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Pulmonary fibrosis is a devastating lung disease with few therapeutic options. CHIT1 (chitinase 1), an 18 glycosyl hydrolase family member, contributes to the pathogenesis of pulmonary fibrosis through the regulation of TGF-b (transforming growth factor-b) signaling and effector function. Therefore, CHIT1 is a potential therapeutic target for pulmonary fibrosis. This study aimed to identify and characterize a druggable CHIT1 inhibitor with strong antifibrotic activity and minimal toxicity for therapeutic application to pulmonary fibrosis. Extensive screening of small molecule libraries identified the aminoglycoside antibiotic kasugamycin (KSM) as a potent CHIT1 inhibitor. Elevated concentrations of CHIT1 were detected in the lungs of patients with pulmonary fibrosis. In in vivo bleomycin- and TGFb- stimulated murine models of pulmonary fibrosis, KSM showed impressive antifibrotic effects in both preventive and therapeutic conditions. In vitro studies also demonstrated that KSM inhibits fibrotic macrophage activation, fibroblast proliferation, and myofibroblast transformation. Null mutation of TGFBRAP1 (TGF-b-associated protein 1), a recently identified CHIT1 interacting signaling molecule, phenocopied antifibrotic effects of KSM in in vivo lungs and in vitro fibroblasts responses. KSM inhibits the physical association between CHIT1 and TGFBRAP1, suggesting that the antifibrotic effect of KSM is mediated through regulation of TGFBRAP1, at least in part. These studies demonstrate that KSM is a novel CHIT1 inhibitor with a strong antifibrotic effect that can be further developed as an effective and safe therapeutic drug for pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

In situ disc regeneration is a meticulously orchestrated process, which involves cell recruitment, proliferation and differentiation within a local inflammatory niche. Thus far, it remains a challenge to establish a multi‐staged regulatory framework for coordinating these cellular events, therefore leading to unsatisfactory outcome. This study constructs a super paramagnetically‐responsive cellular gel, incorporating superparamagnetic iron oxide nanoparticles (SPIONs) and aptamer‐modified palladium‐hydrogen nanozymes (PdH‐Apt) into a double‐network polyacrylamide/hyaluronic acid (PAAm/HA) hydrogel. The Aptamer DB67 within magnetic hydrogel (Mag‐gel) showed a high affinity for disialoganglioside (GD2), a specific membrane ligand of nucleus pulposus stem cells (NPSCs), to precisely recruit them to the injury site. The Mag‐gel exhibits remarkable sensitivity to a magnetic field (MF), which exerts tunable micro/nano‐scale forces on recruited NPSCs and triggers cytoskeletal remodeling, consequently boosting cell expansion in the early stage. By altering the parameters of MF, the mechanical cues within the hydrogel facilitates differentiation of NPSCs into nucleus pulposus cells to restore disc structure in the later stage. Furthermore, the PdH nanozymes within the Mag‐gel mitigate the harsh inflammatory microenvironment, favoring cell survival and disc regeneration. This study presents a remote and multi‐staged strategy for chronologically regulating endogenous stem cell fate, supporting disc regeneration without invasive procedures. [ABSTRACT FROM AUTHOR]

Rationale: Changes in peripheral blood cell populations have been observed, but not detailed, at single-cell resolution in idiopathic pulmonary fibrosis (IPF). Objectives: We sought to provide an atlas of the changes in the peripheral immune system in stable and progressive IPF. Methods: Peripheral blood mononuclear cells (PBMCs) from patients with IPF and control subjects were profiled using 10× chromium 5′ single-cell RNA sequencing. Flow cytometry was used for validation. Protein concentrations of regulatory T cells (Tregs) and monocyte chemoattractants were measured in plasma and lung homogenates from patients with IPF and control subjects. Measurements and Main Results: Thirty-eight PBMC samples from 25 patients with IPF and 13 matched control subjects yielded 149,564 cells that segregated into 23 subpopulations. Classical monocytes were increased in patients with progressive and stable IPF compared with control subjects (32.1%, 25.2%, and 17.9%, respectively; P < 0.05). Total lymphocytes were decreased in patients with IPF versus control subjects and in progressive versus stable IPF (52.6% vs. 62.6%, P = 0.035). Tregs were increased in progressive versus stable IPF (1.8% vs. 1.1% of all PBMCs, P = 0.007), although not different than controls, and may be associated with decreased survival (P = 0.009 in Kaplan-Meier analysis; and P = 0.069 after adjusting for age, sex, and baseline FVC). Flow cytometry analysis confirmed this finding in an independent cohort of patients with IPF. The fraction of Tregs out of all T cells was also increased in two cohorts of lung single-cell RNA sequencing. CCL22 and CCL18, ligands for CCR4 and CCR8 Treg chemotaxis receptors, were increased in IPF. Conclusions: The single-cell atlas of the peripheral immune system in IPF reveals an outcome-predictive increase in classical monocytes and Tregs, as well as evidence for a lung–blood immune recruitment axis involving CCL7 (for classical monocytes) and CCL18/CCL22 (for Tregs). [ABSTRACT FROM AUTHOR]

To realize the high value–added utilization of acid-washed iron red, in this paper, acid-washed iron red is used as raw material. Aiming at the problem of low conductivity of iron-based lithium ion batteries (LIBs) LiFePO4/C materials, different metal ions are doped in the iron position, and the microstructure and electrochemical properties of the obtained material are systematically studied. Here, LiFePO4/C is synthesized through simple carbothermal reduction method using acid-washed iron red as the iron source. On this basis, La (1%, 2%, 3%) doping modification is carried out. Then doped modification is performed on this basis, preferably 2% La-doped LiFePO4/C materials. The XRD patterns show that the diffraction peaks of the samples prepared at all doping amounts can be perfectly matched with the standard card (PDF # 40–1499), and there is no impurity peak, all of which are pure phases. According to the refined data, it is clear that minor amount of La has successfully replaced the position of Fe and incorporated into the lattice. Electrochemical tests show that LiFe0.98La0.02PO4/C has the highest charge and discharge capacity of 146.5/138.2 mAh·g−1 in the first cycle at 0.5C, and the reversible specific capacity of 136.5 mAh·g−1 remains after 50 cycles. Furthermore, the first-principles calculations more strongly confirm that La doping can significantly improve the defects of low electronic conductivity of LiFePO4. [ABSTRACT FROM AUTHOR]

In order to better recycle and reuse metal ions in metallurgical industrial waste and reduce the production cost of lithium-ion batteries (LIBs). In this paper, carbon-coated LiFePO4/C cathode materials are synthesized through the carbothermal reduction method using acid-washed iron red as raw material. In order to make LiFePO4/C exhibit satisfactory electrical properties, the rare earth element Eu is doped in the Fe position, and the doping amount is optimized. The influence of the double coupling effect of coating and doping on the structure and properties of LiFePO4 cathode materials is systematically discussed. The local XRD results of the doped samples show that the diffraction peaks of the doped samples move to the small angle grain boundaries, and the lattice spacing of the materials increases, which is due to the large radius of Eu ions. The experimental results show that the dual coupling of carbon coating and ion doping can improve the conductivity of LiFePO4 cathode materials and improve its electrochemical performance. When the doping amount of Eu is 2%, the electrochemical performance of LiFe0.98Eu0.02PO4/C cathode material is the best. The initial charge–discharge capacity of 153/144.4 mAh·g−1 can be obtained at 0.5C, and a discharge capacity of 143.2 mAh·g−1 remains after 50 cycles. The exploration of this experiment provides a reasonable solution for slowing down the pollution of metallurgical waste to the environment and reducing the production cost of LIBs. [ABSTRACT FROM AUTHOR]

ZnMn2O4 anode material with nanosheet lamellar structure was synthesized using microwave method. The bearing of reaction temperature, reaction time, reactant compactness, and pH of the synthesis environment on the discharge–charge performance of samples were systematically studied. It is confirmed that ZnMn2O4 material presents a nanosheet lamellar structure with a uniform distribution. When the reaction temperature is 200℃, the reaction time is 25 min, reactant compactness is 73%, pH is 7, and initial discharge-specific capacity of the samples is 959.6 mAh·g−1. After 40 cycles, the capacity remains at 346.9 mAh·g−1, and the coulomb efficiency is stable at 100%. Spinel ZnMn2O4 anode material was microwave hydrothermally synthesized from zinc nitrate and manganese nitrate as raw materials in an aqueous solution. The material has a nano lamellar structure and shows good electrochemical properties as anode material of lithium-ion batteries. [ABSTRACT FROM AUTHOR]