Agent-based modeling for the tumor microenvironment (TME).

Cancer is a disease that arises from the uncontrolled growth of abnormal (tumor) cells in an organ and their subsequent spread into other parts of the body. If tumor cells spread to surrounding tissues or other organs, then the disease is life-threatening due to limited treatment options. This work applies an agent-based model to investigate the effect of intra-tumoral communication on tumor progression, plasticity, and invasion, with results suggesting that cell-cell and cell-extracellular matrix (ECM) interactions affect tumor cell behavior.

Metabolic homeostasis in fungal infections from the perspective of pathogens, immune cells, and whole-body systems.

SUMMARYThe ability to overcome metabolic stress is a major determinant of outcomes during infections. Pathogens face nutrient and oxygen deprivation in host niches and during their encounter with immune cells. Immune cells require metabolic adaptations for producing antimicrobial compounds and mounting antifungal inflammation.

The first demonstration of entirely roll-to-roll fabricated perovskite solar cell modules under ambient room conditions.

The rapid development of organic-inorganic hybrid perovskite solar cells has resulted in laboratory-scale devices having power conversion efficiencies that are competitive with commercialised technologies. However, hybrid perovskite solar cells are yet to make an impact beyond the research community, with translation to large-area devices fabricated by industry-relevant manufacturing methods remaining a critical challenge. Here we report the first demonstration of hybrid perovskite solar cell modules, comprising serially-interconnected cells, produced entirely using industrial roll-to-roll printing tools under ambient room conditions.

The C-terminal protein interaction domain of the chromatin reader Yaf9 is critical for pathogenesis of .

Fungal infections cause a large health burden but are treated by only a handful of antifungal drug classes. Chromatin factors have emerged as possible targets for new antifungals. These targets include the reader proteins, which interact with posttranslationally modified histones to influence DNA transcription and repair.

The short-chain fatty acid crotonate reduces invasive growth and immune escape of by regulating hyphal gene expression.

Macrophages curtail the proliferation of the pathogen within human body niches. Within macrophages, adapts its metabolism and switches to invasive hyphal morphology. These adaptations enable fungal growth and immune escape by triggering macrophage lysis.

Synthesis of 2D VO Nanosheets for the Dual Optical Sensor Method by Colorimetric and Fluorometric Sensing of Catecholamines.

For the first time, we report a dual optical sensor method (DOSM) using novel 2D VO nanosheets to act as fluorometric and colorimetric sensors to perform quantitative analysis of epinephrine (EP) and dopamine (DA). The wide color spectrum of the 2D vanadium oxidation series and specifically metastable blue 2D VO nanosheets were used to develop a DOSM biosensor. DA and EP are the major catecholamines in the human body that play vital roles as neurotransmitters and stress-responsive hormones of the endocrine system, respectively.

Leveraging the MMV Pathogen Box to Engineer an Antifungal Compound with Improved Efficacy and Selectivity against .

Fungal infections pose a significant and increasing threat to human health, but the current arsenal of antifungal drugs is inadequate. We screened the Medicines for Malaria Venture (MMV) Pathogen Box for new antifungal agents against three of the most critical species (, , and ). Of the 14 identified hit compounds, most were active against and .

The proteasome regulator Rpn4 controls antifungal drug tolerance by coupling protein homeostasis with metabolic responses to drug stress.

Fungal pathogens overcome antifungal drug therapy by classic resistance mechanisms, such as increased efflux or changes to the drug target. However, even when a fungal strain is susceptible, trailing or persistent microbial growth in the presence of an antifungal drug can contribute to therapeutic failure. This trailing growth is caused by adaptive physiological changes that enable the growth of a subpopulation of fungal cells in high drug concentrations, in what is described as drug tolerance.

The escape of Candida albicans from macrophages is enabled by the fungal toxin candidalysin and two host cell death pathways.

The egress of Candida hyphae from macrophages facilitates immune evasion, but it also alerts macrophages to infection and triggers inflammation. To better define the mechanisms, here we develop an imaging assay to directly and dynamically quantify hyphal escape and correlate it to macrophage responses. The assay reveals that Candida escapes by using two pore-forming proteins to permeabilize macrophage membranes: the fungal toxin candidalysin and Nlrp3 inflammasome-activated Gasdermin D.

Disruption of Iron Homeostasis and Mitochondrial Metabolism Are Promising Targets to Inhibit Candida auris.

Fungal infections are a global threat, but treatments are limited due to a paucity in antifungal drug targets and the emergence of drug-resistant fungi such as Candida auris. Metabolic adaptations enable microbial growth in nutrient-scarce host niches, and they further control immune responses to pathogens, thereby offering opportunities for therapeutic targeting. Because it is a relatively new pathogen, little is known about the metabolic requirements for C.

Fully Roll-to-Roll Processed Efficient Perovskite Solar Cells via Precise Control on the Morphology of PbI:CsI Layer.

Perovskite solar cells (PSCs) have attracted tremendous attention as a promising alternative candidate for clean energy generation. Many attempts have been made with various deposition techniques to scale-up manufacturing. Slot-die coating is a robust and facile deposition technique that can be applied in large-area roll-to-roll (R2R) fabrication of thin film solar cells with the advantages of high material utilization, low cost and high throughput.

The novel Dbl homology/BAR domain protein, MsgA, of Talaromyces marneffei regulates yeast morphogenesis during growth inside host cells.

Microbial pathogens have evolved many strategies to evade recognition by the host immune system, including the use of phagocytic cells as a niche within which to proliferate. Dimorphic pathogenic fungi employ an induced morphogenetic transition, switching from multicellular hyphae to unicellular yeast that are more compatible with intracellular growth. A switch to mammalian host body temperature (37 °C) is a key trigger for the dimorphic switch.

Immunometabolism in fungal infections: the need to eat to compete.

Immune cells, including macrophages and monocytes, remodel their metabolism and have specific nutritional needs when dealing with microbial pathogens. While we are just beginning to understand immunometabolism in fungal infections, emerging themes include recognition of fungal cell surface molecule driving metabolic remodelling to increase glycolysis, the critical role of glycolysis in the production of antifungal cytokines and fungicidal effector molecules, and the need for maintaining host glucose homeostasis to defeat fungal infections. A crosstalk between host and pathogen metabolic pathways determines the fate of immune cells and fungi when they interact.

Mathematical Models of Cancer Cell Plasticity.

Quantitative modelling is increasingly important in cancer research, helping to integrate myriad diverse experimental data into coherent pictures of the disease and able to discriminate between competing hypotheses or suggest specific experimental lines of enquiry and new approaches to therapy. Here, we review a diverse set of mathematical models of cancer cell plasticity (a process in which, through genetic and epigenetic changes, cancer cells survive in hostile environments and migrate to more favourable environments, respectively), tumour growth, and invasion. Quantitative models can help to elucidate the complex biological mechanisms of cancer cell plasticity.

A unique aspartyl protease gene expansion in Talaromyces marneffei plays a role in growth inside host phagocytes.

Aspartyl proteases are a widely represented class of proteolytic enzymes found in eukaryotes and retroviruses. They have been associated with pathogenicity in a range of disease-causing microorganisms. The dimorphic human-pathogenic fungus Talaromyces marneffei has a large expansion of these proteases identified through genomic analyses.

Macrophages protect Talaromyces marneffei conidia from myeloperoxidase-dependent neutrophil fungicidal activity during infection establishment in vivo.

Neutrophils and macrophages provide the first line of cellular defence against pathogens once physical barriers are breached, but can play very different roles for each specific pathogen. This is particularly so for fungal pathogens, which can occupy several niches in the host. We developed an infection model of talaromycosis in zebrafish embryos with the thermally-dimorphic intracellular fungal pathogen Talaromyces marneffei and used it to define different roles of neutrophils and macrophages in infection establishment.

Beyond Fullerenes: Indacenodithiophene-Based Organic Charge-Transport Layer toward Upscaling of Low-Cost Perovskite Solar Cells.

Phenyl-C-butyric acid methyl ester (PCBM) is universally used as the electron-transport layer (ETL) in the low-cost inverted planar structure of perovskite solar cells (PeSCs). PCBM brings tremendous challenges in upscaling of PeSCs using industry-relevant methods due to its aggregation behavior, which undermines the power conversion efficiency and stability. Herein, we highlight these, seldom reported, challenges with PCBM.

Near diffraction-limited performance of an OPA pumped acetylene-filled hollow-core fiber laser in the mid-IR.

We investigate the mid-IR laser beam characteristics from an acetylene-filled hollow-core optical fiber gas laser (HOFGLAS) system. The laser exhibits near-diffraction limited beam quality in the 3 μm region with M = 1.15 ± 0.

Organism-wide studies into pathogenicity and morphogenesis in Talaromyces marneffei.

Organism-wide approaches examining the genetic mechanisms controlling growth and proliferation have proven to be a powerful tool in the study of pathogenic fungi. For many fungal pathogens techniques to study transcription and protein expression are particularly useful, and offer insights into infection processes by these species. Here we discuss the use of approaches such as differential display, suppression subtractive hybridization, microarray, RNA-seq, proteomics, genetic manipulation and infection models for the AIDS-defining pathogen Talaromyces marneffei.

Ultrafast Fabrication of Flexible Dye-Sensitized Solar Cells by Ultrasonic Spray-Coating Technology.

This study investigates novel deposition techniques for the preparation of TiO2 electrodes for use in flexible dye-sensitized solar cells. These proposed new methods, namely pre-dye-coating and codeposition ultrasonic spraying, eliminate the conventional need for time-consuming processes such as dye soaking and high-temperature sintering. Power conversion efficiencies of over 4.

Tools for high efficiency genetic manipulation of the human pathogen Penicillium marneffei.

Penicillium marneffei is an opportunistic pathogen of humans and displays a temperature dependent dimorphic transition. Like many fungi, exogenous DNA introduced by DNA mediated transformation is integrated randomly into the genome resulting in inefficient gene deletion and position-specific effects. To enhance successful gene targeting, the consequences of perturbing components of the non-homologous end joining recombination pathway have been examined.