarize the research progress of nanodelivery systems based on tumor metabolism reprogramming strategies to enhance therapies by depleting glucose, inhibiting glycolysis, depleting lactic acid, inhibiting lipid metabolism, depleting glutamine and glutathione, and disrupting metal metabolisms combined with other therapies, including chemotherapy, radiotherapy, photodynamic therapy, etc. We further discuss in detail the advantages of nanodelivery systems based on tumor metabolism reprogramming strategies for tumor therapy. As well as the opportunities and challenges for integrating nanodelivery systems into tumor metabolism therapy, we analyze the outlook for these emerging areas. This review is expected to improve our understanding of modulating tumor metabolisms for enhanced therapy.

Multifunctional nanoparticles inhibit tumor and tumor-associated macrophages for triple-negative breast cancer therapy.

HYPOTHESIS: Tumor-associated macrophages (TAM) are the mainstay of immunosuppressive cells in the tumor microenvironment, and elimination of M2-type macrophages (M2-TAM) is considered as a potential immunotherapy. However, the interaction of breast cancer cells with macrophages hinders the effectiveness of immunotherapy. In order to improve the efficacy of triple-negative breast cancer (TNBC) therapy, strategies that simultaneously target the elimination of M2-TAM and breast cancer cells may be able to achieve a better therapy. EXPERIMENTS: LyP-SA/AgNP@Dox multifunctional nanoparticles were synthesized by electrostatic adsorption. They were characterized by particle size, potential and spectroscopy. And the efficacy of multifunctional nanoparticles was evaluated in 4 T1 cell lines and M2 macrophages, including their cell uptake intracellular reactive oxygen species (ROS) production and the therapeutic effect. Furthermore, based on the orthotopic xenotransplantation model of triple negative breast cancer, the biological distribution, fluorescence imaging, biosafety evaluation and combined efficacy evaluation of the nanoplatform were performed. FINDINGS: We have successfully prepared LyP-SA/AgNP@Dox and characterized. Administering the nanosystem to 4 T1 tumor cells or M2 macrophages in culture induced accumulation of reactive oxygen species, destruction of mitochondria and apoptosis, and inhibited replication and transcription. Animal experiments demonstrated the nanoparticle had favorable targeting and antitumor activity. Our nanosystem may be useful for simultaneously inhibiting tumor and tumor-associated macrophages in breast cancer and, potentially, other malignancies.

qGLF5 from Oryza rufipogon Griff. improves kernel shape, plant architecture, and yield in rice.

KEY MESSAGE: A novel QTL qGLF5 from Oryza rufipogon Griff. improves yield per plant and plant architecture in rice. Kernel size and plant architecture are critical agronomic traits that are key targets for improving crop yield. From the single-segment substitution lines of Oryza rufipogon Griff. in the indica cultivar Huajingxian74 (HJX74) background, we identified a novel quantitative trait locus (QTL), named qGLF5, which improves kernel shape, plant architecture, and yield per plant in rice. Compared with the control HJX74, the plant height, panicles per plant, panicle length, primary branches per panicle, secondary branches per panicle, and kernels per plant of the near-isogenic line-qGLF5 (NIL-qGLF5) are significantly increased. NIL-qGLF5 has long and narrow kernels by regulating cell number, cell length and width in the spikelet hulls. Yield per plant of NIL-qGLF5 is increased by 35.02% compared with that of HJX74. In addition, qGLF5 significantly improves yield per plant and plant architecture of NIL-gw5 and NIL-GW7. These results indicate that qGLF5 might be beneficial for improving plant architecture and kernel yield in rice breeding by molecular design.

Remarkably enhanced catalytic performance in CoOx/Bi4Ti3O12 heterostructures for methyl orange degradation via piezocatalysis and piezo-photocatalysis.

A novel heterojunction composite of CoOx/Bi4Ti3O12 was synthesized through a combination of molten salt and photodeposition methods. The optimal sample exhibited superior performance in the piezocatalytic degradation of methyl orange (MO) dye with a degradation rate of 1.09 h-1, which was 2.4 times higher than that of pristine Bi4Ti3O12. Various characterizations were conducted to reveal the fundamental nature accountable for the outstanding piezocatalytic performance of CoOx/Bi4Ti3O12. The investigation of the band structure indicated that the CoOx/Bi4Ti3O12 composite formed a type-I p-n heterojunction structure, with CoOx acting as a hole trapper to effectively separate and transfer piezogenerated carriers. Significantly, the MO degradation rate of the best CoOx/Bi4Ti3O12 sample further increased to 2.96 h-1 under combined ultrasonic vibration and simulated sunlight. The synergy between piezocatalysis and photocatalysis can be ascribed to the following factors. The photoexcitation process ensures the sufficient generation of charge carriers in the CoOx/Bi4Ti3O12, while the piezoelectric field within Bi4Ti3O12 promotes the separation of electron-hole pairs in the bulk phase. Furthermore, the heterojunction structure between Bi4Ti3O12 and CoOx significantly facilitates the surface separation of charge carriers. This increased involvement of free electrons and holes in the reaction leads to a remarkable enhancement in catalytic MO degradation. This work contributes to the understanding of the coupling mechanism between the piezoelectric effect and photocatalysis, and also provides a promising strategy for the development of efficient catalysts for wastewater treatment.

qGL3.4 controls kernel size and plant architecture in rice.

Kernel size and plant architecture play important roles in kernel yield in rice. Cloning and functional study of genes related to kernel size and plant architecture are of great significance for breeding high-yield rice. Using the single-segment substitution lines which developed with Oryza barthii as a donor parent and an elite indica cultivar Huajingxian74 (HJX74) as a recipient parent, we identified a novel QTL (quantitative trait locus), named qGL3.4, which controls kernel size and plant architecture. Compared with HJX74, the kernel length, kernel width, 1000-kernel weight, panicle length, kernels per plant, primary branches, yield per plant, and plant height of near isogenic line-qGL3.4 (NIL-qGL3.4) are increased, whereas the panicles per plant and secondary branches per panicle of NIL-qGL3.4 are comparable to those of HJX74. qGL3.4 was narrowed to a 239.18 kb interval on chromosome 3. Cell analysis showed that NIL-qGL3.4 controlled kernel size by regulating cell growth. qGL3.4 controls kernel size at least in part through regulating the transcription levels of EXPANSINS, GS3, GL3.1, PGL1, GL7, OsSPL13 and GS5. These results indicate that qGL3.4 might be beneficial for improving kernel yield and plant architecture in rice breeding.

GS6.1 controls kernel size and plant architecture in rice.

MAIN CONCLUSION: A novel QTL GS6.1 increases yield per plant by controlling kernel size, plant architecture, and kernel filling in rice. Kernel size and plant architecture are critical agronomic traits that greatly influence kernel yield in rice. Using the single-segment substitution lines (SSSLs) with an indica cultivar Huajingxian74 as a recipient parent and American Jasmine as a donor parent, we identified a novel quantitative trait locus (QTL), named GS6.1. Near isogenic line-GS6.1 (NIL-GS6.1) produces long and narrow kernels by regulating cell length and width in the spikelet hulls, thus increasing the 1000-kernel weight. Compared with the control, the plant height, panicles per plant, panicle length, kernels per plant, secondary branches per panicle, and yield per plant of NIL-GS6.1 are increased. In addition, GS6.1 regulates the kernel filling rate. GS6.1 controls kernel size by modulating the transcription levels of part of EXPANSINs, kernel filling-related genes, and kernel size-related genes. These results indicate that GS6.1 might be beneficial for improving kernel yield and plant architecture in rice breeding by molecular design.

A novel NiO/BaTiO3 heterojunction for piezocatalytic water purification under ultrasonic vibration.

This work designed and prepared a novel heterojunction composite NiO/BaTiO3 through a method of photodeposition and used it in piezocatalytic dye removal for the first time. Results of the piezocatalytic test indicated that the NiO/BaTiO3 composite presented superior efficiency and stability in the RhB degradation under the vibration of ultrasonic waves. The best NiO/BaTiO3 sample synthesized under light irradiation for 2 h displayed an RhB degradation rate of 2.41 h-1, which was 6.3 times faster than that of pure BaTiO3. By optimizing the piezocatalytic reaction conditions, the degradation rate constant of NiO/BaTiO3 can further reach 4.14 h-1 A variety of systematic characterizations were executed to determine the reason for the excellent piezocatalytic performance of NiO/BaTiO3. The band potentials of NiO and BaTiO3 are found to coincide, and at their contact interface, they may create a type-II p-n heterojunction structure. Driven by the potential difference and the built-in electric field, piezoelectrically enriched charge carriers can migrate between NiO and BaTiO3, resulting in improved efficiency in charge separation and an increase in the piezoelectric catalytic performance. This study may provide a potential composite catalyst and a promising idea for the design of highly efficient catalysts in the field of piezoelectric catalysis.

Defects Produced during Wet Transfer Affect the Electrical Properties of Graphene.

Graphene has been widely used due to its excellent electrical, mechanical and chemical properties. Defects produced during its transfer process will seriously affect the performance of graphene devices. In this paper, single-layer graphene was transferred onto glass and silicon dioxide (SiO2) substrates by wet transfer technology, and the square resistances thereof were tested. Due to the different binding forces of the transferred graphene surfaces, there may have been pollutants present. PMMA residues, graphene laminations and other defects that occurred in the wet transfer process were analyzed by X-ray photoelectron spectroscopy and Raman spectroscopy. These defects influenced the square resistance of the produced graphene films, and of these defects, PMMA residue was the most influential; square resistance increased with increasing PMMA residue.

Flexible Pressure Sensor with Micro-Structure Arrays Based on PDMS and PEDOT:PSS/PUD&CNTs Composite Film with 3D Printing.

Flexible pressure sensors are widely used in different fields, especially in human motion, robot monitoring and medical treatment. Herein, a flexible pressure sensor consists of the flat top plate, and the microstructured bottom plate is developed. Both plates are made of polydimethylsiloxane (PDMS) by molding from the 3D printed template. The contact surfaces of the top and bottom plates are coated with a mixture of poly (3,4-ethylenedioxythiophene) poly (styrene sulfonate) (PEDOT:PSS) and polyurethane dispersion (PUD) as stretchable film electrodes with carbon nanotubes on the electrode surface. By employing 3D printing technology, using digital light processing (DLP), the fabrication of the sensor is low-cost and fast. The sensor models with different microstructures are first analyzed by the Finite Element Method (FEM), and then the models are fabricated and tested. The sensor with 5 × 5 hemispheres has a sensitivity of 3.54 × 10-3 S/kPa in the range of 0-22.2 kPa. The zero-temperature coefficient is -0.0064%FS/°C. The durability test is carried out for 2000 cycles, and it remains stable during the whole test. This work represents progress in flexible pressure sensing and demonstrates the advantages of 3D printing technology in sensor processing.

Forkhead box protein O1 (FoxO1) /SERPINB1 ameliorates ROS production in diabetic nephropathy.

With the increasing prevalence of diabetes in recent years, diabetic nephropathy (DN) has become a severe disease that greatly threatens human health. DN not only is a common complication of diabetes, but also takes an important place in kidney disease. To this end, the present study was designed to explore the effects of Forkhead box protein O1 (FoxO1) on reactive oxygen species (ROS) production in DN mice. DN mice were treated with recombinant protein of FoxO1. Afterward, inflammation ELISA kits were used to measure the levels of TNF-α, IL-1ß, IL-6, and IL-18. The levels of MDA, SOD, GSH, and GSH-PX were measured using kits according to the manufacturer's instructions. In addition, the production of ROS was assessed. Interestingly, the expression of FoxO1 was down-regulated in DN mice. The treatment of FoxO1 recombinant protein ameliorated MDA levels, increased the levels of SOD, GSH, and GSH-PX, and induced both mRNA and protein expression of hepatic serine protease inhibitor B1 (serpinB1) in ND mice. Similarly, FoxO1 reduced MDA levels and ROS production, increased the levels of SOD, GSH, and GSH-PXs, and induced the mRNA and protein expression of serpinB1 in in vitro model of DN. The inhibition of serpinB1 attenuated the effects of FoxO1 on ROS production-induced oxidative stress in in vitro model of DN. Overall, FoxO1/SERPINB1 ameliorated ROS production-induced oxidative stress in DN.