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Gut microbiota‐derived metabolites are key hubs connecting the gut microbiome and cancer progression, primarily by remodeling the tumor microenvironment and regulating key signaling pathways in cancer cells and multiple immune cells. The use of microbial metabolites in radiotherapy and chemotherapy mitigates the severe side effects from treatment and improves the efficacy of treatment. Immunotherapy combined with microbial metabolites effectively activates the immune system to kill tumors and overcomes drug resistance. Consequently, various novel strategies have been developed to modulate microbial metabolites. Manipulation of genes involved in microbial metabolism using synthetic biology approaches directly affects levels of microbial metabolites, while fecal microbial transplantation and phage strategies affect levels of microbial metabolites by altering the composition of the microbiome. However, some microbial metabolites harbor paradoxical functions depending on the context (e.g., type of cancer). Furthermore, the metabolic effects of microorganisms on certain anticancer drugs such as irinotecan and gemcitabine, render the drugs ineffective or exacerbate their adverse effects. Therefore, a personalized and comprehensive consideration of the patient's condition is required when employing microbial metabolites to treat cancer. The purpose of this review is to summarize the correlation between gut microbiota‐derived metabolites and cancer, and to provide fresh ideas for future scientific research. [ABSTRACT FROM AUTHOR]

Background: Angiogenesis strongly reflects poor breast cancer outcome and an important contributor to breast cancer (BC) metastasis; therefore, anti-angiogenic intervention is a potential tool for cancer treatment. However, currently used antibodies against vascular endothelial growth factor A (VEGFA) or inhibitors that target the VEGFA receptor are not effective due to weak penetration and low efficiency. Herein, we assessed the anti-BC angiogenic role of muscone, a natural bioactive musk constituent, and explored possible anti-cancer mechanisms of this compound. Methods: CCK-8, EdU, scratch and Transwell assessments were employed to detect the muscone-mediated regulation of breast cancer (BC) and human umbilical vein endothelial cells (HUVECs) proliferation and migration. Tube formation, matrigel plug assay and zebrafish assay were employed for assessment of regulation of tumor angiogenesis by muscone. In vivo xenograft mouse model was constructed to compare microvessel density (MVD), vascular leakage, vascular maturation and function in muscone-treated or untreated mice. RNA sequencing was performed for gene screening, and Western blot verified the effect of the VEGFA-VEGFR2 pathway on BC angiogenic inhibition by muscone. Results: Based on our findings, muscone suppressed BC progression via tumor angiogenic inhibition in cellular and animal models. Functionally, muscone inhibited BC cell proliferation and migration as well as tumor cell-conditioned medium-based endothelial cell proliferation and migration. Muscone exhibited a strong suppressive influence on tumor vasculature in cellular and animal models. It abrogated tumor cell growth in a xenograft BC mouse model and minimized tumor microvessel density and hypoxia, and increased vascular wall cell coverage and perfusion. Regarding the mechanism of action, we found that muscone suppressed phosphorylation of members of the VEGF/PI3K/Akt/MAPK axis, and it worked synergistically with a VEGFR2 inhibitor, an Akt inhibitor, and a MAPK inhibitor to further inhibit tube formation. Conclusion: Overall, our results demonstrate that muscone may proficiently suppress tumor angiogenesis via modulation of the VEGF/PI3K/Akt/MAPK axis, facilitating its candidacy as a natural small molecule drug for BC treatment. [ABSTRACT FROM AUTHOR]

Although Nb Ir compounds are promising high-temperature structural materials due to the high melting-point, moderate density and excellent thermal stability, the structural stability and mechanical properties of Nb Ir compounds are unclear. Here, we investigate the influence of Ir concentration on the structure, elastic modulus, elastic anisotropy and brittle-or-ductile behavior of Nb Ir based compounds by using the first-principles calculations. Six Nb Ir compounds are considered. The results show that the structural stability of Nb Ir compounds strongly depends on the Ir concentration. In particular, NbIr 3 is more thermodynamically stable than the other Nb Ir compounds. The calculated elastic modulus of Nb Ir compounds (except for Nb 5 Ir 3) increases with increasing Ir concentration. The calculated bulk modulus, shear modulus and Young's modulus of NbIr 3 are much larger than that of other Nb Ir compounds. It is found that the high elastic modulus of NbIr 3 is attributed to the strong and symmetrical Nb Ir and Ir Ir metallic bonds. Compared to other Nb Ir compounds, Nb 3 Ir and NbIr 3 have the smallest percentage anisotropy in compressibility. However, Nb 3 Ir 2 has the highest percentage anisotropy in shear. Finally, our work indicates that NbIr 3 is a promising high-temperature structural material, which is potential used in advanced aerospace and automotive applications. Image 1 • The influence of Ir on the structure and mechanical properties of Nb Ir compounds is studied. • NbIr 3 is more thermodynamically stable than that of the other Nb Ir compounds. • The elastic modulus of Nb Ir compounds depends on the Ir concentration. • The elastic modulus of NbIr 3 is much stronger than that of the other Nb Ir compounds. • Nb 3 Ir and NbIr 3 have the smallest percentage anisotropy in compressibility. [ABSTRACT FROM AUTHOR]

Background: Disulfidptosis is a novel type of programmed cell death. However, the value of disulfidptosis-related genes (DRGs) in the prediction of breast cancer prognosis is unclear. Methods: RNA-seq data of 1231 patients, together with information on patient clinical characteristics and prognosis, were downloaded from TCGA. DRGs were identified between cancerous and non-cancerous tissues. The LASSO algorithm was used to assign half of the samples to the training set. Risk scores were used for construction of a prognostic model for risk stratification and prognosis prediction, and the clinical applicability was examined using a line diagram. The relationships between risk scores, immune cell infiltration, molecular subtypes, and responses to immunotherapy and chemotherapy were examined. Results: We identified and obtained four DRG-related prognostic lncRNAs (AC009097.2, AC133552.5, YTHDF3-AS1, and AC084824.5), which were used for establishing the risk model. Longer survival was associated with low risk. The DRG-associated lncRNAs were found to independently predict patient prognosis. The AUCs under the ROCs for one-, three-, and 5-year survival in the training cohort were 0.720, 0.687, and 0.692, respectively. The model showed that the high-risk patients had reduced overall survival as well as high tumor mutation burdens. Furthermore, high-risk patients showed increased sensitivity to therapeutic drugs, including docetaxel, paclitaxel, and oxaliplatin. Conclusion: The risk score model was effective for predicting both prognosis and sensitivity to therapeutic drugs, suggesting its possible usefulness for the management of patients with breast cancer. [ABSTRACT FROM AUTHOR]

The 2019 novel coronavirus disease (COVID‐19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is ongoing, and has necessitated scientific efforts in disease diagnosis, treatment, and prevention. Interestingly, extracellular vesicles (EVs) have been crucial in these developments. EVs are a collection of various nanovesicles which are delimited by a lipid bilayer. They are enriched in proteins, nucleic acids, lipids, and metabolites, and naturally released from different cells. Their natural material transport properties, inherent long‐term recycling ability, excellent biocompatibility, editable targeting, and inheritance of parental cell properties make EVs one of the most promising next‐generation drug delivery nanocarriers and active biologics. During the COVID‐19 pandemic, many efforts have been made to exploit the payload of natural EVs for the treatment of COVID‐19. Furthermore, strategies that use engineered EVs to manufacture vaccines and neutralization traps have produced excellent efficacy in animal experiments and clinical trials. Here, the recent literature on the application of EVs in COVID‐19 diagnosis, treatment, damage repair, and prevention is reviewed. And the therapeutic value, application strategies, safety, and biotoxicity in the production and clinical applications of EV agents for COVID‐19 treatment, as well as inspiration for using EVs to block and eliminate novel viruses are discussed. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) has an extremely high global incidence rate. The Xihuang pill (XHP), a traditional Chinese formula, originates from Hongxu Wang's "Life-Saving Manual of Diagnosis and Treatment of External Diseases" written during the Qing Dynasty. In this book, XHP, was first suggested as an anticancer treatment for BC. However, the regulatory mechanism of XHP on BC requires further investigated. To assess the effects of XHP on BC and elucidate the underlying associated signaling network. The influence of XHP on cellular viability, proliferation, and apoptosis of MDA-MB-231 and BT-549 cells were examined. The ability to metastasize was evaluated using Transwell invasion and wound healing tests. Western blotting was used to examine the epithelial-mesenchymal transition (EMT) markers expression. RNA sequencing and bioinformatic analysis were utilized to investigate the regulation mechanism of XHP. A subcutaneous tumor model was developed to study the tumor-inhibitory effects of XHP or/and Doxorubicin (Dox) on BALB/c nude mice, and the EMT marker levels in tumor tissues were determined using immunohistochemical labeling. XHP demonstrated anticancer effects on BC cells by suppressing cell proliferation, inducing cellular apoptosis, and inhibiting EMT progression. XHP may regulate the EMT via the TGF-β axis, as shown by RNA sequencing and Western blotting analysis. Furthermore, the combination of XHP and Dox had a stronger therapeutic effect on BC cell proliferation, apoptosis, and metastasis in both cellular and animal models. We were the first to reveal that XHP abrogated EMT progression via modulating the TGF-β axis. Furthermore, the combination therapy of XHP and Dox presents a promising novel therapeutic candidate for BC patients. [Display omitted] • XHP suppressed malignancy-related activities in breast cancer cells by inhibiting cellular growth and the progression of epithelial-mesenchymal transition. • XHP combined with Doxorubicin enhanced chemotherapy effectiveness in vitro and in vivo. • XHP attenuated breast cancer metastasis by downregulating the TGF-β signaling pathway. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is a prevalent cancer of the female reproductive system and a major contributor to cancer-related mortality. The activation of NLRP3, a key inflammasome, has been extensively associated with tumor-related molecular and cellular processes; however, the regulatory mechanisms and specific role of NLRP3 in breast cancer remain incompletely elucidated. This study aimed to evaluate the molecular mechanisms of NLRP3-related genes in BC. Utilizing bioinformatics methods, the present research analyzed the TCGA-BRCA dataset, which included four groups of transcriptome sequencing data as follows, normal (WT), NLRP3 knockout (KO), non-knockout-BRCA (BC-WT), and NLRP3-knockout-BRCA (BC-KO). Results indicated that NLRP3 was significantly down-regulated in TCGA-BRCA. Key module genes were mainly enriched in leukocyte cell-cell adhesion and cytokine-cytokine receptor interaction. Moreover, correlation analysis showed that NLRP3 was positively associated with cancer-associated fibroblasts and negatively associated with CD4+ Th1 T-cells. In addition, the DEGs1 and DEGs2 overlapping indicated 505 feature genes, with Chac1 (negative) and Ugt8a (positive) had the strongest correlation with differential immune cells (class-switched memory B cells). Pathway intersection revealed 13 co-KEGG pathways. The BC-KO group indicated markedly reduced levels of four genes (Ccl19, Ccl20, Ccl21a, and H2-Oa) and increased levels of two genes (Il2ra and H2-Ob). This study delved into the role of NLRP3 in BC, exploring its regulatory mechanisms and the impact gene knockout. Bioinformatics approaches identified NLRP3-associated genes, their enriched pathways, and interactions within the tumor microenvironment (TME), providing novel insights into NLRP3 function, TME dynamics, and potential targets for BC prevention and treatment. • NLRP3 plays a significant role in breast cancer (BC). • TCGA-BRCA and four transcriptome sequencing data revealed the role of NLRP3 in BC. • NLRP3 may affect the development or function of Class-switched B-memory cells. • Six NLRP3-related genes were identified participating in the progression of BC. [ABSTRACT FROM AUTHOR]

GeAs 2 is an attractive semiconductor. However, the structure, optical properties and electronic properties of GeAs 2 with Ge-vacancy are unclear. Here, we use the first-principles to investigate the effect of Ge-vacancy on the structure, optical and electronic properties of GeAs 2. Two Ge vacancies are considered here. The results show that V –Ge1 -vacancy is more thermodynamically stable than that of V –Ge2 -vacancy because the bond strength of Ge–As bond for V –Ge1 -vacancy is stronger than that of the V –Ge2 -vacancy. GeAs 2 shows the ultraviolet behavior. In particular, those Ge-vacancies decrease the optical absorption coefficient of GeAs 2. The calculated band gap of GeAs 2 is 0.574eV, indicating that GeAs 2 is a semiconducting. GeAs 2 with those Ge vacancies show metallic behavior because Ge-vacancies promote the electronic transfer near the E F. [ABSTRACT FROM AUTHOR]

It has been reported that lncRNA POU3F3 was upregulated in esophageal squamous-cell carcinomas, indicating its role as an oncogene in this disease. However, the mechanism of its function and its involvement in other malignancies is unknown. In the present study we found that expression levels of lncRNA POU3F3 were higher in tumor tissues than in adjacent healthy tissues of triple negative breast cancer (TNBC) patients and were significantly and inversely correlated with levels of cleaved caspase 9 only in tumor tissues. In addition, plasma levels of lncRNA POU3F3 were higher in TNBC patients than in healthy controls and were significantly and inversely correlated with levels of cleaved caspase 9 only in TNBC patients. In addition, treatment of exogenous Cleaved Caspase-9 significantly attenuated the effects of lncRNA POU3F3 overexpression on cancer cell proliferation and apoptosis. lncRNA POU3F3 may promote proliferation and inhibit apoptosis of cancer cells in triple-negative breast cancer. LncRNA POU3F3 overexpression promoted cell proliferation and inhibited cell apoptosis possibly through the interaction with cleaved caspase 9 [ABSTRACT FROM AUTHOR]

Abstract: Plant transpiration, a process of water movement through a plant and its evaporation from aerial parts especially leaves, consumes a large component of the total continental precipitation (≈48%) and significantly influences global water distribution and climate. To date, various chemical and/or biological explorations have been made to tune the transpiration but with uncertain environmental risks. In recent years, interfacial solar steam/vapor generation is attracting a lot of attention for achieving high energy transfer efficiency. Various optical and thermal designs at the solar absorber–water interface for potential applications in water purification, seawater desalination, and power generation appear. In this work, the concept of interfacial solar vapor generation is extended to tunable plant transpiration by showing for the first time that the transpiration efficiency can also be enhanced or suppressed through engineering the solar absorber–leaf interface. By tuning the solar absorption of membrane in direct touch with green leaf, surface temperature of green leaf will change accordingly because of photothermal effect, thus the transpiration efficiency as well as temperature and relative humidity in the surrounding environment will be tuned. This tunable transpiration by interfacial absorber‐leaf engineering can open an alternative avenue to regulate local atmospheric temperature, humidity, and eventually hydrologic cycle. [ABSTRACT FROM AUTHOR]

Chemotherapy remains a critical component of triple-negative breast cancer (TNBC) treatment; however, patients often develop resistance to chemotherapeutic agents. Accumulating evidence indicates that deubiquitylases (DUBs) play pivotal roles in regulating cell proliferation, differentiation, apoptosis, and tumorigenesis. Deubiquitylase OTUD1 is considered a tumor suppressor in various cancers, yet its role in doxorubicin sensitivity in breast cancer patients remains inadequately understood. In this study, we investigated the expression levels and prognostic role of OTUD1 in breast cancer. Our findings demonstrated that OTUD1 was downregulated in TNBC, and lower OTUD1 expression levels were correlated with poor prognosis. We utilized the CCK-8 cell viability assay, flow cytometric analysis, and a TNBC mouse xenograft model to examine the influence of OTUD1 on doxorubicin (DOX) chemotherapy sensitivity in vitro and in vivo. Western blot and immunohistochemistry were employed to explore the correlation between OTUD1 and P16. Our results indicated that upregulation of OTUD1 expression inhibits TNBC cell proliferation and enhances its sensitivity to doxorubicin. Additionally, rescue experiments confirmed that the chemosensitizing effect of OTUD1 overexpression could be reversed by the inhibition of P16. Therefore, our findings reveal that OTUD1 sensitizes TNBC cells to DOX by upregulating P16 expression, suggesting a potential new diagnostic biomarker and therapeutic target for the future treatment of TNBC. [ABSTRACT FROM AUTHOR]

Radiation therapy can be an effective way to kill cancer cells using ionizing radiation, but some tumors are resistant to radiation therapy and the underlying mechanism still remains elusive. It is therefore necessary to establish an appropriate working model to study and monitor radiation-mediated cancer therapy. In response to cellular stress, the metabolome is the integrated profiling of changes in all metabolites in cells, which can be used to investigate radiation tolerance mechanisms and identify targets for cancer radiation sensibilization. In this study, using 1H nuclear magnetic resonance for untargeted metabolic profiling in radiation-tolerant mouse melanoma cell line B16, we comprehensively investigated changes in metabolites and metabolic network in B16 cells in response to radiation. Principal component analysis and partial least squares discriminant analysis indicated the difference in cellular metabolites between the untreated cells and X-ray radiated cells. In radiated cells, the content of alanine, glutamate, glycine and choline was increased, while the content of leucine, lactate, creatine and creatine phosphate was decreased. Enrichment analysis of metabolic pathway showed that the changes in metabolites were related to multiple metabolic pathways including the metabolism of glycine, arginine, taurine, glycolysis, and gluconeogenesis. Taken together, with cellular metabolome study followed by bioinformatic analysis to profile specific metabolic pathways in response to radiation, we deepened our understanding of radiation-resistant mechanisms and radiation sensibilization in cancer, which may further provide a theoretical and practical basis for personalized cancer therapy. [ABSTRACT FROM AUTHOR]