Host-derived Interleukin 1α induces an immunosuppressive tumor microenvironment via regulating monocyte-to-macrophage differentiation.

Tumor-associated macrophages exhibit high heterogeneity and contribute to the establishment of an immunosuppressive tumor microenvironment (TME). Although numerous studies have demonstrated that extracellular factors promote macrophage proliferation and polarization, the regulatory mechanisms governing the differentiation process to generate phenotypically, and functionally diverse macrophage subpopulations remain largely unexplored. In this study, we examined the influence of interleukin 1α (IL-1α) on the development of an immunosuppressive TME using orthotopic transplantation murine models of breast cancer. Deletion of host Il1α led to the rejection of inoculated congenic tumors. Single-cell sequencing analysis revealed that CX3CR1+ macrophage cells were the primary sources of IL-1α in the TME. The absence of IL-1α reprogrammed the monocyte-to-macrophage differentiation process within the TME, characterized by a notable decrease in the subset of CX3CR+ ductal-like macrophages and an increase in iNOS-expressing inflammatory cells. Comparative analysis of gene signatures in both human and mouse macrophage subsets suggested that IL-1α deficiency shifted the macrophage polarization from M2 to M1 phenotypes, leading to enhanced cytotoxic T lymphocyte activity in the TME. Importantly, elevated levels of IL-1α in human cancers were associated with worse prognosis following immunotherapy. These findings underscore the pivotal role of IL-1α in shaping an immune-suppressive TME through the regulation of macrophage differentiation and activity, highlighting IL-1α as a potential target for breast cancer treatment.

Polymer/copper nanocomplex-induced lysosomal cell death promotes tumor lymphocyte infiltration and synergizes anti-PD-L1 immunotherapy for triple-negative breast cancer.

Our previous research discovered that combining the PDA-PEG polymer with copper ions can selectively kill cancer cells. However, the precise mechanism by which this combination functions was not fully understood. This study revealed that the PDA-PEG polymer and copper ions form complementary PDA-PEG/copper (Poly/Cu) nanocomplexes by facilitating copper ion uptake and lysosomal escape. An in vitro study found that Poly/Cu killed 4T1 cells through a lysosome cell death pathway. Furthermore, Poly/Cu inhibited both the proteasome function and autophagy pathway and induced immunogenic cell death (ICD) in 4T1 cells. The Poly/Cu induced ICD coupled with the checkpoint blockade effect of the anti-PD-L1 antibody (aPD-L1) synergistically promoted immune cell penetration into the tumor mass. Benefiting from the tumor-targeting effect and cancer cell-selective killing effect of Poly/Cu complexes, the combinatory treatment of aPD-L1 and Poly/Cu effectively suppressed the progression of triple-negative breast cancer without inducing systemic side effects.

Trim-Away in adult animals through Nano-ERASER and its application in cancer therapy.

Trim-Away is a versatile intracellular protein degradation pathway that has been extensively explored in vitro. However, the in vivo application of Trim-Away is limited at oocyte and zygote stages due to the lack of an in vivo practical approach for intracellular antibody delivery. To broaden the application of Trim-Away, especially for clinical use, we developed a nanogel-based Nano-ERASER system. Here, we demonstrated that the intracellular delivery of anti-programmed cell death ligand 1 (PD-L1) antibody through Nano-ERASER could effectively deplete PD-L1 in triple negative breast cancer (TNBC) cells and induce cancer cell death. Furthermore, with the help of a tumor tissue-targeted nanogel, anti-PD-L1 antibody-loaded Nano-ERASER effectively inhibited tumor progression in a TNBC mouse model. These results confirmed that Nano-ERASER realized Trim-Away in adult animals for the first time, which could be an effective tool for disease treatment and studying gene/protein function both in vitro and in vivo.

Investigation of Energy Cost of Data Compression Algorithms in WSN for IoT Applications.

The exponential growth in remote sensing, coupled with advancements in integrated circuits (IC) design and fabrication technology for communication, has prompted the progress of Wireless Sensor Networks (WSN). WSN comprises of sensor nodes and hubs fit for detecting, processing, and communicating remotely. Sensor nodes have limited resources such as memory, energy and computation capabilities restricting their ability to process large volume of data that is generated. Compressing the data before transmission will help alleviate the problem. Many data compression methods have been proposed but mainly for image processing and a vast majority of them are not pertinent on sensor nodes because of memory impediment, energy utilization and handling speed. To overcome this issue, authors in this research have chosen Run Length Encoding (RLE) and Adaptive Huffman Encoding (AHE) data compression techniques as they can be executed on sensor nodes. Both RLE and AHE are capable of balancing compression ratio and energy utilization. In this paper, a hybrid method comprising RLE and AHE, named as H-RLEAHE, is proposed and further investigated for sensor nodes. In order to verify the efficacy of the data compression algorithms, simulations were run, and the results compared with the compression techniques employing RLE, AHE, H-RLEAHE, and without the use of any compression approach for five distinct scenarios. The results demonstrate the RLE's efficiency, as it surpasses alternative data compression methods in terms of energy efficiency, network speed, packet delivery rate, and residual energy throughout all iterations.

miR-489 Confines Uncontrolled Estrogen Signaling through a Negative Feedback Mechanism and Regulates Tamoxifen Resistance in Breast Cancer.

Approximately 75% of diagnosed breast cancer tumors are estrogen-receptor-positive tumors and are associated with a better prognosis due to response to hormonal therapies. However, around 40% of patients relapse after hormonal therapies. Genomic analysis of gene expression profiles in primary breast cancers and tamoxifen-resistant cell lines suggested the potential role of miR-489 in the regulation of estrogen signaling and development of tamoxifen resistance. Our in vitro analysis showed that loss of miR-489 expression promoted tamoxifen resistance, while overexpression of miR-489 in tamoxifen-resistant cells restored tamoxifen sensitivity. Mechanistically, we found that miR-489 is an estrogen-regulated miRNA that negatively regulates estrogen receptor signaling by using at least the following two mechanisms: (i) modulation of the ER phosphorylation status by inhibiting MAPK and AKT kinase activities; (ii) regulation of nuclear-to-cytosol translocation of estrogen receptor α (ERα) by decreasing p38 expression and consequently ER phosphorylation. In addition, miR-489 can break the positive feed-forward loop between the estrogen-Erα axis and p38 MAPK in breast cancer cells, which is necessary for its function as a transcription factor. Overall, our study unveiled the underlying molecular mechanism by which miR-489 regulates an estrogen signaling pathway through a negative feedback loop and uncovered its role in both the development of and overcoming of tamoxifen resistance in breast cancers.

Plant trait measurement in 3D for growth monitoring.

BACKGROUND: There is a demand for non-destructive systems in plant phenotyping which could precisely measure plant traits for growth monitoring. In this study, the growth of chilli plants (Capsicum annum L.) was monitored in outdoor conditions. A non-destructive solution is proposed for growth monitoring in 3D using a single mobile phone camera based on a structure from motion algorithm. A method to measure leaf length and leaf width when the leaf is curled is also proposed. Various plant traits such as number of leaves, stem height, leaf length, and leaf width were measured from the reconstructed and segmented 3D models at different plant growth stages. RESULTS: The accuracy of the proposed system is measured by comparing the values derived from the 3D plant model with manual measurements. The results demonstrate that the proposed system has potential to non-destructively monitor plant growth in outdoor conditions with high precision, when compared to the state-of-the-art systems. CONCLUSIONS: In conclusion, this study demonstrated that the methods proposed to calculate plant traits can monitor plant growth in outdoor conditions.

Cancer resistance to immunotherapy: What is the role of cancer stem cells?

Immunotherapy is an emerging form of cancer therapy that is associated with promising outcomes. However, most cancer patients either do not respond to immunotherapy or develop resistance to treatment. The resistance to immunotherapy is poorly understood compared to chemotherapy and radiotherapy. Since immunotherapy targets cells within the tumor microenvironment, understanding the behavior and interactions of different cells within that environment is essential to adequately understand both therapy options and therapy resistance. This review focuses on reviewing and analyzing the special features of cancer stem cells (CSCs), which we believe may contribute to cancer resistance to immunotherapy. The mechanisms are classified into three main categories: mechanisms related to surface markers which are differentially expressed on CSCs and help CSCs escape from immune surveillance and immune cells killing; mechanisms related to CSC-released cytokines which can recruit immune cells and tame hostile immune responses; and mechanisms related to CSC metabolites which modulate the activities of infiltrated immune cells in the tumor microenvironment. This review also discusses progress made in targeting CSCs with immunotherapy and the prospect of developing novel cancer therapies.

Network Lifetime Improvement through Energy-Efficient Hybrid Routing Protocol for IoT Applications.

The application of the Internet of Things (IoT) in wireless sensor networks (WSNs) poses serious challenges in preserving network longevity since the IoT necessitates a considerable amount of energy usage for sensing, processing, and data communication. As a result, there are several conventional algorithms that aim to enhance the performance of WSN networks by incorporating various optimization strategies. These algorithms primarily focus on the network layer by developing routing protocols to perform reliable communication in an energy-efficient manner, thus leading to an enhanced network life. For increasing the network lifetime in WSNs, clustering has been widely accepted as an important method that groups sensor nodes (SNs) into clusters. Additionally, numerous researchers have been focusing on devising various methods to increase the network lifetime. The prime factor that helps to maximize the network lifetime is the minimization of energy consumption. The authors of this paper propose a multi-objective optimization approach. It selects the optimal route for transmitting packets from source to sink or the base station (BS). The proposed model employs a two-step approach. The first step employs a trust model to select the cluster heads (CHs) that manage the data communication between the BS and nodes in the cluster. Further, a novel hybrid algorithm, combining a particle swarm optimization (PSO) algorithm and a genetic algorithm (GA), is proposed to determine the routes for data transmission. To validate the efficacy of the proposed hybrid algorithm, named PSOGA, simulations were conducted and the results were compared with the existing LEACH method and PSO, with a random route selection for five different cases. The obtained results establish the efficiency of the proposed approach, as it outperforms existing methods with increased energy efficiency, increased network throughput, high packet delivery rate, and high residual energy throughout the entire iterations.

Immunogenic Cell Death: A Step Ahead of Autophagy in Cancer Therapy.

Immunogenic cell death (ICD) plays a major role in providing long lasting protective antitumor immunity by the chronic exposure of damage associated molecular patterns (DAMPs) in the tumor microenvironment (TME). DAMPs are essential for attracting immunogenic cells to the TME, maturation of DCs, and proper presentation of tumor antigens to the T cells so they can kill more cancer cells. Thus for the proper release of DAMPs, a controlled mechanism of cell death is necessary. Drug induced tumor cell killing occurs by apoptosis, wherein autophagy may act as a shield protecting the tumor cells and sometimes providing multi-drug resistance to chemotherapeutics. However, autophagy is required for the release of ATP as it remains one of the key DAMPs for the induction of ICD. In this review, we discuss the intricate balance between autophagy and apoptosis and the various strategies that we can apply to make these immunologically silent processes immunogenic. There are several steps of autophagy and apoptosis that can be regulated to generate an immune response. The genes involved in the processes can be regulated by drugs or inhibitors to amplify the effects of ICD and therefore serve as potential therapeutic targets.