Reversing the PAI-1-induced fibrotic immune exclusion of solid tumor by multivalent CXCR4 antagonistic nano-permeator.

Fibrosis is one of the key factors that lead to the immune exclusion of solid tumors. Although degradation of fiber is a promising strategy, its application was still bottlenecked by the side effects of causing metastasis, resulting in the failure of immunotherapy. Here, we developed an antimetastatic polymer (HPA) for the delivery of chemo-drug and antifibrotic siPAI-1 to form the nano-permeator. Nano-permeator shrank after protonation and deeply penetrated into the tumor core to down-regulate the expression of PAI-1 for antifibrosis, and further promoted the sustained infiltration and activation of T cells for killing tumor cells. Moreover, metastasis after fiber elimination was prevented by multivalent CXCR4 antagonistic HPA to reduce the attraction of CXCL12 secreted by distant organs. The administration of stroma-alleviated immunotherapy increased the infiltration of CD8+ T cells to 52.5% in tumor tissues, inhibiting nearly 90% metastasis by HPA in distant organs. The nano-permeator reveals the mechanism and correlation between antifibrosis and antimetastasis and was believed to be the optimizing immunotherapy for solid fibrotic tumors.

A Bio-Liposome Activating Natural Killer Cell by Illuminating Tumor Homogenization Antigen Properties.

Natural killer (NK) cell therapies, primarily based on chimeric antigen receptor NK cells (CAR-NK), have been developed and applied clinically for therapeutic treatment of patients with mid-to-late-stage tumors. However, NK cell therapy has limited efficacy due to insufficient antigen expression on the tumor cell surface. Here, a universal "illuminate tumor homogenization antigen properties" (ITHAP) strategy to achieve stable and controlled antigen expression on the surface of tumor cells using nanomedicine, thus significantly enhancing the immune recognizability of tumor cells, is described. The ITHAP strategy is used to generate bio-liposomes (Pt@PL-IgG) composed of intermingled platelet membranes and liposomes with NK-activatable target antigen (IgG antibodies) and cisplatin pre-drug. It is demonstrated that Pt@PL-IgG successfully targets tumor cells using the autonomous drive of platelet membranes and achieves IgG implantation on tumor cells by utilizing membrane fusion properties. Moreover, it is shown that the Pt-DNA complex combined with NK cell-induced pyroptosis causes substantial interferon (IFN) secretion, thus providing a synthase-stimulator of interferon genes (STING)-IFN-mediated positive immune microenvironment to further potentiate NK therapy. These results show that anchoring cancer cells with NK-activatable target antigens is a promising translational strategy for addressing therapeutic challenges in tumor heterogeneity.

Tai Chi versus routine exercise in patients with early- or mild-stage Parkinson's disease: a retrospective cohort analysis.

Parkinson's disease cannot be cured but symptoms can be improved by making use of physical therapy. The objective of the study was to compare the effect of routine exercises and Tai Chi on physical and clinical performance in elderly people suffering from Parkinson's disease. Data from interviews, physical and clinical performance, and levodopa consumption of 500 patients with confirmed Parkinson's disease (severity level I to III) were collected and analyzed. Participants who received 80 min/day Tai Chi 3 times/week for 2 months were included in the Tai Chi (TC) group (n=250) and those who received 90 min/day routine exercise 3 times/week for 2 months were included in routine exercise (RE) group (n=250). Timed up-and-go, 50-foot speed walk, and functional reach were improved by Tai Chi and routine exercise (P<0.05 for all) but intensities of Tai Chi for improvement of such parameters was higher than routine exercise. Incidence of falls was decreased by both physical therapies (P<0.05 for all) but more for the TC group (P<0.0001, q=38.512). In the TC group, at the end of follow-up, 22 (9%) patients were successful in withdrawal of levodopa treatment. Also, the dose of levodopa was decreased in patients of the TC group who had to continue levodopa. Tai Chi had the potential to slow down the progression of symptoms of Parkinson's disease and delayed the introduction of levodopa (level of evidence: III).

Biodegradation of polyethylene microplastic particles by the fungus Aspergillus flavus from the guts of wax moth Galleria mellonella.

Polyethylene (PE) products are widely used in daily life, agriculture, and industry because of their convenience and economic value. However, PE is one of the polymer materials remarkably resistant to degradation. Current methods of plastic waste disposal pose a threat to the environment and produce microplastic particles (MPP), which becomes a global environmental concern because of its accumulation. In this study, a PE-degrading fungus Aspergillus flavus named PEDX3, was isolated from the gut contents of wax moth Galleria mellonella. The results indicated that high-density polyethylene (HDPE) MPP was degraded into the MPP with a lower molecular weight by strain PEDX3 after 28 days incubation. In addition, Fourier Transform - Infrared Spectroscopy (FT-IR) results showed the appearance of carbonyl groups and ether groups of MPP, which also validated the degradation of PE. Furthermore, the potential degradation enzymes were investigated by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Finally, two laccase-like multicopper oxidases (LMCOs) genes, AFLA_006190 and AFLA_053930, displayed up-regulated expression during the degradation process, which may be the candidate PE-degrading enzymes. These results have demonstrated that the A. flavus strain PEDX3 has an ability to degrade microplastic particles and the two PE-degrading enzymes provide a promising application for the PE MPP remediation.

Tai Chi versus routine exercise in patients with early- or mild-stage Parkinson's disease: a retrospective cohort analysis

Parkinson's disease cannot be cured but symptoms can be improved by making use of physical therapy. The objective of the study was to compare the effect of routine exercises and Tai Chi on physical and clinical performance in elderly people suffering from Parkinson's disease. Data from interviews, physical and clinical performance, and levodopa consumption of 500 patients with confirmed Parkinson's disease (severity level I to III) were collected and analyzed. Participants who received 80 min/day Tai Chi 3 times/week for 2 months were included in the Tai Chi (TC) group (n=250) and those who received 90 min/day routine exercise 3 times/week for 2 months were included in routine exercise (RE) group (n=250). Timed up-and-go, 50-foot speed walk, and functional reach were improved by Tai Chi and routine exercise (P<0.05 for all) but intensities of Tai Chi for improvement of such parameters was higher than routine exercise. Incidence of falls was decreased by both physical therapies (P<0.05 for all) but more for the TC group (P<0.0001, q=38.512). In the TC group, at the end of follow-up, 22 (9%) patients were successful in withdrawal of levodopa treatment. Also, the dose of levodopa was decreased in patients of the TC group who had to continue levodopa. Tai Chi had the potential to slow down the progression of symptoms of Parkinson's disease and delayed the introduction of levodopa (level of evidence: III).