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Hydrogen sulfide (H 2 S) has a comprehensive contribution to the normal operation and stability of organisms and is also present in environmental water samples and food deterioration. Thus, it is exceedingly promising and significant to develop a highly sensitive detection technique for tracing H 2 S. Inspired by this, we designed and synthesized a new fluorescent probe 2-[3-[2-[3-bromo-4-(2,4- dinitrobenzenesulfonate)] ethenyl]-5,5-dimethyl-2-cyclohexen-1-ylidene]propanedinitrile (SP-Br) for hydrosulfide ion detection by introducing bromine atom. Compared with reported H 2 S probes based on the same fluorescent parent, SP-Br has longer fluorescence emission (λ em  = 670 nm), shorter response time (3 min), lower detection limit (149 nM), and wider detection range (0-30 nM). SP-Br can emit weak yellow fluorescence, and the emission intensity at 670 nm is considerably enhanced in the presence of hydrosulfide ions. The identification mechanism of hydrosulfide ion by SP-Br was verified by high-resolution mass spectrometry, fluorescence, and UV-vis absorption spectroscopy. In addition, SP-Br has been successfully applied to the monitoring of actual water samples and beer samples and has certain development prospects and value in the fields of environmental pollution and food quality analysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Compared to the activation of acquired immunity by the immune checkpoint blockade, the activation of innate immunity via anti-phagocytosis checkpoint blockade could significantly increase the beneficiary population of immunotherapy. However, the activation of innate immunity and the occurrence of phagocytosis are only accomplished when the interaction between pro-phagocytosis signals and anti-phagocytosis signals is realized. Herein, a versatile nanoplatform (DHMR) based on mesoporous silicon nanoparticles (MSNPs) has been constructed. Two drugs, doxorubicin, a chemotherapeutic drug which could initiate tumor cells to release pro-phagocytosis signals, and RRx-001, an immunoadjuvant that could effectively implement the anti-phagocytosis checkpoint blockade, were loaded in MSNPs. Further decoration of hyaluronic acid encapsulation endows DHMR with the function of tumor targeting and long circulation. Ultimately, the DHMR system could efficiently and accurately target tumor tissue, release the drugs in the tumor microenvironment, achieve the activation of innate immunity, and finally dramatically inhibit the growth and metastasis of tumor cells.

The number of patients who benefit from acquired immunotherapy is limited. Stimulator of interferon genes (STING) signal activation is a significant component to enhance innate immunity, which has been used to realize broad-spectrum immunotherapy. Here, M@P@HA nanoparticles, as a STING signal amplifier, are constructed to enhance innate immunotherapy. Briefly, when M@P@HA was targeted into tumor cells, the nanoparticles decomposed with Mn 2+ and activated the release of protoporphyrin (PpIX). Under light irradiation, the generated reactive oxygen species disrupt the cellular redox homeostasis to lead cytoplasm leakage of damaged mitochondrial double-stranded (ds) DNA, which is the initiator of the STING signal. Simultaneously, Mn 2+ as the immunoregulator could significantly increase the activity of related protein of a STING signal, such as cyclic GMP-AMP synthase (cGAS) and STING, to further amplify the STING signal of tumor cells. Subsequently, the STING signal of tumor-associated macrophages (TAM) is also activated by capturing dsDNA and Mn 2+ that escaped from tumor cells, so as to enhance innate immunity. It is found that, by amplifying the STING signal of tumor tissue, M@P@HA could not only activate innate immunity but also cascade to activate CD8 + T cell infiltration even in a tumor with low immunogenicity.

Immune checkpoint blockade (ICB) has been hailed as the hope for conquering cancer as ICB could produce a significant and durable response to tumor cells. However, the high cost and severe side effects of ICB drugs limited their application for further anticancer therapy. Here, we developed a photoactivated immunotherapy nanoplatform (Apt@AuNC). This nanoplatform could target tumor tissues via enhanced penetration retention (EPR) effect and the aptamer (Apt) could be released from Apt@AuNC in tumor sites via illumination. The immune system in the tumor area was then activated after the combination of Apt and PD-1 protein. The heat generated from AuNC was able to continue killing tumor cells. This nanoplatform could not only achieve the precise immunotherapy but also significantly facilitate the anticancer efficacy.

A new type of dye with advantages of high selectivity and sensitivity is formed by using the strategy of hybridization between the luminescent unit and recognition unit. Based on this strategy, we exploit a novel dye bonding the benzopyrylium salt as a luminescent unit and phenylboronate group as a response site, which is served as a fluorescent probe 1 for specific recognition of hydrogen peroxide in biological application. Probe 1 employs a unique recognition switch, phenylboronate unit, to"turn-on"a highly specific and rapid fluorescence response toward hydrogen peroxide combined with the 1,6-rearrangement elimination reaction strategy. Meanwhile, probe 1 has the ability to glucose assay by taking advantage of glucose oxidase/glucose enzymatic reaction. What's more, the probe 1 is capable of tracking endogenous hydrogen peroxide in living cells and intracellular imaging. Therefore, the newly developed bioprobe 1 is expected to be used to monitor hydrogen peroxide and glucose levels in complex organisms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Osteoporosis, characterized by the destruction of bone resorption and bone formation, is a serious disease that endangers human health. Osteoporosis prevention and treatment has become one of the important research contents in the field of medicine. Acacetin, a natural flavonoid compound, could promote osteoblast differentiation, and inhibit osteoclast formation in vitro . However, the mechanisms of acacetin on osteoclast differentiation and type H vessel formation, as well as the effect of preventing bone loss, remain unclear. Here, we firstly used primary bone marrow derived macrophages (BMMs), endothelial progenitor cells (EPCs), and ovariectomized (OVX) mice to explore the function of acacetin on bone remodeling and H type vessel formation. In this study, we found that acacetin inhibits osteoclast formation and bone resorption of BMMs induced by the macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL) in a concentration of 20 μM without exerting cytotoxic effects. It was accompanied by downregulation of osteoclast differentiation marker genes ( Ctsk , Acp5 , and Mmp9 ) and cell fusion genes ( CD9 , CD47 , Atp6v0d2 , Dc-stamp , and Oc-stamp ). Moreover, acacetin disrupted actin ring formation and extracellular acidification in osteoclasts. Mechanistic analysis revealed that acacetin not only inhibits the expression of the major transcription factor NFATc1 and NF-κB during RANKL-induced osteoclast formation, but also suppresses RANKL-induced the phosphorylation of Akt, GSK3β, IκBα, and p65. Additionally, acacetin enhanced the ability of M-CSF and RANKL-stimulated BMMs to promote angiogenesis and migration of EPCs. We further established that, in vivo , acacetin increased trabecular bone mass, decreased the number of osteoclasts, and showed more type H vessels in OVX mice. These data demonstrate that acacetin prevents OVX-induced bone loss in mice through inhibition of osteoclast function and promotion of type H vessel formation via Akt/GSK3β and NF-κB signalling pathway, suggesting that acacetin may be a novel therapeutic agent for the treatment of osteoporosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lin, Xu, Zhang, Qiu, Zhang, Hao, Li, Deng, Tian, Chen and Qian.)

Exotic high-rank multipolar order parameters have been found to be unexpectedly active in more and more correlated materials in recent years. Such multipoles are usually dubbed "hidden orders" since they are insensitive to common experimental probes. Theoretically, it is also difficult to predict multipolar orders via ab initio calculations in real materials. Here, we present an efficient method to predict possible multipoles in materials based on linear response theory under random phase approximation. Using this method, we successfully predict two pure metastable magnetic octupolar states in monolayer α-RuCl_{3}, which is confirmed by self-consistent unrestricted Hartree-Fock calculations. We then demonstrate that these octupolar states can be stabilized in monolayer α-RuI_{3}, one of which becomes the octupolar ground state. Furthermore, we also predict a fingerprint of an orthogonal magnetization pattern produced by the octupole moment that can be easily detected by experiment. The method and the example presented in this Letter serve as a guide for searching multipolar order parameters in other correlated materials.

Immunotherapy is currently an important adjuvant therapy for malignant tumors besides surgical treatment. However, the heterogeneity and low immunogenicity of the tumor are two main challenges of the immunotherapy. Here, we have constructed a nanoplatform (CP@mRBC-PpIX) to realize reversion of the tumor acidosis and hypoxia through alkali and oxygen generation triggered by tumor acidosis. By targeting tumor universal features other than endogenous biomarkers, it was found that CP@mRBC-PpIX could polarize tumor-associated macrophages to anti-tumor M1 phenotype macrophages to enhance tumor immune response. Furthermore, under regional light irradiation, the reactive oxygen species produced by photosensitizers located in CP@mRBC-PpIX could increase the immunogenicity of tumors, so that tumor changes from an immunosuppressive "cold tumor" to an immunogenic "hot tumor," thereby increasing the infiltration and response of T cells, further amplifying the effect of immunotherapy. This strategy circumvented the problem of tumor heterogeneity to realize a kind of broad-spectrum immunotherapy, which could effectively prevent tumor metastasis and recurrence.

It has been identified that arginine vasopressin (AVP), vasopressin receptor 2(V2R), and the aquaporin 2 (AQP2) signaling pathway in the inner ear play important roles in hearing and balance functions through regulating the endolymph equilibrium; however, the contributions of this signaling pathway to the development of motion sickness are unclear. The present study was designed to investigate whether the activation of the AVP-V2R-AQP2 signaling pathway in the inner ear is involved in the induction of motion sickness and whether mozavaptan, a V2R antagonist, could reduce motion sickness. We found that both rotatory stimulus and intraperitoneal AVP injection induced conditioned taste aversion (a confirmed behavioral index for motion sickness) in rats and activated the AVP-V2R-AQP2 signaling pathway with a responsive V2R downregulation in the inner ears, and AVP perfusion in cultured epithelial cells from rat endolymphatic sacs induced similar changes in this pathway signaling. Vestibular training, V2R antagonist mozavaptan, or PKA inhibitor H89 blunted these changes in the V2R-AQP2 pathway signaling while reducing rotatory stimulus- or DDAVP (a V2R agonist)-induced motion sickness in rats and dogs. Therefore, our results suggest that activation of the inner ear AVP-V2R-AQP2 signaling pathway is potentially involved in the development of motion sickness; thus, mozavaptan targeting AVP V2Rs in the inner ear may provide us with a new application option to reduce motion sickness. SIGNIFICANCE STATEMENT: Motion sickness affects many people traveling or working. In the present study our results showed that activation of the inner ear arginine vasopressin-vaspopressin receptor 2 (V2R)-aquaporin 2 signaling pathway was potentially involved in the development of motion sickness and that blocking V2R with mozavaptan, a V2R antagonist, was much more effective in reducing motion sickness in both rat and dog; therefore, we demonstrated a new mechanism to underlie motion sickness and a new candidate drug to reduce motion sickness., (Copyright © 2020 by The American Society for Pharmacology and Experimental Therapeutics.)

Microtubule actin cross-linking factor 1 (Macf1) is a spectraplakin family member known to regulate cytoskeletal dynamics, cell migration, neuronal growth and cell signal transduction. We previously demonstrated that knockdown of Macf1 inhibited the differentiation of MC3T3-E1 cell line. However, whether Macf1 could regulate bone formation in vivo is unclear. To study the function and mechanism of Macf1 in bone formation and osteogenic differentiation, we established osteoblast-specific Osterix (Osx) promoter-driven Macf1 conditional knockout mice (Macf1 f/f Osx-Cre). The Macf1 f/f Osx-Cre mice displayed delayed ossification and decreased bone mass. Morphological and mechanical studies showed deteriorated trabecular microarchitecture and impaired biomechanical strength of femur in Macf1 f/f Osx-Cre mice. In addition, the differentiation of primary osteoblasts isolated from calvaria was inhibited in Macf1 f/f Osx-Cre mice. Deficiency of Macf1 in primary osteoblasts inhibited the expression of osteogenic marker genes (Col1, Runx2 and Alp) and the number of mineralized nodules. Furthermore, deficiency of Macf1 attenuated Bmp2/Smad/Runx2 signalling in primary osteoblasts of Macf1 f/f Osx-Cre mice. Together, these results indicated that Macf1 plays a significant role in bone formation and osteoblast differentiation by regulating Bmp2/Smad/Runx2 pathway, suggesting that Macf1 might be a therapeutic target for bone disease., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Here, a protein farnesyltransferase (PFTase)-driven plasma membrane (PM)-targeted chimeric peptide, PpIX-C 6 -PEG 8 -KKKKKKSKTKC-OMe (PCPK), was designed for PM-targeted photodynamic therapy (PM-PDT) and enhanced immunotherapy via tumor cell PM damage and fast release of damage-associated molecular patterns (DAMPs). The PM targeting ability of PCPK originates from the cellular K-Ras signaling, which occurs exclusively to drive the corresponding proteins to PM by PFTase. With the conjugation of the photosensitizer protoporphyrin IX (PpIX), PCPK could generate cytotoxic reactive oxygen species to deactivate membrane-associated proteins, initiate lipid peroxidation, and destroy PM with an extremely low concentration (1 μM) under light irradiation. The specific PM damage further induced the fast release of DAMPs (high-mobility group box 1 and ATP), resulting in antitumor immune responses stronger than those of conventional cytoplasm-localized PDT. This immune-stimulating PM-PDT strategy also exhibited the inhibition effect for distant metastatic tumors when combined with programmed cell death receptor 1 blockade therapy.

The only treatment for cataract in clinic is the clouded lens removal combined with artificial lens implantation. In this study, nifedipine (NFP), a classic vasodilator, was loaded in a U.S. FDA-approved polymer PLA-PEG to form NFP-loaded PLA-PEG micelles as a novel eye drop to prevent oxidative cataract formation and progression at the early stage. The NFP-loaded PLA-PEG micelles not only showed satisfactory biocompatibility and bioavailability, but also efficiently improved the anticataract ability through the inhibition of extracellular calcium ions influx. This study may provide a new insight into the development of cataract treatment.

This paper reported on a two-photon excited nanocomposite FCRH to overcome tumor hypoxia for enhanced photodynamic therapy (PDT). Through modified by ruthenium (Ⅱ) complex (Ru(bpy) 3 2+ ) and hyperbranched conjugated copolymer with poly (ethylene glycol) arms (HOP), the water-splitting mediated O 2 generation can be triggered via two-photon irradiation from iron-doped carbon nitride (Fe-C 3 N 4 ) for the first time. While exposured to two-photon laser, Ru(bpy) 3 2+ was activated to generate singlet oxygen ( 1 O 2 ) and Fe-C 3 N 4 was triggered to split water for oxygen supply in the mean time. Owing to the injection of photoinduced electrons from excited Ru(bpy) 3 2+ to Fe-C 3 N 4 , O 2 generation by Fe-C 3 N 4 was significantly accelerated. After accumulation of the nanocomposite by enhanced permeability and retention (EPR) effect, FCRH was demonstrated to alleviate the tumorous hypoxia and consequently enhance the antitumor efficacy of PDT. Furthermore, tumor metabolism evaluations explained the capability of the nanocomposite in reducing intratumoral hypoxia. Our results provide a new diagram for ameliorating the hypoxic tumor microenvironment and accelerating 1 O 2 generation under two-photon excitation, which will find great potential for spatiotemporally controlled tumor treatment in vivo., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Chemotherapy is well recognized to induce immune responses during some chemotherapeutic drugs-mediated tumor eradication. Here, a strategy involving blocking programmed cell death protein 1 (PD-1) to enhance the chemotherapeutic effect of a doxorubicin nanoprodrug HA-Psi-DOX is proposed and the synergetic mechanism between them is further studied. The nanoprodrugs are fabricated by conjugating doxorubicin (DOX) to an anionic polymer hyaluronic acid (HA) via a tumor overexpressed matrix metalloproteinase sensitive peptide (CPLGLAGG) for tumor targeting and enzyme-activated drug release. Once accumulated at the tumor site, the nanoprodrug can be activated to release antitumor drug by tumor overexpressed MMP-2. It is found that HA-Psi-DOX nanoparticles can kill tumor cells effectively and initiate an antitumor immune response, leading to the upregulation of interferon-γ. This cytokine promotes the expression of programmed cell death protein-ligand 1 (PD-L1) on tumor cells, which will cause immunosuppression after interacting with PD-1 on the surface of lymphocytes. The results suggest that the therapeutic efficiency of HA-Psi-DOX nanoparticles is significantly improved when combined with checkpoint inhibitors anti-PD-1 antibody (α-PD1) due to the neutralization of immunosuppression by blocking the interaction between PD-L1 and PD-1. This therapeutic system by combining chemotherapy and immunotherapy further increases the link between conventional tumor therapies and immunotherapy., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Here, a tumor-targeted MnO 2 motor nanosystem (designed as MG/HA) was constructed by the assembly of glucose oxidase (GOD), manganese dioxide (MnO 2 ), and glycoprotein CD44-targeting polymer hyaluronic acid (HA) to elevate cancer-starving therapy efficacy in solid tumor. Upon the specific uptake of MG/HA by CD44 overexpressed cancer cells, GOD catalyzed the oxidation of glucose into gluconic acid and hydrogen peroxide (H 2 O 2 ) accompanying the consumption of oxygen (O 2 ). Meanwhile, MnO 2 would react with H 2 O 2 and acid to generate O 2 , which is in turn supplied to the glucose-depletion process, running like a loop. As a result, MnO 2 is displayed as a motor to promote the rate of glucose depletion that contributed to the starving therapy. In contrast to G/HA, MG/HA could not only achieve effective glucose consumption to depress cancer progression, but also alleviate hypoxia and reduce the expression of Glut1 to inhibit the metabolism for further restraining the tumor aggressiveness and metastasis. The concept of MnO 2 motor shows a promising prospect to overcome the restriction of the starving therapy.

Many viruses have a lipid envelope derived from the host cell membrane that contributes much to the host specificity and the cellular invasion. This study puts forward a virus-inspired technology that allows targeted genetic delivery free from man-made materials. Genetic therapeutics, metal ions, and biologically derived cell membranes are nanointegrated. Vulnerable genetic therapeutics contained in the formed "nanogene" can be well protected from unwanted attacks by blood components and enzymes. The surface envelope composed of cancer cell membrane fragments enables host-specific targeting of the nanogene to the source cancer cells and homologous tumors while effectively inhibiting recognition by macrophages. High transfection efficiency highlights the potential of this technology for practical applications. Another unique merit of this technology arises from the facile combination of special biofunction of metal ions with genetic therapy. Typically, Gd(III)-involved nanogene generates a much higher T 1 relaxation rate than the clinically used Gd magnetic resonance imaging agent and harvests the enhanced MRI contrast at tumors. This virus-inspired technology points out a distinctive new avenue for the disease-specific transport of genetic therapeutics and other biomacromolecules., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Nowadays, cell membrane targeting therapy has drawn much attention for its high anti-tumor effect by avoiding the cellular barriers. In this study, therapeutic agent conjugated chimeric peptide (Cp) was anchored in cracked cancer cell membranes (CCCM) to construct a self-delivery membrane system (M-Cp), which could relize precise cell membrane targeting therapy. It was found that compared with Cp, M-Cp could target to the cancer cell membrane with longer retention time, which is very crucial for in vivo applications. And the superior cell membrane targeting ability was attributed to the specific proteins (focal adhesion proteins, focal adhesion kinase, RHO family proteins, and integrin) on the CCCM surface. Importantly, the M-Cp could promote tumor-specific immune response, which further enhanced anti-tumor effect when combined with therapeutic agents in M-Cp. What's more, this self-delivery membrane system could be used as a template for cell membrane targeting therapy by changing the therapeutic agents as well as the CCCM, and this strategy would open a new window for various cell membrane targeting therapy., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Multidrug resistance (MDR) remains one of the biggest obstacles in chemotherapy of tumor mainly due to P-glycoprotein (P-gp)-mediated drug efflux. Here, a transformable chimeric peptide is designed to target and self-assemble on cell membrane for encapsulating cells and overcoming tumor MDR. This chimeric peptide (C 16 -K(TPE)-GGGH-GFLGK-PEG 8 , denoted as CTGP) with cathepsin B-responsive and cell membrane-targeting abilities can self-assemble into nanomicelles and further encapsulate the therapeutic agent doxorubicin (termed as CTGP@DOX). After the cleavage of the Gly-Phe-Leu-Gly (GFLG) sequence by pericellular overexpressed cathepsin B, CTGP@DOX is dissociated and transformed from spherical nanoparticles to nanofibers due to the hydrophilic-hydrophobic conversion and hydrogen bonding interactions. Thus obtained nanofibers with cell membrane-targeting 16-carbon alkyl chains can adhere firmly to the cell membrane for cell encapsulation and restricting DOX efflux. In comparison to free DOX, 45-time higher drug retention and 49-fold greater anti-MDR ability of CTGP@DOX to drug-resistant MCF-7R cells are achieved. This novel strategy to encapsulate cells and reverse tumor MDR via morphology transformation would open a new avenue towards chemotherapy of tumor., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In this report, a biomimetic theranostic oxygen (O 2 )-meter (cancer cell membrane@Pt(II) porphyrinic-metal organic framework, designated as mPPt) was constructed for cancer targeted and phosphorescence image-guided photodynamic therapy (PDT). mPPt presents high photosensitizers (PSs) loading and evitable self-quenching behaviors for favorable biological O 2 sensing and PDT. Besides, endowed by the surface functionalization of cancer cell membrane, the homotypic targeting and immune escape abilities of mPPt could dramatically enhance its cancer targeting ability. Importantly, the O 2 -dependent phosphorescence responsibility of mPPt could be employed to pre-evaluate the real time O 2 level in situ and guide the PDT under light irradiation. A significant anticancer effect is observed after intravenous injection of mPPt and subsequent treatment with PDT with no obvious side effects. As a versatile platform for cell imaging, O 2 fluctuation monitoring as well as PDT, this biomimetic O 2 -meter exhibits great potential for biological analysis and personalized cancer theranostics., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

A facile and targeted gene delivery system was prepared by conjugating β-cyclodextrin modified polyethylenimine (PEI-CD) and adamantyl peptide (AdGRGDS) based on host-guest interaction. With the rational design between PEI-CD and AdGRGDS, the PEI-CD/AdGRGDS gene delivery system showed excellent DNA binding capability and exhibited good ability to compact DNA into uniform spherical nanoparticles. In vitro luciferase assay showed that gene expression transfected by PEI-CD/AdGRGDS was stronger than that by PEI-CD in HeLa cells, whereas gene expression transfected by PEI-CD/AdGRGDS and PEI-CD was similar to each other in COS7 cells. Internalization of complexes was qualitatively studied using a confocal laser scanning microscope (CLSM) and quantitatively analyzed by flow cytometry, respectively, and targeting specificity was also evaluated by CLSM. Results of CLSM and flow cytometry indicated that PEI-CD/AdGRGDS had good targeting specificity to tumor cells with integrin αvβ3 overexpression. To further evaluate the targeting specificity and transfection efficiency in vivo, a rat model with murine hepatic carcinoma cell line H22 was used. PEI-CD/AdGRGDS showed stronger gene expression efficiency than PEI-CD via in vivo transfection of pORF-LacZ and pGL-3 plasmids after subcutaneous injection. Interestingly, PEI-CD/AdGRGDS also showed high targeting specificity and transfection distribution to tumor xenograft after tail-vein injection. In vitro and in vivo assays highlighted the importance of GRGDS targeting specificity to tumor cells with integrin αvβ3 overexpression and demonstrated that the PEI-CD/AdGRGDS gene delivery system would have great potential for targeted tumor therapy.

In recent decades, diverse drug delivery systems (DDS) constructed by self-assembly of dendritic peptides have shown advantages and improvable potential for cancer treatment. Here, an arginine-enriched dendritic amphiphilic chimeric peptide CRRK(RRCG(Fmoc)) 2 containing multiple thiol groups is programmed to form drug-loaded nano-micelles by self-assembly. With a rational design, the branched hydrophobic groups (Fmoc) of the peptides provide a strong hydrophobic force to prevent the drug from premature release, and the reduction-sensitive disulfide linkages formed between contiguous peptides can control drug release under reducing stimulation. As expected, specific to multidrug resistance (MDR) tumor cells, the arginine-enriched peptide/drug (PD) nano-micelles show accurate nuclear localization ability to prevent the drug being pumped by P-glycoprotein (P-gp) in vitro, as well as exhibiting satisfactory efficacy for MDR tumor treatment in vivo. This design successfully realizes stimuli-responsive drug release aimed at MDR tumor cells via an ingenious sequence arrangement., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Modulating tumor microenvironment to amplify the therapeutic efficiency would be a novel strategy for effective cancer treatment. In this work, based on the TPZ-loaded porphyrinic metal organic framework PCN-224 (PCN stands for porous coordination network), a cancer cell membrane-coated nanoplatform (TPZ@PCN@Mem) was fabricated for tumor targeted PDT and the successively resulting hypoxia-amplified bioreductive therapy. After administration, TPZ@PCN@Mem exhibited the selective accumulation and long-term retention at tumor tissue due to the immune escape and homologous targeting endowed by the cancer membrane coating. Upon light irradiation, PCN-224-mediated toxic reactive oxygen species (ROS) were generated for PDT, and the resulting local hypoxia microenvironment would further accelerate the activation of TPZ for enhanced chemotherapy in 4T1 orthotopic tumor. The cascade synergistic therapeutic effects of TPZ@PCN@Mem could significantly suppress the primary tumor growth, and also inhibit its distal metastasis with minimal side effects. The study indicated an overwhelming superiority of utilizing this bioinspired strategy for tumor targeted PDT and hypoxia-activated bioreductive therapy, which provided a new insight for precise and effective tumor treatment., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Tumor hypoxia severely limits the efficacy of traditional photodynamic therapy (PDT). Here, a liposome-based nanoparticle (designated as LipoMB/CaO 2 ) with O 2 self-sufficient property for dual-stage light-driven PDT is demonstrated to address this problem. Through a short time irradiation, 1 O 2 activated by the photosensitizer methylene blue (MB) can induce lipid peroxidation to break the liposome, and enlarge the contact area of CaO 2 with H 2 O, resulting in accelerated O 2 production. Accelerated O 2 level further regulates hypoxic tumor microenvironment and in turn improves 1 O 2 generation by MB under another long time irradiation. In vitro and in vivo experiments also demonstrate the superior competence of LipoMB/CaO 2 to alleviate tumor hypoxia, suppress tumor growth and antitumor metastasis with low side-effect. The O 2 self-sufficient LipoMB/CaO 2 nanoplatform with dual-stage light manipulation is a successful attempt for PDT against hypoxic tumor., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Electron ptychography has seen a recent surge of interest for phase sensitive imaging at atomic or near-atomic resolution. However, applications are so far mainly limited to radiation-hard samples, because the required doses are too high for imaging biological samples at high resolution. We propose the use of non-convex Bayesian optimization to overcome this problem, and show via numerical simulations that the dose required for successful reconstruction can be reduced by two orders of magnitude compared to previous experiments. As an important application we suggest to use this method for imaging single biological macromolecules at cryogenic temperatures and demonstrate 2D single-particle reconstructions from simulated data with a resolution up to 5.4 Å at a dose of 20e - /Å 2 . When averaging over only 30 low-dose datasets, a 2D resolution around 3.5 Å is possible for macromolecular complexes even below 100 kDa. With its independence from the microscope transfer function, direct recovery of phase contrast, and better scaling of signal-to-noise ratio, low-dose cryo electron ptychography may become a promising alternative to Zernike phase-contrast microscopy.

Selectively cuting off the nutrient supply and the metabolism pathways of cancer cells would be a promising approach to improve the efficiency of cancer treatment. Here, a cancer targeted cascade bioreactor (designated as mCGP) was constructed for synergistic starvation and photodynamic therapy (PDT) by embedding glucose oxidase (GOx) and catalase in the cancer cell membrane-camouflaged porphyrin metal-organic framework (MOF) of PCN-224 (PCN stands for porous coordination network). Due to biomimetic surface functionalization, the immune escape and homotypic targeting behaviors of mCGP would dramatically enhance its cancer targeting and retention abilities. Once internalized by cancer cells, mCGP was found to promote microenvironmental oxygenation by catalyzing the endogenous hydrogen peroxide (H 2 O 2 ) to produce oxygen (O 2 ), which would subsequently accelerate the decomposition of intracellular glucose and enhance the production of cytotoxic singlet oxygen ( 1 O 2 ) under light irradiation. Consequently, mCGP displayed amplified synergistic therapeutic effects of long-term cancer starvation therapy and robust PDT, which would efficiently inhibit the cancer growth after a single administration. This cascade bioreactor would further facilitate the development of complementary modes for spatiotemporally controlled cancer treatment.

The nanoplatform GNR-ACPP-PpIX (designated as GNR-ACPI) is designed for dual image guided combined activatable photodynamic therapy (PDT) and photothermal therapy (PTT). In GNR-ACPI, gold nanorods (GNRs) are modified with a protoporphyrin (PpIX, a PDT agent) conjugated activatable cell penetrating peptide (ACPP), which consists of the matrix metalloproteinases-2 (MMP-2) sensitive peptide sequence GPLGLAG. First, the photoactivity of PpIX is effectively quenched by GNRs due to the strong near infrared region light absorption of GNR and the special "U type" structure of ACPP induced close contact between PpIX and GNR. However, once arriving at the tumor site, the GPLGLAG sequence is hydrolyzed by the MMP-2 overexpressed by tumor cells, resulting in the release of the residual cell membrane penetrating peptide (CPP) attached PpIX (CPP-PpIX) with the recovery of photoactivity of PpIX. In addition, with the help of CPP, more efficient cellular uptake of PpIX by tumor cells can be achieved, which will greatly improve the PDT efficacy. Moreover, the GNR can also be utilized for photothermic imaging as well as PTT for tumors. It is found that the combination of PTT and PDT under the guidance of dual-mode imaging greatly enhances the antitumor effects, while possessing negligible systematic toxicity., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In this study, we developed a general method to decorate plasmonic gold nanorods (GNRs) with a CD44-targeting functional polymer, containing a hyaluronic acid (HA)-targeting moiety and a small molecule Glut1 inhibitor of diclofenac (DC), to obtain GNR/HA-DC. This nanosystem exhibited the superiority of selectively sensitizing tumor cells for photothermal therapy (PTT) by inhibiting anaerobic glycolysis. Upon specifically targeting CD44, sequentially time-dependent DC release could be achieved by the trigger of hyaluronidase (HAase), which abundantly existed in tumor tissues. The released DC depleted the Glut1 level in tumor cells and induced a cascade effect on cellular metabolism by inhibiting glucose uptake, blocking glycolysis, decreasing ATP levels, hampering heat shock protein (HSP) expression, and ultimately leaving malignant cells out from the protection of HSPs to stress (e.g., heat), and then tumor cells were more easy to kill. Owing to the sensitization effect of GNR/HA-DC, CD44 overexpressed tumor cells could be significantly damaged by PTT with an enhanced therapeutic efficiency in vitro and in vivo.

Supramolecular photosensitizers (supraPSs) have emerged as effective photodynamic therapy (PDT) agents. Here, we propose the assembling capacity of supraPSs as a new strategy to construct theranostic nanoplatform with versatile functions aming at high-performance tumor therapy. By coating tirapazamine (TPZ)-loaded mesoporous silica nanoparticles (MSNs) with layer-by-layer (LbL) assembled multilayer, the versatile nanoplatform (TPZ@MCMSN-Gd 3+ ) was obtained with the formation of supraPSs via host-guest interaction and the chelation with paramagnetic Gd 3+ . The TPZ@MCMSN-Gd 3+ could be specifically uptaken by CD44 receptor overexpressed tumor cells and respond to hyaluronidase (HAase) to trigger the release of therapeutics. As confirmed by in vivo studies, TPZ@MCMSN-Gd 3+ showed preferential accumulation in tumor site and significantly inhibited the tumor progression by the collaboration of PDT and bioreductive chemotherapy under NIR fluorescence/MR imaging guidance. Taken together, this supraPSs based strategy paves a new paradigm of the way for the construction of theranostic nanoplatform., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

In this work, mitochondria-targeting gold nanostar (AuNS) and anticarcinogen DOX were co-encapsulated in hyaluronic acid (HA) protective shell for tumor-targeting synergistic photothermal/chemo-therapy. Cationic peptide R 8 and mitochondria-targeting pro-apoptotic peptide TPP-KLA were co-decorated on AuNS to form AuNS-pep via Au-S bonds. Then, electronegative HA was further coated on the surface via electrostatic interaction for cancer cell targeting. During the coating process, DOX was also introduced via electrostatic interaction to obtain a versatile nanoplatform AuNS-pep/DOX@HA. It was found that the nanoplatform could be internalized into tumor cells via CD44 receptor-mediated recognition. Followed digestion by hyaluronidase (HAase), the therapeutic nanoplatform was able to release DOX for chemotherapy and mitochondria-targeting nanoheater AuNS-pep for near infrared (NIR) light triggered subcellular photothermal therapy (PTT). This tumor-targeting nanoplatform AuNS-pep/DOX@HA displayed prominent non-resistant or resistant tumor inhibition both in vitro and in vivo., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Feedback imaging-guided precise photodynamic therapy (PDT) can facilitate the development of personalized medicine. In this work, a Förster resonance energy transfer (FRET) based theranostic probe was fabricated for simultaneous tumor targeting PDT and ratiometric imaging of the therapeutic effect. The theranostic probe (designated as P-PpIX) was comprised of a targeting moiety, a caspase-3 responsive linker, a FRET fluorophore pair and a photosensitizer. It was found that P-PpIX exhibited low intrinsic background fluorescence due to the high FRET quenching efficiency. The Arg-Gly-Asp (RGD) targeting moiety allowed P-PpIX to selectively accumulate in αvβ3 integrin overexpressed tumor cells. Upon photo irradiation, the PDT effect of P-PpIX could induce cell death with apoptosis related mechanism, and the activated caspase-3 would subsequently cleave the Asp-Glu-Val-Asp (DEVD) peptide sequence to terminate the intramolecular FRET process. The activated caspase-3 expression and the real time therapeutic efficacy could be precisely assessed in situ by the fluorescence intensity ratio of the released 5(6)-carboxylfluorescein (FAM, reporter fluorescence) and protoporphyrin IX (PpIX, internal reference fluorescence). This novel ratiometric theranostic probe could provide the real-time feedback for precise PDT., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The ultimate goal in cancer therapy and diagnosis is to achieve highly specific targeting to cancer cells. Coated with the source cancer cell membrane specifically derived from the homologous tumors, the nanoparticles are identified with the self-recognition internalization by the source cancer cell lines in vitro and the highly tumor-selective targeting "homing" to the homologous tumor in vivo even in the competition of another heterologous tumor. As the result, MNP@DOX@CCCM nanovehicle showed strong potency for tumor treatment in vivo and the MR imaging. This bioinspired strategy shows great potential for precise therapy/diagnosis of various tumors merely by adjusting the cell membrane source accordingly on the nanoparticle surface.

In this work, a matrix metalloproteinase (MMP)-triggered tumor targeted mesoporous silica nanoparticle (MSN) is designed to realize near-infrared (NIR) photothermal-responsive drug release and combined chemo/photothermal tumor therapy. Indocyanine green (ICG) and doxorubicin (DOX) are both loaded in the MSN modified with thermal-cleavable gatekeeper (Azo-CD), which can be decapped by ICG-generated hyperthermia under NIR illumination. A peptidic sequence containing a short PEG chain, matrix metalloproteinase (MMP) substrate (PLGVR) and tumor cell targeting motif (RGD) are further decorated on the MSN via a host-guest interaction. The PEG chain can protect the MSN during the circulation and be cleaved off in the tumor tissues with overexpressed MMP, and then the RGD motif is switched on to target tumor cells. After the tumor-triggered targeting process, the NIR irradiation guided by ICG fluorescence can trigger cytosol drug release and realize combined chemo/photothermal therapy., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Recently, a new kind of artificial two dimensional (2D) electron lattice on the nanoscale, i.e. molecular graphene, has drawn a lot of interest, where the metal surface electrons are transformed into a honeycomb lattice via absorbing a molecular lattice on the metal surface [Gomes et al., Nature, 2012, 438, 306; Wang et al., Phys. Rev. Lett., 2014, 113, 196803]. In this work, we theoretically demonstrate that this technique can be readily used to build other complex 2D electron lattices on a metal surface, which are of high interest in the field of condensed matter physics. The main challenge to build a complex 2D electron lattice is that this is a quantum antidot system, where the absorbed molecule normally exerts a repulsive potential on the surface electrons. Thus, there is no straightforward corresponding relation between the molecular lattice pattern and the desired 2D lattice of surface electrons. Here, we give an interesting example about the Kagome lattice, which has exotic correlated electronic states. We design a special molecular pattern and show that this molecular lattice can transform the surface electrons into a Kagome-like lattice. The numerical simulation is conducted using a Cu(111) surface and CO molecules. We first estimate the effective parameters of the Cu/CO system by fitting experimental data of the molecular graphene. Then, we calculate the corresponding energy bands and LDOS of the surface electrons in the presence of the proposed molecular lattice. Finally, we interpret the numerical results by the tight binding model of the Kagome lattice. We hope that our work can stimulate further theoretical and experimental interest in this novel artificial 2D electron lattice system.

In this work, a ZnO based nanococktail with programmed functions is designed and synthesized for self-synergistic tumor targeting therapy. The nanococktail can actively target tumors via specific interaction of hyaluronic acid (HA) with CD44 receptors and respond to HAase-rich tumor microenvironment to induce intracellular cascade reaction for controlled therapy. The exposed cell-penetrating peptide (R8) potentiates the cellular uptake of therapeutic nanoparticles into targeted tumor cells. Then ZnO cocktail will readily degrade in acidic endo/lysosomes and induce the production of desired reactive oxygen species (ROS) in situ. The destructive ROS not only leads to serious cell damage but also triggers the on-demand drug release for precise chemotherapy, thus achieving enhanced antitumor efficiency synergistically. After tail vein injection of ZnO cocktail, a favorable tumor apoptosis rate (71.2 ± 8.2%) is detected, which is significantly superior to that of free drug, doxorubicin (12.9 ± 5.2%). Both in vitro and in vivo studies demonstrate that the tailor-made ZnO cocktail with favorable biocompatibility, promising tumor specificity, and self-synergistically therapeutic capacity opens new avenues for cancer therapy., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In this paper, a multifunctional theranostic magnetic mesoporous silica nanoparticle (MMSN) with magnetic core was developed for magnetic-enhanced tumor-targeted MR imaging and precise therapy. The gatekeeper β-cyclodextrin (β-CD) was immobilized on the surface of mesoporous silica shell via platinum(IV) prodrug linking for reduction-triggered intracellular drug release. Then Arg-Gly-Asp (RGD) peptide ligand was further introduced onto the gatekeeper β-CD via host-guest interaction for cancer targeting purpose. After active-targeting endocytosis by cancer cells, platinum(IV) prodrug in MMSNs would be restored to active platinum(II) drug in response to the innative reducing microenvironment in cancer cells, resulting in the detachment of β-CD gatekeeper and thus simultaneously triggering the in situ release of anticancer drug doxorubicin (DOX) entrapped in the MMSNs to kill cancer cells. It was found that with the aid of an external magnetic field, drug loaded MMSNs showed high contrast in MR imaging in vivo and exhibited magnetically enhanced accumulation in the cancer site, leading to significant inhibition of cancer growth with minimal side effects. This multifunctional MMSN will find great potential as a theranostic nanoplatform for cancer treatment., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

In this paper, we aimed to develop a conjugate of matrix metalloproteinases-2 (MMP-2)-sensitive activable cell-penetrating peptide (R9GPLGLAGE8, ACPP) with protoporphyrin (PpIX) for tumor-targeting photodynamic therapy. In normal tissue, the cell-penetrating function of polycationic CPP (R9) would be blocked by a polyanionic peptide (E8) through intramolecular electrostatic attraction. Once exposed to MMP-2 existing at the tumor site, proteolysis of the oligopeptide linker (GPLGLAG) between the CPP and the polyanionic peptide would dissociate the inhibitory polyanions and release CPP-PpIX for photodynamic therapy (PDT). It was found that after tail vein injection the ACPP-PpIX conjugate could accumulate effectively at the tumor site with the fluorescence enhancement which was beneficial for tumor diagnosis and image-guided PDT. After further administration with irradiation, both the solid tumor size and weight had a significant suppression (reduced by more than 90%) with a low systemic toxicity. This ACPP-PpIX conjugate delivery system activated by MMP-2 would be a promising strategy for tumor-targeted treatment.

Magnetite (Fe 3 O 4 ) microcapsules prepared by layer-by-layer self-assembly are investigated as multi-functional magnetic resonance imaging contrast agents and drug carriers. They are produced by host-guest interactions and Coulombic force from different supramolecular polymers. Drug molecules are released controllably from the microcapsules by non-invasive ultra-violet light induced photo-isomerization of the azobenzene molecule and pH sensitive Schiff's base. In addition, by encapsulation of the superparamagnetic iron oxide nanoparticles (SPION) in the nearby layers, magnetic field targeting and MRI contrast are achieved. Under tumor-like acidic conditions (pH = 5.6), the r2 relaxivity of the microcapsules is 126 mM -1 s -1 which is 37% higher than that in a neutral environment (92 mM -1 s -1 ). As a result of the low pH enhanced MRI contrast agent, the tumor structure can be observed clearly in vivo confirming the high efficacy as a negative MRI agent in T2-weighted imaging. The materials as combined carriers have great potential in clinical applications as drug delivery agents and contrast agents in MRI.

In this paper, adamantane (Ad) substituted reduction-sensitive polyethylenimine (Ad- b -SS-PEI 600 ) was used as cationic polymer gene vector for DNA loading. And then the α,β CD dimers were applied as the bridges between the Ad- b -SS-PEI 600 /DNA polyplexes and the functional moieties, i.e. targeting moiety and fluorescent probe through effective host-guest interactions. Located in the surface of the assemblies, the postdecorated functional moieties can efficiently exert their own function. It was found that gene delivery platforms thus obtained exhibited promising DNA compaction capability, rapid stimuli responsiveness, and good biocompatibility, and moreover they can mediate efficient gene transfection, targeting, and imaging both in vitro and in vivo .

Nanomaterials that integrate diagnostic and therapeutic functions within a single nanoplatform promise great advances in revolutionizing cancer therapy. A smart multifunctional theranostic drug-delivery system (DDS) based on gold nanorods (abbreviated as GNR/TSDOX) is designed for cancer-targeted imaging and imaging-guided therapy. In this intelligent theranostic DDS, the active targeting ligand biotin is introduced to track cancer sites in vivo. With the aid of photothermal/photoacoustic imaging, GNR/TSDOX can ablate cancer specifically and effectively. When stimulated with a single near-infrared (NIR) light source, this NIR light energy is effectively absorbed and converted into heat by GNR/TSDOX for localized photothermal therapy and the increase in temperature also further triggers the cascaded release of the anticancer drug for combined thermo-chemotherapy. More importantly, the in vivo cure effect can be well guided by regulating the irradiation time and intensity of the NIR light., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A novel dual-FRET-based fluorescence probe was designed and synthesized for the sequential detection of MMP-2 and caspase-3. This probe can successfully monitor Dox- and UV-induced cell apoptosis signals in real time and in situ, which demonstrated its great potential for apoptosis-related drug screening and dynamic apoptosis imaging.

In this paper, an activable cell-penetrating peptide (CR8G3PK6, ACPP) with a shielding group of 2,3-dimethylmaleic anhydride (DMA) was conjugated with antitumor drug doxorubicin (DOX) to construct a novel prodrug (DOX-ACPP-DMA) for tumor targeted drug delivery. The shielding group of DMA linked to the primary amines of K6 through the amide bond was used to block the cell-penetrating function of the polycationic CPP (R8) through intramolecular electrostatic attraction at physiological pH 7.4. At tumor extracellular pH 6.8, the hydrolysis of DMA led to charge reversal, activating the pristine function of CPP for improved cellular uptake by tumor cells. Confocal laser scanning microscopy (CLSM) and flow cytometry studies revealed that the cellular uptake of DOX-ACPP-DMA was significantly enhanced after acid-triggered activation in both HeLa and COS7 cells. After cell internalization, the overexpressed intracellular proteases would further trigger drug release in cells. Both in vitro and in vivo investigations showed that the peptidic prodrug exhibited significant tumor growth inhibition and demonstrated great potential for tumor therapy.

The present study reported a lysosome-acidity-targeting bio-responsive nanovehicle self-assembled from dextran (Dex) and phenylboronic acid modified cholesterol (Chol-PBA), aiming at the nucleus-tropic drug delivery. The prominent advantage of this assembled nanoconstruction arose from its susceptibility to acidity-labile dissociation concurrently accompanied with the fast liberation of encapsulated drugs, leading to efficient nuclear drug translocation and consequently favorable drug efficacy. By elaborately exploiting NH4Cl pretreatment to interfere with the cellular endosomal acidification progression, this study clearly evidenced at a cellular level the strong lysosomal-acidity dependency of nuclear drug uptake efficiency, which was shown to be the main factor influencing the drug efficacy. The boronate-linked nanoassembly displayed nearly no cytotoxicity and can remain structural stability under the simulated physiological conditions including 10% serum and the normal blood sugar concentration. The cellular exposure to cholesterol was found to bate the cellular uptake of nanoassembly in a dose-dependent manner, suggesting a cholesterol-associated mechanism of the intracellular internalization. The in vivo antitumor assessment in xenograft mouse models revealed the significant superiority of DOX-loaded Dex/Chol-PBA nanoassembly over the controls including free DOX and the DOX-loaded non-sensitive Dex-Chol, as reflected by the more effective tumor-growth inhibition and the better systematic safety. In terms of the convenient preparation, sensitive response to lysosomal acidity and efficient nuclear drug translocation, Dex/Chol-PBA nanoassembly derived from natural materials shows promising potentials as the nanovehicle for nucleus-tropic drug delivery especially for antitumor agents. More attractively, this study offers a deeper insight into the mechanism concerning the contribution of acidity-responsive delivery to the enhanced chemotherapy performance., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

A novel cancer targeting and pH-responsive prodrug was successfully designed and synthesized. This M-prodrug was demonstrated to have real-time drug release monitoring capability based on the concept of contact-mediated quenching between doxorubicin and a coumarin derivative.

A steady state Level III fate model was established and applied to quantify source-receptor relationship in a coking industry city in Northern China. The local emission inventory of PAHs, as the model input, was acquired based on energy consumption and emission factors. The model estimations were validated by measured data and indicated remarkable variations in the paired isomeric ratios. When a rectification factor, based on the receptor-to-source ratio, was calculated by the fate model, the quantitatively verified molecular diagnostic ratios provided reasonable results of local PAH emission sources. Due to the local ban and measures on small scale coking activities implemented from the beginning of 2004, the model calculations indicated that the local emission amount of PAHs in 2009 decreased considerably compared to that in 2003., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Based on the recent monitoring results, the concentration and distribution of persistent toxic substances in the benthic mussels from the coastal areas of Bohai Sea and North Yellow Sea were determined. The results indicated that, at over 36% of the total sampling sites, the tissue concentrations of petroleum hydrocarbons were higher than the Category I value (15 microg/g, wet weight) of the national marine biological quality standards, especially at the sites near Dalian Bay and Xincun in Hebei Province, the tissue concentrations even exceeded the Category III level (80 microg/g, wet weight). Moreover, higher tissue concentration of PHCs (over the Category I level) during recent years remained in the most monitoring sea areas. At minor sites (mariculture zone in Yantai and Laizhou Bay), the tissue concentrations of As and Pb were relatively higher, and the high levels of Cd (above the Category II value of 2000 ng/g, wet weight) and Hg (above the Category II value of 100 ng/g, wet weight) in mussel bodies presented at several sites situated in coastal areas near Dalian Bay and Xincun of Hebei Province. Additionally, at the sampling sites near Liaodong Bay and Shandong Peninsula, the tissue concentration of Hg showed an annual increase during recent years. At all the monitoring sites, the tissue concentrations of PCBs and HCHs were usually low, while as the case of Hg, the tissue concentrations of PCBs and HCHs in Liaodong Bay increased gradually in these years. The new monitoring results indicated that, most sites with DDTs levels in benthic mussels higher than the Category I value (10 ng/g, wet weight) were located in the coastal areas of Hebei Province belonged to Bohai Bay (such as Zhaojiapu and Xincun). The continuous monitoring in these sea areas demonstrated that, in addition to the historical residues, there may be some fresh input sources of DDT nearby. Consequently, in the neighboring sea areas of Dalian Bay and Xincun, the tissue concentrations of PHCs, Cd and Hg were fairly high (all over their Category II values), and these sea areas could be of relatively stronger potential ecological risk. In view of the gradual increases in tissue concentrations (e. g., Hg, PCBs and HCHs) during the recent years, the coastal areas, for example, of Liaodong Bay and Shandong Peninsula should be addressed with sufficient concern.

Emission properties of polycyclic aromatic hydrocarbons (PAHs) from combustion of six residential coals in North China were investigated. The results indicated that, the total emission factors (EFs) for 15 PAH species in gaseous and particulate phases ranged from 52.8 to 1434.8 mg/kg with a decreasing sequence of local bituminous coals and anthracite coals, and honeycomb briquettes were largely dependent on the raw coals used to produce them. Particulate phase, dominated by median or high molecular weight components, made a major contribution (68.8%-76.5%) to the total EFs for bituminous coals, while gaseous phase with principal low molecular weight species accounted for most (86.3%-97.9%) of the total EFs for anthracite coals. The phase partitioning of PAH emission for honeycomb briquettes was similarly dependent on the crude coals. The total EFs, phase partitioning and component profiles of emitted PAHs were mainly influenced by the inner components of the studied coals. Burning mode and flue number on household coal-stoves also affected the emission characteristics by means of the oxygen supply. A sum of seven carcinogenic PAHs, benzo(a)pyrene(BaP)-equivalent carcinogenic power and total toxicity potency expressed in 2,3,7,8-tetrachlorodibenzo-dioxin(TCDD) toxic equivalence exhibited that bituminous coals and produced honeycomb briquettes had remarkably elevated values. Fluoranthene, benzo(b)fluoranthene, benzo(k)fluoranthene, chrysene and indeno(1,2,3-cd)pyrene from anthracite coals showed higher levels of BaP-based toxic equivalent factor, though the other toxicity indices were rather low for this type of coal.

A passive air sampler was developed for collecting polycyclic aromatic hydrocarbons (PAHs) in air mass from various directions. The airflow velocity within the sampler was assessed for its responses to ambient wind speed and direction. The sampler was examined for trapped particles, evaluated quantitatively for influence of airflow velocity and temperature on PAH uptake, examined for PAH uptake kinetics, calibrated against active sampling, and finally tested in the field. The airflow volume passing the sampler was linearly proportional to ambient wind speed and sensitive to wind direction. The uptake rate for an individual PAH was a function of airflow velocity, temperature and the octanol-air partitioning coefficient of the PAH. For all PAHs with more than two rings, the passive sampler operated in a linear uptake phase for three weeks. Different PAH concentrations were obtained in air masses from different directions in the field test.

Seven gaseous polycyclic aromatic hydrocarbons (PAHs) were determined in the indoor air of 38 folk houses in Beijing during the heating and non-heating seasons, by the passive air samplers. The total average concentration of the gaseous PAHs was around 100 ng/m3, and the dominant components were those with 2 or 3 rings. The inhalation exposure of PAHs by the residents was calculated based on the concentrations of PAHs acquired, average house-staying time and respiratory rates at different ages. The calculated results indicated that, the potential total exposure rates of the seven gaseous PAHs for the adults (including senior people) during the heating and non-heating periods were 66 ng/h and 58 ng/h, respectively; while those for juvenile people were 56 ng/h and 50 ng/h, respectively.

7 gas phase PAHs components in indoor air collected from 38 families were investigated by modified passive air samplers in Beijing areas during the local heating and non-heating seasons, and the influencing factors were discussed as well. The analytical results indicate that the gasous PAHs in local indoor air are dominated by 2 and 3 rings compounds, the mean concentrations for the 7 individual gaseous components range from 1 to 40 ng/m3, and the average concentration of total gaseous PAHs is about 100 ng/m3. There is no significant difference in total gaseous PAHs concentrations between the heating and the non-heating seasons, while some apparent seasonal changes occur in ACY and FLA concentrations. Compared with heating season, contribution of 2 rings compounds decreases while the proportions of 3 and 4 rings species increase during the non-heating season. Based on household activity questionnaires and actual analytical concentrations, the main influencing factors accounted for gaseous PAHs in indoor air, identified by multifactor analysis of variance, include cigarette smoking, use of moth ball, intensity of draft, cuisine frequency and built age.