Stochastic process is main factor to affect plateau river fish community assembly.

Plateau river ecosystems are often highly vulnerable and responsive to environmental change. The driving mechanism of fish diversity and community assembly in plateau rivers under changing environments presents a significant complexity to the interdisciplinary study of ecology and environment. This study integrated molecular biological techniques and mathematical models to identify the mechanisms influencing spatial heterogeneity of freshwater fish diversity and driving fish community assembly in plateau rivers. By utilizing environmental-DNA metabarcoding and the null model, this study revealed the impact of the stochastic process on fish diversity variations and community assembly in the Huangshui Plateau River of the Yellow River Basin (YRB) in China. This research identified 30 operational taxonomic units (OTUs), which correspond to 20 different fish species. The findings of this study revealed that the fish α-diversity in the upstream region of Xining is significantly higher than in the middle-lower reach (Shannon index: P = 0.017 and Simpson: P = 0.035). This pattern was not found to be related to any other environmental factors besides altitude (P = 0.023) that we measured. Further, the study indicated that the assembly of fish communities in the Huangshui River primarily depends on stochastic ecological processes. These findings suggested that elevation was not the primary factor impacting the biodiversity patterns of fish in plateau rivers. In plateau rivers, spatial heterogeneity of fish community on elevation is mainly determined by stochastic processes under habitat fragmentation, rather than any other physicochemical environmental factors. The limitations of connectivity in the downstream channel of the river could be taken the mainly responsibility for stochastic processes of fish community in Huangshui River. Incorporating ecological processes in the eDNA approach holds great potential for future monitoring and evaluation of fish biodiversity and community assembly in plateau rivers.

Suggestion of creatine as a new neurotransmitter by approaches ranging from chemical analysis and biochemistry to electrophysiology.

The discovery of a new neurotransmitter, especially one in the central nervous system, is both important and difficult. We have been searching for new neurotransmitters for 12 y. We detected creatine (Cr) in synaptic vesicles (SVs) at a level lower than glutamate and gamma-aminobutyric acid but higher than acetylcholine and 5-hydroxytryptamine. SV Cr was reduced in mice lacking either arginine:glycine amidinotransferase (a Cr synthetase) or SLC6A8, a Cr transporter with mutations among the most common causes of intellectual disability in men. Calcium-dependent release of Cr was detected after stimulation in brain slices. Cr release was reduced in Slc6a8 and Agat mutants. Cr inhibited neocortical pyramidal neurons. SLC6A8 was necessary for Cr uptake into synaptosomes. Cr was found by us to be taken up into SVs in an ATP-dependent manner. Our biochemical, chemical, genetic, and electrophysiological results are consistent with the possibility of Cr as a neurotransmitter, though not yet reaching the level of proof for the now classic transmitters. Our novel approach to discover neurotransmitters is to begin with analysis of contents in SVs before defining their function and physiology.

Self-assembled c-oriented Ni(OH)2 films for enhanced electrocatalytic activity towards the urea oxidation reaction.

This study investigates the electrocatalytic properties of the transparent c-oriented Ni(OH)2 films self-assembled from colloidal 2D Ni(OH)2 nanosheets for urea oxidation. The synthesis process yields highly uniform close-packed superlattices with a dominant c-axis orientation. The self-assembled c-oriented Ni(OH)2 films exhibit advantageous electrocatalytic performance in urea oxidation, presenting significantly lower overpotentials and higher current densities compared to randomly distributed Ni(OH)2 particles. In-depth in situ impedance analysis and Raman spectroscopy demonstrate that the c-oriented Ni(OH)2 films possess a higher propensity for a Ni valence transition from +2 to +3 during the urea oxidation process. This finding provides crucial insights into the catalytic behavior and electronic transformations of c-oriented Ni(OH)2 films, shedding light on their superior electrocatalytic activity for urea oxidation. Overall, this study advances our understanding of urea electrooxidation mechanisms and contributes to the design of efficient urea electrocatalysts.

Directly and ultrasensitivity detecting SARS-CoV-2 spike protein in pharyngeal swab solution by using SERS-based biosensor.

The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a great disaster to the economy and human society. Nowadays, SARS-CoV-2 is fading away from people's memory but it still exists around us. PCR plays an important role in detecting SARS-CoV-2 but it requires a long detecting time, equipped laboratory, and professional operators. In comparison with polymerase chain reaction (PCR), surface-enhanced Raman scattering (SERS) is a promising method for detecting SARS-CoV-2 due to its fast, easily operated, and high-sensitivity properties. In this study, the monolayer Ag nanoparticles (MAgNPs) covered with single-layer graphene (SLG) are applied as a SERS substrate. The angiotensin converting enzyme 2 (ACE2) is selected as a bio-probes that can specifically bind to the SARS-CoV-2 S protein. The SERS-based biosensor is formed by ACE2 functionalized SLG/MAgNPs and the LODs of detecting SARS-CoV-2 S protein in phosphate-buffered saline (PBS) and in pharyngeal swabs solution (PSS) are 0.1 fg mL-1 and 10 fg mL-1, respectively. This biosensor provides a way of directly detecting SARS-CoV-2 S protein with high sensitivity and specificity. It illustrates a practical potential in the rapid detection of the SARS-CoV-2 virus.

Importance of glutamine in synaptic vesicles revealed by functional studies of SLC6A17 and its mutations pathogenic for intellectual disability.

Human mutations in the gene encoding the solute carrier (SLC) 6A17 caused intellectual disability (ID). The physiological role of SLC6A17 and pathogenesis of SLC6A17-based-ID were both unclear. Here, we report learning deficits in Slc6a17 knockout and point mutant mice. Biochemistry, proteomic, and electron microscopy (EM) support SLC6A17 protein localization in synaptic vesicles (SVs). Chemical analysis of SVs by liquid chromatography coupled to mass spectrometry (LC-MS) revealed glutamine (Gln) in SVs containing SLC6A17. Virally mediated overexpression of SLC6A17 increased Gln in SVs. Either genetic or virally mediated targeting of Slc6a17 reduced Gln in SVs. One ID mutation caused SLC6A17 mislocalization while the other caused defective Gln transport. Multidisciplinary approaches with seven types of genetically modified mice have shown Gln as an endogenous substrate of SLC6A17, uncovered Gln as a new molecule in SVs, established the necessary and sufficient roles of SLC6A17 in Gln transport into SVs, and suggested SV Gln decrease as the key pathogenetic mechanism in human ID.

Nano-biosensor for SARS-CoV-2/COVID-19 detection: methods, mechanism and interface design.

The epidemic of coronavirus disease 2019 (COVID-19) was a huge disaster to human society. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which led to COVID-19, has resulted in a large number of deaths. Even though the reverse transcription-polymerase chain reaction (RT-PCR) is the most efficient method for the detection of SARS-CoV-2, the disadvantages (such as long detection time, professional operators, expensive instruments, and laboratory equipment) limit its application. In this review, the different kinds of nano-biosensors based on surface-enhanced Raman scattering (SERS), surface plasmon resonance (SPR), field-effect transistor (FET), fluorescence methods, and electrochemical methods are summarized, starting with a concise description of their sensing mechanism. The different bioprobes (such as ACE2, S protein-antibody, IgG antibody, IgM antibody, and SARS-CoV-2 DNA probes) with different bio-principles are introduced. The key structural components of the biosensors are briefly introduced to give readers an understanding of the principles behind the testing methods. In particular, SARS-CoV-2-related RNA mutation detection and its challenges are also briefly described. We hope that this review will encourage readers with different research backgrounds to design SARS-CoV-2 nano-biosensors with high selectivity and sensitivity.

Monodisperse MoS2/Graphite Composite Anode Materials for Advanced Lithium Ion Batteries.

Traditional graphite anode material typically shows a low theoretical capacity and easy lithium decomposition. Molybdenum disulfide is one of the promising anode materials for advanced lithium-ion batteries, which possess low cost, unique two-dimensional layered structure, and high theoretical capacity. However, the low reversible capacity and the cycling-capacity retention rate induced by its poor conductivity and volume expansion during cycling blocks further application. In this paper, a collaborative control strategy of monodisperse MoS2/graphite composites was utilized and studied in detail. MoS2/graphite nanocomposites with different ratios (MoS2:graphite = 20%:80%, 40%:60%, 60%:40%, and 80%:20%) were prepared by mechanical ball-milling and low-temperature annealing. The graphite sheets were uniformly dispersed between the MoS2 sheets by the ball-milling process, which effectively reduced the agglomeration of MoS2 and simultaneously improved the electrical conductivity of the composite. It was found that the capacity of MoS2/graphite composites kept increasing along with the increasing percentage of MoS2 and possessed the highest initial discharge capacity (832.70 mAh/g) when MoS2:graphite = 80%:20%. This facile strategy is easy to implement, is low-cost, and is cosmically produced, which is suitable for the development and manufacture of advance lithium-ion batteries.

Fabrication and characterization of Ti/polyaniline-Co/PbO2-Co for efficient electrochemical degradation of cephalexin in secondary effluents.

The traditional interlayer of PbO2 electrode possessed many problems, such as short service lifetime and limited specific surface area. Herein, a novel and efficient Ti/polyaniline-Co/PbO2-Co electrode was conctructed employing cyclic voltammetry to introduce a Co-doped polyaniline interlayer and anodic electrodeposition to synthetize a ß-PbO2-Co active layer. Compared with pristine PbO2 electrode, Ti/polyaniline-Co/PbO2-Co exhibited more compact crystalline shape and higher active sites amounts. Pratically, the electrochemical degradation of 5 mg L-1 cephalexin in real secondary effluents was effectively achieved by the novel anode with 87.42% cephalexin removal and 71.8% COD mineralization after 120 min of 15 mA cm-2 electrolysis. The hydroxyl radical production and electrochemical stability were increased by 3.16 and 3.27 times respectively. The cephalexin degradation pathway was investigated by combining a density functional theory-based theoretical approach and LC-QTrap-MS/MS. The most likely cleavage point of the ß-lactam ring was the O=C-N bond, whose attack would produce small molecular compounds containing the thiazole and 4, 6-thiazine rings. Further oxidation produced inorganic ions; quantitative investigations indicated the amino groups to undergo decomposition to form aqueous NH4+, which was further oxidized to NO3-. The accumulation of NO3- and SO42-, combined with a decrease in toxicity toward Escherichia coli, demonstrated the efficient mineralization of cephalexin on the Ti/polyaniline-Co/PbO2-Co electrode.

[May-July NDVI variation for the middle Qinling Mountains over the past 194 years indicated by tree rings of Pinus tabuliformis]. / æ²¹æ¾æ ‘è½®æŒ‡ç¤ºçš„ç§¦å²­ä¸­éƒ¨è¿‡åŽ»194å¹´5­7月NDVI变化.

Due to the short-term observation record of the normalized difference vegetation index (NDVI), the research on long-term NDVI changes is scarce, which limits our understanding of the impacts of NDVI changes in the context of global warming. In this study, a regional tree-ring chronology was developed based on the tree-ring samples of Pinus tabuliformis in the middle Qinling Mountains. The results showed that tree-ring width of P. tabuliformis was significantly positively correlated with May-July NDVI (r=0.624, P<0.01, n=34). The Sig-Free tree-ring width chronology was used to reconstruct May-July NDVI during the period 1825-2018, which explained 38.9% of the total NDVI variance. Results of spatial analysis showed that the reconstructed series could better represent the NDVI changes in the study area. There were six high NDVI periods and five low NDVI periods in the past 194 years. The vegetation grew best in 2006-2018, indicating vegetation cove-rage in the middle of Qinling Mountains had been improved during the warming hiatus. Low NDVI periods in the reconstruction series were consistent with drought over much of study area. Results of wavelet analysis indicated the existence of 2-4 years and 12-16 years cycles in the reconstruction series. SEA analysis showed that the reconstruction series decreased significantly in the El Nino year, while increased significantly in the first to third years after the La Nina event. The growth of P. tabuliformis was predicted to increase slightly under the SSP2-4.5, SSP3-7.0 and SSP5-8.5 scenarios.

Fabrication of NiO-carbon nanotube/sulfur composites for lithium-sulfur battery application.

The practical applications of lithium-sulfur batteries are still a great challenge due to the polysulfide shuttle and capacity decay. Herein, we report a NiO-carbon nanotube/sulfur (NiO-CNT/S) composite by hydrothermal and thermal treatments. This hybrid combines the high conductivity of CNTs and double adsorption of CNTs and NiO (physical and chemical adsorption) to improve the electrochemical performance for the sulfur electrodes. Compared with CNT/S and NiO/S, the developed NiO-CNT/S composites present a preferable initial reversible discharge capacity (1072 mA h g-1) and is maintained at 609 mA h g-1 after 160 cycles at 0.1C.

Increasing anthropogenic salinisation leads to declines in community diversity, functional diversity and trophic links in mountain streams.

Anthropogenic salinisation is becoming an increasing global issue for freshwater ecosystems, leading to serious biodiversity loss and ecosystem degradation. While the effect of anthropogenic salinisation on freshwater ecosystems has been intensively studied in recent years, most studies focus on salinisation effects on the individual or single groups of organisms without considering the effect on the ecosystem levels, such as diversity and trophic links. Therefore, we conducted a long-term field survey from May 2009 to August 2016 at 405 sites in northeast China to investigate the effect of a gradient of salinisation on community diversity, functional diversity and trophic links in mountain streams. Samples of water chemistry, periphyton, macroinvertebrates and fish were collected. Our results showed that as anthropogenic salinisation increased, Ca2+, Mg2+, HCO3- and SO42- exhibited significant increases (p < 0.05). These increased ions caused decreases in taxonomic evenness and biotic integrity, but an increase in the beta diversity for periphyton and macroinvertebrates, and a slight increase in the evenness of fish. The increased salinisation resulted in the extirpation of salt-sensitive taxa and declines in macroinvertebrate functional richness and functional redundancy, which consequently led to simplified trophic links. Our results implied that if salt-tolerant taxa in high salinisation sites were not functionally redundant with less tolerant taxa, alterations of their functional composition probably decrease the stability of ecosystem functions. Overall, our study suggests that the ongoing anthropogenic salinisation is posing serious threats to biodiversity and trophic links in river ecosystems, and should be considered in future river restoration and biodiversity conservation.

River algal blooms are well predicted by antecedent environmental conditions.

River algal blooms have become a challenging environmental problem worldwide due to strong interference of human activities and megaprojects (e.g., big dams and large-scale water transfer projects). Previous studies on algal blooms were mainly focused on relatively static water bodies (i.e., lakes and reservoirs), but less on the large rivers. As the largest tributary of the Yangtze River of China and the main freshwater source of the South-to-North Water Diversion Project (SNWDP), the Han River has experienced frequent algal blooms in recent decades. Here we investigated the algal blooms during a decade (2003-2014) in the Han River by two gradient boosting machine (GBM) models with k-fold cross validation, which used explanatory variables from current 10-day (GBMc model) or previous 10-day period (GBMp model). Our results advocate the use of GBMp due to its higher accuracy (median Kappa = 0.9) and practical predictability (using antecedent observations) compared to GBMc. We also revealed that the algal blooms in the Han River were significantly modulated by antecedent water levels in the Han River and the Yangtze River and water level variation in the Han River, whereas the nutrient concentrations in the Han River were usually above thresholds and not limiting algal blooms. This machine-learning-based study potentially provides scientific guidance for preemptive warning and risk management of river algal blooms through comprehensive regulation of water levels during the dry season by making use of water conservancy measures in large rivers.

Decadal patterns of anthropogenic salinisation in typical mountain streams in northeastern China: Increased rates and sources.

Salt pollution and anthropogenic-accelerated weathering is globally shifting the ionic composition and increasing salinisation of fresh water. We analyzed a 40-year data set (1970s-2010s) to characterize the drastic change of dissolved ionic composition, conductivity and pH levels. We also identified causative factors in these highly polluted mountain streams in northeastern China. Dissolved salt ions (Ca2+, Mg2+ and SO42-) increased by 3.02-5.21 fold and conductivity (a proxy for salinisation) increased by 3.09 fold. The average pH values increased from 7.08 to 8.49. The dominant ions, Ca2+, Mg2+, SO42- and HCO3- + CO32-, accounted for ∼90% of ionic composition based on mass concentration. Between the 1970s and 2010s, the dominant anion shifted from HCO3- + CO32- to a mixture of SO42- and HCO3- + CO32-. Increasing mining and land development appear to be the primary driving factors for the change of Ca2+, Mg2+, SO42- and HCO3- + CO32- concentrations; whereas, agricultural land was the main driving factor for the variation in K+, Na+ and Cl- concentrations. The source of ions has shifted from a more natural weathering of carbonate rocks to one of mineral dissolution that is affected by anthropogenic activities. Our study shows that freshwater mountain streams are at risk of long lasting anthropogenic salinisation and should be considered in future management and conservation plans.

Gradient Redox-Responsive and Two-Stage Rocket-Mimetic Drug Delivery System for Improved Tumor Accumulation and Safe Chemotherapy.

Recent drug delivery nanosystems for cancer treatment still suffer from the poor tumor accumulation and low therapeutic efficacy due to the complex in vivo biological barriers. To resolve these problems, in this work, a novel gradient redox-responsive and two-stage rocket-mimetic drug nanocarrier is designed and constructed for improved tumor accumulation and safe chemotherapy. The nanocarrier is constructed on the basis of the disulfide-doped organosilica-micellar hybrid nanoparticles and the following dual-functional modification with disulfide-bonded polyethylene glycol (PEG) and amido-bonded polyethylenimine (PEI). First, prolonged circulation duration in the bloodstream is guaranteed due to the shielding of the outer PEG chains. Once the nanocarrier accumulates at the tumoral extracellular microenvironment with low glutathione (GSH) concentrations, the first-stage redox-responsive behavior with the separation of PEG and the exposure of PEI is triggered, leading to the improved tumor accumulation and cellular internalization. Furthermore, with their endocytosis by tumor cells, a high concentration of GSH induces the second-stage redox-responsiveness with the degradation of silsesquioxane framework and the release of the encapsulated drugs. As a result, the rocket-mimetic drug carrier displays longer circulation duration in the bloodstream, higher tumor accumulation capability, and improved antitumor efficacy (which is 2.5 times higher than that with inseparable PEG). It is envisioned that the rocket-mimetic strategy can provide new solutions for improving tumor accumulation and safety of nanocarriers in further cancer chemotherapy.

Large area growth of few-layer In2Te3 films by chemical vapor deposition and its magnetoresistance properties.

In this work we report a facile route to grow large area, uniform, continuous and few-layer α-In2Te3 film via chemical vapor deposition (CVD) methods. The characterizations show the large area of CVD-grown few-layer α-In2Te3. This method guarantees the precise control of thickness down to few layers and large area preparation. The magnetoresistance (MR) properties of few-layer In2Te3 was investigated from 2 to 300 K and its MR stability under long exposure to ambient air was studied for the first time. Few-layer of α-In2Te3 shows a positive MR and the largest transverse MR was observed to about 11% at 2 K and a high stability of MR to long time exposure in air up to 21 weeks.

Biodegradable organosilica magnetic micelles for magnetically targeted MRI and GSH-triggered tumor chemotherapy.

Recently, block copolymer micelles have attracted widespread attention due to their controlled biodegradability and excellent loading capability. Unfortunately, the poor in vivo stability and low delivery efficiency of drug-loaded micelles greatly hampered their biomedical applications. Herein, we develop a new kind of biodegradable magnetite/doxorubicin (Fe3O4/DOX) co-loaded PEGylated organosilica micelles (designated as FDPOMs) with both high circulating stability and smart GSH-triggered biodegradability for magnetically targeted magnetic resonance imaging (MRI) and tumor chemotherapy. The FDPOMs are prepared by the self-assembly of biodegradable polycaprolactone-block-poly(glutamic acid) (PCL-b-PGA), a chemotherapeutic DOX drug and Fe3O4 nanoparticles in an oil/water system, subsequent organosilica cross-linking with 3-mercaptopropyltrimethoxysilane (MPTMS) molecules and surface PEGylation. The resultant FDPOMs exhibit excellent dispersity and stability in biological media, remarkable T2-weighted MR imaging capability, unique GSH-responsive release behavior and selective toxicity to tumor cells. The in vivo experiments show that the FDPOMs not only have improved MR tumor imaging capability, but also exhibit high anti-tumor efficacy due to the strong magnetic targeting ability under an external magnetic field. Consequently, the FDPOMs are promising candidates for magnetically targeted MR imaging and imaging-guided tumor chemotherapy.

Confined growth of multiple gold nanorices in dual-mesoporous silica nanospheres for improved computed tomography imaging and photothermal therapy.

INTRODUCTION: In this work, we have developed a novel "confined-growth" strategy to synthesize PEGylated multiple gold nanorices-encapsulated dual-mesoporous silica nanospheres (designated as PEGylated MGNRs@DMSSs) containing both small mesopores (2.5 nm) in the shell and large mesopores (21.7 nm) in the core based on a well-established, seed-mediated growth method. The photothermal effect and CT imaging ability were also studied. METHODS: The nanoparticles were characterized by Fourier transform infrared (FT-IR) spectra, N2 absorption isotherms, Field-emission scanning electron microscopy (FE-SEM), Transmission electron microscopy (TEM), Inductively coupled plasma atomic emission spectroscopy (ICP-AES) and Confocal microscopy. RESULTS: The longitudinally-localized surface (LSPR) absorption properties of MGNRs@DMSSs can be easily tuned by altering the amount of HAuCl4 in the gold growth solution. Additionally, the resultant PEGylated MGNRs@DMSSs have monodispersed, spherical morphology and good colloidal stability in an aqueous solution. More importantly, when exposed to NIR irradiation, the PEGylated MGNRs@DMSSs exhibit both higher temperature increments and better photothermal effects than that of single PEGylated gold nanorods at nearly an equivalent LSPR absorption. In addition, as CT contrast agents, the PEGylated MGNRs@DMSSs display a better CT imaging performance, in comparison with single PEGylated gold nanorods at the same Au concentration. CONCLUSION: Taken together, results indicate the potential for MGNRs@DMSSs used in CT imaging-guided photothermal therapy. Such a simple "confined-growth" strategy within a porous matrix offers a promising platform to design and prepare novel metal(s) oxide@silica nanocomposites for use in further cancer bio-imaging and therapy.

Facile synthesis of organosilica-capped mesoporous silica nanocarriers with selective redox-triggered drug release properties for safe tumor chemotherapy.

As drug-delivery carriers for cancer chemotherapy, gatekeeper-capped mesoporous silica nanoparticles (MSNs) have been widely studied due to their high drug-loading capability, controlled drug release property and good biocompatibility. However, the currently reported gatekeeper-capped MSNs suffer from complex synthetic procedures, potential toxicity of gatekeepers, unsatisfactory control on drug stimuli-release, etc. In this work, we develop a simple but efficient approach to fabricate PEGylated organosilica-capped mesoporous silica nanoparticles (POMSNs) by employing a disulfide-doped organosilica coating as the gatekeeper formed by the hydrolysis and condensation of a silane coupling agent 3-(mercaptopropyl)trimethoxysilane (MPTMS) to block the mesopores of MSNs. Owing to the glutathione (GSH)-responsive biodegradation behavior of the disulfide-doped organosilica gatekeeper, the DOX-loaded POMSNs exhibit only 20% cell viability towards SMMC-7721 tumor cells, and almost no toxicity towards L-02 cells at a DOX concentration of 50 µg mL-1 was measured, demonstrating their selective cytotoxicity in vitro. More importantly, it is demonstrated that the DOX-loaded POMSNs exhibit a tumor inhibition rate of 71.3% and negligible systematic toxicity. Consequently, the resultant POMSNs show great potential as drug nanocarriers for redox-responsive drug release and passive-targeting tumor chemotherapy.

Extraction-Induced Fabrication of Yolk-Shell-Structured Nanoparticles with Deformable Micellar Cores and Mesoporous Silica Shells for Multidrug Delivery.

Yolk-shell-structured nanoparticles (YSNs) provide useful carriers for applications in biomedicine and catalysis due to the excellent loading capability and versatile functionality of the flexible core and porous shell. Unfortunately, the reported YSNs always require complex multistep synthesis processes and a harsh hard-template etching strategy. Herein, a facile "selective extraction" strategy is developed to synthesize yolk-shell-structured polymer@void@mSiO2 nanoparticles (designated as YSPNs) comprising deformable and soft polystyrene-b-poly(acrylic acid) (PS-b-PAA) micellar cores and mesoporous silica shells. The YSPNs are formed by a morphological change and volume shrinkage of the PS-b-PAA aggregates from large compound vesicles to large compound micelles during the extraction process. As a multidrug vehicle, both hydrophobic curcumin (Cur, 6.4 wt %) and hydrophilic doxorubicin hydrochloride (Dox, 19.4 wt %) can be coloaded onto YSPNs through a successive impregnation method. Moreover, the resulting Cur/Dox@YSPNs possess intelligent pH-responsive capability, time-sequenced release behavior, and high in vivo antitumor efficiency, demonstrating excellent potential as safe and efficient multidrug nanocarriers for tumor chemotherapy. We envision that such a facile "selective extraction" strategy will enable pathways to construct organic-inorganic hybrid nanoparticles with yolk-shell structures for various applications.

Dual Intratumoral Redox/Enzyme-Responsive NO-Releasing Nanomedicine for the Specific, High-Efficacy, and Low-Toxic Cancer Therapy.

Chemotherapy suffers numbers of limitations including poor drug solubility, nonspecific biodistribution, and inevitable adverse effects on normal tissues. Tumor-targeted delivery and intratumoral stimuli-responsive release of drugs by nanomedicines are considered to be highly promising in solving these problems. Compared with traditional chemotherapeutic drugs, high concentration of nitric oxide (NO) exhibits unique anticancer effects. The development of tumor-targeting and intratumoral microenvironment-responsive NO-releasing nanomedicines is highly desired. Here a novel kind of organic-inorganic composite nanomedicine (QM-NPQ@PDHNs) is presented by encapsulating a glutathione S-transferases π (GSTπ)-responsive drug O2 -(2,4-dinitro-5-{[2-(ß-d-galactopyranosyl olean-12-en-28-oate-3-yl)-oxy-2-oxoethyl] piperazine-1-yl} phenyl) 1-(methylethanolamino)diazen-1-ium-1,2-dilate (NPQ) as NO donor and an aggregation-induced-emission (AIE) red fluorogen QM-2 into the cores of the hybrid nanomicelles (PEGylated disulfide-doped hybrid nanocarriers (PDHNs)) with glutathione (GSH)-responsive shells. The QM-NPQ@PDHN nanomedicine is able to respond to the intratumoral over-expressed GSH and GSTπ, resulting in the responsive biodegradation of the protective organosilica shell and NPQ release, and subsequent NO release within the tumor, respectively, and thus normal organs remain unaffected. This work demonstrates a paradigm of dual intratumoral redox/enzyme-responsive NO-release nanomedicine for tumor-specific and high-efficacy cancer therapy.