Angiogenesis is increasingly recognized as an important prognosticator associated with the progression of lymphoma and as an attractive target for novel modalities. We report a previously unrecognized mechanism by which lymphoma endothelium facilitates the growth and dissemination of lymphoma by interacting with circulated T cells and suppresses the activation of CD4+ T cells. Global gene expression profiles of microdissected endothelium from lymphoma and reactive lymph nodes revealed that T cell immunoglobulin and mucin domain–containing molecule 3 (Tim-3) was preferentially expressed in lymphoma-derived endothelial cells (ECs). Clinically, the level of Tim-3 in B cell lymphoma endothelium was closely correlated to both dissemination and poor prognosis. In vitro, Tim-3+ ECs modulated T cell response to lymphoma surrogate antigens by suppressing activation of CD4+ T lymphocytes through the activation of the interleukin-6–STAT3 pathway, inhibiting Th1 polarization, and providing protective immunity. In a lymphoma mouse model, Tim-3–expressing ECs promoted the onset, growth, and dissemination of lymphoma by inhibiting activation of CD4+ T cells and Th1 polarization. Our findings strongly argue that the lymphoma endothelium is not only a vessel system but also a functional barrier facilitating the establishment of lymphoma immune tolerance. These findings highlight a novel molecular mechanism that is a potential target for enhancing the efficacy of tumor immunotherapy and controlling metastatic diseases.

Lanthanides possess similar chemical properties rendering their separation from one another a challenge of fundamental chemical and global importance given their incorporation into many advanced technologies. New separation strategies combining green chemistry with low cost and high efficiency remain highly desirable. We demonstrate that the subtle bonding differences among trivalent lanthanides can be amplified during the crystallization of borates, providing chemical recognition of specific lanthanides that originates from Ln3+ coordination alterations, borate polymerization diversity and soft ligand coordination selectivity. Six distinct phases are obtained under identical reaction conditions across lanthanide series, further leading to an efficient and cost-effective separation strategy via selective crystallization. As proof of concept, Nd/Sm and Nd/Dy are used as binary models to demonstrate solid/aqueous and solid/solid separation processes. Controlling the reaction kinetics gives rise to enhanced separation efficiency of Nd/Sm system and a one-step quantitative separation of Nd/Dy with the aid of selective density-based flotation.

Objective. To explore the influence of M2-polarized tumor-associated macrophages (TAMs) on high-risk human papillomavirus (hr-HPV)-related cervical carcinogenesis and metastasis.Methods. CD68+ and CD163+ macrophages were examined immunohistochemically in a series of 130 samples, including 26 cases of normal cervical tissues, 59 cases of cervical intraepithelial neoplasia (CIN), and 45 cases of squamous cell carcinoma (SCC), and the results were statistically analyzed. The macrophage count was corrected for the epithelial and stromal compartments respectively. Clinical data were also obtained.Results. High counts of CD68+ and CD163+ macrophages were associated with hr-HPV infection (both p < 0.05) and positively correlated with cervical carcinogenesis (Spearman's rho = 0.478, p = 0.000; Spearman's rho = 0.676, p =0.000, respectively). The immunostaining pattern of CD163 exhibited clearer background than that of CD68. CD163+ macrophages showed a more obviously increasing migration into the epithelium along with the progression of CIN to invasive cancer. Notably, a high index of CD163+ macrophages was significantly associated with higher FIGO stages (p = 0.009) and lymph node metastasis (p = 0.012), but a similar finding was not found for CD68+ macrophages (p = 0.067, p = 0.079, respectively).Conclusions. Our study supported a critical role of TAMs as a prospective predictor for hr-HPV-related cervical carcinogenesis. CD163, as a promising TAMs marker, is superior to CD68 for predicting the malignant transformation and metastatic potential of cervical cancer.

Zinc oxide nanoparticles (ZnONPs) have been widely studied as the bacteriostatic reagents. However, synthesis of small ZnO nanoparticles with good monodispersion and stability in aqueous solution is still a challenge. Anti-infection research of ZnONPs used as antibacterial agent in vivo is rare. In this paper, a novel, sustainable, and simple method to synthesize ZnO nanoparticles with good monodispersion in aqueous low-temperature conditions and with a small molecule agent is reported. Inhibition zone test and the minimum inhibitory concentration test were performed to examine the antibacterial activity of ZnONPs against bacteria Staphylococcus aureus and Escherichia coli in vitro. For further application in vivo, low cytotoxicity and low acute toxicity in mice of ZnO were demonstrated. Finally, 4 nm ZnONPs combined with poly(vinyl alcohol) gel was used as antibacterial agent in rodent elytritis model, and significant anti-infection effect was proven. In one word, the present research would shed new light on the designing of antibacterial materials like ZnO with promising application in disinfection.

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Synthetic immune-stimulatory drugs such as agonists of the Toll-like receptors (TLR) 7/8 are potent activators of antigen-presenting cells (APCs), however, they also induce severe side effects due to leakage from the site of injection into systemic circulation. Here, we report on the design and synthesis of an amphiphilic polymer-prodrug conjugate of an imidazoquinoline TLR7/8 agonist that in aqueous medium forms vesicular structures of 200 nm. The conjugate contains an endosomal enzyme-responsive linker enabling degradation of the vesicles and release of the TLR7/8 agonist in native form after endocytosis, which results in high in vitro TLR agonist activity. In a mouse model, locally administered vesicles provoke significantly more potent and long-lasting immune stimulation in terms of interferon expression at the injection site and in draining lymphoid tissue compared to a nonamphiphilic control and the native TLR agonist. Moreover, the vesicles induce robust activation of dendritic cells in the draining lymph node in vivo.

Herein, hierarchical Co9S8@carbon hollow microspheres (Co9S8@CHSs) were designed and facilely prepared via a simple solvothermal approach, following a thermal treatment process. The surfaces of the hierarchical Co9S8 hollow microspheres are homogeneously coated by a fluffy ultrathin carbon layer, which not only acts as a buffer material to suppress pulverization but also serves as a conductive matrix to boost charge transfer. Leveraging the advantage of the fascinating hierarchical structure and the synergistic effect with carbon layers, they show impressive electrochemical properties. They deliver a large sodium storage capacity of 492 mAh g–1 after 100 cycles at a current density of 0.5 A g–1 and excellent rate performance. Additionally, a high capacity of 223 mAh g–1 is maintained, even after 10 000 cycles at 5 A g–1, demonstrating prolonged cycle stability. The remarkable sodium storage performance expects a future application for sodium ion batteries.

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