Akkermansia muciniphila phospholipid induces homeostatic immune responses.

Multiple studies have established associations between human gut bacteria and host physiology, but determining the molecular mechanisms underlying these associations has been challenging1-3. Akkermansia muciniphila has been robustly associated with positive systemic effects on host metabolism, favourable outcomes to checkpoint blockade in cancer immunotherapy and homeostatic immunity4-7. Here we report the identification of a lipid from A. muciniphila's cell membrane that recapitulates the immunomodulatory activity of A. muciniphila in cell-based assays8. The isolated immunogen, a diacyl phosphatidylethanolamine with two branched chains (a15:0-i15:0 PE), was characterized through both spectroscopic analysis and chemical synthesis. The immunogenic activity of a15:0-i15:0 PE has a highly restricted structure-activity relationship, and its immune signalling requires an unexpected toll-like receptor TLR2-TLR1 heterodimer9,10. Certain features of the phospholipid's activity are worth noting: it is significantly less potent than known natural and synthetic TLR2 agonists; it preferentially induces some inflammatory cytokines but not others; and, at low doses (1% of EC50) it resets activation thresholds and responses for immune signalling. Identifying both the molecule and an equipotent synthetic analogue, its non-canonical TLR2-TLR1 signalling pathway, its immunomodulatory selectivity and its low-dose immunoregulatory effects provide a molecular mechanism for a model of A. muciniphila's ability to set immunological tone and its varied roles in health and disease.

RNA velocity of single cells.

RNA abundance is a powerful indicator of the state of individual cells. Single-cell RNA sequencing can reveal RNA abundance with high quantitative accuracy, sensitivity and throughput1. However, this approach captures only a static snapshot at a point in time, posing a challenge for the analysis of time-resolved phenomena such as embryogenesis or tissue regeneration. Here we show that RNA velocity-the time derivative of the gene expression state-can be directly estimated by distinguishing between unspliced and spliced mRNAs in common single-cell RNA sequencing protocols. RNA velocity is a high-dimensional vector that predicts the future state of individual cells on a timescale of hours. We validate its accuracy in the neural crest lineage, demonstrate its use on multiple published datasets and technical platforms, reveal the branching lineage tree of the developing mouse hippocampus, and examine the kinetics of transcription in human embryonic brain. We expect RNA velocity to greatly aid the analysis of developmental lineages and cellular dynamics, particularly in humans.

X-ray Insights into Formation of -O Functional Groups on MXenes: Two-Step Dehydrogenation of Adsorbed Water.

Engineered MXene surfaces with more -O functional groups are feasible for realizing higher energy density due to their higher theoretical capacitance. However, there have been only a few explorations of this regulation mechanism. Investigating the formation source and mechanism is conducive to expanding the adjustment method from the top-down perspective. Herein, for the first time, the formation dynamics of -O functional groups on Mo2CTx are discovered as a two-step dehydrogenation of adsorbed water through in situ near-ambient-pressure X-ray photoelectron spectroscopy, further confirmed by ab initio molecular dynamics simulations. From this, the controllable substitution of -F functional groups with -O functional groups is achieved on Mo2CTx during electrochemical cycling in an aqueous electrolyte. The obtained Mo2CTx with rich -O groups exhibits a high capacitance of 163.2 F g -1 at 50 mV s -1, together with excellent stability. These results offer new insights toward engineering surface functional groups of MXenes for many specific applications.

Electrosynthesis of an Improbable Directly Bonded Phosphorene-Fullerene Heterodimensional Hybrid toward Boosted Photocatalytic Hydrogen Evolution.

Phosphorene and fullerene are representative two-dimensional (2D) and zero-dimensional (0D) nanomaterials respectively, constructing their heterodimensional hybrid not only complements their physiochemical properties but also extends their applications via synergistic interactions. This is however challenging because of their diversities in dimension and chemical reactivity, and theoretical studies predicted that it is improbable to directly bond C60 onto the surface of phosphorene due to their strong repulsion. Here, we develop a facile electrosynthesis method to synthesize the first phosphorene-fullerene hybrid featuring fullerene surface bonding via P-C bonds. Few-layer black phosphorus nanosheets (BPNSs) obtained from electrochemical exfoliation react with C602- dianion prepared by electroreduction of C60, fulfilling formation of the "improbable" phosphorene-fullerene hybrid (BPNS-s-C60). Theoretical results reveal that the energy barrier for formation of [BPNS-s-C60]2- intermediate is significantly decreased by 1.88 eV, followed by an oxidization reaction to generate neutral BPNS-s-C60 hybrid. Surface bonding of C60 molecules not only improves significantly the ambient stability of BPNSs, but also boosts dramatically the visible light and near-infrared (NIR) photocatalytic hydrogen evolution rates, reaching 1466 and 1039 µmol h-1 g-1 respectively, which are both the highest values among all reported BP-based metal-free photocatalysts.

Real-time nondemolition measurement method for alkali vapor density and its application in a spin-exchange relaxation-free co-magnetometer.

This study presents a novel method for measuring the number density of K in K-Rb hybrid vapor cells using circularly polarized pump light on polarized alkali metal atoms. This proposed method eliminates the need for additional devices such as absorption spectroscopy, Faraday rotation, or resistance temperature detector technology. The modeling process involved considering wall loss, scattering loss, atomic absorption loss, and atomic saturation absorption, with experiments designed to identify the relevant parameters. The proposed method is real-time, highly stable, and a quantum nondemolition measurement that does not disrupt the spin-exchange relaxation-free (SERF) regime. Experimental results demonstrate the effectiveness of the proposed method, as the longitudinal electron spin polarization long-term stability increased by 204% and the transversal electron spin polarization long-term stability increased by 44.8%, as evaluated by the Allan variance.

Fine Particulate Matter Triggers α-Synuclein Fibrillization and Parkinson-like Neurodegeneration.

BACKGROUND: The deposition of α-synuclein (α-Syn) in the brain is the pathological hallmark of Parkinson's disease (PD). Epidemiological data indicate that exposure to fine particulate matter (≤2.5 µm in aerodynamic diameter [PM2.5]) is associated with an increased risk for PD. OBJECTIVE: The aim of this study is to investigate whether PM2.5 has a direct effect on α-Syn pathology and how it drives the risk for PD. METHODS: PM2.5 was added into α-Syn monomers and different cell models to test whether PM2.5 can promote the fibrillization and aggregation of α-Syn. α-Syn A53T transgenic mice and α-Syn knockout mice were used to investigate the effects of PM2.5 on PD-like pathology. RESULTS: PM2.5 triggers the fibrillization of α-Syn and promotes the formation of α-Syn fibrils with enhanced seeding activity and neurotoxicity. PM2.5 also induces mitochondrial dysfunction and oxidative stress. Intrastriatal injection or intranasal administration of PM2.5 exacerbates α-Syn pathology and dopaminergic neuronal degeneration in α-Syn A53T transgenic mice. The detrimental effect of PM2.5 was attenuated in α-Syn knockout mice. CONCLUSIONS: Our results identify that PM2.5 exposure could promote the α-Syn pathology, providing mechanistic insights into how PM2.5 increases the risk for PD. © 2022 International Parkinson and Movement Disorder Society.

Urinary concentrations of bisphenol analogues in the south of China population and their contribution to the per capital mass loads in wastewater.

Bisphenol analogues (BPs) are heavily used and negatively affect the health of human beings, however, there is little knowledge regarding human exposure to BPs other than BPA. This study aims to assess human exposure to BPs through investigating pooled urine and wastewater samples. Twenty-four pooled urine samples were prepared from 960 specimens (classified by age and gender). Wastewater samples were collected from six major wastewater treatment plants (WWTPs) in Guangzhou, South of China. BPA, BPS, and BPAF were widely detected in urine samples, with a median concentration of 0.96, 0.42, and 0.15 µg/L, respectively. Median urinary levels of BPA and BPS were higher in males than females (p > 0.05). In addition, BPA and BPS urinary levels in young adults (15-30 years old) were greater than those in children (0-15 years old) (p > 0.05). Nevertheless, most of the BPs were detected in wastewater samples, of which BPA and BPS were predominant BPs, with a median concentration of 1.0 and 0.29 µg/L. The average per capital mass loads of ΣBPs on the weekdays of mix typed WWTP was much higher than those of the weekends. Nonetheless, the average loads of ΣBPs on the weekdays of domestic WWTP was slightly lower than those of the weekends. This indicated that important sources of BPs might include industrial wastewater and household cleaning products. Urinary BPA, BPS, and BPAF accounted for less than 5% per capital mass loads in wastewater, suggesting that much of the BPA, BPS, and BPAF in municipal wastewater originate non-human excretion. Hence, the wastewater-based epidemiology (WBE) approach based on parent compounds is not available for assessing human exposure to BPs, neither for other industrial chemicals with diverse sources in municipal wastewater. These results contributes to the development of an efficient surveillance system which can provide insight in the trends of human exposure of BPs.

Inhibiting Phase Transfer of Protein Nanoparticles by Surface Camouflage-A Versatile and Efficient Protein Encapsulation Strategy.

Engineering a system with a high mass fraction of active ingredients, especially water-soluble proteins, is still an ongoing challenge. In this work, we developed a versatile surface camouflage strategy that can engineer systems with an ultrahigh mass fraction of proteins. By formulating protein molecules into nanoparticles, the demand of molecular modification was transformed into a surface camouflage of protein nanoparticles. Thanks to electrostatic attractions and van der Waals interactions, we camouflaged the surface of protein nanoparticles through the adsorption of carrier materials. The adsorption of carrier materials successfully inhibited the phase transfer of insulin, albumin, ß-lactoglobulin, and ovalbumin nanoparticles. As a result, the obtained microcomposites featured with a record of protein encapsulation efficiencies near 100% and a record of protein mass fraction of 77%. After the encapsulation in microcomposites, the insulin revealed a hypoglycemic effect for at least 14 d with one single injection, while that of insulin solution was only ∼4 h.

Gleevec and Rapamycin Synergistically Reduce Cell Viability and Inhibit Proliferation and Angiogenic Function of Mouse Bone Marrow-Derived Endothelial Progenitor Cells.

OBJECTIVE: This study investigates the synergistic effects of Gleevec (imatinib) and rapamycin on the proliferative and angiogenic properties of mouse bone marrow-derived endothelial progenitor cells (EPCs). MATERIALS AND METHODS: EPCs were isolated from mouse bone marrow and treated with different concentrations of Gleevec or rapamycin individually or in combination. The cell viability and proliferation were examined using the MTT assay. An analysis of cell cycle and apoptosis was performed using flow cytometry. Formation of capillary-like tubes was examined in vitro, and the protein expression of cell differentiation markers was determined using Western blot analysis. RESULTS: Gleevec significantly reduced cell viability, cell proliferation, and induced cell apoptosis in EPCs. Rapamycin had similar effects on EPCs, but it did not induce cell apoptosis. The combination of Gleevec and rapamycin reduced the cell proliferation but increased cell apoptosis. Although rapamycin had no demonstratable effect on tube formation, the combined therapy of Gleevec and rapamycin significantly reduced tube formation when compared with Gleevec alone. Mechanistically, Gleevec, but not rapamycin, induced a significant elevation in caspase-3 activity in EPCs, and it attenuated the expression of the endothelial protein marker platelet-derived growth factor receptor α. Functionally, rapamycin, but not Gleevec, significantly enhanced the expression of endothelial differentiation marker proteins, while attenuating the expression of mammalian target of rapamycin signaling-related proteins. CONCLUSIONS: Gleevec and rapamycin synergistically suppress cell proliferation and tube formation of EPCs by inducing cell apoptosis and endothelial differentiation. Mechanistically, it is likely that rapamycin enhances the proapoptotic and antiangiogenic effects of Gleevec by promoting the endothelial differentiation of EPCs. Given that EPCs are involved in the pathogenesis of some cardiovascular diseases and critical to angiogenesis, pharmacological inhibition of EPC proliferation by combined Gleevec and rapamycin therapy may be a promising approach for suppressing cardiovascular disease pathologies associated with angiogenesis.

Simultaneous determination of triclosan, triclocarban, triclocarban metabolites and byproducts in urine and serum by ultra-high-performance liquid chromatography/electrospray ionization tandem mass spectrometry.

RATIONALE: Triclosan (TCS) and triclocarban (TCC) are ubiquitous antimicrobial agents incorporated in consumer and personal care products. Due to their human health risks, it is essential to develop a sensitive and accurate analytical method to simultaneously quantify TCS, TCC, as well as their metabolites and byproducts in urine and serum samples. METHODS: The quantitative parameters of TCS, TCC, TCC metabolites and byproducts (2'-OH-TCC, 3'-OH-TCC, 6-OH-TCC, DHC, DCC, NCC) were optimized by using ultra-high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (UHPLC/ESI-MS/MS). Enzymatic hydrolysis of the samples was optimized based on enzyme dosage and incubation time. The efficiencies of solid-phase extraction (SPE) and liquid-liquid extraction (LLE) were compared. The effectiveness of the established method was evaluated, and method application was validated using real urine and serum samples. RESULTS: The conjugates were sufficiently hydrolyzed under 500 U/mL ß-glucuronidase and 80 U/mL sulfatase at 37°C for 4 h. Compared with the LLE method, SPE achieved higher extraction efficiency in both urine and serum samples. The optimized SPE-UHPLC/ESI-MS/MS method showed low limits of detection (LODs) in the range 0.001-0.3 ng/mL and good linearity (R2 > 0.99) at 0.01-150 ng/mL in both matrices. Excellent recoveries of 82.0%-120.7% (urine) and 76.7%-113.9% (serum) were obtained with low relative standard deviation (RSD, <7.6%) for inter-day and intra-day injections. This method was applicable to quantify target compounds in multiple biological urine and serum samples. Notably, TCS and TCC were detected with average concentrations of 8.37 and 10.46 ng/mL, respectively, in 15 Chinese female urine samples, with the simultaneous detection of TCC metabolites and byproducts. CONCLUSIONS: A reliable method was established to simultaneously determine TCS, TCC, TCC metabolites and byproducts in urine and serum samples by using UHPLC/ESI-MS/MS. This sensitive methodology provides the basis for the evaluation of TCS and TCC exposure at the metabolic level.

A review of 17α-ethynylestradiol (EE2) in surface water across 32 countries: Sources, concentrations, and potential estrogenic effects.

17α-ethynylestradiol (EE2) is a synthetic estrogen with very strong estrogenic potency. Due to its wide usage in human and livestock as well as its high recalcitration to biodegradation, it was ubiquitous in different environment. This review summarized EE2 concentration levels in surface waters among 32 countries across seven continents. EE2 concentrations varied greatly in different surface waters, which ranged from not detected to 17,112 ng/L. The top 10 countries ranked in the order of high to low average EE2 concentration in surface water, were Vietnam, Cambodia, China, Laos, Brazil, Argentina, Kuwait, Thailand, Indonesia and Portugal, with the respective mean concentrations of 27.7, 22.1, 21.5, 21.1, 13.6, 9.6, 9.5, 8.8, 7.6 and 6.6 ng/L. Generally speaking, the EE2 concentration levels in surface waters in developing countries were much higher than those in developed countries. EE2 in effluent of municipal wastewater treatment plant (WWTP) was the dominant source to most countries, which suggested that improving the EE2 removal performance of municipal WWTP is the key to mitigate EE2 contamination to surface water body. Livestock, hospital, pharmacy factory and aquaculture wastewaters were also the important sources, but further work should be performed to elucidate their contribution. Evaluation based on estrogenic effects, the EE2-derived estrogen equivalence in surface waters ranged from 0 to 33 ng E2/L, among which about 65% of surface waters among 32 countries were at risk or high risk, indicating global serious EE2 contamination. MAIN FINDING: EE2 concentration in surface waters across 32 countries were summarized, along which its potential estrogenic effects were evaluated.

Designed Core-Shell Fe3O4@Polydopamine for Effectively Removing Uranium(VI) from Aqueous Solution.

Adsorbents with the combination of magnetic separation and removal performance are expected for reducing the adverse impact of nuclear pollution. In this study, the core-shell Fe3O4@polydopamine (Fe3O4@PDA) was successfully synthesized and used for removal of uranium (U(VI)) ion from aqueous solution. The abundant N-containing groups derived from PDA exist as the chelate sites for U(VI) and contribute greatly for U(VI) removal. Experimental results show that Fe3O4@PDA (56.39 mg g-1) exhibits greater sorption capacity for U(VI) removal compared with the pure Fe3O4 (9.17 mg g-1). The sorption isotherm can be well fitted with Freundlich model and the sorption process is endothermic and spontaneous. The removal of U(VI) can be explained by the complexation of U(VI) with -NH-, -NH2 and C-O in the surface of Fe3O4@PDA by X-ray photoelectron spectroscopy (XPS) analysis.

Microfluidics for Production of Particles: Mechanism, Methodology, and Applications.

In the past two decades, microfluidics-based particle production is widely applied for multiple biological usages. Compared to conventional bulk methods, microfluidic-assisted particle production shows significant advantages, such as narrower particle size distribution, higher reproducibility, improved encapsulation efficiency, and enhanced scaling-up potency. Herein, an overview of the recent progress of the microfluidics technology for nano-, microparticles or droplet fabrication, and their biological applications is provided. For both nano-, microparticles/droplets, the previously established mechanisms behind particle production via microfluidics and some typical examples during the past five years are discussed. The emerging interdisciplinary technologies based on microfluidics that have produced microparticles or droplets for cellular analysis and artificial cells fabrication are summarized. The potential drawbacks and future perspectives are also briefly discussed.

Phosphor-converted laser-diode-based white lighting module with high luminous flux and color rendering index.

A laser-diode-based white lighting module is fabricated via spectral component optimization, which can achieve both high luminous flux and high color rendering index (CRI). In this work, the laser module is constituted by blue laser diodes (LDs) which excite YAG:Ce-Al2O3 and red LDs that can compensate for the lack of red spectrum to improve the CRI of the light source. To fulfill the requirements of flexibility and compactness of light source, the blue and red LDs beams are combined by optical fiber coupling. A simulation framework is employed to optimize the dominant wavelength of red LDs and the power ratio of red to blue LDs. According to the results of the integrating sphere, high luminous flux of 1102 lm and high CRI of 77.8 are achieved simultaneously, which is consistent with the simulation results. The tunable correlated color temperature (CCT) varying from 4000 K to 2800 K and high angular color uniformity (ACU) can be obtained.

Macaca leonina has a wider niche breadth than sympatric M. mulatta in a fragmented tropical forest in southwest China.

Niche differentiation has long been identified as an essential stabilizing mechanism for the coexistence of sympatric species. Using camera trapping data obtained during 2012-2016, we identified Macaca leonina and M. mulatta as the dominant macaque species in the Naban River Watershed National Nature Reserve (NRW-NNR), a tropical forest in southwestern China. In general, M. leonina exhibited a wider distribution and greater niche breadth than co-occurring M. mulatta. According to a fitted maximum entropy model (MaxEnt), M. leonina was predicted to predominantly occur in forest at higher elevation, whereas M. mulatta was predicted at lower elevation; the broadleaved evergreen forest was predicted as the most suitable vegetation for both species to inhabit, while the unsuitable area was bordered by rubber plantation, in which both food scarcity and human disturbance restricted the movement of macaques. Although the niches of these two species highly overlapped across space and time, we also found evidence for their spatiotemporal niche differentiation. When the two species inhabited independent areas with different elevations and vegetation, they maintained a similar activity pattern; however, in the zones of overlap, their activity patterns differed significantly. Further comparative field studies of these two macaques, considering other niche dimensions, are required to ensure their coexistence and long-term conservation.

Radiomics signature based on FDG-PET predicts proliferative activity in primary glioma.

AIM: To investigate a radiomics method based on 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET) to non-invasively evaluate proliferative activity in gliomas. MATERIALS AND METHODS: A total of 123 patients with histopathologically confirmed primary glioma were reviewed retrospectively and assigned randomly into the primary cohort (n=82) and validation cohort (n=41). Tumour proliferative activity was defined by the Ki-67 index based on immunohistochemistry. Standard uptake value (SUV) maps were generated, and 1,561 radiomics features were extracted. Radiomics features were selected through the sequential application of three algorithms. Three predictive signatures were generated: a radiomics signature, a clinical signature, and a fusion signature. The predictive performances were evaluated by receiver operating characteristic (ROC) curve analysis, and patient prognoses were stratified based on the Ki-67 index and the signature with the most reliable performance. RESULTS: Nine radiomics features were selected to construct the radiomics signature that achieved an accuracy of 81.7% and 73.2% and an area under the curve (AUC) of 0.88 and 0.76 in the primary cohort and the validation cohort, respectively. The clinical signature and fusion signature demonstrated comparable performance in the primary cohort but were over-fitted judging from the result in the validation cohort. Both the Ki-67 index and the radiomics signature could stratify patients into two distinctive prognostic groups, and the difference within each prognostic group was not statistically significant. CONCLUSION: Radiomics signature based on 18F-FDG-PET is a promising method for the non-invasive measurement of glioma proliferative activity and facilitates the prediction of patient prognoses.

Chemical composition, antibacterial activity and related mechanism of valonia and shell from Quercus variabilis Blume (Fagaceae) against Salmonella paratyphi a and Staphylococcus aureus.

BACKGROUND: Plant secondary metabolites and phytochemicals that exhibit strong bioactivities have potential to be developed as safe and efficient natural antimicrobials against food contamination and addressing antimicrobial resistance caused by the overuse of chemical synthetic preservative. In this study, the chemical composition, antibacterial activities and related mechanism of the extracts of the valonia and the shell of Quercus variabilis Blume were studied to determine its potential as a safe and efficient natural antimicrobial. METHODS: The phenolic compositions of valonia and shell extracts were determined by folin-ciocalteau colourimetric method, sodium borohydride/chloranil-based assay and the aluminium chloride method and then further identified by the reverse-phase HPLC analysis. The antibacterial activities of valonia and shell extracts were evaluated by the agar disk diffusion method and agar dilution method. The related antibacterial mechanism was explored successively by the membrane of pathogens effect, phosphorous metabolism, whole-cell proteins and the microbial morphology under scanning electron microscopy. RESULTS: The n-butanol fraction and water fraction of valonia along with n-butanol fraction of the shell contains enrich phenolics including ellagic acid, theophylline, caffeic acid and tannin acid. The n-butanol fraction and ethanol crude extracts of valonia exhibited strong antibacterial activities against Salmonella paratyphi A (S. paratyphi A) and Staphylococcus aureus (S. aureus) with the DIZ values ranged from 10.89 ± 0.12 to 15.92 ± 0.44, which were greater than that of the Punica granatum (DIZ: 10.22 ± 0.18 and 10.30 ± 0.21). The MIC values of the n-butanol fraction and ethanol crude extracts of valonia against S. paratyphi A and S. aureus were 1.25 mg/ml and 0.625 mg/ml. The related antibacterial mechanism of n-butanol fraction and ethanol crude extracts of valonia may be attributed to their strong impact on membrane permeability and cellular metabolism. Those extracts exhibited strong antibacterial activity according to inhibit the synthesis of bacterial proteins and seriously change morphological structure of bacterial cells. CONCLUSIONS: The n-butanol fraction and ethanol crude extracts of valonia had reasonably good antibacterial activities against S. paratyphi A and S. aureus. This study suggests possible application of valonia and shell as natural antimicrobials or preservatives for food and medical application.

Liposomal Codelivery of Doxorubicin and Andrographolide Inhibits Breast Cancer Growth and Metastasis.

Effective treatment of metastatic (stage IV) breast cancers remains a formidable challenge. To address this issue, a cell-penetrating peptide-assisted liposomal system was developed for codelivery of doxorubicin and andrographolide. This nanomedicine-based combination therapy showed the ability to inhibit the in vitro migration and invasion of 4T1 cells through the wound healing and transwell invasion assays. Furthermore, this delivery system exhibited the enhanced accumulation in the tumor tissues and deep intratumoral penetration. The synergistic effect of doxorubicin and andrographolide led to an evident inhibition of tumor growth in an orthotopic breast tumor mouse model and efficient prevention of lung metastasis. The therapeutic mechanism was associated with the anti-angiogenesis effect. In conclusion, this nanomedicine-based combination therapy provides a potential method for overcoming metastatic breast cancers.

Novel Core-Interlayer-Shell DOX/ZnPc Co-loaded MSNs@ pH-Sensitive CaP@PEGylated Liposome for Enhanced Synergetic Chemo-Photodynamic Therapy.

PURPOSE: This work was intended to develop novel doxorubicin (DOX)/zinc (II) phthalocyanine (ZnPc) co-loaded mesoporous silica (MSNs)@ calcium phosphate (CaP)@PEGylated liposome nanoparticles (NPs) that could efficiently achieve collaborative anticancer therapy by the combination of photodynamic therapy (PDT) and chemotherapy. The interlayer of CaP could be utilized to achieve pH-triggered controllable drug release, promote the cellular uptake, and induce cell apoptosis to further enhance the anticancer effects. METHODS: MSNs were first synthesized as core particles in which the pores were diffusion-filled with DOX, then the cores were coated by CaP followed by the liposome encapsulation with ZnPc to form the final DOX/ZnPc co-loaded MSNs@CaP@PEGylated liposome. RESULTS: A core-interlayer-shell MSNs@CaP@PEGylated liposomes was developed as a multifunctional theranostic nanoplatform. In vitro experiment indicated that CaP could not only achieve pH-triggered controllable drug release, promote the cellular uptake of the NPs, but also generate high osmotic pressure in the endo/lysosomes to induce cell apoptosis. Besides, the chemotherapy using DOX and PDT effect was achieved by the photosensitizer ZnPc. Furthermore, the MSNs@CaP@PEGylated liposomes showed outstanding tumor-targeting ability by enhanced permeability and retention (EPR) effect. CONCLUSIONS: The novel prepared MSNs@CaP@PEGylated liposomes could serve as a promising multifunctional theranostic nanoplatform in anticancer treatment by synergic chemo-PDT and superior tumor-targeting ability.

Cadmium-induced stress response of Phanerochaete chrysosporium during the biodegradation of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47).

Cd-induced stress response of Phanerochaete chrysosporium during the biodegradation of BDE-47 was investigated in this study, with the goal of elucidating the tolerance behavior and the detoxification mechanisms of P. chrysosporium to resist the Cd stress in the course of BDE-47 biodegradation, which has implications for expanding the application of P. chrysosporium in the bioremediation of Cd and BDE-47 combined pollution. The results suggested that single BDE-47 exposure did not induce obvious oxidative stress in P. chrysosporium, but coexistent Cd significantly triggered ROS generation, both intracellular ROS level and H2O2 content showed positive correlation with Cd concentration. The activities of SOD and CAT were enhanced by low level of Cd (≤ 1 mg/L), but Cd of higher doses (＞1 mg/L) depressed the expression of these two antioxidant enzymes at the later exposure period (3-5 days). The intracellular content of GSH along with GSH/GSSG ratio also exhibited a bell-shaped response with a maximum value at Cd of 1 mg/L. Furthermore, Cd-induced ROS generation resulted in the lipid peroxidation, as indicated by a noticeable increment of MDA content found after 3 days. Moreover, the study also indicated that Cd less than 1 mg/L promoted the production of extracellular protein and quickened the decrease of pH value in the medium, while excessive Cd (＞1 mg/L) would lead to inhibition. These findings obtained demonstrated that P. chrysosporium had a certain degree of tolerance to Cd within a specific concentration range via regulating the antioxidant levels, inducing the synthesis of extracellular protein as well as stimulating the production of organic acids, and 1 mg/L is suggested to be the tolerance threshold of this strains under Cd stress during BDE-47 biodegradation.