Extracellular vesicles released by hypoxia-induced tumor-associated fibroblasts impart chemoresistance to breast cancer cells via long noncoding RNA H19 delivery.

Recently, extracellular vesicles (EVs) have been emphasized in regulating the hypoxic tumor microenvironment of breast cancer (BC), where tumor-associated fibroblasts (TAFs) play a significant role. In this study, we describe possible molecular mechanisms behind the pro-tumoral effects of EVs, secreted by hypoxia (HP)-induced TAFs, on BC cell growth, metastasis, and chemoresistance. These mechanisms are based on long noncoding RNA H19 (H19) identified by microarray analysis. We employed an in silico approach to identify differentially expressed lncRNAs that were associated with BC. Subsequently, we explored possible downstream regulatory mechanisms. We isolated EVs from TAFs that were exposed to HP, and these EVs were denoted as HP-TAF-EVs henceforth. MTT, transwell, flow cytometry, and TUNEL assays were performed to assess the malignant phenotypes of BC cells. A paclitaxel (TAX)-resistant BC cell line was constructed, and xenograft tumor and lung metastasis models were established in nude mice for in vivo verification. Our observation revealed that lncRNA H19 was significantly overexpressed, whereas miR-497 was notably downregulated in BC. HP induced activation of TAFs and stimulated the secretion of EVs. Coculture of HP-TAF-EVs and BC cells led to an increase in TAX resistance of the latter. HP-TAF-EVs upregulated methylation of miR-497 by delivering lncRNA H19, which recruited DNMT1, thus lowering the expression of miR-497. In addition, lncRNA H19-containing HP-TAF-EVs hindered miR-497 expression, enhancing tumorigenesis and TAX resistance of BC cells in vivo. Our study presents evidence for the contribution of lncRNA H19-containing HP-TAF-EVs in the reduction of miR-497 expression through the recruitment of DNMT1, which in turn promotes the growth, metastasis, and chemoresistance of BC cells.

Pseudouridine synthase 1 promotes hepatocellular carcinoma through mRNA pseudouridylation to enhance the translation of oncogenic mRNAs.

BACKGROUND AND AIMS: Pseudouridine is a prevalent RNA modification and is highly present in the serum and urine of patients with HCC. However, the role of pseudouridylation and its modifiers in HCC remains unknown. We investigated the function and underlying mechanism of pseudouridine synthase 1 (PUS1) in HCC. APPROACH AND RESULTS: By analyzing the TCGA data set, PUS1 was found to be significantly upregulated in human HCC specimens and positively correlated with tumor grade and poor prognosis of HCC. Knockdown of PUS1 inhibited cell proliferation and the growth of tumors in a subcutaneous xenograft mouse model. Accordingly, increased cell proliferation and tumor growth were observed in PUS1-overexpressing cells. Furthermore, overexpression of PUS1 significantly accelerates tumor formation in a mouse HCC model established by hydrodynamic tail vein injection, while knockout of PUS1 decreases it. Additionally, PUS1 catalytic activity is required for HCC tumorigenesis. Mechanistically, we profiled the mRNA targets of PUS1 by utilizing surveying targets by apolipoprotein B mRNA-editing enzyme 1 (APOBEC1)-mediated profiling and found that PUS1 incorporated pseudouridine into mRNAs of a set of oncogenes, thereby endowing them with greater translation capacity. CONCLUSIONS: Our study highlights the critical role of PUS1 and pseudouridylation in HCC development, and provides new insight that PUS1 enhances the protein levels of a set of oncogenes, including insulin receptor substrate 1 (IRS1) and c-MYC, by means of pseudouridylation-mediated mRNA translation.

Cortisol synergizing with endoplasmic reticulum stress induces regulatory T-cell dysfunction.

The dysfunction of regulatory T cell (Treg) is associated with the pathogenesis of many immune diseases. The regiments used to re-establish Treg's function are currently unsatisfactory and need to be improved. The purpose of this study is to elucidate the synergistic effects of cortisol and endoplasmic reticulum (ER) stress on impairing regulatory T cell functions. In this study, blood samples were collected from patients with food allergy (FA). Immune cells were purified from blood specimens by flow cytometry. A mouse model of FA was established with ovalbumin as a specific antigen. We observed that serum cortisol levels of FA patients were negatively correlated with peripheral Treg counts. Overwhelmed ER stress status was detected in Tregs of FA patients. The antigen-specific immune response induced ER stress in Tregs, which was exacerbated by concurrent cortisol exposure. ER stress mediated the effects of cortisol on impairing the immune suppressive ability of Tregs. The expression of Rnf20 was observed in Tregs upon exposure to cortisol. Rnf20 reduced the expression of Foxp3 and transforming growth factor (TGF)-ß in Tregs. Rnf20 inhibition re-established the immunosuppressive functions of Tregs obtained in patients with FA. The experimental FA in mice was attenuated by inhibition of Rnf20 in Tregs. In summary, specific immune response in synergy with cortisol to induce the expression of Rnf20 in Tregs. Rnf20 reduces the levels of Foxp3 and TGF-ß to impair the immune suppressive function. Inhibition of Rnf20 can restore the immune suppressive ability of Tregs obtained from FA patients.

Relationship between the circulating N-terminal pro B-type natriuretic peptide and the risk of carotid artery plaque in different glucose metabolic states in patients with coronary heart disease: a CSCD-TCM plus study in China.

OBJECTIVE: Circulating N-terminal pro B-type natriuretic peptide (NT-proBNP) is a marker for heart failure in patients with coronary heart disease (CHD) and associated with glycemic abnormalities. Studies on the association and diagnostic value of NT-proBNP in carotid plaques (CAP) in patients with CHD are limited. METHODS: The relationships between NT-proBNP and the risk of CAP in different glucose metabolic states, sexes, and age categories were also examined using 5,093 patients diagnosed with CHD. The NT-proBNP tertiles were used to divide patients into three groups in which the NT-proBNP levels, blood glucose levels, the occurrence of CAP, and the number and nature of CAP were measured using normoglycemic (NG), prediabetes (Pre-DM), and diabetes mellitus (DM) glucose metabolic statuses. Logistic regression analyses were used to compare the relationship between NT-proBNP and the risk of CAP occurrence and the number and nature of CAP. The diagnostic value of NT-proBNP for CAP risk was measured using receiver operating characteristic (ROC) curves. RESULTS: We found a 37% relative increase in the correlation between changes in NT-proBNP per standard deviation (SD) and the incidence of CAP. After adjusting for potential confounders, NT-proBNP at the T3 level was found to be associated with an increased CAP odds ratio (OR) when T1 was used as the reference. This relationship was also present in males, patients aged > 60 years, or both pre-DM and DM states. NT-proBNP was more likely to present as hypoechoic plaques at T1 and as mixed plaques at T3. We also measured the diagnostic accuracy of CAP for NT-proBNP in patients with CHD, with an AUC value of 0.627(95% CI 0.592-0.631), sensitivity of 50.7%, and specificity of 68.0%. CONCLUSION: An increase in NT-proBNP was significantly associated with the risk of CAP in patients with CHD, especially in males and patients aged > 60 years, and exhibited specific characteristics under different glucose metabolism states. Trial registration The study was approved by the Ethics Committee of Tianjin University of Traditional Chinese Medicine (Approval number TJUTCM-EC20210007) and certified by the Chinese Clinical Trials Registry on April 4, 2022 (Registration number ChiCTR2200058296) and March 25, 2022 by ClinicalTrials.gov (registration number NCT05309343).

KIF20A promotes the development of fibrosarcoma via PI3K-Akt signaling pathway.

Adult fibrosarcoma is an aggressive subtype of soft tissue sarcoma (STS), in which high expression of KIF20A indicates a poor prognosis. However, the precise role of KIF20A in fibrosarcoma progression remains unknown. In this study, we initially examined KIF20A expression and function in the human fibrosarcoma cell line HT-1080. The results showed that KIF20A was highly expressed in HT-1080, knockdown of KIF20A impaired cell proliferation, migration, invasion and induced G2/M arrest and cell apoptosis. Transcriptome study suggested that PI3K-Akt signal pathway was involved in these biological changes. We confirmed that PI3K-Akt and NF-κB signaling pathways were impaired after the down-regulation of KIF20A, which can be reversed by the Akt activator SC79 in HT-1080 in vitro. In a xenograft mouse model, knockdown of KIF20A inhibited tumor growth, Ki67 expression and liver metastasis. Taken together, our results suggested that KIF20A promoted fibrosarcoma progression via PI3K-Akt signaling pathway and might be a potential therapeutic target for fibrosarcoma.

MicroRNA-640 Inhibition Enhances the Chemosensitivity of Human Glioblastoma Cells to Temozolomide by Targeting Bcl2 Modifying Factor.

Glioblastoma (GBM) is the most malignant and challenging type of astrocytoma and also notoriously acknowledged as the most common primary brain tumor globally. Currently, chemotherapy is the most master therapy for tumor and is essential in clinical treatment for GBM. Nevertheless, the characterization of chemotherapy resistance seriously hinders clinical chemotherapy treatment. Accordingly, there are imperious demands for the exploitation of novel chemosensitizer to promote the efficacy of chemotherapy. Our current study was conducted to probe into the potential impacts of microRNA (miR)-640 on the chemosensitivity in GBM and the associated underlying mechanism. Initially, TargetScan software was utilized to predict the targeted genes of miR-640, and the target relationship between miR-640 and Bcl-2-modifying factor (BMF) was validated by double luciferase report assay. Additionally, to explore the role of miR-640/BMF in U251 cells, miR-640 inhibitor/BMF-siRNA was used. U251 cells were processed with 100 µM temozolomide (TMZ) and detected with CCK-8 kit. Eventually, RT-qPCR and Western blotting were used for evaluating Bcl-2, Bax mRNA, and protein expression level. Flow cytometry analysis was performed to measure cellular apoptosis. Initially, the results indicated that BMF was the target gene of miR-640. MiR-640 negatively regulated BMF expression in GBM cells. Besides, the findings revealed that miR-640 inhibition significantly inhibited U251 cell proliferation, promoted cell apoptosis, and increased the sensitivity of GBM cells to TMZ by targeting BMF. Moreover, BMF overexpression significantly suppressed U251 cell proliferation, induced cell apoptosis, and increased the sensitivity of GBM cells to TMZ. Inhibition of miR-640 expression enhances chemosensitivity of human GBM cells to TMZ by targeting BMF.

The CGRP/macrophage axis signal facilitates inflammation recovery in the intestine.

The mechanism of the recovery of immune inflammation in the intestine remains to be investigated. The calcitonin-related protein (CGRP; neuropeptide) has immune regulatory capacity. We observed that lower levels of CGRP were found in the colon biopsies of UC patients. CGRP were negatively correlated to TNF-α, IL-1ß and IFN-γ in biopsy samples. The levels of TGF-ß were lower in the UC group than that of the normal control (NC) group, which were positively correlated with the CGRP levels. Blocking CGRP significantly delayed recovery from colitis inflammation. CGRP induced the TGF-ß-expressing CD4+ Tim4+ macrophages in the intestine. CD4+ Tim4+ macrophages demonstrated immune regulatory function in suppressing proliferation of isolated T cells of colitis and induced apoptosis of T cells. Ablation of the Tgfb1 expression in macrophages resulted in a significant delay in recovery of inflammation in colitis, which was rescued by reconstitution of the CD4+ Tim4+ macrophages in mice.

N6-methyladenine demethylase ALKBH1 inhibits the differentiation of skeletal muscle.

DNA N6-methyladenine (N6-mA) was recently recognized as a new epigenetic modification in mammalian genome, and ALKBH1 was discovered as its demethylase. Knock-out mice studies revealed that ALKBH1 was indispensable for normal embryonic development. However, the function of ALKBH1 in myogenesis is largely unknown. In this study, we found that N6-mA showed a steady increase, going along with a strong decrease of ALKBH1 during skeletal muscle development. Our results also showed that ALKBH1 enhanced proliferation and inhibited differentiation of C2C12 cells. Genome-wide transcriptome analysis and reporter assays further revealed that ALKBH1 accomplished the differentiation inhibiting function by regulating a core set of genes and multiple signaling pathways, including increasing chemokine (C-X-C motif) ligand 14 (CXCL14) and activating ERK signaling. Taken together, our results demonstrated that ALKBH1 is critical for the myogenic differentiation of C2C12 cells, and suggested that N6-mA might be a new epigenetic mechanism for the regulation of myogenesis.

METTL3 regulates skeletal muscle specific miRNAs at both transcriptional and post-transcriptional levels.

METTL3 increasing the mature miRNA levels via N6-Methyladenosine (m6A) modification of primary miRNA (pri-miRNA) transcripts has emerged as an important post-transcriptional regulation of miRNA biogenesis. Our previous studies and others have showed that muscle specific miRNAs are essential for skeletal muscle differentiation. Whether these miRNAs are also regulated by METTL3 is still unclear. Here, we found that m6A motifs were present around most of these miRNAs, which were indeed m6A modified as confirmed by m6A-modified RNA immunoprecipitation (m6A RIP). However, we surprisingly found that these muscle specific miRNAs were repressed instead of increased by METTL3 in C2C12 in vitro differentiation and mouse skeletal muscle regeneration after injury in vivo model. To elucidate the underlined mechanism, we performed reporter assays in 293T cells and validated METTL3 increasing these miRNAs at post-transcriptional level as expected. Furthermore, in myogenic C2C12 cells, we found that METTL3 not only repressed the expression of myogenic transcription factors (TFs) which can enhance the muscle specific miRNAs, but also increased the expression of epigenetic regulators which can repress these miRNAs. Thus, METTL3 could repress the muscle specific miRNAs at transcriptional level indirectly. Taken together, our results demonstrated that skeletal muscle specific miRNAs were repressed by METTL3 and such repression is likely synthesized transcriptional and post-transcriptional regulations.

Response of Soil Properties and Microbial Communities to Increasing Salinization in the Meadow Grassland of Northeast China.

Secondary salinization is a serious environmental issue and a major threat to the sustainable use of grasslands. Information about the response of microbial communities and soil properties in already saline soils to increasing salinity is lacking. We investigated soil properties and the structures of soil bacterial and fungal communities across a gradient of salinization in the Horqin Grassland, China. Three sites with relatively lightly (average soluble salt content = 0.11%), relatively moderately (average soluble salt content = 0.44%), and heavily (average soluble salt content = 1.07%) degraded grassland, were selected as experimental sites. We examined variations in the composition and structure of the soil bacterial and fungal communities by using high-throughput sequencing of the 16S and 18S rRNA genes, respectively. We found degrading effects of salinization on soil properties, i.e., decreased soil moisture, organic matter, total N, NH4-N, and NO3-N and increased soil bulk density, pH, and electrical conductivity. The bacterial and fungal community structures changed with increasing salinity. However, dominant microbial taxa (including phylum, genus, and operational taxonomic unit levels) were similar among experimental sites, indicating that increasing salinization slightly affected the basic compositions of microbial communities in already saline grasslands. Furthermore, the relative abundances of most dominant taxa sensitively responded to the soil salt content. Acidobacteria, Actinobacteria, Chloroflexi, RB4, Rubrobacter, Blastocatella, H16, Glomeromycota, and Aspergillus linearly increased with increasing salinization, suggesting that they could be used as bioindicators for salt-tolerant communities. Overall, the changes in the structures of soil bacterial and fungal communities were determined by the relative quantities of dominant taxa rather than community composition. The structures of soil bacterial and fungal communities were linked to soil properties and vegetation. Increasing soil salt content, and thereby varied pH and organic matter, were likely the direct influencing factors of microbial communities in these saline grasslands.

Construction of a Robust Radiative Cooling Emitter for Efficient Food Storage and Transportation.

Nowadays, food safety is still facing great challenges. During storage and transportation, perishable goods have to be kept at a low temperature. However, the current logistics still lack enough preservation ability to maintain a low temperature in the whole. Hence, considering the temperature fluctuation in logistics, in this work, the passive radiative cooling (RC) technology was applied to package to enhance the temperature control capability in food storage and transportation. The RC emitter with selective infrared emission property was fabricated by a facile coating method, and Al2O3 was added to improve the wear resistance. The sunlight reflectance and infrared emittance within atmospheric conditions could reach up to 0.92 and 0.84, respectively. After abrasion, the sunlight reflection only decreased by 0.01, and the infrared emission showed a negligible change, revealing excellent wear resistance. During outdoor measurement, the box assembled by RC emitters (RC box) was proved to achieve temperature drops of ∼9 and ∼4 °C compared with the corrugated box and foam box, respectively. Besides, the fruits stored in the RC box exhibited a lower decay rate. Additionally, after printing with patterns to meet the aesthetic requirements, the RC emitter could also maintain the cooling ability. Given the superior optical properties, wear resistance, and cooling capability, the emitter has great potential for obtaining a better temperature control ability in food storage and transportation.

Glutathione-Responsive Polymersome with Continuous Glutathione Depletion for Enhanced Photodynamic Therapy and Hypoxia-Activated Chemotherapy.

The high glutathione (GSH) level of the tumor microenvironment severely affects the efficacy of photodynamic therapy (PDT). The current GSH depletion strategies have difficulty meeting the dual needs of security and efficiency. In this study, we report a photosensitizer Chlorin e6 (Ce6) and hypoxia-activated prodrug tirapazamine (TPZ) coloaded cross-linked multifunctional polymersome (TPZ/Ce6@SSPS) with GSH-triggered continuous GSH depletion for enhanced photodynamic therapy and hypoxia-activated chemotherapy. At tumor sites, the disulfide bonds of TPZ/Ce6@SSPS react with GSH to realize decross-linking for on-demand drug release. Meanwhile, the generated highly reactive quinone methide (QM) can further deplete GSH. This continuous GSH depletion will amplify tumor oxidative stress, enhancing the PDT effect of Ce6. Aggravated tumor hypoxia induced by PDT activates the prodrug TPZ, resulting in an enhanced combination of PDT and hypoxia-activated chemotherapy. Both in vitro and in vivo results demonstrate the efficient GSH depletion and potent antitumor activities by TPZ/Ce6@SSPS. This work provides a strategy for the design of a continuous GSH depletion platform, which holds great promise for enhanced combination tumor therapy.

Endoplasmic Reticulum Stress Promotes Telomerase Reverse Transcriptase Expression Contributes to Development of Allergic Rhinitis.

BACKGROUND: The Th2 cell polarization is a crucial factor in the pathogenesis of allergic diseases. The underlying mechanism requires further investigation. Telomerase has an immune-regulating ability. The aim of this study is to elucidate the association between telomerase and Th2 cell polarization in patients with allergic rhinitis (AR). METHODS: CD4+ T cells were isolated from blood samples collected from AR patients and healthy control subjects. RNA sequencing was employed to analyze RNA samples extracted from CD4+ T cells. An AR mouse model was established using the ovalbumin-alum protocol. RESULTS: High telomerase gene activity and high endoplasmic reticulum (ER) stress status were observed in CD4+ T-cells in patients with AR. Positive correlation between the telomerase reverse transcriptase (TERT) gene expression in CD4+ T cells and AR response in patients with AR. TERT facilitated the degradation of Foxp3 proteins in CD4+ T cells, resulting in the polarization of Th2 cells. Sensitization with the ovalbumin-alum protocol enhanced the Tert expression in CD4+ T cells by exacerbating ER stress. Conditional inhibition of the Tert or eukaryotic translation initiation factor 2-α (Eif2a) expression in CD4+ T cells effectively attenuated experimental AR in mice. CONCLUSIONS: Elevated amounts of telomerase in CD4+ T cells were found in CD4+ T cells of subjects with AR. Telomerase promoted Th2 cell polarization by inducing Foxp3 protein degradation and promotes GATA3 activation. Inhibition of TERT or eIF2a alleviated experimental AR.

Colorectal cancer cell-derived exosomal miRNA-372-5p induces immune escape from colorectal cancer via PTEN/AKT/NF-κB/PD-L1 pathway.

Tumor cells can escape immune surveillance by changing their own escape or expressing abnormal genes and proteins, resulting in unlimited proliferation and invasive growth of cells. These changes are related to microRNAs (miRNAs), which reduce the killing effect of immune cells, devastate the immune response, and interfere with apoptosis through the aberrant expression of relevant miRNAs. In the preliminary phase of this study, miRNAs in clinical plasma exosomes of colorectal cancer patients were differentially analyzed by RNA sequencing technology, and miR-372-5p derived from extracellular vesicles (sEVs) was found to be a key signaling molecule mediating the regulation of macrophages by colorectal cancer (CRC). miRNA-372-5p is upregulated in colorectal cancer patient tissues and serum, as well as colorectal cancer cell lines and their exosomes. Subsequently, we found that macrophages could take up sEV secreted by colorectal cancer cells HCT116, affecting the expression of the immune checkpoint PD-L1, resulting in the generation of a tumor-immunosuppressive microenvironment and suppression of T cell activation in CRC. Gene enrichment mapping and database revealed that miR-372-5p regulates PD-L1 expression in colorectal cancer through the homologous phosphatase-tensin (PTEN)-phosphatidylinositol 3-kinase-protein kinase B (AKT)-nuclear factor-κB (NF-κB) pathway. Further studies confirmed that miRNA-372-5p-treated macrophages co-cultured with T cells affected the regulation of PD-L1 expression through the PTEN/AKT/NF-κB signaling pathway, resulting in decreased CD3+CD8+ T cell activity, decreased cytokine IL-2 and increased IFN-γ. And miRNA-372-5p could down-regulate the expression of PD-L1 in HCT116 through the PTEN/AKT/NF-κB pathway, inhibit tumor cell proliferation and promote apoptosis. Conclusion: Colorectal cancer cell-derived exosome miR-372-5p can be phagocytosed by colorectal cancer and macrophage cells, regulate the expression of PD-L1 in colorectal cancer cells and macrophages by targeting the PTEN/AKT/NF-κB pathway, and induce the immunosuppressive microenvironment of CRC to promote CRC development. This suggests that inhibiting the secretion of HCT116-specific sEV-miR-372-5p or targeting PD-L1 in tumor-associated macrophages could be a novel approach for CRC treatment and possibly a sensitizing approach for CRC anti-PD-L1 therapy.

Drug-resistant exosome miR-99b-3p induces macrophage polarization and confers chemoresistance on sensitive cells by targeting PPP2CA.

The most frequent cancer in women to be diagnosed is breast cancer, and chemotherapy's ability to be effective is still significantly hampered by drug resistance. Tumor-derived exosomes play a significant role in drug resistance, immunological modulation, metastasis, and tumor proliferation. In this work, the differential miRNAs in the exosomes of drug-resistant and susceptible breast cancer cell lines were screened using miRNA-seq. It was demonstrated that drug-resistant human breast cancer cells and their exosomes expressed more miR-99b-3p than did susceptible cells and their exosomes. While drug-resistant cells' migration and paclitaxel resistance can be inhibited by driving down the expression of miR-99b-3p in those cells, exosomes containing miR-99b-3p from those cells can help susceptible cells migrate and become resistant. miR-99b-3p affects cell migration and paclitaxel resistance by targeting PPP2CA to promote AKT/mTOR phosphorylation. The drug-resistant cell exosome miR-99b-3p can be taken up by macrophages and affect the drug resistance and migration ability of sensitive cells by promoting the M2 polarization of macrophages. Downregulating miR-99b-3p has been shown in vivo to reverse macrophage M2 polarization, suppress tumor development, and prevent treatment resistance. The present study shows that drug-resistant cell exosomes miR-99b-3p can directly influence the migration, proliferation, and paclitaxel sensitivity of sensitive cells via PPP2CA. Additionally, the exosomes from drug-resistant cells can influence the polarization of macrophage M2 in the tumor microenvironment, which can also have an impact on the proliferation, migration, and paclitaxel sensitivity of sensitive cells.

Synergistic Effect of Layered Double Hydroxides Nanodosage Form to Induce Apoptosis and Ferroptosis in Breast Cancer.

Background: Breast cancer is the most common cancer in women and one of the leading causes of cancer death worldwide. Ferroptosis, a promising mechanism of killing cancer cells, has become a research hotspot in cancer therapy. Simvastatin (SIM), as a potential new anti-breast cancer drug, has been shown to cause ferroptosis of cancer cells and inhibit breast cancer metastasis and recurrence. The purpose of this study is to develop a novel strategy boosting ferroptotic cascade for synergistic cancer therapy. Methods: In this paper, iron base form of layered double hydroxide supported simvastatin (LDHs-SIM) was synthesized by hydrothermal co-precipitation method. The characterization of LDHs-SIM were assessed by various analytical techniques, including ultraviolet-visible (UV-vis) spectroscopy, X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, and transmission electron microscopy (TEM). Biological activity, ferroptosis mechanism and biocompatibility were analyzed through in vivo and in vitro analysis, so as to evaluate its therapeutic effect on breast cancer. Results: The constructed LDHs-SIM nanosystem can not only release SIM through mevalonate (MVA) pathway, inhibit the expression of glutathione peroxidase 4 (GPX4), inhibit the expression of SLC7A11 and reduce the synthesis efficiency of GSH, but also promote the accumulation of Fe2+ in cells through the release of Fe3+, and increase the intracellular ROS content. In addition, LDHs-SIM nanosystem can induce apoptosis of breast cancer cells to a certain extent, and achieve the synergistic effect of apoptosis and ferroptosis. Conclusion: In the present study, we demonstrated that nanoparticles of layered double hydroxides (LDHs) loaded with simvastatin were more effective than a free drug at inhibiting breast cancer cell growth, In addition, superior anticancer therapeutic effects were achieved with little systemic toxicity, indicating that LDHs-SIM could serve as a safe and high-performance platform for ferroptosis-apoptosis combined anticancer therapy.

Expression, regulating mechanism and therapeutic target of KIF20A in multiple cancer.

Kinesin family member 20A (KIF20A) is a member of the kinesin family. It transports chromosomes during mitosis, plays a key role in cell division. Recently, studies proved that KIF20A was highly expressed in cancer. High expression of KIF20A was correlated with poor overall survival (OS). In this review, we summarized all the cancer that highly expressed KIF20A, described the role of KIF20A in cancer. We also organized phase I and phase II clinical trials of KIF20A peptides vaccine. All results indicated that KIF20A was a promising therapeutic target for multiple cancer.

Mechanically Switchable Multifunctional Device for Regulating Passive Radiative Cooling and Solar Heating.

Energy consumption during cooling and heating poses a great threat to the development of society. Thermal regulation, as switchable cooling and heating in a single platform, is therefore urgently demanded. Herein, a switchable multifunctional device integrating heating, cooling, and latent energy storage was proposed for temperature regulation and window energy saving for buildings. A radiative cooling (RC) emitter, a phase-change (PC) membrane, and a solar-heating (SH) film were connected layer by layer to form a sandwich structure. The RC emitter exhibited selective infrared emission (emissivity in the atmospheric window: 0.81, emissivity outside the atmospheric window: 0.39) and a high solar reflectance (0.92). Meanwhile, the SH film had a high solar absorptivity (0.90). More importantly, both the RC emitter and the SH film displayed excellent wear resistance and UV resistance. The PC layer can control the temperature at a steady state under dynamic weather conditions, which could be verified by indoor and outdoor measurements. The thermal regulation performance of the multifunctional device was also verified by outdoor measurements. The temperature difference between the RC and SH models of the multifunctional device could reach up to 25 °C. The as-constructed switchable multifunctional device is a promising candidate for alleviating the cooling and heating energy consumption and realizing energy saving for windows.