An immunological electrospun scaffold for tumor cell killing and healthy tissue regeneration

Antibody-based cancer immune therapy has attracted lots of research interest in recent years; however, it is greatly limited by the easy distribution and burst release of antibodies. In addition, after the clearance of the tissue, healthy tissue regeneration is another challenge for cancer treatment. Herein, we have developed a specific immunological tissue engineering scaffold using the agonistic mouse anti-human CD40 antibody (CD40mAb) incorporated into poly(l-lactide) (PLLA) electrospun fibers through the dopamine (PDA) motif (PLLA-PDA-CD40mAb). CD40mAb is successfully incorporated onto the surface of the electrospun fibrous scaffold, which is proved by immunofluorescence staining, and the PLLA-PDA-CD40mAb scaffold has an anti-tumor effect by locally releasing CD40mAb. Therefore, this immunological electrospun scaffold has very good potential to be developed as a powerful tool for localized tumor treatment, and this is the first to be reported in this area.Peer reviewe

Efficacy and Safety of Ligation Combined With Sclerotherapy for Patients With Acute Esophageal Variceal Bleeding in Cirrhosis: A Meta-Analysis

Objective: To evaluate the efficacy and safety of endoscopic variceal ligation + endoscopic injection sclerotherapy (EVL+EIS) to control acute variceal bleeding (AVB).Methods: Online databases, including Web of Science, PubMed, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM) disc, VIP, and Wanfang, were searched to identify the studies comparing the differences between EVB+EIS and EVB, EIS from the inception of the databases up to December 30, 2020. STATA 13.0 was used for the meta-analysis.Results: A total of eight studies involving 595 patients (317 patients in the EVL group and 278 patients in the EVL+EIS group) were included. The results of the meta-analysis did not reveal any statistically significant differences in the efficacy of acute bleeding control (P = 0.981), overall rebleeding (P = 0.415), variceal eradication (P = 0.960), and overall mortality (P = 0.314), but a significant difference was noted in the overall complications (P = 0.01).Conclusion: EVL is superior to the combination of EVL and EIS in safety, while no statistically significant differences were detected in efficacy. Further studies should be designed with a large sample size, multiple centers, and randomized controlled trials to assess both clinical interventions

Plasmonically enhanced photoluminescence of monolayer MoS2 via nanosphere lithography-templated gold metasurfaces

We demonstrate a simple, cost-effective method to enhance the photoluminescence intensity of monolayer MoS2. A hexagonal symmetric Au metasurface, made by polystyrene nanosphere lithography and metal coating, is developed to enhance the photoluminescence intensity of monolayer MoS2. By using nanospheres of different sizes, the localized surface plasmon resonances of the Au metasurfaces can be effectively tuned. By transferring monolayer MoS2 onto the Au metasurface, the photoluminescence signal of the monolayer MoS2 can be significantly enhanced up to 12-fold over a square-centimeter area. The simple, large-area, cost-effective fabrication technique could pave a new way for plasmon-enhanced light-mater interactions of atomically thin two-dimensional materials.This work was supported in part by National Natural Science Foundation of China (Grant No. 62075093 and 61805113), China Postdoctoral Science Foundation (2020M672697), Natural Science Foundation of Guangdong Province (Grant No. 2018A030310224 and 2019A1515110864), Guangdong Innovative and Entrepreneurial Research Team Program (Grant No. 2017ZT07C071), and Shenzhen Science and Technology Innovation Commission (Grant No. GJHZ201809281552 07206, JCYJ20170817111349280, and JCYJ2018030518063 5082). Meng Zhao acknowledges the support from the Agency for Science, Technology and Research (A*STAR) (Grant No. 152700014 and H19H6a0025)

An immunological electrospun scaffold for tumor cell killing and healthy tissue regeneration

Antibody-based cancer immune therapy has attracted lots of research interest in recent years; however, it is greatly limited by the easy distribution and burst release of antibodies. In addition, after the clearance of the tissue, healthy tissue regeneration is another challenge for cancer treatment. Herein, we have developed a specific immunological tissue engineering scaffold using the agonistic mouse anti-human CD40 antibody (CD40mAb) incorporated into poly(l-lactide) (PLLA) electrospun fibers through the dopamine (PDA) motif (PLLA-PDA-CD40mAb). CD40mAb is successfully incorporated onto the surface of the electrospun fibrous scaffold, which is proved by immunofluorescence staining, and the PLLA-PDA-CD40mAb scaffold has an anti-tumor effect by locally releasing CD40mAb. Therefore, this immunological electrospun scaffold has very good potential to be developed as a powerful tool for localized tumor treatment, and this is the first to be reported in this area

Loss of p53 in mesenchymal stem cells promotes alteration of bone remodeling through negative regulation of osteoprotegerin.

p53 plays a pivotal role in controlling the differentiation of mesenchymal stem cells (MSCs) by regulating genes involved in cell cycle and early steps of differentiation process. In the context of osteogenic differentiation of MSCs and bone homeostasis, the osteoprotegerin/receptor activator of NF-κB ligand/receptor activator of NF-κB (OPG/RANKL/RANK) axis is a critical signaling pathway. The absence or loss of function of p53 has been implicated in aberrant osteogenic differentiation of MSCs that results in higher bone formation versus erosion, leading to an unbalanced bone remodeling. Here, we show by microCT that mice with p53 deletion systemically or specifically in mesenchymal cells possess significantly higher bone density than their respective littermate controls. There is a negative correlation between p53 and OPG both in vivo by analysis of serum from p53+/+, p53+/-, and p53-/- mice and in vitro by p53 knockdown and ChIP assay in MSCs. Notably, high expression of Opg or its combination with low level of p53 are prominent features in clinical cancer lesion of osteosarcoma and prostate cancer respectively, which correlate with poor survival. Intra-bone marrow injection of prostate cancer cells, together with androgen can suppress p53 expression and enhance local Opg expression, leading to an enhancement of bone density. Our results support the notion that MSCs, as osteoblast progenitor cells and one major component of bone microenvironment, represent a cellular source of OPG, whose amount is regulated by the p53 status. It also highlights a key role for the p53-OPG axis in regulating the cancer associated bone remodeling

Generalized Accelerated Failure Time Frailty Model for Systems Subject to Imperfect Preventive Maintenance

Imperfect preventive maintenance (PM) activities are very common in industrial systems. For condition-based maintenance (CBM), it is necessary to model the failure likelihood of systems subject to imperfect PM activities. In this paper, the models in the field of survival analysis are introduced into CBM. Namely, the generalized accelerated failure time (AFT) frailty model is investigated to model the failure likelihood of industrial systems. Further, on the basis of the traditional maximum likelihood (ML) estimation and expectation maximization (EM) algorithm, the hybrid ML-EM algorithm is investigated for the estimation of parameters. The hybrid iterative estimation procedure is analyzed in detail. In the evaluation experiment, the generated data of a typical degradation model are verified to be appropriate for the real industrial processes with imperfect PM activities. The estimates of the model parameters are calculated using the training data. Then, the performance of the model is analyzed through the prediction of remaining useful life (RUL) using the testing data. Finally, comparison between the results of the proposed model and the existing model verifies the effectiveness of the generalized AFT frailty model

Earthquake trend around Sumatra indicated by a New Implementation of LURR Method

The current implementation of LURR (Load/Unload Response Ratio) theory has shown promise in intermediate to short-term earthquake forecasting through past practice, but has also met difficulties at the same time. In this paper a new implementation of LURR method is presented to address one of the problems. The major change in the new implementation is that LURR values will result from a calculated maximum faulting orientation (MFO) instead of any focal mechanism selected by users. After comparison with the world stress map, the calculated MFO has been found to be in good agreement with the observation from the regional tectonic stress regime. The MFO pattern in the Indonesia region has a special feature which may be related to the unique subduction complexity. The MFO pattern in the Sumatra region in general is different from that in the Java region after the 2004 M 9.0 Sumatra Andaman Islands earthquake. This phenomenon may be supported by the evidence of the recent observation that a section in the southern part of the Sumatran arc is locked. Furthermore, the MFO pattern before the 2004 main shock is different from that after the event. Retrospective examination of the Indonesia region by means of this implementation can produce significant LURR anomaly not only prior to the 2004 main shock but also before the 2006 M 7.7 South Java earthquake. Therefore future great earthquakes might favorably be forecasted if the LURR anomaly detected by MFO method could be considered a precursor