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The development of a suitable three dimensional (3D) culture system for anticancer drug development remains an unmet need. Despite progress, a simple, rapid, scalable and inexpensive 3D-tumor model that recapitulates in vivo tumorigenesis is lacking. Herein, we report on the development and characterization of a 3D nanofibrous scaffold produced by electrospinning a mixture of poly(lactic-co-glycolic acid) (PLGA) and a block copolymer of polylactic acid (PLA) and mono-methoxypolyethylene glycol (mPEG) designated as 3P. Cancer cells cultured on the 3P scaffold formed tight irregular aggregates similar to in vivo tumors, referred to as tumoroids that depended on the topography and net charge of the scaffold. 3P scaffolds induced tumor cells to undergo the epithelial-to-mesenchymal transition (EMT) as demonstrated by up-regulation of vimentin and loss of E-cadherin expression. 3P tumoroids showed higher resistance to anticancer drugs than the same tumor cells grown as monolayers. Inhibition of ERK and PI3K signal pathways prevented EMT and reduced tumoroid formation, diameter and number. Fine needle aspirates, collected from tumor cells implanted in mice when cultured on 3P scaffolds formed tumoroids, but showed decreased sensitivity to anticancer drugs, compared to tumoroids formed by direct seeding. These results show that 3P scaffolds provide an excellent platform for producing tumoroids from tumor cell lines and from biopsies and that the platform can be used to culture patient biopsies, test for anticancer compounds and tailor a personalized cancer treatment.

Ultraviolet (UV) irradiation-based methods used for viral inactivation have provided an important avenue targeting severe acute respiratory-syndrome coronavirus-2 (SARS-CoV-2) virus. A major problem with state-of-the-art UV inactivation technology is that it is based on UV lamps, which have limited efficiency, require high power, large doses, and long irradiation times. These drawbacks limit the use of UV lamps in air filtering systems and other applications. To address these limitations, herein we report on the fabrication of a device comprising a pulsed nanosecond 266 nm UV laser coupled to an integrating cavity (LIC) composed of a UV reflective material, polytetrafluoroethylene. Previous UV lamp inactivation cavities were based on polished walls with specular reflections, but the diffuse reflective UV ICs were not thoroughly explored for virus inactivation. Our results show that LIC device can inactivate several respiratory viruses including SARS-CoV-2, at ~ 1 ms effective irradiation time, with > 2 orders of magnitude higher efficiency compared to UV lamps. The demonstrated 3 orders of magnitude cavity enhancement relative to direct exposure is crucial for the development of efficient real-time UV air and water purification systems. To the best of our knowledge this is the first demonstration of LIC application for broad viral inactivation with high efficiency.

This article presents a feminist critical reading of the Plague Tale game series, addressing the lack of complex portrayals of mothers and mothering in games. Through close reading using Ruddick's maternal thinking framework as an analytical lens, it focuses on how narrative, gameplay, and character design depict player-character Amicia's 'motherly sister' role, positioning motherliness as a uniquely feminine strength. Particular attention is given to Amicia's psychological and emotional conflicts and their reflection of real-world lived experiences of mothers, demonstrated through interconnected themes of bonding and tension, childliness and growth, and maternal guilt and power. The analysis also explores the reversal of gendered role dynamics, with male characters occupying support roles traditionally assigned to females, further signifying the centrality of feminine strength. These male characters are also imbued with motherly thinking traits, demonstrating how 'motherliness' can enhance complex gender role representations across the gender spectrum. Positioned as a 'Double-A' title between the experimental indie and risk-averse but wider-reaching 'Triple-A' sectors, Plague Tale's critical and commercial success demonstrates the market viability of mothering and caregiving narratives in games. As such, it provides a significant contribution to progressive advancement of gender role and motherhood discourses in games culture and industry practice.

The emergence of a novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), in December 2019 led to a worldwide pandemic with over 170 million confirmed infections and over 3.5 million deaths (as of May 2021). Early studies have shown higher mortality rates from SARS-CoV-2 infection in cancer patients than individuals without cancer. Herein, we review the evidence that the gut microbiota plays a crucial role in health and has been linked to the development of colorectal cancer (CRC). Investigations have shown that SARS-CoV-2 infection causes changes to the gut microbiota, including an overall decline in microbial diversity, enrichment of opportunistic pathogens such as Fusobacterium nucleatum bacteremia, and depletion of beneficial commensals, such as the butyrate-producing bacteria. Further, these changes lead to increased colonic inflammation, which leads to gut barrier disruption, expression of genes governing CRC tumorigenesis, and tumor immunosuppression, thus further exacerbating CRC progression. Additionally, a long-lasting impact of SARS-CoV-2 on gut dysbiosis might result in a greater possibility of new CRC diagnosis or aggravating the condition in those already afflicted. Herein, we review the evidence relating to the current understanding of how infection with SARS-CoV-2 impacts the gut microbiota and the effects this will have on CRC carcinogenesis and progression.

The satellite-based techniques for the monitoring of extreme ice features (EIFs) in the Canadian Arctic were investigated and demonstrated using synthetic aperture radar (SAR) and electro-optical data sources. The main EIF types include large ice islands and ice-island fragments, multiyear hummock fields (MYHF) and other EIFs, such as fragments of MYHF and large, newly formed hummock fields. The main objectives for the paper included demonstration of various satellite capabilities over specific regions in the Canadian Arctic to assess their utility to detect and characterize EIFs. Stereo pairs of very-high-resolution (VHR) imagery provided detailed measurements of sea ice topography and were used as validation information for evaluation of the applied techniques. Single-pass interferometric SAR (InSAR) data were used to extract ice topography including hummocks and ice islands. Shape from shading and height from shadow techniques enable us to extract ice topography relying on a single image. A new method for identification of EIFs in sea ice based on the thermal infrared band of Landsat 8 was introduced. The performance of the methods for ice feature height estimation was evaluated by comparing with a stereo or InSAR digital elevation models (DEMs). Full polarimetric RADARSAT-2 data were demonstrated to be useful for identification of ice islands.

Soil moisture is one of the main factors affecting microwave radar backscatter from the ground. While there are other factors that affect backscatter levels (for instance, surface roughness, vegetation, and incident angle), relative variations in soil moisture can be estimated using space-based, medium resolution, multi-temporal synthetic aperture radar (SAR). Understanding the distribution and identification of water-saturated areas using SAR soil moisture can be important for wetland mapping. The SAR soil moisture retrieval algorithm provides a relative assessment and requires calibration over wet and dry periods. In this work, relative soil moisture indicators are derived from a time series of the RADARSAT Constellation Mission (RCM) SAR compact polarimetric (CP) data over reclaimed areas of an oil sands mine in Alberta, Canada. An evaluation of the soil moisture product is performed using in situ measurements showing agreement from June to September. The surface scattering component of m-chi CP decomposition and the RL SAR products demonstrated a good agreement with the field data (low RMSE values and a perfect alignment with field-identified wetlands).

The axis of Programmed cell death-1 receptor (PD-1) with its ligand (PD-L1) plays a critical role in colorectal cancer (CRC) in escaping immune surveillance, and blocking this axis has been found to be effective in a subset of patients. Although blocking PD-L1 has been shown to be effective in 5–10% of patients, the majority of the cohorts show resistance to this checkpoint blockade (CB) therapy. Multiple factors assist in the growth of resistance to CB, among which T cell exhaustion and immunosuppressive effects of immune cells in the tumor microenvironment (TME) play a critical role along with other tumor intrinsic factors. We have previously shown the polyketide antibiotic, Mithramycin-A (Mit-A), an effective agent in killing cancer stem cells (CSCs) in vitro and in vivo in a subcutaneous murine model. Since TME plays a pivotal role in CB therapy, we tested the immunomodulatory efficacy of Mit-A with anti-PD-L1 mAb (αPD-L1) combination therapy in an immunocompetent MC38 syngeneic orthotopic CRC mouse model. Tumors and spleens were analyzed by flow cytometry for the distinct immune cell populations affected by the treatment, in addition to RT-PCR for tumor samples. We demonstrated the combination treatment decreases tumor growth, thus increasing the effectiveness of the CB. Mit-A in the presence of αPD-L1 significantly increased CD8 + T cell infiltration and decreased immunosuppressive granulocytic myeloid-derived suppressor cells and anti-inflammatory macrophages in the TME. Our results revealed Mit-A in combination with αPD-L1 has the potential for augmented CB therapy by turning an immunologically “cold” into “hot” TME in CRC.

A novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), arose late in 2019, with disease pathology ranging from asymptomatic to severe respiratory distress with multi-organ failure requiring mechanical ventilator support. It has been found that SARS-CoV-2 infection drives intracellular complement activation in lung cells that tracks with disease severity. However, the cellular and molecular mechanisms responsible remain unclear. To shed light on the potential mechanisms, we examined publicly available RNA-Sequencing data using CIBERSORTx and conducted a Ingenuity Pathway Analysis to address this knowledge gap. In complement to these findings, we used bioinformatics tools to analyze publicly available RNA sequencing data and found that upregulation of complement may be leading to a downregulation of T-cell activity in lungs of severe COVID-19 patients. Thus, targeting treatments aimed at the modulation of classical complement and T-cell activity may help alleviate the proinflammatory effects of COVID-19, reduce lung pathology, and increase the survival of COVID-19 patients.

The failure of lung cancer treatments has been attributed mostly to the development of drug resistance, however the underlying cellular and molecular mechanisms are poorly understood. Cancer initiating stem cells (CSCs), present in tumors in a small percentage, play critical roles in the development of drug resistance, metastasis, and cancer relapse. Hence, novel treatments targeting both bulk cancer cells and CSCs are under intense investigation. Herein, we report that lung cancer cells grown on a 3D fibrous scaffold form tumoroids that resemble in vivo tumors, expand CSCs, and provide a platform to identify anti-CSC drugs. The screening of an NCI library of FDA-approved drugs using tumoroid cultures led to identification of Actinomycin D (AD) as a top CSC inhibitor. Since CSCs are mostly resident in the tumor’s inner core, AD was combined with an angiotensin receptor antagonist, Telmisartan (TS), which is known to increase drug permeability in tumors and was shown to have anti-CSC activity. Our results showed that AD + TS administered intra-tumorally was significantly more effective than either drug alone in both syngeneic and xenograft mouse models. The results of mechanistic studies revealed that CSC expansion in tumoroids was associated with activation of β catenin signaling and that AD + TS treatment reduced active β catenin levels in tumors. Together, these results establish the utility of the tumoroid culture system to expand CSCs ex vivo for targeted drug screening, to identify promising novel treatments with both anti-CSC and anti-cancer effects, and to individualize treatments for metastatic drug resistant lung cancer patients.

Detection and quantification of cell viability and growth in two-dimensional (2D) and three-dimensional (3D) cell cultures commonly involve harvesting of cells and therefore requires a parallel set-up of several replicates for time-lapse or dose–response studies. Thus, developing a non-invasive and touch-free detection of cell growth in longitudinal studies of 3D tumor spheroid cultures or of stem cell regeneration remains a major unmet need. Since surface acoustic waves (SAWs) permit mass loading-based biosensing and have been touted due to their many advantages including low cost, small size and ease of assembly, we examined the potential of SAW-biosensing to detect and quantify cell growth. Herein, we demonstrate that a shear horizontal-surface acoustic waves (SH-SAW) device comprising two pairs of resonators consisting of interdigital transducers and reflecting fingers can be used to quantify mass loading by the cells in suspension as well as within a 3D cell culture platform. A 3D COMSOL model was built to simulate the mass loading response of increasing concentrations of cells in suspension in the polydimethylsiloxane (PDMS) well in order to predict the characteristics and optimize the design of the SH-SAW biosensor. The simulated relative frequency shift from the two oscillatory circuit systems (one of which functions as control) were found to be concordant to experimental data generated with RAW264.7 macrophage and A549 cancer cells. In addition, results showed that SAW measurements per se did not affect viability of cells. Further, SH-SAW biosensing was applied to A549 cells cultured on a 3D electrospun nanofiber scaffold that generate tumor spheroids (tumoroids) and the results showed the device's ability to detect changes in tumor spheroid growth over the course of eight days. Taken together, these results demonstrate the use of SH-SAW device for detection and quantification of cell growth changes over time in 2D suspension cultures and in 3D cell culture models, which may have potential applications in both longitudinal 3D cell cultures in cancer biology and in regenerative medicine.