The increase in drug resistance and invasion caused by biofilm formation brings enormous challenges to the management of Candida infection. Aspirin's antibiofilm activity in vitro was discovered recently. The spectrophotometric method and the XTT {2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide} reduction assay used for data generation make it possible to evaluate fungal biofilm growth accurately. The combined use of the most commonly used methods, the fractional inhibitory concentration index (FICI) and a newly developed method, the ⌬E model, which uses the concentration-effect relationship over the whole concentration range instead of using the MIC index alone, makes the interpretation of results more reliable. As an attractive tool for studying the pharmacodynamics of antimicrobial agents, time-kill curves can provide detailed information about antimicrobial efficacy as a function of both time and concentration. In the present study, in vitro interactions between aspirin (acetylsalicylic acid [ASA]) and amphotericin B (AMB) against planktonic cells and biofilm cells of Candida albicans and C. parapsilosis were evaluated by the checkerboard microdilution method and the time-kill test. Synergistic and indifferent effects were found for the combination of ASA and AMB against planktonic cells, while strong synergy was found against biofilm cells analyzed by FICI. The ⌬E model gave more consistent results with FICI. The positive interactions in concentration were also confirmed by the time-kill test. Moreover, this approach also revealed the pharmacodynamics changes of ASA and synergistic action on time. Our findings suggest a potential clinical use for combination therapy with ASA and AMB to augment activity against biofilm-associated infections.

The effect of Cr­(VI) and bisphenol A (BPA) on U­(VI) photoreduction by C3N4 photocatalyst was demonstrated by the batch experiments, electron spin resonance (ESR), X-ray photoelectron spectroscopy (XPS), X-ray absorption near edge structure (XANES), and extended X-ray absorption fine structure (EXAFS) techniques. The batch experiments manifested that Cr­(VI) and BPA enhanced the photocatalytic activity of C3N4 for U­(VI) photoreduction, whereas U­(VI) photoreduction was significantly diminished with increased pH from 4.0 to 8.0. According to radical scavengers and ESR analysis, U­(VI) was photoreduced to U­(IV) by photogenerated electrons of conduction band edge, whereas Cr­(VI) was reduced to Cr­(III) by H2O2. BPA and its products such as organic acid and alcohols can capture photoinduced holes, which resulted in the enhancement of U­(VI) photoreduction to U­(IV). XPS and XANES analyses demonstrated that U­(VI) was gradually photoreduced to U­(IV) by C3N4 within irradiation 60 min, whereas U­(IV) was reoxidized to U­(VI) with increasing irradiation time. EXAFS analysis determined that the dominant interaction mechanisms of U­(VI) on C3N4 after irradiation for 240 min were reductive precipitation and inner-sphere surface complexation. This work highlights the synergistic removal of radionuclides, heavy metals, and persistent organic pollutants by C3N4, which is crucial for the design and application of a high-performance photocatalyst in actual environmental cleanup.

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Osteoarthritis (OA) is a highly prevalent and debilitating joint disorder characterized by the degeneration of articular cartilage. However, no effective medical therapy has been found yet for such condition. In this study, we directly confirmed the existence of articular cartilage stem cells (ACSCs) in vivo and in situ for the first time both in normal and OA articular cartilage, and explored their chondrogenesis in Interleukin-1b (IL-1b) induced inflammation environment and disclose whether the inhibition of NF-jB signaling can induce ACSCs activation thus improve the progression of experimental OA. We found an interesting phenomenon that ACSCs were activated and exhibited a transient proliferative response in early OA as an initial attempt for selfrepair. During the in vitro mechanism study, we discovered IL-1b can efficiently activate the NFjB pathway and potently impair the responsiveness of ACSCs, whereas the NF-jB pathway inhibitor rescued the ACSCs chondrogenesis. The final in vivo experiments further confirmed ACSCs' activation were maintained by NF-jB pathway inhibitor, which induced cartilage regeneration, and protected articular cartilage from injury in an OA animal model. Our results provided in vivo evidence of the presence of ACSCs, and disclosed their action in the early OA stage and gradual quiet as OA process, presented a potential mechanism for both cartilage intrinsic repair and its final degradation, and demonstrated the feasibility of inducing endogenous adult tissuespecific mesenchymal stem cells for articular cartilage repair and OA therapy. STEM CELLS 2015;33:3125-3137 SIGNIFICANCE STATEMENTThe study confirmed the existence of articular cartilage stem cells (ACSCs) in vivo and in situ for the first time both in normal and OA articular cartilage, found an interesting phenomenon that ACSCs were activated and exhibited a transient proliferative response in early OA as an initial attempt for self-repair, confirmed ACSCs' activation were maintained by NF-jB pathway inhibitor, which induced cartilage regeneration, and protected articular cartilage from injury in an OA animal model, demonstrated the feasibility of inducing endogenous adult tissue-specific mesenchymal stem cells for articular cartilage repair and OA therapy.

A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-20254-5

Background The health impacts of ambient air pollution impose large costs on society. Although all people are exposed to air pollution, the older population (ie, those aged ≥60 years) tends to be disproportionally affected. As a result, there is growing concern about the health impacts of air pollution as many countries undergo rapid population ageing. We investigated the spatial and temporal variation in the economic cost of deaths attributable to ambient air pollution and its interaction with population ageing from 2000 to 2016 at global and regional levels. MethodsIn this global analysis, we developed an age-adjusted measure of the value of a statistical life-year (VSLY) to estimate the economic cost of deaths attributable to ambient PM 2•5 pollution using Global Burden of Diseases, Injuries, and Risk Factors Study 2017 data and country-level socioeconomic information. First, we estimated the global age-specific and cause-specific mortality and years of life lost (YLLs) attributable to PM 2•5 pollution using the global exposure mortality model and global estimates of exposure at 0•1° × 0•1° (about 11 km × 11 km at the equator) resolution. Second, for each year between 2000 and 2016, we translated the YLLs within each age group into a healthrelated cost using a country-specific, age-adjusted measure of VSLY. Third, we decomposed the major driving factors that contributed to the temporal change in health costs related to PM 2•5 . Finally, we did a sensitivity test to analyse the variability of the estimated health costs to four alternative valuation measures. We identified the uncertainty intervals (UIs) from 1000 draws of the parameters and concentration-response functions by age, cause, country, and year. All economic values are reported in 2011 purchasing power parity-adjusted US dollars. All simulations were done with R, version 3.6.0. Findings Globally, in 2016, PM 2•5 was estimated to have caused 8•42 million (95% UI 6•50-10•52) attributable deaths, which was associated with 163•68 million (116•03-219•44) YLLs. In 2016, the global economic cost of deaths attributable to ambient PM 2•5 pollution for the older population was US$2•40 trillion (1•89-2•93) accounting for 59% (59-60) of the cost for the total population ($4•09 trillion [3•19-5•05]). The economic cost per capita for the older population was $2739 (2160-3345) in 2016, which was 10 times that of the younger population (ie, those aged <60 years). By assessing the factors that contributed to economic costs, we found that increases in these factors changed the total economic cost by 77% for gross domestic product (GDP) per capita, 21% for population ageing, 16% for population growth, -41% for age-specific mortality, and -0•4% for PM 2•5 exposure.Interpretation The economic cost of ambient PM 2•5 borne by the older population almost doubled between 2000 and 2016, driven primarily by GDP growth, population ageing, and population growth. Compared with younger people, air pollution leads to disproportionately higher health costs among older people, even a...

The present study aims to explore the neuro-protective effects of purified Sparassis crispa polysaccharides against l-glutamic acid (l-Glu)-induced differentiated PC12 (DPC12) cell damages and its underlying mechanisms. The Sparassis crispa water extract was purified by a DEAE-52 cellulose anion exchange column and a Sepharose G-100 column. A fraction with a molecular weight of 75 kDa and a diameter of 88.9 nm, entitled SCWEA, was obtained. SCWEA was identified with a triple helix with (1→3)-linked Rha in the backbone, and (1→2) linkages and (1→6) linkages in the side bone. Our results indicated that the pre-treatment of DPC12 cells with SCWEA prior to l-Glu exposure effectively reversed the reduction on cell viability (by 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay) and reduced l-Glu-induced apoptosis (by Hoechst staining). SCWEA decreased the accumulation of intracellular reactive oxygen species, blocked Ca2+ influx and prevented depolarization of the mitochondrial membrane potential in DPC12 cells. Furthermore, SCWEA normalized expression of anti-apoptotic proteins in l-Glu-explored DPC12 cells. These results suggested that SCWEA protects against l-Glu-induced neuronal apoptosis in DPC12 cells and may be a promising candidate for treatment against neurodegenerative disease.

The theory of targeting cancer stem-like cells (CSCs) provides novel strategy for cancer treatment. In the present study, we examined the inhibitory effect of Huaier aqueous extract on eradicating breast cancer stem cells and explored the underlying mechanisms. Our data demonstrated that various concentrations of Huaier extract significantly decreased the viabilities, numbers, and sizes of mammospheres. After incubation with Huaier extract for 24 h, the clonogenicity of MCF7 cell line was obviously impaired, along with less holoclones. In addition, Huaier extract reduced the number of cells expressing CD44+/CD24- and decreased the level of stem cell markers (OCT-4, NESTIN, and NANOG). The hedgehog (Hh), notch, and Wnt/β-catenin pathways were essential stem cell signaling pathways involved in regulating CSC renewal and maintenance. We reported that the inhibitory effect of Huaier extract was partly depended on the inactivation of Hh pathway. These findings provided experimental evidence that Huaier extract was a promising therapeutic drug for eliminating the breast cancer stem cells.