Owing to the fast-paced growth and cross-infiltration of oncology, immunology and molecular biology, tumor immunotherapy technology represented by immune checkpoint blockade and chimeric antigen receptor (CAR) T cell therapy has lately made remarkable advancements. In comparison with traditional chemotherapy, immunotherapy has the potential to elicit a stronger sustained antitumor immune response in those patients who have advanced malignant malignancies. In spite of the advancements made, a significant number of clinical research works have validated that an extensive proportion of cancer patients still manifest insensitivity to immunotherapy, primarily because of the immunomodulatory interactions between tumor cells and the immunosuppressive tumor microenvironment (TME), together mediating the immune tolerance of tumors and accordingly impacting the positive response to immunotherapy. The intricate immunosuppressive networks formed by stromal cells, inflammatory cells, vasculature, extracellular matrix (ECM), and their secreted cytokines in the TME, play a pivotal role in tumor immune escape. Specific blocking of inhibition pathways in the TME is expected to effectively prevent immune escape and tolerance of tumor cells in addition to their metastasis, accordingly improving the antitumor immune response at various phases of tumor growth. Emerging nanoscale targeted drug carriers truly suit this specific requirement due to their specificity, biocompatibility, and convenience of production. This review emphasizes recent attempts to remodel the tumor immune microenvironment using novel nanoparticles, which include specifically eliminating immunosuppressive cells, reprogramming immune regulatory cells, promoting inflammatory cytokines and blocking immune checkpoints. Targeted remodeling of the immunosuppressive TME using well-designed and fabricated nanoparticles provides a promising strategy for improving the effectiveness of current immunotherapy and is greatly significant.

Recent studies about brain network have suggested that normal aging is associated with alterations in coordinated patterns of the large-scale brain functional and structural systems. However, age-related changes in functional networks constructed via positron emission tomography (PET) data are still barely understood. Here, we constructed functional brain networks composed of regions in younger (mean age years) and older (mean age years) age groups with PET data. younger and older healthy individuals were separately selected for two age groups, from a physical examination database. Corresponding brain functional networks of the two groups were constructed by thresholding average cerebral glucose metabolism correlation matrices of regions and analysed using graph theoretical approaches. Although both groups showed normal small-world architecture in the PET networks, increased clustering and decreased efficiency were found in older subjects, implying a degeneration process that brain system shifts from a small-world network to regular one along with normal aging. Moreover, normal senescence was related to changed nodal centralities predominantly in association and paralimbic cortex regions, e.g. increasing in orbitofrontal cortex (middle) and decreasing in left hippocampus. Additionally, the older networks were about equally as robust to random failures as younger counterpart, but more vulnerable against targeted attacks. Finally, methods in the construction of the PET networks revealed reasonable robustness. Our findings enhanced the understanding about the topological principles of PET networks and changes related to normal aging.

In traditional nano drug-delivery systems, the complex chemical bonds between drug and carrier often complicate the preparation process and are less prone to rupture upon entry into the target, which is detrimental to the timely release of the drug. The π–π stacking provides us with a promising alternative as it is a weak interaction between the aromatic rings. Since most antitumor drugs are hydrophobic molecules with complex aromatic π–π-conjugated structures, the construction of self-assembly based on π–π stacking between drugs and carriers has the advantage of improving the stability and drug loading capacity as well as the improvement of hydrophilicity and biosafety. This article introduces the recent advances in π–π stacking-guided nano self-assembly for antineoplastic delivery.

To elucidate compositional changes of the olfactory bulb and tract with aging, the authors investigated age-related changes of elements in the olfactory bulbs and tracts of Japanese and the relationships among the elements. After ordinary dissection at Nara Medical University was finished, the olfactory bulbs were resected with the olfactory tracts from 40 subjects. The subjects consisted of 15 men and 25 women, ranging in age from 65 to 102 years (average age = 84.6 +/- 7.5 years). After ashing with nitric acid and perchloric acid, element contents in the olfactory bulbs and tracts were analyzed by inductively coupled plasma-atomic emission spectrometry. Seven elements of Ca, P, S, Mg, Zn, Fe, and Na did not change significantly in the olfactory bulbs and tracts with aging. The Ca, P, and S contents of major elements were less than 10 mg/g in all of the olfactory bulbs and tracts. Regarding the relationships among the elements, extremely or very significant direct correlations were found among the contents of Ca, P, Mg, Zn, and Na in the olfactory bulbs and tracts, with one exception. In addition, an extremely significant direct correlation was found between S and Mg contents and a very significant direct correlation was found between P and S contents. As P increased in the olfactory bulb and tract, Ca, Mg, Zn, Na, and S also increased in the olfactory bulb and tract.