With their unique biological effects on tumor microenvironment, catabolites of nanoparticles can make a significant difference for tumor suppression. We report a facile synthesis method of ultrasmall calcium peroxide nanoparticles and demonstrate their rapid decomposition in tumor region. This can trigger a destructive calcium overload process in tumor cells, lead to cell death, and further tissue calcification, which also allows for medical imaging.

Background Checkpoint-blockade immunotherapy targeting programmed cell death protein 1 (PD-1) has recently shown promising efficacy in hepatocellular carcinoma (HCC). However, the factors affecting and predicting the response to anti-PD-1 immunotherapy in HCC are still unclear. Herein, we report the dynamic variation characteristics and specificities of the gut microbiome during anti-PD-1 immunotherapy in HCC using metagenomic sequencing. Results Fecal samples from patients responding to immunotherapy showed higher taxa richness and more gene counts than those of non-responders. For dynamic analysis during anti-PD-1 immunotherapy, the dissimilarity of beta diversity became prominent across patients as early as Week 6. In non-responders, Proteobacteria increased from Week 3, and became predominant at Week 12. Twenty responder-enriched species, including Akkermansia muciniphila and Ruminococcaceae spp., were further identified. The related functional genes and metabolic pathway analysis, such as carbohydrate metabolism and methanogenesis, verified the potential bioactivities of responder-enriched species. Conclusions Gut microbiome may have a critical impact on the responses of HCC patients treated with anti-PD-1 immunotherapy. The dynamic variation characteristics of the gut microbiome may provide early predictions of the outcomes of immunotherapy in HCC, which is critical for disease-monitoring and treatment decision-making. Electronic supplementary material The online version of this article (10.1186/s40425-019-0650-9) contains supplementary material, which is available to authorized users.

Chemodynamic therapy (CDT) by introducing the Fenton-/Fenton-like reaction in an acidic and H 2 O 2 environment for toxic hydroxyl radical (•OH) generation, is a newly developed tumor-selective therapeutic. However, tumor acidosis, characterized by extracellular acidity (pH e ≈ 6.5) and intracellular alkalinity (pH i ≈ 7.2), undoubtedly confers a large chemical barrier for effective implementation of intracellular CDT and thus limits its functional activity and therapeutic efficacy. Here, the unique amorphous iron nanoparticles (AFeNPs) loaded with carbonic anhydrase IX inhibitor (CAI) are constructed to re-establish tumor acidosis with decreased pH i and increased pH e via inhibiting the over-expressed CA IX in cancer cells by CAI for self-enhanced CDT. The suppression of CA IX leads to H + accumulation in cells that could accelerate the AFeNPs-based Fenton reaction to drastically exacerbate oxidative stress in cells and subsequently induce cell death; meanwhile, the inhibition of H + formation outside cells efficiently represses the potential of tumor invasion and metastasis owing to the insufficient acidic ions for degradation of tumor extracellular matrix. Re-establishedtumor acidosis not only assists in the optimization of CDT, but also presents an opportunity for the development of new antitumor methods that are more tumor-acidity specific.

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Novel hierarchical porous carbon nanosheets (HPCS) with quantities of micropores and mesopores were prepared on a large-scale by using thermoplastic phenolic formaldehyde resin as the carbon source and copper nitrate as the template precursor. The HPCS, possessing a thickness of about 40 nm and the width of several microns, exhibited a high specific capacity and favorable high-rate performance when used as an anode material for lithium ion batteries (LIBs). The reversible capacities were 748 mA h g À1 at a current density of 20 mA g À1 and 460 mA h g À1 even at 1 A g À1 , which were much higher than those of traditional porous carbon materials. It also showed superior cyclical stability for only 0.3% capacity loss per cycle under high rate charge-discharge process, suggesting that HPCS should be a promising candidate for anode materials in high-rate LIBs. The roles of various-sized pores in HPCS in Li storage were discussed briefly.

for lithium storage by magnetron sputtering, [ 6a ] templateassistant, [ 9 ] and chemical vapor deposition methods. [ 10 ] Unfortunately, VN materials commonly accompany large volume change (≈240%, calculated based on the density of VN, Li 3 N, and V) during cycle processes, leading to severe particleparticle electronic contact loss and poor cycle performances for lithium storage. Furthermore, this phenomenon of VN is more critical for sodium storage due to 34% greater ionic radius of Na + (0.102 nm) than that of Li + (0.076 nm). [ 1e , 2g ] Hence, developing a VN-based electrode material with excellent electrochemical performances for sodium storage remains a big challenge.Herein, we develop an effi cient approach to fabricate hybrid 2D-0D graphene-VN quantum dots via a hydrothermal treatment of graphene oxide with NH 4 VO 3 and subsequently annealing at different temperatures under ammonia gas. In the resultant hybrids, VN quantum dots with sizes of 2-5 nm are homogeneously dispersed onto graphene, which not only could accommodate the volume changes of VN and prevent their aggregation during cycle processes effectively, but also overcome the sluggishness of mass transport during the conversion reactions with lithium and sodium. Additional multiporous structure and continuous graphene backbone in our graphene-VN hybrids further facilitate the easy access of the electrolyte and fast diffusion of electrons. Consequently, the high reversible capacities, high-rate capabilities, and excellent cycle performances are achieved as hybrid 2D-0D graphene-VN quantum dots are utilized for both lithium and sodium storage.As illustrated in Figure 1 , the overall synthetic procedure of hybrid 2D-0D graphene-VN quantum dots involves two steps. The fi rst is hydrothermal treatment of graphene oxide with NH 4 VO 3 (1:10 in weight proportion) at 180 °C. During this hydrothermal process, NH 4 VO 3 was in situ grown onto the surface of graphene oxide and both of them simultaneously assembled into a 3D foam. The second is annealing of as-prepared hybrid foams at different temperatures (400, 500, and 600 °C) under ammonia gas, generating hybrid 2D-0D graphene-VN quantum dots, denoted as G-VNQD-X, X represents the annealing temperature.The morphology and microstructure of hybrid 2D-0D graphene-VN quantum dots were identifi ed by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and HRTEM measurements ( Figure 2 ). Apparently, a 3D porous confi guration with interconnected nanowalls is observed (Figure 2 a), which is similar to the reported graphene and graphene oxide hydrogels. [ 11 ] The ultrathin and wrinkle features of the nanowalls are further disclosed by the highly magnifi ed SEM image (Figure 2 b). Many nanocrystallines with quantum dot level of 2-5 nm are homogeneously and closely Rechargeable lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs) are regarded as two of the most promising candidates for applications in electric and hybrid vehicles due to their high energy densities, long lifes...

IMPORTANCE Evidence on the association of lifespan cognitive reserve (CR) with dementia is limited, and the strength of this association in the presence of brain pathologies is unknown.OBJECTIVE To examine the association of lifespan CR with dementia risk, taking brain pathologies into account. DESIGN, SETTING, AND PARTICIPANTSThis study used data from 2022 participants in the Rush Memory and Aging Project, an ongoing community-based cohort study with annual follow-up from 1997 to 2018 (mean follow-up, 6 years; maximum follow-up, 20 years). After excluding 420 individuals who had prevalent dementia, missing data on CR, or dropped out, 1602 dementia-free adults were identified at baseline and evaluated to detect incident dementia. During follow-up, 611 died and underwent autopsies. Data were analyzed from May to September 2018.EXPOSURES Information on CR factors (education; early-life, midlife, and late-life cognitive activities; and social activities in late life) was obtained at baseline. Based on these factors, lifespan CR scores were captured using a latent variable from a structural equation model and was divided into tertiles (lowest, middle, and highest).MAIN OUTCOMES AND MEASURES Dementia was diagnosed following international criteria. Neuropathologic evaluations for Alzheimer disease and other brain pathologies were performed in autopsied participants. The association of lifespan CR with dementia or brain pathologies was estimated using Cox regression models or logistic regression. RESULTSOf the 1602 included participants, 1216 (75.9%) were women, and the mean (SD) age was 79.6 (7.5) years. During follow-up, 386 participants developed dementia (24.1%), including 357 participants with Alzheimer disease-related dementia (22.3%). The multiadjusted hazards ratios (HRs) of dementia were 0.77 (95% CI, 0.59-0.99) for participants in the middle CR score tertile and 0.61 (95% CI, 0.47-0.81) for those in the highest CR score tertile compared with those in the lowest CR score tertile. In autopsied participants, CR was not associated with most brain pathologies, and the association of CR with dementia remained significant after additional adjustment for brain pathologies (HR, 0.60; 95% CI, 0.42-0.86). The highest CR score tertile was associated with a reduction in dementia risk, even among participants with high Alzheimer disease pathology (HR, 0.57; 95% CI, 0.37-0.87) and any gross infarcts (HR, 0.34; 95% CI, 0.18-0.62). CONCLUSIONS AND RELEVANCEHigh lifespan CR is associated with a reduction in dementia risk, even in the presence of high brain pathologies. Our findings highlight the importance of lifespan CR accumulation in dementia prevention.

Oil-contaminated water caused by either oil spill disasters or industrial disposal has posed a global risk to environmental sustainability and human health. To address the ever-growing need for highly efficient separation of oil/water mixtures, nanostructured TiO 2 /CuO dual coatings were fabricated on the copper mesh by a combination of electrochemical anodization and layer-by-layer self-assembly deposition to render its surface with superhydrophilic, underwater superoleophobic and self-cleaning functionality. Cu(OH) 2 nanoneedle arrays (NNA) were vertically grown from the copper mesh surfaces by electrochemical anodization processes, followed by the deposition of TiO 2 multilayer on the Cu(OH) 2 NNA via layer-by-layer assembly prior to being calcinated to form TiO 2 /CuO dual coatings. The nanostructured TiO 2 /CuO NNA dual-coated copper meshes were demonstrated to exhibit a high separation efficiency (oil residue content less than 20 ppm), excellent water flux (more than 80 kL•h-1 •m-2), and desirable self-cleaning ability under ultraviolet (UV) illumination. The photo-catalytic ability of the deposited TiO 2 layers enabled the facile and rapid removal of the oil contaminants on the mesh surface under UV illumination to recover oil/water separation ability of the as-fabricated mesh for recycle use. With the adherent features of superhydrophilicity, underwater superoleophobicity and self-cleaning ability, the proposed TiO 2 /CuO NNA dual-coated meshes are potentially useful in practical oil/water separation applications.