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Mineral-based bulk structural materials (MBSMs) are known for their long history and extensive range of usage. The inherent brittleness of minerals poses a major problem to the performance of MBSMs. To overcome this problem, design principles have been extracted from natural biominerals, in which the extraordinary mechanical performance is achieved via the hierarchical organization of minerals and organics. Nevertheless, precise and efficient fabrication of MBSMs with bioinspired hierarchical structures under mild conditions has long been a big challenge. This Perspective provides a panoramic view of an emerging fabrication strategy, matrix-directed mineralization, which imitates the in vivo growth of some biominerals. The advantages of the strategy are revealed by comparatively analyzing the conventional fabrication techniques of artificial hierarchically structured MBSMs and the biomineral growth processes. By introducing recent advances, we demonstrate that this strategy can be used to fabricate artificial MBSMs with hierarchical structures. Particular attention is paid to the mass transport and the precursors that are involved in the mineralization process. We hope this Perspective can provide some inspiring viewpoints on the importance of biomimetic mineralization in material fabrication and thereby spur the biomimetic fabrication of high-performance MBSMs.

BackgroundThe antibiotic resistance in various bacteria is consistently increasing and is posing a serious threat to human health, prompting the need for the discovery of novel structurally featured natural products with promising biological activities in drug research and development. Endolichenic microbes have been proven to be a fertile source to produce various chemical components, and therefore these microbes have been on a prime focus for exploring natural products. In this study, to explore potential biological resources and antibacterial natural products, the secondary metabolites of an endolichenic fungus have been investigated.MethodsThe antimicrobial products were isolated from the endolichenic fungus using various chromatographic methods, and the antibacterial and antifungal activities of the compounds were evaluated by the broth microdilution method under in vitro conditions. The antimicrobial mechanism has been discussed with measuring the dissolution of nucleic acid and protein, as well as the activity of alkaline phosphatase (AKP) in preliminary manner. Chemical synthesis of the active product compound 5 was also performed, starting from commercially available 2,6-dihydroxybenzaldehyde through a sequence of transformations that included methylation, the addition of propylmagnesium bromide on formyl group, the oxidation of secondary alcohol, and the deprotection of methyl ether motif.ResultsAmong the 19 secondary metabolites of the endolichenic fungus, Daldinia childiae (compound 5) showed attractive antimicrobial activities on 10 of the 15 tested pathogenic strains, including Gram-positive bacteria, Gram-negative bacteria, and fungus. The Minimum Inhibitory Concentration (MIC) of compound 5 for Candida albicans 10213, Micrococcus luteus 261, Proteus vulgaris Z12, Shigella sonnet, and Staphylococcus aureus 6538 was identified as 16 μg/ml, whereas the Minimum Bactericidal Concentration (MBC) of other strains was identified as 64 μg/ml. Compound 5 could dramatically inhibit the growth of S. aureus 6538, P. vulgaris Z12, and C. albicans 10213 at the MBC, likely affecting the permeability of the cell wall and cell membrane. These results enriched the library of active strains and metabolites resources of endolichenic microorganisms. The chemical synthesis of the active compound was also performed in four steps, providing an alternative pathway to explore antimicrobial agents.

Human tumor xenograft models do not replicate the human immune system and tumor microenvironment. We developed an improved humanized mouse model, derived from fresh cord blood CD34+ stem cells (CD34+ HSC), and combined it with lung cancer cell line–derived human xenografts or patient-derived xenografts (Hu-PDX). Fresh CD34+ HSCs could reconstitute detectable mature human leukocytes (hCD45+) in mice at four weeks without the onset of graft-versus-host disease (GVHD). Repopulated human T cells, B cells, natural killer (NK) cells, dendritic cells (DC), and myeloid-derived suppressor cells (MDSC) increased in peripheral blood, spleen, and bone marrow over time. Although cultured CD34+ HSCs labeled with luciferase could be detected in mice, the cultured HSCs did not develop into mature human immune cells by four weeks, unlike fresh CD34+ HSCs. Ex vivo, reconstituted T cells, obtained from the tumor-bearing humanized mice, secreted IFNγ upon treatment with phorbol myristate acetate (PMA) or exposure to human A549 lung tumor cells and mediated antigen-specific CTL responses, indicating functional activity. Growth of engrafted PDXs and tumor xenografts was not dependent on the human leukocyte antigen status of the donor. Treatment with the anti–PD-1 checkpoint inhibitors pembrolizumab or nivolumab inhibited tumor growth in humanized mice significantly, and correlated with an increased number of CTLs and decreased MDSCs, regardless of the donor HLA type. In conclusion, fresh CD34+HSCs are more effective than their expanded counterparts in humanizing mice, and do so in a shorter time. The Hu-PDX model provides an improved platform for evaluation of immunotherapy.

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Picturing the atomic migration pathways of catalysts in a reactive atmosphere is of central significance for uncovering the underlying catalytic mechanisms and directing the design of high-performance catalysts. Here, we describe a reduction-controlled atomic migration pathway that converts nanoparticles to single atom alloys (SAAs), which has remained synthetically challenging in prior attempts due to the elusive mechanism. We achieved this by thermally treating the noble-metal nanoparticles M (M = Ru, Rh, Pd, Ag, Ir, Pt, and Au) on metal oxide (CuO) supports with H

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Cellulose aerogels are plagued by intermolecular hydrogen bond-induced structural plasticity, otherwise rely on chemicals modification to extend service life. Here, we demonstrate a petrochemical-free strategy to fabricate superelastic cellulose aerogels by designing hierarchical structures at multi scales. Oriented channels consolidate the whole architecture. Porous walls of dehydrated cellulose derived from thermal etching not only exhibit decreased rigidity and stickiness, but also guide the microscopic deformation and mitigate localized large strain, preventing structural collapse. The aerogels show exceptional stability, including temperature-invariant elasticity, fatigue resistance (∼5 % plastic deformation after 10

With the increasing popularity of new energy electric vehicles, the demand for lithium-ion batteries (LIBs) has been growing rapidly, which will produce a large number of spent LIBs. Therefore, recycling of spent LIBs has become an urgent task to be solved, otherwise it will inevitably lead to serious environmental pollution. Herein, a unique recycling strategy is proposed to achieve the concurrent reuse of cathode and anode in the spent graphite/LiFePO4 batteries. Along with such recycling process, a unique cathode composed of recycled LFP/graphite (RLFPG) with cation/anion-co-storage ability is designed for new-type dual-ion battery (DIB). As a result, the recycle-derived DIB of Li/RLFPG is established with good electrochemical performance, such as an initial discharge capacity of 117.4 mA h g−1 at 25 mA g−1 and 78% capacity retention after 1000 cycles at 100 mA g−1. The working mechanism of Li/RLFPG DIB is also revealed via in situ X-ray diffraction and electrode kinetics studies. This work not only presents a far-reaching significance for large-scale recycling of spent LIBs in the future, but also proposed a sustainable and economical method to design new-type secondary batteries as recycling of spent LIBs.

Background: Abelmoschus manihot (L.) Medik (“Huangkui” in Chinese, HK) has been widely used for the treatment of kidney diseases. Nephrotoxicity is the side effect of cisplatin (CDDP), which greatly limits its clinical application. Therefore, CDDP could be used to establish the chronic kidney disease (CKD) model. However, the protective effects of HK on CDDP-induced CKD have not been investigated.Purpose: To explore the protective effect and underlying mechanisms of HK on multiple low-dose CDDP-induced CKD in rats by the integrated analysis of serum, kidney, and urine metabolomics and network pharmacology.Methods: The CKD model was induced by multiple low-dose CDDP. Body weight, organ index, serum biochemical, and kidney histology were examined to evaluate the effect of HK. Serum, kidney, and urine were collected and profiled by HILIC/RPLC-Q-TOF/MS-based metabolomics. Potential biomarkers (PBs) were screened according to the criteria of VIP >1, p < 0.01, and FC > 2, and then identified or assigned. The pathway analysis and PBs enrichment were conducted by MetaboAnalyst and ChemRICH. Furthermore, network pharmacology was adopted to dig out the active components and targets. Finally, the results from metabolomics and network pharmacology were integrated to confirm each other.Results: HK could recover the CDDP-induced abnormal pharmacological and metabolic profile changes. A total of 187 PBs were screened and identified from the serum, kidney, and urine metabolomics. Pathway analysis showed that multiple metabolic pathways, mainly related to amino acid and lipid metabolisms, were involved in the nephroprotective effect of HK, and especially, HK could significantly alleviate the disorder of tryptophan metabolism pathway in serum, kidney, and urine. Meanwhile, network pharmacology analysis revealed that 5 components in HK and 4 key genes could be responsible for the nephroprotection of HK, which also indicated that the metabolism of tryptophan played an important role in HK against CKD.Conclusion: HK has a nephroprotection on CDDP-induced CKD, mainly by restoring the dysregulation of tryptophan metabolism. Integrated analysis of serum, kidney, and urine metabolomics and network pharmacology was a powerful method for exploring pharmacological mechanisms and screening active components and targets of traditional Chinese medicine.

As the key intermediate phase of crystalline calcium carbonate biominerals, amorphous calcium carbonate (ACC) remains mysterious in its structures because of its long-range disorder and instability. We herein report the synthesis of ACC nanospheres in a water-deficient organic solvent system. The obtained ACC nanospheres are very stable under dry conditions. Cryo-TEM reveals that each nanospheres consists of smaller nanosized clusters. We further demonstrate that these clusters can precipitate on other substrates to form an ultrathin ACC coating, which should be an ACC cluster monolayer. The results demonstrate that the presence of small ACC clusters as the subunits of larger aggregates is inherent to ACC synthesized in water-alcohol system but not induced by polymer additives.