Search

Growth plate cartilage has limited self-repair ability, leading to poor bone bridge formation post-injury and ultimately limb growth defects in children. The current corrective surgeries are highly invasive, and outcomes can be unpredictable. Following growth plate injury, the direct loss of extracellular matrix (ECM) coupled with further ECM depletion due to the inhibitory effects of inflammation on the cartilage matrix protein greatly hinder chondrocyte regeneration. We designed an exosome (Exo) derived from bone marrow mesenchymal stem cells (BMSCs) loaded ECM-mimic hydrogel to promote cartilage repair by directly supplementing ECM and anti-inflammatory properties. Aldehyde-functionalized chondroitin sulfate (OCS) was introduced into gelatin methacryloyl (GM) to form GMOCS hydrogel. Our results uncovered that GMOCS hydrogel could significantly promote the synthesis of ECM due to the doping of OCS. In addition, the GMOCS-Exos hydrogel could further promote the anabolism of chondrocytes by inhibiting inflammation and ultimately promote growth plate injury repair through ECM remodeling., Graphical abstract Image 1, Highlights • Chondrocytes are difficult to regenerate after growth plate injury due to extensive degradation of ECM (extracellular matrix). • GMOCS-Exos can promote the synthesis of ECM by directly supplementing ECM and anti-inflammatory properties. • GMOCS-Exos can boost cartilage regeneration after growth plate injury and reduce bone bridge formation.

A series of three-dimensional ordered macroporous (3DOM) W–TiO2 catalysts have been prepared through a facile colloidal crystal template method. The prepared materials characterized in detail exhibited enhanced catalytic activity in aerobic oxidative desulfurization process. The experimental results indicated that the as-prepared materials possessed excellent 3DOM structure, which is beneficial for the catalytic activity. The sample 3DOM W–TiO2-20 exhibited the highest activity in ODS process, and the sulfur removal can reach 98% in 6 h. Furthermore, the oxidative product was also analyzed in the reaction process.

Injectable biomaterial-based treatment is a promising strategy to enhance tissue repair after traumatic spinal cord injury (SCI) by bridging cavity spaces. However, there are limited reports of injectable, electroconductive hydrogels with self-healing properties being employed for the treatment of traumatic SCI. Hence, a natural extracellular matrix (ECM) biopolymer (chondroitin sulphate and gelatin)-based hydrogel containing polypyrrole, which imparted electroconductive properties, is developed for traumatic SCI repair. The resulting hydrogels showed mechanical (~928 Pa) and conductive properties (4.49 mS/cm) similar to natural spinal cord tissues. Moreover, the hydrogels exhibited shear-thinning and self-healing abilities, which allows it to be effectively injected into the injury site and to fill the lesion cavity to accelerate the tissue repair of traumatic SCI. In vitro, electroconductive ECM hydrogels promoted neuronal differentiation, enhanced axon outgrowth, and inhibited astrocyte differentiation. The electroconductive ECM hydrogel activated endogenous neural stem cell neurogenesis in vivo (n = 6), and induced myelinated axon regeneration into the lesion site via activation of the PI3K/AKT and MEK/ERK pathways, thereby achieving significant locomotor function restoration in rats with spinal cord injury (p, Graphical abstract An injectable, electroconductive hydrogels with self-healing properties based on natural extracellular matrix biopolymer is developed. The hydrogel can effectively be injected into the injury site and to fill the lesion cavity and promote new endogenous neurogenesis and induce myelinated axon regeneration in vivo, thus achieving significant locomotor function restoration in rats with spinal cord injury.Image 1, Highlights • Injectable, electroconductive hydrogels with self-healing properties was designed. • The injectable hydrogel was adhesive, biocompatible and biodegradable. • The injectable hydrogel promoted neuronal differentiation and axon outgrowth in vivo. • Injection of the hydrogel enhanced endogenous neurogenesis and function restoration.

The nickel based bifunctional catalyst with enhanced hydroisomerization performance was developed using an in-situ solid synthesis method. It was achieved to stabilize smaller Ni active sites on SAPO-5 using ethylenediaminetetraacetic acid (EDTA) ligands. The role of EDTA ligands was clarified by controlling the molar ratio of EDTA to Ni2+ (EDTA/Ni2+) over Ni/SAPO-5 catalysts. EDTA ligands inhibited the formation of nickel aluminate spinel and aggregation of NiO species during calcination, which dispersed Ni nanoparticles in a mean size of 4.7 nm on SAPO-5. The size of Ni nanoparticles could be controlled by regulating EDTA/Ni2+ ratio in [Ni-EDTA]2- complex. The prepared catalyst exhibited high yield of isomers (54.0%) and di-branched isomers selectivity (18.0%) in the n-hexane hydroisomerization, which was approximately 2 times higher than that of the Ni/SAPO-5 catalyst without EDTA ligands at similar conversion. These results are important to propose a facile approach for the preparation of highly dispersed non-noble metal based bifunctional catalysts at a high loading.

The secondary salinization of soil in facility agriculture is becoming increasingly serious. Cucumber is a moderately salt-sensitive crop, but because of the weak root system and poor resistance to salt stress in cucumber seedlings, it is sensitive to the accumulation of salt in facility soils. Hydrogen, a selective antioxidant and signal molecule, is nontoxic and harmless, and can repair damage in plants under stress. Therefore, the aim of the present paper was to understand the specific mechanism by which hydrogen-rich water (HRW) alleviated salt stress in cucumber seedlings (Cucumis sativus L.). Our results showed that the addition of 50% saturation HRW significantly promoted seedling growth, development and photosynthetic efficiency. Pretreatment with HRW significantly alleviated salt stress symptoms, including the inhibition of fresh and dry weight, root length, lateral roots, and the root/shoot ratio of cucumber seedlings. Pretreatment with HRW increased the chlorophyll content, chlorophyll a/b ratio, and photochemical reaction efficiency, and reduced energy dissipation. These responses to HRW pretreatment were consistent with significant decreases in the superoxide anion, hydrogen peroxide, and malondialdehyde contents and the degree of lipid peroxidation, and increases in the activities of SOD, POD, CAT, APX and GR, and the contents of ASA and GSH in cucumber seedlings under salt stress. In addition, HRW pretreatment under salt stress inhibited the expression of the protein kinase ROP1, which promoted the production of reactive oxygen, but upregulated the protein kinase LecRLK. The transcription factor TGA5, which was involved in osmotic stress, ion stress and ROS clearance, and the expression of NHX1 and SOS2, which were parts of the SOS signaling pathway. HRW enhanced the expression of genes that encoded antioxidant enzymes, including SOD, CAT and POD, and the expressions of GR and APX2, which were key genes in the ASA-GSH cycle under salt stress. Taken together, these results suggested that HRW enhanced the active oxygen scavenging ability in cucumber seedlings, promoted the redox balance in cells, and reduced the degree of oxidative damage in plants under salt stress by reducing the content of active oxygen. Therefore, the application of HRW might be a promising strategy for improving salt stress tolerance in cucumber seedlings.

Oxidative stress modulation is effective to kill cancer. While considerable effort has focused on the promotion of reactive oxygen species (ROS) levels, an additional crucial aspect of ROS regulati...

The viscoelastic wormlike micelles composed of the ionic liquid surfactant, 1-hexadecyl-3-octyl imidazolium bromide ([C16imC8]Br), and the β-cyclodextrin (β-CD) were utilized to mimic the formation of lithangiuria, that is the calcium oxalate monohydrate (COM). The influence of different additives, such as CaCl2 and Na2C2O4 (precursors for the synthesis of COM) and the β-CD on the viscoelasticity of the [C16imC8]Br solution, was studied by the rheology. The [C16imC8]Br rod-like micelles transit to the wormlike micelles induced by different additives. The [C16imC8]Br/β-CD wormlike micelles containing the [C16imC8]Br/β-CD inclusion complexes were characterized by the small angle X-ray scattering, surface tension measurements, zeta potential measurements, and cryo-TEM. The COM particles were synthesized in the [C16imC8]Br/β-CD wormlike micelles which were characterized by the transmission electron microscopy and X-ray diffraction. The β-CD has important influence on the formation of COM. In the end, the mechanism of the synthesis of COM in the [C16imC8]Br/β-CD wormlike micelles is proposed.

Conductive scaffolds have been shown to exert a therapeutic effect on patients suffering from peripheral nerve injuries (PNIs). However, conventional conductive conduits are made of rigid structures and have limited applications for impaired diabetic patients due to their mechanical mismatch with neural tissues and poor plasticity. We propose the development of biocompatible electroconductive hydrogels (ECHs) that are identical to a surgical dressing in this study. Based on excellent adhesive and self-healing properties, the thin film-like dressing can be easily attached to the injured nerve fibers, automatically warps a tubular structure without requiring any invasive techniques. The ECH offers an intimate and stable electrical bridge coupling with the electrogenic nerve tissues. The in vitro experiments indicated that the ECH promoted the migration and adhesion of the Schwann cells. Furthermore, the ECH facilitated axonal regeneration and remyelination in vitro and in vivo through the MEK/ERK pathway, thus preventing muscle denervation atrophy while retaining functional recovery. The results of this study are likely to facilitate the development of non-invasive treatment techniques for PNIs in diabetic patients utilizing electroconductive hydrogels., Graphical abstract Image 1, Highlights • Conventional conductive conduits are made of rigid structures and have limited applications for diabetic patients. • Self-curling electroconductive hydrogel with porous, highly conductive, and adhesive properties were identical to a surgical dressing. • Electroconductive hydrogel facilitates axonal regeneration and remyelination via MEK/ERK pathway. • ECH dressing prevent muscle denervation atrophy and retain functional recovery in diabetic rats.

This study (ORIENT-4) aimed to assess the efficacy and safety of sintilimab, a humanized anti-PD-1 antibody, in patients with relapsed/refractory extranodal NK/T cell lymphoma (r/r ENKTL). ORIENT-4 is a multicenter, single-arm, phase 2 clinical trial (NCT03228836). Patients with r/r ENKTL who failed to at least one asparaginase-based regimen were enrolled to receive sintilimab 200 mg intravenously every 3 weeks for up to 24 months. The primary endpoint was the objective response rate (ORR) based on Lugano 2014 criteria. Twenty-eight patients with r/r ENKTL were enrolled from August 31, 2017 to February 7, 2018. Twenty-one patients (75.0%, 95% CI: 55.1–89.3%) achieved an objective response. With a median follow-up of 30.4 months, the median overall survival (OS) was not reached. The 24-month OS rate was 78.6% (95% CI, 58.4–89.8%). Most treatment-related adverse events (TRAEs) were grade 1–2 (71.4%), and the most common TRAE was decreased lymphocyte count (42.9%). Serious adverse events (SAEs) occurred in 7 (25.0%) patients, and no patient died of adverse events. Sintilimab is effective and well tolerated in patients with r/r ENKTL and could be a novel therapeutic approach for the control of ENKTL in patients.

Titanium-based scaffolds are widely used implant materials for bone defect treatment. However, the unmatched biomechanics and poor bioactivities of conventional titanium-based implants usually lead to insufficient bone integration. To tackle these challenges, it is critical to develop novel titanium-based scaffolds that meet the bioadaptive requirements for load-bearing critical bone defects. Herein, inspired by the microstructure and mechanical properties of natural bone tissue, we developed a Ti–6Al–4V alloy (TC4)/gelatin methacrylate (GelMA) hybrid scaffold with dual bionic features (GMPT) for bone defect repair. GMPT is composed of a hard 3D-printed porous TC4 metal scaffold (PT) backbone, which mimics the microstructure and mechanical properties of natural cancellous bone, and a soft GelMA hydrogel matrix infiltrated into the pores of PT that mimics the microenvironment of the extracellular matrix. Ascribed to the unique dual bionic design, the resultant GMPT demonstrates better osteogenic and angiogenic capabilities than PT, as confirmed by the in vitro and rabbit radius bone defect experimental results. Moreover, controlling the concentration of GelMA (10%) in GMPT can further improve the osteogenesis and angiogenesis of GMPT. The fundamental mechanisms were revealed by RNA-Seq analysis, which showed that the concentration of GelMA significantly influenced the expression of osteogenesis- and angiogenesis-related genes via the Pi3K/Akt/mTOR pathway. The results of this work indicate that our dual bionic implant design represents a promising strategy for the restoration of large bone defects., Graphical abstract Image 1, Highlights • A novel TC4/GelMA hybrid scaffold (GMPT) was designed to mimic natural bone microstructure and mechanical property. • The GMPT with 10 wt% of GelMA showed best capability for promoting osteogenesis and angiogenesis. • A bioactive soft surface with suitable stiffness can activate focal adhesion pathway and the downstream PI3K/AKT pathway.

The effects of Cl−, Cu2+ and Fe3+ ions and their combinations on the corrosion behaviour of aluminium alloy 6063 (AA6063) in ethylene glycol and water solutions at 50 °C were investigated by electrochemical and immersion methods. Cl− resulted in pitting corrosion of the alloy. In the Cl−-free solutions, Fe3+ was prone to accelerate uniform corrosion, while Cu2+ tended to accelerate pitting corrosion. Severe pitting corrosion of AA6063 was observed in the cases of Cl− combined with Cu2+ or Fe3+, especially in the case of Cl− combined with Cu2+ and Fe3+ ions.

Biopolymer based hydrogels are characteristic of their biocompatibility and capability of mimicking extracellular matrix structure to support cellular behavior. However, these hydrogels suffer from low mechanical properties, uncontrolled degradation, and insufficient osteogenic activity, which limits their applications in bone regeneration. In this study, we developed hybrid gelatin (Gel)/oxidized chondroitin sulfate (OCS) hydrogels that incorporated mesoporous bioactive glass nanoparticles (MBGNs) as bioactive fillers for bone regeneration. Gel-OCS hydrogels could be self-crosslinked in situ under physiological conditions in the presence of borax. The incorporation of MBGNs enhanced the crosslinking and accelerated the gelation. The gelation time decreased with increasing the concentration of MBGNs added. Incorporation of MBGNs in the hydrogels significantly improved the mechanical properties in terms of enhanced storage modulus and compressive strength. The injectability of the hydrogels was not significantly affected by the MBGN incorporation. Also, the proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells in vitro and rat cranial defect restoration in vivo were significantly promoted by the hydrogels in the presence of MBGNs. The hybrid Gel-OCS/MBGN hydrogels show promising potential as injectable biomaterials or scaffolds for bone regeneration/repair applications given their tunable degradation and gelation behavior as well as favorable mechanical behavior and osteogenic activities., Graphical abstract Image 1, Highlights • In situ self-crosslinking of hybrid Gel-OCS/MBGN hydrogels. • Hybrid hydrogels are porous, injectable and bioadhesive. • Incorporation of MBGNs enhances mechanical and mineralization properties of hydrogels. • Osteogenic differentiation of BMSCs enhanced after incorporating MBGNs into hydrogels. • The presence of MBGNs enhances in vivo rat cranial defect restoration.

In this study, graphene oxide–cerium oxide (GO–CeO2) hybrids were synthesized through an in situ hydrothermal approach and were incorporated into epoxy resin to prepare a robust coating for aluminum alloy protection. The mechanical properties of the GO–CeO2-loaded coating were characterized by nano-indentation, friction-wear test and pull-off adhesion test, using pristine epoxy coating and GO-loaded epoxy coating for comparison. Results revealed that GO–CeO2 addition could increase the hardness, elastic modulus and the wear resistance and decrease the friction coefficient of the composite coating. Compared with pristine epoxy coating, the adhesion strength of GO–CeO2/epoxy coating increased from 7.3 MPa to 12.2 MPa. Such improvement in the mechanical properties can be explained by the good dispersion of GO–CeO2 in the composite coating. In addition, salt spray and electrochemical impedance spectroscopy (EIS) measurement results showed that the corrosion resistance of the GO–CeO2-loaded coating was significantly enhanced. After 30 days of salt spray test, the coating resistance of the GO–CeO2/epoxy coating was 17.8 and 3.5 times higher compared with that of the blank epoxy coating and GO/epoxy coating, respectively. The superior barrier performance of the composite coating was mainly ascribed to the synergistic effects of the prolonged pathway against corrosive media permeation and the corrosion inhibition effect of CeO2 particles.

Multi-yolk-shell MnO@mesoporous carbon (MnO@m-carbon) nanopomegranates, featuring MnO nanoparticles within cavities of m-carbon with internal space between the MnO nanoparticle and a cavity carbon shell, were subtly constructed. Moreover, the buffer space was well controlled by means of regulating the size of the cavity in m-carbon or the content of MnO. The results of electrochemical measurements demonstrated that MnO(10)@m-carbon(22) nanopomegranates (MnO nanoparticle, 15 nm; cavity size, 22 nm) had the best cycling and rate performance for lithium ion storage. The pomegranate-like MnO@m-carbon nanostructures have shown several advantages for their excellent performance: the nanocavity in m-carbon can restrict the growth and agglomeration of MnO nanoparticles; the well-interconnected mesoporous carbon matrix provides a "highway" for electrons and lithium ion transport; the voids between the MnO nanoparticle and cavity shell can alleviate the volume expansion.

The host immune response effecting on biomaterials is critical to determine implant fates and bone regeneration property. Bone marrow stem cells (BMSCs) derived exosomes (Exos) contain multiple biosignal molecules and have been demonstrated to exhibit immunomodulatory functions. Herein, we develop a BMSC-derived Exos–functionalized implant to accelerate bone integration by immunoregulation. BMSC-derived Exos were reversibly incorporated on tannic acid (TA) modified sulfonated polyetheretherketone (SPEEK) via the strong interaction of TA with biomacromolecules. The slowly released Exos from SPEEK can be phagocytosed by co-cultured cells, which could efficiently improve the biocompatibilities of SPEEK. In vitro results showed the Exos loaded SPEEK promoted macrophage M2 polarization via the NF-κB pathway to enhance BMSCs osteogenic differentiation. Further in vivo rat air-pouch model and rat femoral drilling model assessment of Exos loaded SPEEK revealed efficient macrophage M2 polarization, desirable new bone formation, and satisfactory osseointegration. Thus, BMSC-derived Exos–functionalized implant exerted osteoimmunomodulation effect to promote osteogenesis., Graphical abstract Image 1, Highlights • The implanted biomaterials as foreign substances trigger a cascade of immune responses. • BMSC-derived exosomes with immunomodulatory were suitable for bioactive coating to exert osteoimmunomodulation effect. • Exosome-functionalized SPEEK can modulate macrophages M2 polarization via NF‐κB pathway. • Exosome-functionalized SPEEK with osteoimmunomodulation properties can promote osseointegration.

Porous organic polymers (POPs) are a class of promising materials for overcoming environmental and energy issues worldwide. However, their amorphous nature makes structural characterization in the solid state very challenging. In addition, developing facile synthesis methods and applications for POPs with novel structures remain urgent issues requiring improvement. In this work, novel porous organic polymers (named BIT-POPs) with isolated trans-alkene linkages were synthesized via cross-linking bis-norbornene via ring opening metathesis polymerization (ROMP) in an extremely mild and fast manner. Spectral editing approaches, such as 13C-CPMAS, 13C-CPPI, and 13C-CPNQS, relating to solid-state NMR were used to distinguish the overlapping NMR signals of insoluble BIT-POPs, and two-dimensional 1H–13C HETCOR spectra were used. Also, BIT-POP-5 was added to a polysulfone matrix as a porous filler to form a mixed-matrix membrane, which showed a 126% increase in CO2 permeability during gas separation.

Highlights • SHC014748M was proved to be more selective for PI3Kδ inhibition relative to other class i PI3K enzymes. • SHC014748M showed in vitro activity in most of 23 B lymphoma cell lines and primary CLL cells and also inhibited phosphorylation of AKT, targets downstream of PI3Kδ. • In vivo study revealed that SHC014748M significantly reduced lymphoma cell growth in the treatment group compared with control mice. • SHC014748M seemed to be a novel promising compound in the treatment of B cell lymphomas and CLL., PI3Kδ (phosphatidylinositol 3-kinase-δ), one of the class I PI3Ks, is found expressed primarily in leukocytes and plays an essential role in B-cell development and function. This provides a rationale for the development of small molecule inhibitors that selectively target p110δ for patients with indolent non-Hodgkin lymphomas. Here in this paper, we comprehensively evaluated the in vitro and in vivo antitumor activity of SHC014748M, an oral selective inhibitor of PI3Kδ under Phase I clinical evaluation. Biochemical and cell-based assays were used to measure compound potency and selectivity in lymphoma cell lines as well as primary chronic lymphocytic leukemia (CLL) cells. Scid mice were subcutaneously inoculated with the SU-DHL-6 cell line. SHC014748M was more selective for PI3Kδ inhibition relative to other class I PI3K enzymes and showed in vitro activity in most of 23 B lymphoma cell lines and primary CLL cells. SHC014748M also inhibited phosphorylation of AKT, targets downstream of PI3Kδ, in both lymphoma cells and primary CLL cells. In vivo study revealed that SHC014748M significantly reduced lymphoma cell growth in the treatment group compared with control mice. CCL4, CCL17, CCL22 and CXCL13 in patient serum decreased sharply after SHC014748M treatment. According to the results, SHC014748M appeared to be a novel promising compound in the treatment of B cell lymphomas and CLL.

Many cancer treatments including photodynamic therapy (PDT) utilize reactive oxygen species (ROS) to kill tumor cells. However, elevated antioxidant defense systems in cancer cells result in resistance to the therapy involving ROS. Here we describe a highly effective phototherapy through regulation of redox homeostasis with a biocompatible and versatile nanotherapeutic to inhibit tumor growth and metastasis. We systematically explore and exploit methylene blue adsorbed polydopamine nanoparticles as a targeted and precise nanocarrier, oxidative stress amplifier, photodynamic/photothermal agent, and multimodal probe for fluorescence, photothermal and photoacoustic imaging to enhance anti-tumor efficacy. Remarkably, following the glutathione-stimulated photosensitizer release to generate exogenous ROS, polydopamine eliminates the endogenous ROS scavenging system through depleting the primary antioxidant, thus amplifying the phototherapy and effectively suppressing tumor growth in vitro and in vivo. Furthermore, this approach enables a robust inhibition against breast cancer metastasis, as oxidative stress is a vital impediment to distant metastasis in tumor cells. Innovative, safe and effective nanotherapeutics via regulation of redox balance may provide a clinically relevant approach for cancer treatment., Amplified oxidative stress achieved by modulating redox homeostasis with PDA–MB for highly effective synergistic phototherapy to inhibit primary tumors and metastases.

Paraneoplastic pemphigus (PNP) is a severe autoimmune syndrome commonly triggered by neoplasms. The prognosis of CLL-associated PNP is dismal due to its refractory course and secondary infection and no standard treatment was recommended. We retrospectively reported six CLL with PNP cases from 842 cases of CLL including diagnosis, treatment and prognosis. The median time between the initial of CLL to PNP was 36 months while the median overall survival from the diagnosis of PNP was 26 months. And three cases died of lung infection while 5 developed pulmonary symptoms. And 5 cases received fludarabine-based chemotherapy before developing PNP, which suggesting fludarabine was one of potential causes of PNP. For the treatment, five patients were rescued by combined regimens including rituximab, methylprednisolone, immunoglobulin, fresh frozen plasma and the last received ibrutinib combined with short-term prednisone. Fludarabine-based regimen may be one of the potential causes of PNP. The combined regimen might shed a new light, while ibrutinib is a promising drug for CLL with PNP, but needs much more evidence. PNP should be carefully treated to guide early diagnosis and intervention for a better prognosis.

The effect of pre-oxidation on the corrosion behavior of pure Ti covered with a solid NaCl deposit in the humid O2 flow at 600 °C is studied. The oxide scale, formed by pre-oxidation, protects the substrate from the NaCl induced corrosion during the initial stage. However, the corrosion of the pre-oxidized sample is severely accelerated by solid NaCl after an incubation period. The chlorine, generated from the decomposition of solid NaCl, diffuses into the oxide/substrate interface as ions during the incubation period, which was observed by ToF–SIMS. The chlorine at the oxide/substrate interface induces the fast corrosion after the incubation period although the pre-oxidation scale is complete and compact.

Cancer, which has been cursed for human beings for long time is considered as one of the leading causes of morbidity and mortality across the world. In spite of different types of treatments available, chemotherapy is still deemed as a favored treatment for the cancer. Unfortunately, many currently accessible anticancer agents have developed multidrug resistance along with fatal adverse effects. Therefore, intensive efforts have been made to seek for new active drugs with improved anticancer efficacy and reduced adverse effects. In recent years, the emergence of heterocyclic ring-containing anticancer agents has gained a great deal of attention among medicinal chemists. 1,3- oxazole is a versatile heterocyclic compound, and its derivatives possess broad-spectrum pharmacological properties, including anticancer activity against both drug-susceptible, drug-resistant and even multidrug-resistant cancer cell lines through multiple mechanisms. Thus, the 1,3-oxazole moiety is a useful template for the development of novel anticancer agents. This review will provide a comprehensive overview of the recent advances on 1,3-oxazole derivatives with potential therapeutic applications as anticancer agents, focus on the chemical structures, anticancer activity, and mechanisms of action.

Increased use of nitrogen fertilizers has deleterious impact on the environment. Increase in yield potential at low nitrogen supply is regarded as a cereal breeding goal for future agricultural sustainability. Although natural variations of nitrogen transporters have been investigated, key genes associated with assimilation remain largely unexplored for nitrogen use efficiency (NUE) enhancement. Here, we identified a NIN‐like protein NLP4 associated with NUE through a GWAS in rice. We found that OsNLP4 transactivated OsNiR encoding nitrite reductase that was critical in nitrogen assimilation in rice. We further constructed quadrupling NREs (Nitrate‐responsive cis‐elements) in the promoter of OsNiR (p4xNRE:OsNiR) and enhanced nitrogen assimilation significantly. We demonstrated that OsNLP4‐OsNiR increased tiller number and yield through enhancing nitrogen assimilation and NUE. Our discovery highlights the genetic modulation of OsNLP4‐OsNiR signalling cascade as a strategy for high NUE and yield breeding in rice.

Background α2A-adrenoceptor (AR) is a potential target for the treatment of degenerative diseases of the central nervous system, and α2A-AR agonists are effective drugs for this condition. However, the lack of high selectivity for α2A-AR subtype of traditional drugs greatly limits their clinic usage. Methods A series of homobivalent 4-aminoquinolines conjugated by two 4-aminoquinoline moieties via varying alkane linker length (C2-C12) were characterized for their affinities for each α2-AR subtype. Subsequently, docking, molecular dynamics and mutagenesis were applied to uncover the molecular mechanism. Results Most 4-aminoquinolines (4-aminoquinoline monomer, C2-C6, C8-C10) were selective for α2A-AR over α2B- and α2C-ARs. Besides, the affinities are of similar linker length-dependence for each α2-AR subtype. Among all the compounds tested, C10 has the highest affinity for α2A-AR (pKi=-7.45±0.62), which is 12-fold and 60-fold selective over α2B-AR and α2C-AR, respectively. Docking and molecular dynamics suggest that C10 simultaneously interacts with orthosteric and "allosteric" sites of the α2A-AR. The mutation of F205 decreases the affinity by 2-fold. The potential allosteric residues include S90, N93, E94 and W99. Conclusion The specificity of C10 for the α2A-AR and the potential orthosteric and allosteric binding sites proposed in this study provide valuable guidance for the development of novel α2A-AR subtype selective compounds.

A rechargeable Li metal anode coupled with a high-voltage cathode is a promising approach to high-energy-density batteries exceeding 300 Wh kg-1 . Reported here is an advanced dual-additive electrolyte containing a unique solvation structure and it comprises a tris(pentafluorophenyl)borane additive and LiNO3 in a carbonate-based electrolyte. This system generates a robust outer Li2 O solid electrolyte interface and F- and B-containing conformal cathode electrolyte interphase. The resulting stable ion transport kinetics enables excellent cycling of Li/LiNi0.8 Mn0.1 Co0.1 O2 for 140 cycles with 80 % capacity retention under highly challenging conditions (≈295.1 Wh kg-1 at cell-level). The electrolyte also exhibits high cycling stability for a 4.6 V LiCoO2 (160 cycles with 89.8 % capacity retention) cathode and 4.95 V LiNi0.5 Mn1.5 O4 cathode.

The influence of pH and metallographic structure on the corrosion behavior of copper–drawn steel is studied with the simulated system. The effect of pH on the corrosion behavior of copper–drawn steel has been investigated using open-circuit potential, potentiodynamic polarization, galvanic current measurement, scanning electron microscopy and scanning vibrating electrode technique techniques. The steel is corroded as anode, while the corrosion of copper plate is protected as cathode. All the results revealed that pH and metallographic structure had a significant influence on the corrosion behavior of copper–drawn steel. With the decrease in pH value from 6 to 2.4, the corrosion rate of copper–drawn steel galvanic couple (Cu–Fe GC) obviously increased in the simulated solution of acidic red soil. The electric field formed by the Cu–Fe GC changes the direction of ion migration between the copper and drawn steel electrodes, which impacts the composition and microstructure of corrosion products formed on the electrode surface.

Lithium–sulfur (Li–S) batteries are one of the most promising battery technologies to support the fast-expanding electrical vehicle and large-scale energy storage market. Reducing the electrolyte amount is critical for the high specific energy of Li–S batteries in practice. However, using lean electrolytes (that is, with a low Electrolyte to Sulfur (E/S) ratio) always leads to a sluggish sulfur reaction kinetics. Herein, a design strategy based on electrostatic attractions between the cations of ionic liquids and the polysulfide anions is proposed to boost the reaction. The positively charged ionic liquid grafted carbon nanofibers can offer a non-contact coulomb force to attract the polysulfides, accelerate the transport of S species for further strong adsorption and therefore improve the reactant kinetics, especially in a lean electrolyte condition. The electrostatic properties are verified by Zeta potential analysis, Kelvin probe force microscopy test and DFT calculation. As a result, it maintains a high stable discharge capacity of 830 mAh g−1 after 400 cycles (sulfur mass loading: 4.0 mg cm−2; electrolyte/sulfur ratio = 5 μl mg−1) and a capacity up to 845 mAh g−1 with an extremely challenging E/S ratio of 3.5 μl mg−1. This work provides a rational guidance for electrostatic design and a new strategy for the development of lean-electrolyte Li-S batteries.

Two kinds of vacancy defects, rhombic and square nanoholes, were produced in graphene/hexagonal BN (g/h-BN) superlattice nanoribbons by ion irradiation. The effects of the type (rhombus and square), area, number density and position of the nanoholes, and the period length of the nanoribbons on their mechanical properties were investigated by molecular dynamics simulation. The results show that the failure strength and strain of the nanoribbons are more sensitive to vacancy defects than is the Young's modulus. The mechanical properties are insensitive to the period length of the nanoribbons and those with rhombus nanoholes have inferior mechanical properties to those with square nanoholes under the same conditions. The mechanical properties of the nanoribbons are largely affected by the positions of the nanoholes, such that they should be in the graphene and not in boron nitride as much as possible. By increasing the number density of the nanoholes, the toughness of the nanoribbons is increased.

The morbidity of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is also increasing with the use of bisphosphonates (BPs). Removing affected bone accurately is the most effective treatment. This study aimed to explore the feasibility of Indocyanine green (ICG)-based Near-Infrared fluorescence (NIF) imaging to remove BRONJ affected bone. Firstly, the rat model of BRONJ was constructed. And 5 mg/kg ICG were injected via tail vein, after 12 hr, the affected and healthy bone were dissected for ICG-based NIF imaging and quantification detection of fluorescence intensity. Finally, all the bone samples were sent for further pathological examination. All the affected bone tissues in rat BRONJ model were fluorescence developed with ICG. And the fluorescence developed regions were further confirmed as affected bone tissues with pathological examination. The fluorescence intensity in affected bone tissues, adjacent, and opposite bone tissues was 1.93*107 ± 2.08*106, 1.19*106 ± 2.33*105, and 1.24*106 ± 1.57*105, respectively (p < .05). Conclusions It was feasible that the extent of affected bone in rat model with BRONJ could be estimated intraoperative via ICG-based NIF imaging. This novel approach would become an auxiliary method in the treatment of patients with BRONJ in the future.

In this study, we investigate the coupling of an internal field (defect field-sp3 bonds and nanopores) and an external field (strain and temperature). Simultaneously, we provide a design idea of hybrid materials. The mechanical properties of hybrid materials under the condition of internal and external field coupling were studied. When nanopores and sp3 bonds are considered simultaneously, we found that internal (sp3 bonds and defects) and external field (temperature and strain fields) have a negative chain reaction on the mechanical properties of BN-graphene-BN/BN vertically-stacked nanostructures, and the negative chain reaction will gradually increase with the change in parameters (such as the increase in temperature). The sp3 bonds can be regarded as a special defect, which will increase the initial strain of the system. In addition, the mechanical properties of the nanostructure, containing square nanopores in the boron nitride region are most sensitive to temperature change, relative to the nanopore in the other two regions. Atoms (around square nanopores) are more likely to overcome the binding energy and lose stability from the inherent equilibrium position, relative to that of circular nanopores.

Developing alternative treatment strategies against methicillin-resistant Staphylococcus aureus (MRSA) infections is a challenge but could have many potential applications. In this paper, we developed a novel approach to eradicate MRSA through photolysis of the staphyloxanthin (STX) pigment found within the MRSA membranes and intracellular molecules (e.g. genomic DNA and proteins). Specifically, Cu-doped hollow carbon spheres (Cu-HCSs) were employed here for antibacterial treatment. Unlike blue-light treatment alone, which only "injured" MRSA, Cu-HCSs in combination with blue-light irradiation promoted photobleaching of STX to destroy membrane integrity, and further caused oxidative cleavage of DNA and proteins inside MRSA, working as a nuclease/protease mimicking nanozyme, resulting in efficient killing of MRSA. Mechanism analysis showed that the cleavage activity resulted from the elevated levels of singlet oxygen (1O2) generated from the photosensitized oxidation of Cu-HCSs. Further animal studies demonstrated that the photolysis activity of Cu-HCSs could be used to treat subcutaneous abscesses and bacteremia caused by MRSA. Thus, this photolysis-based antibacterial platform may help avoid bacterial resistance, with the potential to kill multidrug resistant bacteria.

Nitrogen-doped carbon has been receiving tremendous research interest due to its exotic electrochemical performance and catalyzing capability. Nevertheless, large-scale synthesis of ordered, mesoporous, nitrogen-doped carbon for supercapacitors is rarely reported due to the complexity and uncontrollable property of polymerization of carbon/nitrogen precursors. In this work, we report a facile and efficient approach for mass production of nitrogen-doped carbon, with a narrow pore size distribution and a sheet morphology, via a simple solution casting of biomass-based mixture. Upon drying, the gelatin molecules self-assemble into sheets, and guide the homogeneous loading of sacrificial silica nanospheres. Further carbonization and template removal procedures allow the low-cost production of nitrogen-doped carbon sheets in the absence of complex polymerization. As a result, nitrogen-doped carbon sheets possess a high nitrogen content and ordered, interconnected mesoporous channels, with porosity parameters being carbonization temperature and template size dependence. Additionally, nitrogen-doped, ordered carbon sheets exhibit high performance for supercapacitor application, including high specific capacitances and energy/power densities. This work demonstrates a unique route to synthesizing ordered mesoporous nitrogen-doped carbon sheets via a scalable, low-cost method, which may shed light on many other applications aside from energy storage, such as water splitting, catalysis and sensor.

Cell isolation from blood is an important process for diagnosing immune diseases. There are still demands for a user-friendly approach to achieve high cell extraction efficiency and purity of a target immune cell subtype for more promising diagnosis and monitoring. For selective immune cell isolation, we developed a microstructured device, which consists of antibody-coated micropillars and micro-sieve arrays, for isolating a target immune cell subtype from bovine blood samples. The focusing micropillars can guide immune cells flowing to the subsequent micro-sieves based on deterministic lateral shifts of the cells. The arrangement of these microstructures is characterized and configured for the maximal cell capture rate. Surface modification with a selected antibody offers selective cell capture in the micro-sieves based on the antigen-antibody reaction. We prepare a cell mixture of human CD14-expressing leukemia cells (THP-1) and epithelial cells (MDA-MB-231) in diluted blood to characterize the cell isolation operation, with a selective cell isolation yield of >80%, cell purity of ∼100% and cell viability of >93%. Together, this microstructured device strategy can achieve high-yield selective isolation of immune cells from blood samples and support downstream genetic and biochemical cell analyses, contributing to the medical diagnosis of a broad range of immune diseases.

Inflammation, including infectious and noninfectious inflammation, are a growing threat to public health worldwide. For different types of inflammation, more specific and intensified therapy is needed. Nanozymes are able to regulate levels of radical reactive oxygen species (ROS) to suppress inflammation, becoming potential anti-inflammatory agents. Herein, hollow porous carbon spheres codoped with nitrogen and iron (Fe/N-HCNs) are synthesized through a one-pot strategy, which exerted multienzyme mimicking activities, including peroxidase (POD)-, oxidase (OXD)-, catalase (CAT)-, and superoxide dismutase (SOD)-like activities. Moreover, these activities were promoted by the removal of iron oxides produced in the synthesis process. Based on the study of multienzyme activities, we designed two kinds of animal inflammatory models, bacteria-infected wound and inflammatory bowel disease, to evaluate the anti-inflammation ability of Fe/N-HCNs. The results indicated that Fe/N-HCNs could increase ROS levels through performing their POD-like activity in a weak acid environment to catalyze H

Background It has been confirmed that the triglyceride to high-density lipoprotein cholesterol ratio (THR) is associated with insulin resistance and metabolic syndrome. However, to the best of our knowledge, only a few studies with small sample sizes have investigated the relationship between THR and coronary artery disease (CAD). Therefore, we aimed to assess the correlation between the THR and long-term mortality in patients with CAD after undergoing percutaneous coronary intervention (PCI) in our study that enrolled a large number of patients. Methods A total of 3269 post-PCI patients with CAD were enrolled in the CORFCHD-ZZ study from January 2013 to December 2017. The mean follow-up time was 37.59 ± 22.24 months. Patients were divided into two groups according to their THR value: the lower group (THR n = 1232) and the higher group (THR ≥ 2.84, n = 2037). The primary endpoint was long-term mortality, including all-cause mortality (ACM) and cardiac mortality (CM). The secondary endpoints were major adverse cardiac events (MACEs) and major adverse cardiac and cerebrovascular events (MACCEs). Results In our study, ACM occurred in 124 patients: 30 (2.4%) in the lower group and 94 (4.6%) in the higher group (P = 0.002). MACEs occurred in 362 patients: 111 (9.0%) in the lower group and 251 (12.3%) in the higher group (P = 0.003). The number of MACCEs was 482: 152 (12.3%) in the lower group and 320 (15.7%) in the higher group (P = 0.008). Heart failure occurred in 514 patients: 89 (7.2%) in the lower group and 425 (20.9%) in the higher group (P P = 0.044) and the occurrence of heart failure (log-rank, P P = 0.004) and heart failure (adjusted HR = 1.700 [1.347–2.147], P Conclusions An increased THR is an independent predictor of long-term ACM and heart failure in post-PCI patients with CAD.