A biomimetic spore nanoplatform for boosting chemodynamic therapy and bacteria-mediated antitumor immunity for synergistic cancer treatment

Bacterial-based antitumor immunity has become a promising strategy to activate the immune system for fighting cancer.However,the potential application of bacterial therapy is hindered by the presence of instability and susceptibility to infections within bacterial populations.Furthermore,monotherapy is ineffective in completely eliminating complex cancer with multiple contributing factors.In this study,based on our discovery that spore shell(SS)of Bacillus coagulans exhibits excellent tumor-targeting ability and adjuvant activity,we develop a biomimetic spore nanoplatform to boost bacteria-mediated antitumor therapy,chemodynamic therapy and antitumor immunity for synergistic cancer treatment.In detail,SS is separated from probiotic spores and then attached to the surface of liposome(Lipo)that was loaded with hemoglobin(Hb),glucose oxidase(GOx)and JQ1to construct SS@Lipo/Hb/GOx/JQ1.In tumor tissue,highly toxic hydroxyl radicals(·OH)are generated via sequential catalytic reactions:GOx catalyzing glucose into H_(2)O_(2)and Fe^(2+)in Hb decomposing H_(2)O_(2)into·OH.The combination of·OH and SS adjuvant can improve tumor immunogenicity and activate immune system.Meanwhile,JQ1-mediated down-regulation of PD-L1 and Hb-induced hypoxia alleviation synergistically reshape immunosuppressive tumor microenvironment and potentiate immune response.In this manner,SS@Lipo/Hb/GOx/JQ1 significantly suppresses tumor growth and metastasis.To summarize,the nanoplatform represents an optimum strategy to potentiate bacteria-based cancer immunotherapy.

IL-17 induces radiation resistance of B lymphoma cells by suppressing p53 expression and thereby inhibiting irradiation-triggered apoptosis

p53 is a well-known tumor suppressor. However, the regulatory mechanism（s） for p53 expression in B lymphoma cells, and the possible role of p53 in the development of the radioresistance in tumor cells are largely unknown. A human B lymphoma cell line, Karpas1106 （k1106）, was used as a model of radioresistance. Apoptosis of k1106 cells was determined using flow cytometry. Expression of p53 was assessed using real time RT-PCR and western blotting. The results showed that irradiation at 8 Gy induced apoptosis in up to 40% of k1106 cells. At the same time, the irradiation markedly increased IL-6 production of the k1106 cells. When k1106 cells were cocultured with regulatory T cells （Tregs） and irradiated, the rate of apoptotic k1106 cells was significantly reduced, indicating an acquired resistance to irradiation. IL-6 derived from the irradiation-treated k1106 cells induced IL-17 expression in Tregs. The IL- 17＋Foxp3＋ T cells suppressed p53 expression in k1106 cells. Collectively, irradiated k1106 cells induce the expression of IL-17 in Tregs, which interferes with the expression of p53 protein in k1106 cells and thereby represses irradiation-triggered apoptosis in k1106 cells.

Biophilic design in architecture and its contributions to health,well-being,and sustainability:A critical review

In the last ten years,‘nature’and biophilic design have received widespread attention in architecture,especially in response to growing environmental challenges.However,open questions and controversies remain regarding conceptualizing and addressing‘nature’in practice and research.This study conducts a literature review to discuss biophilic design as a theoretical framework to interpret‘nature’in architecture.The following questions are answered:(1)How has the concept of biophilic design emerged,and how can it be defined?(2)In what ways can biophilic design contribute to the goals of sustainable architecture?(3)What are the key design strategies in biophilic design?This review identifies and compares the key frameworks of biophilic design and explains their major elements.We then analyse the benefits(e.g.,enhance health,well-being,productivity,biodiversity,and circularity)of biophilic design in achieving sustainability,as framed through the UN Sustainable Development Goals.The results indicate that biophilic design is more complex and richer than the mere application of vegetation in buildings;it broadens the variety through encompassing different types of nature from physical,sensory,metaphorical,morphological,material to spiritual.Moreover,knowledge gaps are identified to motivate future research and critical reflections on biophilic design practices.

Rituximab or irradiation promotes IL-17 secretion and thereby induces resistance to rituximab or irradiation

Lymphoma is a hematological malignancy that involves T or B cells.Diffuse large B-cell lymphoma(DLBCL)accounts for~40%of cases of non-Hodgkin’s lymphoma(NHL)and is a highly aggressive and heterogeneous subtype of NHL.1 The pathogenesis of DLBCL remains unclear.DLBCL is also closely related to inflammatory factors and immune cells in the tumor microenvironment(TME),and alterations of the cytokine network in the TME may activate oncogenes or inactivate tumor suppressor genes.2–4 In the TME,a variety of immune cells and cytokines have crucial roles in the pathogenesis of tumors.

Designing with nature:Advancing threedimensional green spaces in architecture through frameworks for biophilic design and sustainability

In the transition to a more sustainable built environment over the last two decades,the“greening”of architecture as a popular approach has received widespread attention.However,there are still many open questions and contradictions regarding how to design with“nature”and contribute to sustainability.In addition,explorations of built examples are rare,and three-dimensional(3D)green spaces in buildings are often overlooked.Therefore,we introduce“green pockets”(3D green spaces)as a typology distinct from two-dimensional green roofs and walls/facades.We draw on a mixed-method approach to study two cases(Erasmus MC and Hotel Jakarta),comprising 12 semi-structured interviews with different stakeholders,design document analysis,and site observation.We develop a critical reflection(a framework)on the impacts of“green architecture”on sustainability from unpacked benefits and adopt a biophilic design framework to analyse designing with“nature”in architectural practice.These findings demonstrate that green pockets contribute to integrating multiple experiences of“nature”into buildings and developing sustainable architecture.Designing green pockets with visibility,accessibility,and spatial characteristics(e.g.,prospect and refuge,organised complexity,peril,and mystery)of“nature”improves building quality.Furthermore,we provide design recommendations to advance green pocket designs and make suggestions for future research.