PYCR1 expresses in cancer-associated fibroblasts and accelerates the progression of C6 glioblastoma.

BACKGROUND: Cancer-associated fibroblasts (CAFs) play important roles in tumor microenvironments. Pyrroline-5-carboxylate reductase 1 (PYCR1) is a potential cancer therapy target. This study aimed to explore the expression of PYCR1 in glioma-associated CAFs and analyze the effects of PYCR1 expression in CAFs on the proliferation of C6 glioma. METHODS: A rat glioma model was induced by injecting C6 cells in the right caudate putamen via a microliter syringe. After 14 days, tumor tissues were collected, and the levels of COL1A1 and PYCR1 were measured by immunohistochemistry. The colocalization of fibroblast activation protein α (FAP) and PYCR1 in tissues was measured by double-immunofluorescence. The CAFs were labeled by FAP and isolated from the tumor tissues using a fluorescence-activated cell sorting (FACS) machine. The isolated CAFs were further separated into CAFs with different PYCR1 expressions using the FACS machine. CAFs with different PYCR1 expressions were respectively cocultured with C6 cells or MUVECs for 48h using a Transwell permeable support. The invasion and proliferation of C6 cells were measured using a Transwell assay and colony formation assay, and the angiogenesis of MUVECs was measured using a Tube formation assay. The expression of COL1A1 and PYCR1 proteins in C6 cells and VEGF-A and EGF proteins in MUVECs was measured by western blotting. PYCR1 silencing in C6 cells was induced by PYCR1 siRNA transfection, the effects of which on the proliferation of C6 cells were measured using a wound healing assay, a Transwell assay, and western blotting. RESULTS: The PYCR1 and COL1A1 upregulation co-occurred in the rat glioma, and PYCR1 was expressed in CAFs. The CAF coculture enhanced the invasion and proliferation of C6 cells and the angiogenesis of MUVECs. Meanwhile, the levels of COL1A1 protein in C6 cells, and the levels of VEGF-A and EGF proteins in MUVECs were increased after CAF coculture. Moreover, the effects of CAF coculture were increased with PYCR1 expression in the CAF. Silencing PYCR1 suppressed the migration and invasion of C6 cells, and decreased the levels of COL1A1 and VEGF-A proteins in C6 cells. CONCLUSIONS: PYCR1 is expressed in glioma-associated CAFs, and promotes the proliferation of C6 cells and angiogenesis of MUVECs, suggesting that targeting PYCR1 may be a therapeutic strategy for glioma.

Terahertz label-free detection of nicotine-induced neural cell changes and the underlying mechanisms.

Nicotine exposure can lead to neurological impairments and brain tumors, and a label-free and nondestructive detection technique is urgently required by the scientific community to assess the effects of nicotine on neural cells. Herein, a terahertz (THz) time-domain attenuated total reflection (TD-ATR) spectroscopy approach is reported, by which the effects of nicotine on normal and cancerous neural cells, i.e., HEB and U87 cells, are successfully investigated in a label/stain-free and nondestructive manner. The obtained THz absorption coefficients of HEB cells exposed to low-dose nicotine and high-dose nicotine are smaller and larger, respectively, than the untreated cells. In contrast, the THz absorption coefficients of U87 cells treated by nicotine are always smaller than the untreated cells. The THz absorption coefficients can be well related to the proliferation properties (cell number and compositional changes) and morphological changes of neural cells, by which different types of neural cells are differentiated and the viabilities of neural cells treated by nicotine are reliably assessed. Collectively, this work sheds new insights on the effects of nicotine on neural cells, and provides a useful tool (THz TD-ATR spectroscopy) for the study of chemical-cell interactions.

Authentication of a survival nomogram for non-invasive micropapillary breast cancer.

Purpose: We aimed at establishing a nomogram to accurately predict the overall survival (OS) of non-metastatic invasive micropapillary breast carcinoma (IMPC). Methods: In the training cohort, data from 429 patients with non-metastatic IMPC were obtained through the Surveillance, Epidemiology, and End Results (SEER) database. Other 102 patients were enrolled at the Xijing Hospital as validation cohort. Independent risk factors affecting OS were ascertained using univariate and multivariate Cox regression. A nomogram was established to predict OS at 3, 5 and 8 years. The concordance index (C-index), the area under a receiver operating characteristic (ROC) curve and calibration curves were utilized to assess calibration, discrimination and predictive accuracy. Finally, the nomogram was utilized to stratify the risk. The OS between groups was compared through Kaplan-Meier survival curves. Results: The multivariate analyses revealed that race (p = 0.047), surgery (p = 0.003), positive lymph nodes (p = 0.027), T stage (p = 0.045) and estrogen receptors (p = 0.019) were independent prognostic risk factors. The C-index was 0.766 (95% CI, 0.682-0.850) in the training cohort and 0.694 (95% CI, 0.527-0.861) in the validation cohort. Furthermore, the predicted OS was consistent with actual observation. The AUCs for OS at 3, 5 and 8 years were 0.786 (95% CI: 0.656-0.916), 0.791 (95% CI: 0.669-0.912), and 0.774 (95% CI: 0.688-0.860) in the training cohort, respectively. The area under the curves (AUCs) for OS at 3, 5 and 8 years were 0.653 (95% CI: 0.498-0.808), 0.683 (95% CI: 0.546-0.820), and 0.716 (95% CI: 0.595-0.836) in the validation cohort, respectively. The Kaplan-Meier survival curves revealed a significant different OS between groups in both cohorts (p<0.001). Conclusion: Our novel prognostic nomogram for non-metastatic IMPC patients achieved a good level of accuracy in both cohorts and could be used to optimize the treatment based on the individual risk factors.

Binding of different hyaluronan to CD44 mediates distinct cell adhesion dynamics under shear flow.

As a known receptor-ligand pair for mediating cell-cell or cell-extracellular matrix adhesions, cluster of differentiation 44 (CD44)-hyaluronan (HA) interactions are not only determined by molecular weight (MW) diversity of HA, but also are regulated by external physical or mechanical factors. However, the coupling effects of HA MW and shear flow are still unclear. Here, we compared the differences between high molecular weight HA (HHA) and low molecular weight HA (LHA) binding to CD44 under varied shear stresses. The results demonstrated that HHA dominated the binding phase but LHA was in favour of the shear resistance phase, respectively, under shear stress range ≤ 1.0 dyne·cm-2 . This difference was attributed to the high binding strength of the CD44-HHA interaction, as well as the optimal distribution matching between both CD44 and HA sides. Activation of the intracellular signal pathway was sensitive to both HA MW and shear flow. Our findings also indicate that only CD44-HHA interaction under shear stress of 0.2 dyne·cm-2 could significantly enhance the clustering of CD44, as well as induce the increase in both CD44 and CD18 expression. The present study offers the basis for further quantification of the features of CD44-HA interactions and their biological functions.

Terahertz time-domain attenuated total reflection spectroscopy integrated with a microfluidic chip.

The integration of a microfluidic chip into terahertz time-domain attenuated total reflection (THz TD-ATR) spectroscopy is highly demanded for the accurate measurement of aqueous samples. Hitherto, however little work has been reported on this regard. Here, we demonstrate a strategy of fabricating a polydimethylsiloxane microfluidic chip (M-chip) suitable for the measurement of aqueous samples, and investigate the effects of its configuration, particularly the cavity depth of the M-chip on THz spectra. By measuring pure water, we find that the Fresnel formulae of two-interface model should be applied to analyze the THz spectral data when the depth is smaller than 210 µm, but the Fresnel formula of one-interface model can be applied when the depth is no less than 210 µm. We further validate this by measuring physiological solution and protein solution. This work can help promote the application of THz TD-ATR spectroscopy in the study of aqueous biological samples.

Multiple interactions steered high affinity toward PFAS on ultrathin layered rare-earth hydroxide nanosheets: Remediation performance and molecular-level insights.

The global occurrence of per- and polyfluoroalkyl substances (PFAS) in aquatic systems has raised concerns about their adverse effects on ecosystems and human health. Adsorption is a promising technique for the remediation of PFAS, yet effective adsorbents with rapid uptake kinetics and high adsorption capacity are still in high demand, and molecular-level understanding of the interfacial adsorption mechanisms is lacking. In this study, we developed a superior layered rare-earth hydroxide (LRH) adsorbent, ultrathin Y2(OH)4.86Cl1.44·1·07H2O (namely YOHCl) nanosheets, to achieve the effective removal of perfluorooctanoic acid (PFOA). YOHCl nanosheets exhibited ultra-high adsorption capacity toward PFOA (up to 957.1 mg/g), which is 1.9 times and 9.3 times higher than the state-of-the-art layered double hydroxides (MgAl-LDH) and benchmark granular activated carbon (GAC) under the same conditions, respectively. Furthermore, YOHCl nanosheets pose stable performance on the removal of PFOA under various water matrices with robust reusability. We also developed YOHCl-based continuous-flow column, demonstrating its promise in simultaneously removing multiple PFAS with wide range of chain lengths at environmentally relevant concentrations. With the molecular-level investigations, we have revealed that multi-mechanism, including ion exchange, electrostatic attraction and bidentate/bridging coordination, contributed to the strong PFOA-YOHCl affinity, leading to the ultra-high adsorption capacity of PFOA. We have provided emerging LRHs-based adsorbents for the effective remediation of PFAS with molecular-level insights on the interfacial mechanisms.

METTL3-mediated N6-methyladenosine modification and HDAC5/YY1 promote IFFO1 downregulation in tumor development and chemo-resistance.

Ovarian cancer (OC) is a malignant tumor that seriously threatens women's health. Due to the difficulty of early diagnosis, most patients exhibit advanced disease or peritoneal metastasis at diagnosis. We discovered that IFFO1 is a novel tumor suppressor, but its role in tumorigenesis, development and chemoresistance is unknown. In this study, IFFO1 levels were downregulated across cancers, leading to the acceleration of tumor development, metastasis and/or cisplatin resistance. Overexpression of IFFO1 inhibited the translocation of ß-catenin to the nucleus and decreased tumor metastasis and cisplatin resistance. Furthermore, we demonstrated that IFFO1 was regulated at both the transcriptional and posttranscriptional levels. At the transcriptional level, the recruitment of HDAC5 inhibited IFFO1 expression, which is mediated by the transcription factor YY1, and the METTL3/YTHDF2 axis regulated the mRNA stability of IFFO1 in an m6A-dependent manner. Mice injected with IFFO1-overexpressing cells had lower ascites volumes and tumor weights throughout the peritoneal cavity than those injected with parental cells expressing the vector control. In conclusion, we demonstrated that IFFO1 is a novel tumor suppressor that inhibits tumor metastasis and reverses drug resistance in ovarian cancer. IFFO1 was downregulated at both the transcriptional level and posttranscriptional level by histone deacetylase and RNA methylation, respectively, and the IFFO1 signaling pathway was identified as a potential therapeutic target for cancer.

Phase mismatch induced suppression of eigenmode resonance in terahertz metasurfaces.

In this paper, we observe the distinguishable modulation of the different eigenmodes by lattice mode in terahertz U-shaped metasurfaces, and a remarkable lattice induced suppression of the high order eigenmode resonance is demonstrated. With the quantitative analysis of Q factor and loss of the resonances, we clarify that the peculiar phenomenon of suppression is originated from the phase mismatch of the metasurfaces via introducing the phase difference between the neighboring structures. These results provide new insights into the phase mismatch mediated transmission amplitude of eigenmode resonance in metasurfaces and open a new path to developing terahertz multifunctional devices.

The effect and mechanistic study of encequidar on reversing the resistance of SW620/AD300 cells to doxorubicin.

Encequidar, a gut-specific P-glycoprotein (P-gp) inhibitor, makes oral paclitaxel possible, and has been used in clinical treatment of metastatic breast cancer, however, its pharmacological effect and mechanism of reversal of drug resistance in drug-resistant colon cancer cells SW620/AD300 are still unknown. Herein, we first synthesized encequidar and demonstrated that it could inhibit the transport activity of P-gp, reduced doxorubicin (DOX) efflux, enhanced DOX cytotoxicity and promoted tumor-apoptosis in SW620/AD300 cells. Metabolomic analysis of cell samples was performedusing liquid chromatography Q-Exactive mass spectrometer, the results of metabolite enrichment analysis and pathway analysis showed that the combination of encequidar and DOX could: i) significantly affect the citric acid cycle (TCA cycle) and reduce the energy supply required for P-gp to exert its transport activity; ii) affect the metabolism of glutathione, which is the main component of the anti-oxidative stress system, and reduce the ability of cells to resist oxidative stress; iii) increase the intracellular reactive oxygen species (ROS) production and enhance ROS-induced cell damage and lipid peroxidation, which in turn restore the sensitivity of drug-resistant cells to DOX. In conclusion, these results provide sufficient data support for the therapeutical application of the P-gp inhibitor encequidar to reverse MDR, and are of great significance to further understand the therapeutic advantages of encequidar in anti-tumor therapy and guide clinical rational drug use.

Construction of a ferroptosis-related five-lncRNA signature for predicting prognosis and immune response in thyroid carcinoma.

BACKGROUND: Thyroid carcinoma (THCA) is the most common endocrine-related malignant tumor. Despite the good prognosis, some THCA patients may deteriorate into more aggressive diseases, leading to poor survival. This may be alleviated by developing a novel model to predict the risk of THCA, including recurrence and survival. Ferroptosis is an iron-dependent, oxidative, non-apoptotic form of cell death initially described in mammalian cells, and plays an important role in various cancers. To explore the potential prognostic value of ferroptosis in THCA, ferroptosis-related long non-coding RNAs (FRLs) were used to construct model for risk prediction of THCA. METHODS: RNA-sequencing data of THCA patients and ferroptosis-related genes were downloaded from The Cancer Genome Atlas (TCGA) and FerrDb, respectively. A total of 502 patients with complete data were randomly separated into a training cohort and a validation cohort at the ratio of 2:1. The Pearson correlation coefficients were calculated to determine the correlation between ferroptosis-related genes (FRGs) and the corresponding lncRNAs, and those meeting the screening conditions were defined as FRLs. Gene Expression Omnibus (GEO) database and qRT-PCR were used to verify the expression level of FRLs in THCA tissues. Univariate and multivariate cox regression analysis were performed to construct a FRLs signature based on lowest Akaike information criterion (AIC) value in the training cohort, then further tested in the validation cohort and the entire cohort. Gene set enrichment analysis (GSEA) and functional enrichment analysis were used to analyze the biological functions and signal pathways related to differentially expressed genes between the high-risk and low-risk groups. Finally, the relative abundance of different tumor-infiltrating immune cells were calculated by CIBERSORT algorithm. RESULTS: The patients were divided into high-risk group and low-risk group based on a 5-FRLs signature (AC055720.2, DPP4-DT, AC012038.2, LINC02454 and LINC00900) in training cohort, validation cohort and entire cohort. Through Kaplan-Meier analysis and area under ROC curve (AUC) value, patients in the high-risk group exhibited worse prognosis than patients in the low-risk group. GEO database and qRT-PCR confirmed that LINC02454 and LINC00900 were up-regulated in THCA. Univariate and multivariate cox regression analyses showed that the risk score was an independent prognostic indicator. GSEA and functional enrichment analysis confirmed that immune-related pathways against cancer were significantly activated in the low-risk THCA patients. Further analysis showed that the immune cells such as plasma cells, T cells CD8 and macrophages M1, and the expression of immune checkpoint molecules, including PD-1, PD-L1, CTLA4, and LAG3, were remarkably higher in the low-risk group. CONCLUSION: Our study used the TCGA THCA dataset to construct a novel FRLs prognostic model which could precisely predict the prognosis of THCA patients. These FRLs potentially mediate anti-tumor immunity and serve as therapeutic targets for THCA, which provided the novel insight into treatment of THCA.

Regulated Li2 S Deposition toward Rapid Kinetics Li-S Batteries by a Separator Modified by CeO2 -Decorated Porous Carbon Nanostructure.

Although the high-energy-density lithium sulfur (Li-S) battery has been considered one of the most promising next-generation energy storage technology, the practical applications have been plagued by the sluggish reaction kinetics and the shuttle effect of lithium polysulfides intermediates. Here, to address the above issues, the authors report a novel separator modified by CeO2 -decorated porous carbon nanostructure (CeO2 /KB/PP). Benefiting from the strong polar surface and large specific surface area, (CeO2 -doped Ketjen Black) delivers efficient chemical adsorption toward lithium polysulfides. Moreover, rich oxygen vacancies of CeO2 provide abundant active sites to expedite lithium polysulfides conversion and regulate deposition and nucleation of Li2 S. Taking advantage of these merits, the battery with the CeO2 /KB/PP separator exhibits remarkable electrochemical performance, including low-capacity decay of only 0.06% per cycle over 1000 cycles at 2 C and superior rate capability of 627 mAh g-1 at 3 C. Even with a high sulfur loading of 6.6 mg cm-2 , the battery can achieve a high areal capacity of 3.6 mAh cm-2 after 100 cycles. This work provides a new application of rare-earth-based materials to facilitate Li-S batteries.

Label-free study on the effect of a bioactive constituent on glioma cells in vitro using terahertz ATR spectroscopy.

In this work, we report that the effect of bioactive constituent on living glioma cells can be evaluated using terahertz time-domain attenuated total reflection (THz TD-ATR) spectroscopy in a label-free, non-invasive, and fast manner. The measured THz absorption coefficient of human glioma cells (U87) in cell culture media increases with ginsenoside Rg3 (G-Rg3) concentration in the range from 0 to 50 µM, which can be interpreted as that G-Rg3 deteriorated the cellular state. This is supported either by the cell growth inhibition rate measured using a conventional cell viability test kit or by the cellular morphological changes observed with fluorescence microscopy. These results verify the effectiveness of using the THz TD-ATR spectroscopy to detect the action of G-Rg3 on glioma cells in vitro. The demonstrated technique thus opens a new route to assessing the efficacy of bioactive constituents on cells or helping screen cell-targeted drugs.

Single-Molecule Identification of the Conformations of Human C-Reactive Protein and Its Aptamer Complex with Solid-State Nanopores.

Human C-reactive protein (CRP) is an established inflammatory biomarker and was proved to be potentially relevant to disease pathology and cancer progression. A large body of methodologies have been reported for CRP analysis, including electrochemical/optical biosensors, aptamer, or antibody-based detection. Although the detection limit is rather low until pg/uL, most of which are time-consuming and relatively expensive, and few of them provided CRP single-molecule information. This work demonstrated the nanopore-based approach for the characterization of CRP conformation under versatile conditions. With an optimized pore of 14 nm in diameter, we achieved the detection limit as low as 0.3 ng/µL, voltage polarity significantly influences the electro-osmotic force and CRP translocation behavior, and the pentameric conformation of CRP may dissociate into pro-inflammatory CRP isoforms and monomeric CRP at bias potential above 300 mV. CRP tends to translocate through nanopores faster along with the increase in pH values, due to more surface charge on both CRP and pore inner wall and stronger electro-osmotic force. The CRP could specifically bind with its aptamer of different concentrations to form complexes, and the complexes exhibited distinguishable nanopore translocation behavior compared with CRP alone. The variation of the molar ratio of aptamer significantly influences the orientation of CRP translocation. The plasma test under physiological conditions displayed the ability of the nanopore system on the CRP identification with a concentration of 3 ng/µL.

The mouse resource at National Resource Center for Mutant Mice.

Mouse models are essential for dissecting disease mechanisms and defining potential drug targets. There are more than 18,500 mouse strains available for research communities in National Resource Center for Mutant Mice (NRCMM) of China, affiliated with Model Animal Research Center of Nanjing University and Gempharmatech Company. In 2019, Gempharmatech launched the Knockout All Project (KOAP) aiming to generate null mutants and gene floxed strains for all protein-coding genes in mouse genome within 5 years. So far, KOAP has generated 8,004 floxed strains and 9,769 KO (knockout) strains (updated to Oct, 2021). NRCMM also created hundreds of Cre transgenic lines, mutant knock-in models, immuno-deficient models, and humanized mouse models. As a member of the international mouse phenotyping consortium (IMPC), NRCMM provides comprehensive phenotyping services for mouse models. In summary, NRCMM will continue to support biomedical community with new mouse models as well as related services.

A Rare Case of Craniocervical Penetrating Injury by a Steel Bar.

RATIONALE: Non-missile penetrating injuries caused by foreign bodies, such as knives or sharp wood, are infrequent. We report a 49-year-old male suffering from severe craniocervical penetrating injury by a steel bar was successfully treated by surgery. CHIEF COMPLAINT: The male patient was a 49-year-old builder. Although working on the construction site, an approximately 60 cm steel bar penetrated the patient's brain vertically through the left top of the head presenting with unconsciousness and intermittent irritability. DIAGNOSIS: Computed tomography of the head showed the entrance and exit of the skull damaged by the steel bar. Three-dimensional reconstruction showed that the steel bar entered the skull from the posterior left coronal suture and penetrated the ipsilateral occipital bone, about 5 cm into the neck soft tissue. INTERVENTION: We successfully performed the operation and removed the steel bar. OUTCOMES: The patient was followed up for 5 years; muscle strength returned to normal. LESSONS: Penetrating injuries caused by steel bars are rare, which always cause severe intracranial injury combined with peripheral tissue injury, by sharing our experience in the treatment of this rare case, we hope to provide a reference for similar injuries in the future.

Fast and efficient generation of a full-length balancer chromosome by a single Cre/loxP recombination event.

Balancer chromosomes, primarily discovered and used in Drosophila melanogaster, are valuable tools to maintain lethal mutations in a particular genomic segment. Full-length balancer chromosomes would be particularly useful because of the capacity to maintain whole genomic traits. However, murine full-length balancer chromosomes generated via a single Cre/loxP recombination are still not demonstrated. In this study, we developed a novel mouse strain with full-length inverted chromosome 17 (Ch17Inv balancer) via a single Cre/loxP recombination event in mES cells. The Ch17Inv balancer mice are viable and phenotypically normal. When bred with other strains, the haplotype of chromosome 17 can be stably maintained as determined by the high throughput SNPs assay. Interestingly, we found that the recombination events were efficiently reduced within the inverted region but not eliminated. The method established in this study can be applied to generate other full-length balancer chromosomes. Moreover, the Ch17Inv balancer strain would be a valuable resource to maintain the entire chromosome 17 from different donor strains.

Distinct binding kinetics of E-, P- and L-selectins to CD44.

Molecular-level selectin-cluster of differentiation 44 (CD44) interactions are far from clear because of the complexity and diversity of CD44 glycosylation and isoforms expressed on various types of cells. By combining experimental measurements and simulation predictions, the binding kinetics of three selectin members to the recombinant CD44 were quantified and the corresponding microstructural mechanisms were explored, respectively. Experimental results showed that the E-selectin-CD44 interactions mainly mediated the firm adhesion of microbeads under shear flow with the strongest rupture force. P- and L-selectins had similar interaction strength but different association and dissociation rates by mediating stable rolling and transient adhesions of microbeads, respectively. Molecular docking and molecular dynamics (MD) simulations predicted that the binding epitopes of CD44 to selectins are all located at the side face of each selectin, although the interfaces denoted as the hinge region are between lectin and epidermal growth factor domains of E-selectin, Lectin domain side of P-selectin and epidermal growth factor domain side of L-selectin, respectively. The lowest binding free energy, the largest rupture force and the longest lifetime for E-selectin, as well as the comparable values for P- and L-selectins, demonstrated in both equilibration and steered MD simulations, supported the above experimental results. These results offer basic data for understanding the functional differences of selectin-CD44 interactions.

Modified radical mastectomy for level III axillary lymph node clearance: a case report.

While modified radical mastectomy with level I and level II axillary lymph node clearance is a typical operating method in breast surgery, level III axillary lymph node clearance is necessary in some cases such as those involving apical axillary nodes. Level III dissection can provide accurate postoperative staging and essential guidance for postoperative adjuvant therapy. Although it is often difficult to expose the subclavian region and dissect level III axillary lymph nodes, in this case, the author split the pectoralis major muscle 2 cm inferior to the collarbone and performed a skeletonized complete level III axillary lymph node dissection. The author cut apart the fat on the surface of subclavian vein, lifted the fascia on the surface of the subclavian vein, removed the lymphoid adipose tissue along the fascial space completely and skeletonized subclavian vein. This approach provides less operating space, but it can fully expose the subclavian area, making it easier to dissociate and dissect the parasternal ligament, subclavian vein, medial border of the pectoralis minor muscle, and other important anatomical landmarks. In addition, the pectoralis branches of the thoracoacromial artery and the lateral cutaneous branches of the intercostal nerves were protected when removing the axillary nodes, which reduced postoperative complications such as upper limb numbness, tingling sensation, and muscle atrophy. Axillary lymph nodes were completely resected from inside to outside, and the important anatomical markers of axilla such as axillary vein, long thoracic nerve, thoracodorsal nerve and thoracodorsal vessels were clearly exposed.

LncRNA SNHG1 promotes tumor progression and cisplatin resistance through epigenetically silencing miR-381 in breast cancer.

The long-non-coding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) is a known cause of tumorigenesis. Nevertheless, it's yet unclear how lncRNA SNHG1 influences breast cancer. Herein, we explored the mechanisms through which SNHG1 modulates breast cancer tumor progression. Our findings demonstrated that SNHG1 is significantly upregulated in breast cancer tissues and cells. High SNHG1 levels were closely linked to reduced survival rates in breast cancer patients. SNHG1 silencing has been shown to inhibit the proliferative, migratory, and invasive activity of breast cancer cells. Moreover, SNHG1 silencing enhanced cisplatin (DDP) sensitivity of these cells through improving DDP-induced cell apoptosis. Mechanistically, SNHG1 was found to interact with enhancer of zeste homolog 2 (EZH2), recruiting EZH2 to trigger trimethylation of histone H3 lysine 27 (H3K27me3), thus epigenetically inhibiting miR-381 transcription in these cells. Overexpression of miR-381 inhibited tumor progression and sensitized cells to the chemotherapeutic reagent DDP. More importantly, rescue experiments demonstrated that miR-381 inhibition could inverse the tumor-suppressive effect of SNHG1 silencing in breast cancer. In summary, SNHG1 silencing suppressed tumor progression and overcame breast cancer cell DDP resistance via the epigenetic suppression of miR-381 expression. Our study revealed that SNHG1 served as a novel therapeutic target for breast cancer chemoresistance.

A novel battery separator coated by a europium oxide/carbon nanocomposite enhances the performance of lithium sulfur batteries.

Lithium sulfur (Li-S) batteries represent one of the most promising future power batteries due to their remarkable advantages of low cost and ultrahigh theoretical energy density. However, the commercial applications of Li-S batteries have long been plagued by the shuttling effect of polysulfides and sluggish redox kinetics of these species. Herein, we designed a novel battery separator coated by a europium oxide-doped porous Ketjen Black (Eu2O3/KB) and tested its performance for the Li-S batteries for the first time. Experimental results and theoretical calculations reveal that the improved electrochemical performance can be attributed to the presence of Eu2O3. The strong binding effect between Eu2O3 and polysulfides is demonstrated in two aspects: (1) there exist strong interactions between Eu2O3 as a Lewis acid and polysulfides of strong Lewis basicity; (2) Eu2O3 with oxygen-vacancy defects provides active sites for catalyzing polysulfide conversion and polysulfide trapping. Thus, a Li-S battery with the Eu2O3/KB modified separator delivers highly stable cycling performance and excellent rate capability, with the capacity decay ratio of merely 0.05% per cycle under 1 C rate during 500 cycles, and high specific capacity of 563 mAh g-1 at 3 C rate. This work offers a meaningful exploration of the application of rare earth oxides for the modification of the separator towards high performance Li-S batteries.