A c-di-GMP binding effector controls cell size in a cyanobacterium.

Cyclic-di-GMP (c-di-GMP) is a ubiquitous bacterial signaling molecule. It is also a critical player in the regulation of cell size and cell behaviors such as cell aggregation and phototaxis in cyanobacteria, which constitute an important group of prokaryotes for their roles in the ecology and evolution of the Earth. However, c-di-GMP receptors have never been revealed in cyanobacteria.

Controlled Covalent Self-Assembly of a Homopolymer for Multiscale Materials Engineering.

Polymer self-assembly is a crucial process in materials engineering. Currently, almost all polymer self-assembly is limited to non-covalent bonding methods, even though these methods have drawbacks as they require complicated synthesis techniques and produce relatively unstable structures. Here, a novel mechanism of covalent polymer self-assembly is discovered and employed to address drawbacks of non-covalent polymer self-assembly.

Ultrasound-directed enzyme-prodrug therapy (UDEPT) using self-immolative doxorubicin derivatives.

Enzyme-activatable prodrugs are extensively employed in oncology and beyond. Because enzyme concentrations and their (sub)cellular compartmentalization are highly heterogeneous in different tumor types and patients, we propose ultrasound-directed enzyme-prodrug therapy (UDEPT) as a means to increase enzyme access and availability for prodrug activation locally. We synthesized β-glucuronidase-sensitive self-immolative doxorubicin prodrugs with different spacer lengths between the active drug moiety and the capping group.

Promoter analysis of TLR5M and TLR5S revealed NF-κB might be a conserved cis-element in TLR5S promoter of large yellow croaker.

Toll like receptor 5 (TLR5) plays a crucial role in the innate immune response by recognizing bacterial flagellin proteins. In the present study, the genomic and 5'-flanking sequences of LcTLR5M (membrane) and LcTLR5S (soluble) were cloned from the large yellow croaker, Larimichthys crocea. Then, their promoter activities were determined in human embryonic kidney (HEK293T) cells.

Π electron-stabilized polymeric micelles potentiate docetaxel therapy in advanced-stage gastrointestinal cancer.

Gastrointestinal (GI) cancers are among the most lethal malignancies. The treatment of advanced-stage GI cancer involves standard chemotherapeutic drugs, such as docetaxel, as well as targeted therapeutics and immunomodulatory agents, all of which are only moderately effective. We here show that Π electron-stabilized polymeric micelles based on PEG-b-p(HPMAm-Bz) can be loaded highly efficiently with docetaxel (loading capacity up to 23 wt%) and potentiate chemotherapy responses in multiple advanced-stage GI cancer mouse models.

Optical imaging of the whole-body to cellular biodistribution of clinical-stage PEG-b-pHPMA-based core-crosslinked polymeric micelles.

Core-crosslinked polymeric micelles (CCPM) based on PEG-b-pHPMA-lactate are clinically evaluated for the treatment of cancer. We macroscopically and microscopically investigated the biodistribution and target site accumulation of CCPM. To this end, fluorophore-labeled CCPM were intravenously injected in mice bearing 4T1 triple-negative breast cancer (TNBC) tumors, and their localization at the whole-body, tissue and cellular level was analyzed using multimodal and multiscale optical imaging.

Cancer nanomedicine meets immunotherapy: opportunities and challenges.

Cancer nanomedicines have shown promise in combination immunotherapy, thus far mostly preclinically but also already in clinical trials. Combining nanomedicines with immunotherapy aims to reinforce the cancer-immunity cycle, via potentiating key steps in the immune reaction cascade, namely antigen release, antigen processing, antigen presentation, and immune cell-mediated killing. Combination nano-immunotherapy can be realized via three targeting strategies, i.

Nanomedicine and macroscale materials in immuno-oncology.

Immunotherapy is revolutionizing the treatment of cancer. It can achieve unprecedented responses in advanced-stage patients, including complete cures and long-term survival. However, immunotherapy also has limitations, such as its relatively low response rates and the development of severe side effects.

The interaction of TAK1 and TAB1 enhances LPS-induced cytokine release via modulating NF-κB activation (Larimichthys crocea).

Transforming growth factor-β-activating kinase 1 (TAK1) is triggered by foreign pathogenic infection and involves in proinflammatory response through the activation of nuclear factor-κB (NF-κB), which is specifically regulated by TAK1-binding protein 1 (TAB1). However, the expression and regulatory characterizations of TAK1 and TAB1 in fish immune response remain largely unknown. In the present study, the cDNA sequences of TAK1 (LcTAK1) and TAB1 (LcTAB1) were identified from large yellow croaker, Larimichthys crocea.

Enhancing Tumor Penetration of Nanomedicines.

Tumor-targeted nanomedicines have been extensively applied to alter the drawbacks and enhance the efficacy of chemotherapeutics. Despite the large number of preclinical nanomedicine studies showing initial success, their therapeutic benefit in the clinic has been rather modest, which is partially due to the inefficient tumor penetration caused by the tumor microenvironment (high density of cells and extracellular matrix, increased interstitial fluid pressure). Furthermore, tumor penetration of nanomedicines is significantly influenced by physicochemical characteristics, such as size, surface chemistry, and shape.

Tissue distribution and pulmonary targeting studies of cefpiramide sodium-loaded liposomes.

The aim of this study was to evaluate the pharmacokinetics (PK), tissue distribution, and the specific drug targeting of cefpiramide sodium-loaded liposomes (CPMS-Lips) compared with cefpiramide sodium solution (CPMS-Sol) in mice. CPMS-Lips were prepared by reverse phase evaporation method. In the PK and biodistribution study, mice received a single intravenous (i.