Phenylboronic ester-modified polymeric nanoparticles for promoting TRP2 peptide antigen delivery in cancer immunotherapy

The tremendous development of peptide-based cancer vaccine has attracted incremental interest as a powerful approach in cancer management, prevention and treatment. As successful as tumor vaccine has been, major challenges associated with achieving efficient immune response against cancer are (1) drainage to and retention in lymph nodes; (2) uptake by dendritic cells (DCs); (3) activation of DCs. In order to overcome these barriers, here we construct PBE-modified TRP2 nanovaccine, which comprises TRP2 peptide tumor antigen and diblock copolymer PEG-b-PAsp grafted with phenylboronic ester (PBE). We confirmed that this TRP2 nanovaccine can be effectively trapped into lymph node, uptake by dendritic cells and induce DC maturation, relying on increased negative charge, ROS response and pH response. Consistently, this vehicle loaded with TRP2 peptide could boost the strongest T cell immune response against melanoma in vivo and potentiate antitumor efficacy both in tumor prevention and tumor treatment without any exogenous adjuvant. Furthermore, the TRP2 nanovaccine can suppress the tumor growth and prolong animal survival time, which may result from its synergistic effect of inhibiting tumor immunosuppression and increasing cytotoxic lymphocyte (CTL) response. Hence this type of PBE-modified nanovaccine would be widely used as a simple, safe and robust platform to deliver other antigen in cancer immunotherapy

Recent advances in non-ionic surfactant vesicles (niosomes): fabrication, characterization, pharmaceutical and cosmetic applications

Development of nanocarriers for drug delivery has received considerable attention due to their potential in achieving targeted delivery to the diseased site while sparing the surrounding healthy tissue. Safe and efficient drug delivery has always been a challenge in medicine. During the last decade, a large amount of interest has been drawn on the fabrication of surfactant-based vesicles to improve drug delivery. Niosomes are self-assembled vesicular nano-carriers formed by hydration of non-ionic surfactant, cholesterol or other amphiphilic molecules that serve as a versatile drug delivery system with a variety of applications ranging from dermal delivery to brain-targeted delivery. A large number of research articles have been published reporting their fabrication methods and applications in pharmaceutical and cosmetic fields. Niosomes have the same advantages as liposomes, such as the ability to incorporate both hydrophilic and lipophilic compounds. Besides, niosomes can be fabricated with simple methods, require less production cost and are stable over an extended period, thus overcoming the major drawbacks of liposomes. This review provides a comprehensive summary of niosomal research to date, it provides a detailed overview of the formulation components, types of niosomes, effects of components on the formation of niosomes, fabrication and purification methods, physical characterization techniques of niosomes, recent applications in pharmaceutical field such as in oral, ocular, topical, pulmonary, parental and transmucosal drug delivery, and cosmetic applications. Finally, limitations and the future outlook for this delivery system have also been discussed

A UN SDGs-Based Sustainability Evaluation Framework for Globally Important Agricultural Heritage Systems (GIAHS): A Case Study on the Kuaijishan Ancient Chinese Torreya Community

The Food and Agriculture Organization of the United Nations (FAO) launched the conservation initiative of the Globally Important Agricultural Heritage Systems (GIAHS) in 2002, providing a new solution to current global problems such as widening gap between rich and poor, environmental pollution, biodiversity destruction and degradation of agro-ecological functions. However, since the implementation of GIAHS, few studies have evaluated the role of GIAHS in regional sustainable development. To fill this research gap, this paper attempts to build an evaluation index system that integrates economic, social and environmental sustainability by matching the 169 subgoals and 232 indices of the UN Sustainable Development Goals (SDGs) with five FAO-GIAHS selection criteria and selecting the indices. The index weights are determined through Delphi method (expert scoring) and Analytic Hierarchy Process (AHP). Then the GIAHS site of the Kuaijishan Ancient Chinese Torreya Community in Shaoxing City, Zhejiang Province is taken as an example for evaluation to enhance the empirical study. The results show that the comprehensive score for this heritage site is 77.90 points, of which economic, social and environmental sustainability scores 88.27, 86.12 and 69.71 points respectively, showing a descending trend. Thus, ecological protection of the Kuaijishan Ancient Chinese Torreya Community should be strengthened and be given prominence in the future. As for the contribution to further research, this SDGs-based GIAHS sustainability evaluation framework can serve as an important guide for assessing the approaches and effects of GIAHS in promoting the achievement of the SDGs. It can also be used for future international GIAHS sustainability assessment and comparison and provide a basis for adjusting the development model of GIAHS sites

Pluripotent stem cells secrete Activin A to improve their epiblast competency after injection into recipient embryos

Abstract It is not fully clear why there is a higher contribution of pluripotent stem cells (PSCs) to the chimera produced by injection of PSCs into 4-cell or 8-cell stage embryos compared with blastocyst injection. Here, we show that not only embryonic stem cells (ESCs) but also induced pluripotent stem cells (iPSCs) can generate F0 nearly 100% donor cell-derived mice by 4-cell stage embryo injection, and the approach has a “dose effect”. Through an analysis of the PSC-secreted proteins, Activin A was found to impede epiblast (EPI) lineage development while promoting trophectoderm (TE) differentiation, resulting in replacement of the EPI lineage of host embryos with PSCs. Interestingly, the injection of ESCs into blastocysts cultured with Activin A (cultured from 4-cell stage to early blastocyst at E3.5) could increase the contribution of ESCs to the chimera. The results indicated that PSCs secrete protein Activin A to improve their EPI competency after injection into recipient embryos through influencing the development of mouse early embryos. This result is useful for optimizing the chimera production system and for a deep understanding of PSCs effects on early embryo development

Artificial intelligence learning landscape of triple-negative breast cancer uncovers new opportunities for enhancing outcomes and immunotherapy responses

Abstract Triple-negative breast cancer (TNBC) is a relatively aggressive breast cancer subtype due to tumor relapse, drug resistance, and multi-organ metastatic properties. Identifying reliable biomarkers to predict prognosis and precisely guide TNBC immunotherapy is still an unmet clinical need. To address this issue, we successfully constructed a novel 25 machine learning (ML) algorithms-based immune infiltrating cell (IIC) associated signature of TNBC (MLIIC), achieved by multiple transcriptome data of purified immune cells, TNBC cell lines, and TNBC entities. The TSI index was employed to determine IIC-RNAs that were accompanied by an expression pattern of upregulation in immune cells and downregulation in TNBC cells. LassoLR, Boruta, Xgboost, SVM, RF, and Pamr were utilized for further obtaining the optimal IIC-RNAs. Following univariate Cox regression analysis, LassoCox, CoxBoost, and RSF were utilized for the dimensionality reduction of IIC-RNAs from a prognostic perspective. RSF, Ranger, ObliqueRSF, Rpart, CoxPH, SurvivalSVM, CoxBoost, GlmBoost, SuperPC, StepwiseCox, Enet, LassoCox, CForest, Akritas, BlackBoost, PlsRcox, SurvReg, GBM, and CTree were used for determining the most potent MLIIC signature. Consequently, this MLIIC signature was correlated significantly with survival status validated by four independent TNBC cohorts. Also, the MLIIC signature had a superior predictive capability for TNBC prognosis, compared with 148 previously reported signatures. In addition, MLIIC signature scores developed by immunofluorescent staining of tissue arrays from TNBC patients showed a substantial prognostic value. In TNBC immunotherapy, the low MLIIC profile demonstrated significant immune-responsive efficacy in a dataset of multiple cancer types. MLIIC signature could also predict m6A epigenetic regulation which controls T cell homeostasis. Therefore, this well-established MLIIC signature is a robust predictive indicator for TNBC prognosis and the benefit of immunotherapy, thus providing an efficient tool for combating TNBC

Visible-Light-Responsive Graphitic Carbon Nitride: Rational Design and Photocatalytic Applications for Water Treatment

Graphitic carbon nitride (g-C₃N₄) has recently emerged as a promising visible-light-responsive polymeric photocatalyst; however, a molecular-level understanding of material properties and its application for water purification were underexplored. In this study, we rationally designed nonmetal doped, supramolecule-based g-C₃N₄ with improved surface area and charge separation. Density functional theory (DFT) simulations indicated that carbon-doped g-C₃N₄ showed a thermodynamically stable structure, promoted charge separation, and had suitable energy levels of conduction and valence bands for photocatalytic oxidation compared to phosphorus-doped g-C₃N₄. The optimized carbon-doped, supramolecule-based g-C₃N₄ showed a reaction rate enhancement of 2.3–10.5-fold for the degradation of phenol and persistent organic micropollutants compared to that of conventional, melamine-based g-C₃N₄ in a model buffer system under the irradiation of simulated visible sunlight. Carbon-doping but not phosphorus-doping improved reactivity for contaminant degradation in agreement with DFT simulation results. Selective contaminant degradation was observed on g-C₃N₄, likely due to differences in reactive oxygen species production and/or contaminant-photocatalyst interfacial interactions on different g-C₃N₄ samples. Moreover, g-C₃N₄ is a robust photocatalyst for contaminant degradation in raw natural water and (partially) treated water and wastewater. In summary, DFT simulations are a viable tool to predict photocatalyst properties and oxidation performance for contaminant removal, and they guide the rational design, fabrication, and implementation of visible-light-responsive g-C₃N₄ for efficient, robust, and sustainable water treatment