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BackgroundRadiotherapy (RT) is one of the most important treatments for patients with colorectal cancer (CRC). Radioresistance is the crucial cause of poor therapeutic outcomes in colorectal cancer. However, the underlying mechanism of radioresistance in colorectal cancer is still poorly defined. Herein we established a radioresistant colorectal cancer cell line and performed transcriptomics analyses to search for the underlying genes that contribute to radioresistance and investigate its association with the prognosis of CRC patients.MethodsThe radioresistant cell line was developed from the parental HCT116 cell by a stepwise increased dose of irradiation. Differential gene analysis was performed using cellular transcriptome data to identify genes associated with radioresistance, from which extracellular matrix (ECM) and cell adhesion-related genes were screened. Survival data from a CRC cohort in the TCGA database were used for further model gene screening and validation. The correlation between the risk score model and tumor microenvironment, clinical phenotype, drug treatment sensitivity, and tumor mutation status were also investigated.ResultsA total of 493 different expression genes were identified from the radioresistant and wild-type cell line, of which 94 genes were associated with ECM and cell adhesion-related genes. The five model genes TNFRSF13C, CD36, ANGPTL4, LAMB3, and SERPINA1 were identified for CRC radioresistance via screening using the best model. A ROC curve indicated that the AUC of the resulting prognostic model (based on the 5-gene risk score and other clinical parameters, including age, sex, and tumor stages) was 0.79, 0.77, and 0.78 at 1, 2, and 3 years, respectively. The calibration curve showed high agreement between the risk score prediction and actual survival probability. The immune microenvironment, drug treatment sensitivity, and tumor mutation status significantly differed between the high- and low-risk groups.ConclusionsThe risk score model built with five radioresistance genes in this study, including TNFRSF13C, CD36, ANGPTL4, LAMB3, and SERPINA1, showed favorable performance in prognosis prediction after radiotherapy for CRC.

Additional file 5. The primer sequence. The forward and reverse primer sequence of PER1, AKAP12 and MMP17.

Additional file 2. Angiogenesis-related gene signature. The gene signatures were intersection of published papers investigating angiogenesis in ovarian cancer and the HALLMARK_ANGIOGENESIS from Molecular Signatures Database.

Additional file 3. The immune gene signatures. The gene signatures involved in immunity from 5 literatures and their coefficients.

Additional file 1. MSC-related gene signature. The gene signatures were extracted from the GOBP_MESENCHYMAL_STEM_CELL_DIFFERENTIATION and GOBP_MESENCHYMAL_STEM_CELL_PROLIFERATION in Molecular Signatures Database.

Additional file 12. Genes in the MSC score related prognostic model. Multivariate Cox regression analysis was conducted to identify MSC-score-related genes associated with OS and three genes (MMP17, AKAP12, andPER1) were used to construct the prognostic model.

Additional file 15. Difference between staining index of PER1, AKAP12 and MMP17 and tumor size among SOC samples. Difference between staining index of PER1, AKAP12 and MMP17 and tumor size among SOC samples via Mann-Whitney U test.

Additional file 10. KEGG pathway analysis between low and high MSC score group. KEGG pathway analysis of DEGs between groups with low and high MSC scores.

Additional file 11. Genes related to prognosis in brown module. Prognostic genes in module correlated with MSC score.

Additional file 4. The tumor mutational burden of GSE91061. The tumor mutation burden of GSE91061.

Additional file 7. Protocol for immune-histochemistry. Details for immune-histochemistry.

Additional file 13. C-index of TCGA cohort, GEO cohorts and nomogram. Standard error, minimum value, maximum value and P value of C-index of TCGA cohort, GEO cohorts and nomogram.

Additional file 9. GO enrichment analysis between low and high MSC score group. GO enrichment analysis of DEGs between groups with low and high MSC scores.

Additional file 6. Protocol for reverse transcription and real-time polymerase chain reaction. Details for reverse transcription and real-time polymerase chain reaction.

We present the mass-metallicity relation (MZR) at $z=2-3$ in the stellar mass range of $M_\star\approx 10^{6.5}-10^{9.5}M_\odot$ using 55 dwarf galaxies in the Abell 2744 and SMACS J0723-3732 galaxy cluster fields. These dwarf galaxies are identified and confirmed by deep JWST/NIRISS imaging and slitless grism spectroscopic observations. Taking advantage of the gravitational lensing effect, we extend the previous MZR relation at $z=2-3$ to a much lower mass regime by more than 2.5 orders of magnitude compared with previous studies. We find that the MZR has a shallower slope at the low-mass end ($M_\star10^{9}M_\odot$), with a slope turnover point at around the stellar mass of $10^9 M_\odot$. This implies that dominating feedback processes in dwarf galaxies may be different from that in galaxies with higher mass. From $z=3$ to $z=2$, the metallicity of the dwarf galaxies is enhanced by $\approx0.1$ dex for a given stellar mass, consistent with the mild evolution found in galaxies with higher mass. Further, we confirm the existence of a 3D relation between the gas-phase metallicity, stellar mass, and star formation rate, i.e., fundamental metallicity relation (FMR), in dwarf galaxies at $z=2-3$. Our derived FMR, which has no significant redshift evolution, can be used as a benchmark to understand the origin of the anti-correlation between SFR and metallicity of dwarf galaxies in the high-redshift Universe., 16 pages, 4 figures, 1 table, submitted to AAS Journal; welcome comments

Metastasis, a primary cause of death in patients with malignancies, is promoted by intrinsic changes in both tumor and non-malignant cells in the tumor microenvironment (TME). As major components of the TME, tumor-associated neutrophils (TANs) promote tumor progression and metastasis through communication with multiple growth factors, chemokines, inflammatory factors, and other immune cells, which together establish an immunosuppressive TME. In this review, we describe the potential mechanisms by which TANs participate in tumor metastasis based on recent experimental evidence. We have focused on drugs in chemotherapeutic regimens that target TANs, thereby providing a promising future for cancer immunotherapy.

The physical and chemical properties of the circumgalactic medium (CGM) at $z\gtrsim6$ have been studied successfully through the absorption in the spectra of background Quasi-Stellar Objects (QSOs). One of the most crucial questions is to investigate the nature and location of the source galaxies that give rise to these early metal absorbers. Theoretical models suggest that momentum-driven outflows from typical star-forming galaxies can eject metals into the CGM and the intergalactic medium (IGM) at z=5-6. Deep, dedicated surveys have searched for Ly$��$ emission associated with strong CIV absorbers at $z\approx 6$, but only a few Ly$��$ emitter candidates have been detected. Interpreting these detections is moreover ambiguous because Ly$��$ is a resonant line, raising the need for complementary techniques for detecting absorbers' host galaxies. Here, using Atacama Large Millimeter Array (ALMA), we report a [C II] 158$��$m emitter associated with a strong low-ionization absorber, OI, at $z=5.978$. The projected impact parameter between OI and [C II] emitter is 20.0 kpc. The measured [C II] luminosity is $7.0\times 10^7$ solar luminosities. Further analysis indicates that strong OI absorbers may reside in the circumgalactic medium of massive halos one to two orders of magnitude more massive than expected values., Published in Nature Astronomy on Sep 27, 2021; 45 pages; authors' version. Link to the paper: https://www.nature.com/articles/s41550-021-01471-4

Additional file 3: Supplementary tables.

Malignant tumors still pose serious threats to human health due to their high morbidity and mortality. Recurrence and metastasis are the most important factors affecting patient prognosis. Chemotherapeutic drugs and radiation used to treat these tumors mainly interfere with tumor metabolism, destroy DNA integrity, and inhibit protein synthesis. The upregulation of small ubiquitin-like modifier (SUMO) is a prevalent posttranslational modification (PTM) in various cancers and plays a critical role in tumor development. The dysregulation of SUMOylation can protect cancer cells from stresses exerted by external or internal stimuli. SUMOylation is a dynamic process finely regulated by SUMOylation enzymes and proteases to maintain a balance between SUMOylation and deSUMOylation. An increasing number of studies have reported that SUMOylation imbalance may contribute to cancer development, including metastasis, angiogenesis, invasion, and proliferation. High level of SUMOylation is required for cancer cells to survive internal or external stresses. Downregulation of SUMOylation may inhibit the development of cancer, making it an important potential clinical therapeutic target. Some studies have already begun to treat tumors by inhibiting the expression of SUMOylation family members, including SUMO E1 or E2. The tumor cells become more aggressive under internal and external stresses. The prevention of tumor development, metastasis, recurrence, and radiochemotherapy resistance by attenuating SUMOylation requires further exploration. This review focused on SUMOylation in tumor cells to discuss its effects on tumor suppressor proteins and oncoproteins as well as classical tumor pathways to identify new insights for cancer clinical therapy.

Adipogenesis is the process through which preadipocytes differentiate into adipocytes. During this process, the preadipocytes cease to proliferate, begin to accumulate lipid droplets, and develop morphologic and biochemical characteristics of mature adipocytes. Mesenchymal stem cells (MSCs) are a type of adult stem cells known for their high plasticity and capacity to generate mesodermal and nonmesodermal tissues. Many mature cell types can be generated from MSCs, including adipocyte, osteocyte, and chondrocyte. The differentiation of stem cells into multiple mature phenotypes is at the basis for tissue regeneration and repair. Cancer stem cells (CSCs) play a very important role in tumor development and have the potential to differentiate into multiple cell lineages. Accumulating evidence has shown that cancer cells can be induced to differentiate into various benign cells, such as adipocytes, fibrocytes, osteoblast, by a variety of small molecular compounds, which may provide new strategies for cancer treatment. Recent studies have reported that tumor cells undergoing epithelial-to-mesenchymal transition can be induced to differentiate into adipocytes. In this review, molecular mechanisms, signal pathways, and the roles of various biological processes in adipose differentiation are summarized. Understanding the molecular mechanism of adipogenesis and adipose differentiation of cancer cells may contribute to cancer treatments that involve inducing differentiation into benign cells.

Additional file 1: Supplementary figures and figure legends.

Additional file 2. Supplementary materials and methods.

Peer-reviewed journal article, Applied Rheology

We previously reported that polyploid giant cancer cells (PGCGs) induced by CoCl2 could form through endoreduplication or cell fusion. A single PGCC formed tumors in immunodeficient mice. PGCCs are also the key contributors to the cellular atypia and associate with the malignant grade of tumors. PGCCs have the properties of cancer stem cells and produce daughter cells via asymmetric cell division. Compared with diploid cancer cells, these daughter cells express less epithelial markers and acquire mesenchymal phenotype with importance in cancer development and progression. Tumor budding is generally recognized to correlate with a high recurrence rate, lymph node metastasis, chemoresistance, and poor prognosis of colorectal cancers (CRCs) and is a good indicator to predict the metastasis and aggressiveness in CRCs. Micropapillary pattern is a special morphologic pattern and also associates with tumor metastasis and poor prognosis. There are similar morphologic features and molecular phenotypes among tumor budding, micropapillary carcinoma pattern, and PGCCs with their budding daughter cells and all of them show strong ability of tumor invasion and migration. In this review, we discuss the cancer stem cell properties of PGCCs, the molecular mechanisms of their regulation, and the relationships with tumor budding and micropapillary pattern in CRCs.

Asymmetric cell division is critical for generating cell diversity in low eukaryotic organisms. We previously have reported that polyploid giant cancer cells (PGCCs) induced by cobalt chloride demonstrate the ability to use an evolutionarily conserved process for renewal and fast reproduction, which is normally confined to simpler organisms. The budding yeast, Saccharomyces cerevisiae, which reproduces by asymmetric cell division, has long been a model for asymmetric cell division studies. PGCCs produce daughter cells asymmetrically in a manner similar to yeast, in that both use budding for cell polarization and cytokinesis. Here, we review the results of recent studies and discuss the similarities in the budding process between yeast and PGCCs.

Paclitaxel is widely used to treat cancer patients through the blocking of mitosis and result in formation of polyploidy giant cancer cells (PGCCs), which are generally believed to be non-dividing cells or in mitotic catastrophe. Here we showed that PGCCs following the treatment of paclitaxel of MCF-7 breast cancer cell line have capability to generate regular-sized progeny cells through budding. The PGCCs not only grew into well differentiated cancer cells that formed cancer organotypic structures in vitro but also trans-differentiated into multiple tumor stromal cells including myoepithelial, endothelial, and erythroid cells. PGCCs formed glandular and vessel-like cancer organotypic structures that expressed normal stem cell markers. These progeny cells generated from PGCCs showed decreased ability of proliferation, invasion and tumor growth and became more resistant to paclitaxel than parental MCF-7 cells. These results demonstrated that paclitaxel-induced PGCCs have properties of cancer stem cells that can generate both epithelial cancer cells and multi-lineage of stromal cells. PGCCs are not only the morphogenic determinant to tumor histogenesis and but also contribute to paclitaxel resistance.

Materials with programmable conductivity and stiffness offer new design opportunities for next-generation engineered systems in soft robotics and electronic devices. However, existing approaches fail to harness variable electrical and mechanical properties synergistically and lack the ability to self-respond to environmental changes. We report an electro-mechano responsive Field’s metal hybrid elastomer exhibiting variable and tunable conductivity, strain sensitivity, and stiffness. By synergistically harnessing these properties, we demonstrate two applications with over an order of magnitude performance improvement compared to state-of-the-art, including a self-triggered multiaxis compliance compensator for robotic manipulators, and a resettable, highly compact, and fast current-limiting fuse with an adjustable fusing current. We envisage that the extraordinary electromechanical properties of our hybrid elastomer will bring substantial advancements in resilient robotic systems, intelligent instruments, and flexible electronics.