Computational redesign of a hydrolase for nearly complete PET depolymerization at industrially relevant high-solids loading.

Biotechnological plastic recycling has emerged as a suitable option for addressing the pollution crisis. A major breakthrough in the biodegradation of poly(ethylene terephthalate) (PET) is achieved by using a LCC variant, which permits 90% conversion at an industrial level. Despite the achievements, its applications have been hampered by the remaining 10% of nonbiodegradable PET. Herein, we address current challenges by employing a computational strategy to engineer a hydrolase from the bacterium HR29. The redesigned variant, TurboPETase, outperforms other well-known PET hydrolases. Nearly complete depolymerization is accomplished in 8 h at a solids loading of 200 g kg-1. Kinetic and structural analysis suggest that the improved performance may be attributed to a more flexible PET-binding groove that facilitates the targeting of more specific attack sites. Collectively, our results constitute a significant advance in understanding and engineering of industrially applicable polyester hydrolases, and provide guidance for further efforts on other polymer types.

Ultrasound -Induced Thermal Effect Enhances the Efficacy of Chemotherapy and Immunotherapy in Tumor Treatment.

Background: The inadequate perfusion, frequently resulting from abnormal vascular configuration, gives rise to tumor hypoxia. The presence of this condition hinders the effective delivery of therapeutic drugs and the infiltration of immune cells into the tumor, thereby compromising the efficacy of treatments against tumors. The objective of this study is to exploit the thermal effect of ultrasound (US) in order to induce localized temperature elevation within the tumor, thereby facilitating vasodilation, augmenting drug delivery, and enhancing immune cell infiltration. Methods: The selection of US parameters was based on intratumor temperature elevation and their impact on cell viability. Vasodilation and hypoxia improvement were investigated using enzyme-linked immunosorbent assay (ELISA) and immunofluorescence examination. The distribution and accumulation of commercial pegylated liposomal doxorubicin (PLD) and PD-L1 antibody (anti-PD-L1) in the tumor were analyzed through frozen section analysis, ELISA, and in vivo fluorescence imaging. The evaluation of tumor immune microenvironment was conducted using flow cytometry (FCM). The efficacy of US-enhanced chemotherapy in combination with immunotherapy was investigated by monitoring tumor growth and survival rate after various treatments. Results: The US irradiation condition of 0.8 W/cm2 for 10 min effectively elevated the tumor temperature to approximately 40 °C without causing any cellular or tissue damage, and sufficiently induced vasodilation, thereby enhancing the distribution and delivery of PLD and anti-PD-L1 in US-treated tumors. Moreover, it effectively mitigated tumor hypoxia while significantly increasing M1-phenotype tumor-associated macrophages (TAMs) and CD8+ T cells, as well as decreasing M2-phenotype TAMs. By incorporating US irradiation, the therapeutic efficacy of PLD and anti-PD-L1 was substantially boosted, leading to effective suppression of tumor growth and prolonged survival in mice. Conclusion: The application of US (0.8 W/cm2 for 10 min) can effectively induce vasodilation and enhance the delivery of PLD and anti-PD-L1 into tumors, thereby reshaping the immunosuppressive tumor microenvironment and optimizing therapeutic outcomes.

Vesselplasty using the Mesh-Hold™ bone-filling container for the treatment of pathological vertebral fractures due to osteolytic metastases: A retrospective study.

PURPOSE: To evaluate the clinical benefits and complications of vesselplasty using the Mesh-Hold™ bone-filling container in the treatment of vertebral osteolytic fractures. METHODS: This was a retrospective study of patients with vertebral osteolytic pathological fractures treated by vesselplasty at Sichuan Cancer Hospital between 09/2014 and 01/2018. VAS1 (Visual analog scale) scores and ODI2 (Oswestry disability index) were recorded routinely 1 day preoperative, at 1 day, 1 month, 3 months, 6 months, and 1 year postoperation, and at the last follow-up. V13 (The of bone cement injection volume) and V24 (vertebral body osteolytic volume) were evaluated, and the R5 (ratio) of bone cement filling was obtained according to the V1/V2. RESULTS: Sixty-three patients were included (105 segments with osteolytic fractures). The amount of bone cement for each vertebra was 2.4-5.2 ml (3.1 ± 0.7 ml). The ratio (R) of bone cement filling was not related to pain relief or functional recovery (all P > 0.05).The VAS scores and ODI at different time points after surgery were decreased compared with before surgery (all P < 0.05). The bone cement leakage rate was 16.2 % (17/105). The follow-up was 4-30 months (mean of 13 ± 6 months). Thirty patients had died by the last follow-up, all from their cancer. CONCLUSIONS: The Mesh-Hold™ bone-filling container in the treatment of vertebral fractures induced by osteolytic metastases could reduce pain, improve function, and reduce the bone cement leakage rate in the process of vesselplasty.