Novel Carrier-Free Nanodrug Enhances Photodynamic Effects by Blocking the Autophagy Pathway and Synergistically Triggers Immunogenic Cell Death for the Efficient Treatment of Breast Cancer.

Photosensitizers have been widely used to cause intratumoral generation of reactive oxygen species (ROS) for cancer therapy, but they are easily disturbed by the autophagy pathway, a self-protective mechanism by mitigating oxidative damage. Hereby, we reported a simple and effective strategy to construct a carrier-free nanodrug, Ce6@CQ namely, based on the self-assembly of the photosensitizer chlorin e6 (Ce6) and the autophagy inhibitor chloroquine (CQ). Specifically, Ce6@CQ avoided the unexpected toxicity caused by the regular nanocarrier and also ameliorated its stability in different conditions. Light-activated Ce6 generated cytotoxic ROS and elicited part of the immunogenic cell death (ICD). Moreover, CQ induced autophagy dysfunction, which hindered self-healing in tumor cells and enhanced photodynamic therapy (PDT) to exert a more potent killing effect and more efficient ICD. Also, Ce6@CQ could effectively accumulate in the xenograft breast tumor site in a mouse model through the enhanced permeability and retention (EPR) effect, and the growth of breast tumors was effectively inhibited by Ce6@CQ with light. Such a carrier-free nanodrug provided a new strategy to improve the efficacy of PDT via the suppression of autophagy to digest ROS-induced toxic substances.

Geochemical mercury pools regulate diverse communities of hgcA microbes and MeHg levels in paddy soils.

Rice paddies are unique artificial wetlands generating methylmercury (MeHg), a highly potent neurotoxin. However, the impact of diverse mercury (Hg) pools on the Hg-methylating communities during rice growth is unclear. This study investigates soil treated with five mercury forms (HgCl2, α-HgS, ß-HgS, nano-HgS, and Hg-DOM) at two levels (5 mg/kg and 50 mg/kg). The results showed a varying abundance of sulphate-reducing bacteria, Geobacteraceae, methanogens, and hgcA microbes in the soils across rice grown under different mercury treatments and concentrations. Soils treated with HgCl2, nano-HgS and ß-HgS had higher than average levels of hgcA-methanogen abundance, and the abundance significantly and positively correlated with MeHg concentration in all samples (p < 0.05). The shifting trends in Hg-methylating microbial structure following treatment with α-HgS, ß-HgS, nano-HgS and Hg-DOM at both 5 and 50 mg/kg Hg levels were diverse compared with the control group. HgCl2 treatment showed contrasting trends in community distribution of Hg methylators at 5 and 50 mg/kg Hg levels during rice growth. Dissolved organic carbon, redox potential and sulphate levels significantly correlated with variation in the Hg-methylating microbial community structure and MeHg production in soils.

Application of injectable hydrogels in cancer immunotherapy.

Immunotherapy is a revolutionary and promising approach to cancer treatment. However, traditional cancer immunotherapy often has the disadvantages of limited immune response rate, poor targeting, and low treatment index due to systemic administration. Hydrogels are drug carriers with many advantages. They can be loaded and transported with immunotherapeutic agents, chemical anticancer drugs, radiopharmaceuticals, photothermal agents, photosensitizers, and other therapeutic agents to achieve controlled release of drugs, extend the retention time of drugs, and thus successfully trigger anti-tumor effects and maintain long-term therapeutic effects after administration. This paper reviews recent advances in injectable hydrogel-based cancer immunotherapy, including immunotherapy alone, immunotherapy with combination chemotherapy, radiotherapy, phototherapy, and DNA hydrogel-based immunotherapy. Finally, we review the potential and limitations of injectable hydrogels in cancer immunotherapy.

Toxicity Analysis of Mesoporous Polydopamine on Intestinal Tissue and Microflora.

As a promising therapy, photothermal therapy (PTT) converts near-infrared (NIR) light into heat through efficient photothermal agents (PTAs), causing a rapid increase in local temperature. Considering the importance of PTAs in the clinical application of PTT, the safety of PTAs should be carefully evaluated before their widespread use. As a promising PTA, mesoporous polydopamine (MPDA) was studied for its clinical applications for tumor photothermal therapy and drug delivery. Given the important role that intestinal microflora plays in health, the impacts of MPDA on the intestine and on intestinal microflora were systematically evaluated in this study. Through biological and animal experiments, it was found that MPDA exhibited excellent biocompatibility, in vitro and in vivo. Moreover, 16S rRNA analysis demonstrated that there was no obvious difference in the composition and classification of intestinal microflora between different drug delivery groups and the control group. The results provided new evidence that MPDA was safe to use in large doses via different drug delivery means, and this lays the foundation for further clinical applications.

Psychometric Properties and Factor Structures of the CERQ, DERS, and RESE Measures: A Bifactor Approach.

This study aims to simultaneously compare the psychometric properties and examine the factor structures of 3 emotion regulation (ER) strategy scales using a bifactor approach. Due to good reliability and validity, extensive use, and the same scoring method, the Cognitive Emotion Regulation Questionnaire, Difficulties in Emotion Regulation Scale, and Regulatory Emotional Self-Efficacy Scale were used to assess ER strategies in 1,036 Chinese respondents. A bifactor confirmatory factor analysis was designed to address the multidimensionality of the factor structure, and the corresponding bifactor structures were then applied in a subsequent bifactor multidimensional item response theory (MIRT) analysis. Finally, bifactor MIRT was used to compare the psychometric properties of the 3 measures. The results indicated that bifactor structures were appropriate for the 3 ER strategy measures, which performed well overall. Different measures provide the highest accuracy for specific groups and designs. Some strengths and limitations of this article are discussed.