Bacteria colonization in tumor microenvironment creates a favorable niche for immunogenic chemotherapy.

The tumor microenvironment (TME) presents differential selective pressure (DSP) that favors the growth of cancer cells, and monovalent therapy is often inadequate in reversing the cancer cell dominance in the TME. In this work, we introduce bacteria as a foreign species to the TME and explore combinatorial treatment strategies to alter DSP for tumor eradication. We show that cancer-selective chemotherapeutic agents and fasting can provide a strong selection pressure against tumor growth in the presence of bacteria. Moreover, we show that an immunogenic drug (oxaliplatin), but not a non-immunogenic one (5-FU), synergizes with the bacteria to activate both the innate and adaptive immunity in the TME, resulting in complete tumor remission and a sustained anti-tumor immunological memory in mice. The combination of oxaliplatin and bacteria greatly enhances the co-stimulatory and antigen-presenting molecules on antigen-presenting cells, which in turn bridge the cytotoxic T cells for cancer-cell killing. Our findings indicate that rational combination of bacterial therapy and immunogenic chemotherapy can promote anticancer immunity against the immunosuppressive TME.

Ubiquitous Computing in Sports and Physical Activity-Recent Trends and Developments.

The use of small, interconnected and intelligent tools within the broad framework of pervasive computing for analysis and assessments in sport and physical activity is not a trend in itself but defines a way for information to be handled, processed and utilised: everywhere, at any time. The demand for objective data to support decision making prompted the adoption of wearables that evolve to fulfil the aims of assessing athletes and practitioners as closely as possible with their performance environments. In the present paper, we mention and discuss the advancements in ubiquitous computing in sports and physical activity in the past 5 years. Thus, recent developments in wearable sensors, cloud computing and artificial intelligence tools have been the pillars for a major change in the ways sport-related analyses are performed. The focus of our analysis is wearable technology, computer vision solutions for markerless tracking and their major contribution to the process of acquiring more representative data from uninhibited actions in realistic ecological conditions. We selected relevant literature on the applications of such approaches in various areas of sports and physical activity while outlining some limitations of the present-day data acquisition and data processing practices and the resulting sensors' functionalities, as well as the limitations to the data-driven informed decision making in the current technological and scientific framework. Finally, we hypothesise that a continuous merger of measurement, processing and analysis will lead to the development of more reliable models utilising the advantages of open computing and unrestricted data access and allow for the development of personalised-medicine-type approaches to sport training and performance.

Development of a TNF-α-mediated Trojan Horse for bacteria-based cancer therapy.

Tumor necrosis factor α (TNF-α) is upregulated in a chronic inflammatory environment, including tumors, and has been recognized as a pro-tumor factor in many cancers. Applying the traditional TNF-α antibodies that neutralize TNF-α activity, however, only exerts modest anti-tumor efficacy in clinical studies. Here, we develop an innovative approach to target TNF-α that is distinct from the neutralization mechanism. We employed phage display and yeast display to select non-neutralizing antibodies that can piggyback on TNF-α and co-internalize into cells through receptor ligation. When conjugating with toxins, the antibody exhibited cytotoxicity to cancer cells in a TNF-α-dependent manner. We further implemented the immunotoxin to an E. coli vehicle specially engineered for a high secretion level. In a syngeneic murine melanoma model, the bacteria stimulated TNF-α expression that synergized with the secreted immunotoxin and greatly inhibited tumor growth. The treatment also dramatically remodeled the tumor microenvironment in favor of several anti-tumor immune cells, including N1 neutrophils, M1 macrophages, and activated CD4+ and CD8+ lymphocytes. We anticipate that our new piggyback strategy is generalizable to targeting other soluble ligands and/or conjugates with different drugs for managing a diverse set of diseases.

Preventive strategy of flatfoot deformity using fully automated procedure.

A non-invasive, no radiation, out-of-hospital automated system is proposed to identify low arch integrated in the design and manufacturing of personalized orthoses using parametric modelling. The aim of the design process is to integrate assistive technology with assessment and prevent low arch progressing to a more serious case - flatfoot. In the automated procedure, we developed an assessment method including reliable thresholds of foot type classification and test protocol to reduce interferences due to preceding activities, an automation to translate scanned data into parametric design for orthotic customization, finite element model evaluating effectiveness of the personalized design, and a personalized comparative test to evaluate the long-term improvement of foot arch shape. Our low arch threshold established by subject-specific 3D models reduced the misclassification rate from 55%, as previously reported to 6.9%. Individuals who engaged in sedentary activity (i.e. sitting) had the greater change in arch height compared to active activity (i.e. standing and walking), which is more likely to affect the obtained measure. Therefore, a test protocol now states that participants are not allowed to sit over 100 min prior the measurement to reduce such interference. We have proposed and tested an automated algorithm to translate scanned data including seven foot's parameters into customised parametric design of the insert. The method decreases the required time of orthotic computer-aided design from over 3 h to less than 2 min. A finite element analysis procedure was additionally developed to assess the performance of geometries and material of designed orthotic based on the distribution of plantar pressure and internal stress. The personalized comparative assessment based on midfoot contact area was carried out periodically for follow-up and the orthotic could be re-designed if necessary. The proposed automated procedure develops a pre-screening system to distinguish low arch and provide preventatives before it becomes symptomatic. Furthermore, non-symptom flatfoot can be detected at early stages and referred to medics for further diagnosis or treatment.

Development of a Novel Cytokine Vehicle Using Filamentous Phage Display for Colorectal Cancer Treatment.

Due to its highly immunogenic nature and the great engineerability, filamentous phage has shown promising antitumor activities in preclinical studies. Previous designs of antitumor phage mainly focused on tumor targeting using a cancer-specific moiety displayed on the minor capsid protein, pIII. In this work, we developed a new therapeutic platform of filamentous phage, in which the major capsid protein pVIII was utilized for displaying an antitumor cytokine. We showcased that a 16.1-kD cytokine GM-CSF could be efficiently presented on the M13 phage particle using the 8 + 8 type display system through a highly tolerable pVIII variant P8(1a). We verified that the GM-CSF phage was a potent activator for STAT5 signaling in murine macrophage. The GM-CSF phage significantly reduced the tumor size by more than 50% as compared to the unmodified phage in a murine colorectal cancer model. Immunological profiling of the tumor-infiltrating leukocytes revealed that an increase of CD4+ lymphocytes in the GM-CSF phage treatment group. Furthermore, the combined therapy of the GM-CSF phage and radiation greatly improved the therapeutic potency with a 100% survival rate and a 25% complete remission rate. We observed that the IFN-γ expression was dramatically up-regulated by the combined therapy in multiple types of tumor-infiltrating immune cells. Overall, we created a novel vehicle for cytokine therapy using the pVIII filamentous phage display. This new platform can be multiplexed with other phage engineering approaches, such as displaying targeting ligands on pIII or encapsulating therapeutic genes inside phage capsids, to create multifunctional nanoparticles for cancer therapy.

Pigment production by a new thermotolerant microalga Coelastrella sp. F50.

Microalgae are good crops to produce natural pigments because of their high growth rates. Tropical zones are better locations than temperate areas for microalgal cultivation because they have longer duration of daylight and more stable temperatures throughout the year, but the high temperatures pose a challenge to microalgal cultivation. A newly isolated thermotolerant microalga produces reddish pigments under environmental stress. Morphological and molecular evidence including meridional ribs on the cell wall, pigment production, and its 18S rDNA sequence suggests that this microalga belongs to the genus Coelastrella. Salt stress and high light intensity accelerated biosynthesis of the pigments, and significant quantities of oil accumulated as the cells experienced stress due to nutrient deficiency. This microalga could withstand temperature of 50°C for more than 8h, which is a necessary trait for outdoor cultivation in tropical areas. The pigments contain astaxanthin, lutein, canthaxanthin, and ß-carotene as analysed by using HPLC.