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"Liu, Zhuang"
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Liangzhu culture : society, belief, and art in Neolithic China
\"Liangzhu culture (5,300-4,300 cal B.P.) represented the peak of prehistoric cultural and social development in the Yangtze Delta. Its centre is located near nowadays Hangzhou city and is considered one of the earliest urban centres in prehistoric China, called by archaeologists the Liangzhu Site Complex. Although it remains a mystery for many in the west, Liangzhu is well known in China for its fine jade crafting industry; its enormous, well-structured earthen compound and recently discovered hydraulic system; and its far-flung impact on contemporary and succeeding cultures. With six chapters contributed by frontline archaeologists, Liangzhu Culture contextualises Liangzhu in broad socioeconomic and cultural backgrounds and provides new, first-hand data to help explain the development and structure of this early urban centre. Among its many insights, the volume reveals how elites used jade as a means of acquiring social power, and how Liangzhu and its centre stand in comparison to other prehistoric urban centres in the world. This book, the first of its kind published in English language, will be a useful guide to students at all levels interested in material cultures and social structures in prehistoric China and beyond\"-- Provided by publisher.
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Programmable probiotics modulate inflammation and gut microbiota for inflammatory bowel disease treatment after effective oral delivery
Reactive oxygen species (ROS) play vital roles in intestinal inflammation. Therefore, eliminating ROS in the inflammatory site by antioxidant enzymes such as catalase and superoxide dismutase may effectively curb inflammatory bowel disease (IBD). Here,
Escherichia coli
Nissle 1917 (ECN), a kind of oral probiotic, was genetically engineered to overexpress catalase and superoxide dismutase (ECN-pE) for the treatment of intestinal inflammation. To improve the bioavailability of ECN-pE in the gastrointestinal tract, chitosan and sodium alginate, effective biofilms, were used to coat ECN-pE via a layer-by-layer electrostatic self-assembly strategy. In a mouse IBD model induced by different chemical drugs, chitosan/sodium alginate coating ECN-pE (ECN-pE(C/A)
2
) effectively relieved inflammation and repaired epithelial barriers in the colon. Unexpectedly, such engineered EcN-pE(C/A)
2
could also regulate the intestinal microbial communities and improve the abundance of
Lachnospiraceae
_NK4A136 and
Odoribacter
in the intestinal flora, which are important microbes to maintain intestinal homeostasis. Thus, this study lays a foundation for the development of living therapeutic proteins using probiotics to treat intestinal-related diseases.
Inflammatory bowel disease (IBD) is a complex disease that is associated with multiple genetic and environmental variables. Here the authors develop genetically engineered probiotics with selfproducing functional proteins and biofilm self-coating for safe and efficient IBD treatment in mice.
Journal Article
Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy
A therapeutic strategy that can eliminate primary tumours, inhibit metastases, and prevent tumour relapses is developed herein by combining adjuvant nanoparticle-based photothermal therapy with checkpoint-blockade immunotherapy. Indocyanine green (ICG), a photothermal agent, and imiquimod (R837), a Toll-like-receptor-7 agonist, are co-encapsulated by poly(lactic-co-glycolic) acid (PLGA). The formed PLGA-ICG-R837 nanoparticles composed purely by three clinically approved components can be used for near-infrared laser-triggered photothermal ablation of primary tumours, generating tumour-associated antigens, which in the presence of R837-containing nanoparticles as the adjuvant can show vaccine-like functions. In combination with the checkpoint-blockade using anti-cytotoxic T-lymphocyte antigen-4 (CTLA4), the generated immunological responses will be able to attack remaining tumour cells in mice, useful in metastasis inhibition, and may potentially be applicable for various types of tumour models. Furthermore, such strategy offers a strong immunological memory effect, which can provide protection against tumour rechallenging post elimination of their initial tumours.
Photothermal therapy can induce an anti-tumour immune response by producing tumour-associated antigens. Here, the authors design a nanoparticle that simultaneously acts as a photothermal agent and an immune-adjuvant and demonstrate the anti-tumour efficacy in combination with anti-CTLA4 therapy in preclinical murine cancer models.
Journal Article
A general strategy towards personalized nanovaccines based on fluoropolymers for post-surgical cancer immunotherapy
Cancer metastases and recurrence after surgical resection remain an important cause of treatment failure. Here we demonstrate a general strategy to fabricate personalized nanovaccines based on a cationic fluoropolymer for post-surgical cancer immunotherapy. Nanoparticles formed by mixing the fluoropolymer with a model antigen ovalbumin, induce dendritic cell maturation via the Toll-like receptor 4 (TLR4)-mediated signalling pathway, and promote antigen transportation into the cytosol of dendritic cells, which leads to an effective antigen cross-presentation. Such a nanovaccine inhibits established ovalbumin-expressing B16-OVA melanoma. More importantly, a mix of the fluoropolymer with cell membranes from resected autologous primary tumours synergizes with checkpoint blockade therapy to inhibit post-surgical tumour recurrence and metastases in two subcutaneous tumour models and an orthotopic breast cancer tumour. Furthermore, in the orthotopic tumour model, we observed a strong immune memory against tumour rechallenge. Our work offers a simple and general strategy for the preparation of personalized cancer vaccines to prevent post-operative cancer recurrence and metastasis.A fluoropolymer-based cancer nanovaccine that delivers antigens directly to the cytosol of dendritic cells and elicits strong antitumour immune responses inhibiting tumour growth in animal models can be used to produce personalized treatment for post-surgical immunotherapy.
Journal Article
Recent advances in the development of organic photothermal nano-agents
Recently, photothermal therapy （PTT） has attracted tremendous attention because of its high efficacy in tumor ablation and minimal damage to normal tissues. While many inorganic nanomaterials, especially various gold nanostructures and nanocarbons, have been extensively explored for near-infrared （NIR） light triggered PTT in the past decade, a variety of organic photothermal agents have also emerged in recent years, aiming at replacing their inorganic counterparts which usually are not biodegradable. In this mini-review, we will summarize several typical classes of recently developed NIR-absorbing organic PTT nano- agents, which include NIR dye-containing micelles, porphysomes, protein-based agents, conjugated polymers, and organic/inorganic nanocomposites. The development of imaging-guided PTT and combination therapy will be introduced as well. Finally, the perspectives and challenges in the future development of PTT will be discussed.
Journal Article
Water-stable porous Al24 Archimedean solids for removal of trace iodine
In this paper, we report a unique type of core-shell crystalline material that combines an inorganic zeolitic cage structure with a macrocyclic host arrangement and that can remove trace levels of iodine from water effectively. These unique assemblies are made up of an inorganic Archimedean truncatedhexahedron (
tcu
) polyhedron in the kernel which possesses six calixarene-like shell cavities. The cages have good adaptability to guests and can be assembled into a series of supramolecular structures in the crystalline state with different lattice pore shapes. Due to the unique core-shell porous structures, the compounds are not only stable in organic solvents but also in water. The characteristics of the cages enable rapid iodine capture from low concentration aqueous I
2
/KI solutions (down to 4 ppm concentration). We have studied the detailed process and mechanism of iodine capture and aggregation at the molecular level. The facile synthesis, considerable adsorption capacity, recyclability, and β- and γ-radiation resistance of the cages should make these materials suitable for the extraction of iodine from aqueous effluent streams (most obviously, radioactive iodide produced by atomic power generation).
The removal of radioactive elements is important to human health and sustainable development. Here, the authors reveal the synthesis of water-stable Archimedean solids based on the earth-abundant element for the fast removal of trace iodine.
Journal Article
Hollow MnO2 as a tumor-microenvironment-responsive biodegradable nano-platform for combination therapy favoring antitumor immune responses
Herein, an intelligent biodegradable hollow manganese dioxide (H-MnO
2
) nano-platform is developed for not only tumor microenvironment (TME)-specific imaging and on-demand drug release, but also modulation of hypoxic TME to enhance cancer therapy, resulting in comprehensive effects favoring anti-tumor immune responses. With hollow structures, H-MnO
2
nanoshells post modification with polyethylene glycol (PEG) could be co-loaded with a photodynamic agent chlorine e6 (Ce6), and a chemotherapy drug doxorubicin (DOX). The obtained H-MnO
2
-PEG/C&D would be dissociated under reduced pH within TME to release loaded therapeutic molecules, and in the meantime induce decomposition of tumor endogenous H
2
O
2
to relieve tumor hypoxia. As a result, a remarkable in vivo synergistic therapeutic effect is achieved through the combined chemo-photodynamic therapy, which simultaneously triggers a series of anti-tumor immune responses. Its further combination with checkpoint-blockade therapy would lead to inhibition of tumors at distant sites, promising for tumor metastasis treatment.
MnO
2
nanostructures are promising TME-responsive theranostic agents in cancer. Here, the authors develop a nano-platform based on hollow H-MnO
2
nanoshells able to modulate the tissue microenvironment, release a drug and inhibit tumor growth alone or in combination with check-point blockade therapy.
Journal Article
Formation Mechanism of AlN Inclusion in High-Nitrogen Stainless Bearing Steels
The existence of angular and hard AlN inclusions would seriously deteriorate the service life of high-nitrogen stainless bearing steels (HNSBSs). In this work, the formation mechanism of AlN inclusion in HNSBSs under as-cast, annealing and austenitizing states was systematically investigated by microstructure observation and thermodynamic, kinetic analyses. The results showed that the concentration product of Al and N could exceed the critical solubility of AlN inclusion at liquidus temperature with the Al content higher than 0.050 wt pct, which led to the formation of AlN inclusions about 1 to 5 μm (equivalent diameter) in liquid steel. Based on the ‘Clyne-Kurz’ model, AlN inclusion could form at the solidifying front due to the enrichment of N in the residual liquid steel with the Al content higher than 0.030 wt pct. Besides, the precipitation of Cr2N and the extremely low diffusion coefficient of Al in α phase restrained the precipitation of AlN during annealing at 1023 K. However, AlN and AlN-MnS composite inclusions less than 0.6 μm could precipitate during austenitizing at 1323 K with the Al content higher than 0.006 wt pct, which was the critical Al content to avoid AlN formation in HNSBSs after melting, solidification, and heat treatment processes.
Journal Article
H₂O₂-responsive liposomal nanoprobe for photoacoustic inflammation imaging and tumor theranostics via in vivo chromogenic assay
Abnormal H₂O₂ levels are closely related to many diseases, including inflammation and cancers. Herein, we simultaneously load HRP and its substrate, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), into liposomal nanoparticles, obtaining a Lipo@HRP&ABTS optical nanoprobe for in vivo H₂O₂-responsive chromogenic assay with great specificity and sensitivity. In the presence of H₂O₂, colorless ABTS would be converted by HRP into the oxidized form with strong near-infrared (NIR) absorbance, enabling photoacoustic detection of H₂O₂ down to submicromolar concentrations. Using Lipo@HRP&ABTS as an H₂O₂-responsive nanoprobe, we could accurately detect the inflammation processes induced by LPS or bacterial infection in which H₂O₂ is generated. Meanwhile, upon systemic administration of this nanoprobe we realize in vivo photoacoustic imaging of small s.c. tumors (∼2 mm in size) as well as orthotopic brain gliomas, by detecting H₂O₂ produced by tumor cells. Interestingly, local injection of Lipo@HRP&ABTS further enables differentiation of metastatic lymph nodes from those nonmetastatic ones, based on their difference in H₂O₂ contents. Moreover, using the H₂O₂-dependent strong NIR absorbance of Lipo@HRP&ABTS, tumor-specific photothermal therapy is also achieved. This work thus develops a sensitive H₂O₂-responsive optical nanoprobe useful not only for in vivo detection of inflammation but also for tumor-specific theranostic applications.
Journal Article
Magnesium galvanic cells produce hydrogen and modulate the tumor microenvironment to inhibit cancer growth
Hydrogen can be used as an anti-cancer treatment. However, the continuous generation of H
2
molecules within the tumor is challenging. Magnesium (Mg) and its alloys have been extensively used in the clinic as implantable metals. Here we develop, by decorating platinum on the surface of Mg rods, a Mg-based galvanic cell (MgG), which allows the continuous generation of H
2
in an aqueous environment due to galvanic-cell-accelerated water etching of Mg. By implanting MgG rods into a tumor, H
2
molecules can be generated within the tumor, which induces mitochondrial dysfunction and intracellular redox homeostasis destruction. Meanwhile, the Mg(OH)
2
residue can neutralize the acidic tumor microenvironment (TME). Such MgG rods with the micro-galvanic cell structure enable hydrogen therapy to inhibit the growth of tumors, including murine tumor models, patient-derived xenografts (PDX), as well as VX
2
tumors in rabbits. Our research suggests that the galvanic cells for hydrogen therapy based on implantable metals may be a safe and effective cancer treatment.
The production of hydrogen inside cells can stimulate cell death. Here, the authors made magnesium galvanic rods that continuously produce hydrogen and result in tumor inhibition in vitro and in vivo.
Journal Article