Left ventricular unloading with gentle chest compressions for patients on veno-arterial extracorporeal membrane oxygenation: two case reports.

Insufficient ventricular unloading is a serious complication during veno-arterial extracorporeal membrane oxygenation (VA-ECMO) that has a crucial impact on patient outcomes. The existing conservative treatment options are limited, while mechanical decompression techniques are challenging and restricted in terms of their adoption and application. Two patients with cardiogenic shock experienced insufficient left ventricular unloading with no pulsatile contraction and aortic valve closure during VA-ECMO support. Gentle chest compression was applied to establish an active left ventricular drainage mechanism, which prevented the formation of intracardiac thrombi. No life-threatening complications or technical problems occurred. Therefore, gentle chest compression was established as an effective and safe method for treating insufficient left ventricular unloading in VA-ECMO patients.

Efficacy and safety of ultrasound-guided thermal ablation of graves' disease: a retrospective cohort study.

BACKGROUND: Ultrasound-guided thermal ablation (TA) has emerged as a robust therapeutic approach for treating solid tumors in multiple organs, including the thyroid. Yet, its efficacy and safety profile in the management of Graves' Disease (GD) remains to be definitively established. METHODS: A retrospective study was conducted on 50 GD patients treated with TA between October 2017 and December 2021. Key metrics like thyroid volume, volume reduction rate (VRR), thyroid hormones, and basal metabolic rate (BMR) were evaluated using paired Wilcoxon tests. RESULTS: The intervention of ultrasound-guided TA yielded a statistically significant diminution in total thyroid volume across all postoperative follow-up intervals-1, 3, 6, and 12 months-relative to pre-intervention baselines (p < 0.001). The median VRR observed at these time points were 17.5%, 26.5%, 34.4%, and 39.8%, respectively. Euthyroid status was corroborated in 96% of patients at the one-year follow-up milestone. Transient tachycardia and dysphonia were observed in three patients, while a solitary case of skin numbness was noted. Crucially, no instances of enduring injury to the recurrent laryngeal nerve (RLN) were documented. CONCLUSIONS: Our investigation substantiates ultrasound-guided TA as a pragmatic, well-tolerated, and safe therapeutic modality for GD. It effectively improves symptoms of hyperthyroidism, engenders a substantial reduction in thyroid volume, and restores thyroid hormone and BMR to physiological levels. Given its favorable safety profile, enhanced cosmetic outcomes, and minimally invasive nature, ultrasound-guided TA is a compelling alternative to thyroidectomy for GD patients.

Trigger-activated autonomous DNA machine for amplified liver cancer biomarker microRNA21 imaging.

MicroRNA-21 (miRNA-21) is a kind of RNA that exists in biological fluids such as blood, urine and saliva. It has over expression in liver cancer and has different expression in different stages of cancer. However, due to the characteristics of small base number, short length, low abundance and easy degradation of miRNA-21, the detection of miRNA-21 is a challenging subject. Visualization, sensitive, specific and stable detection of tumor suppressor or oncogene microRNAs (miRNAs) remains challenging and is highly significant for clinical diagnostics. To solve this problem, we have developed a target-triggered hybridization assembly DNA machine for intracellular miRNA imaging based on strand displacement amplification (SDA) and branched hybridization chain reaction (B-HCR). In this approach, the target miRNA could hybridize with the template probe to trigger the SDA, resulting in the formation of nicked fragments (NFs) that hybridized with hairpin probe1 (HP1). The opened HP1 could hybridize with hairpin probe2 (HP2), leading to the self-assembly of hyperbranched DNA nanostructures through B-HCR. As expected, the newly developed method exhibits a detection limit down to 11.3 pM miRNA-21 and achieves high selectivity toward miRNA-21 against other interfering miRNAs. Due to its superior sensitivity and selectivity, our method can be further used to detect miRNA-21 in human serum samples. By taking advantage of intelligent design, the proposed method was also used for image miRNA-21 expression levels in different cell lines. This method shows a broad application in clinical diagnosis.

Machine learning models-based on integration of next-generation sequencing testing and tumor cell sizes improve subtype classification of mature B-cell neoplasms.

Background: Next-generation sequencing (NGS) panels for mature B-cell neoplasms (MBNs) are widely applied clinically but have yet to be routinely used in a manner that is suitable for subtype differential diagnosis. This study retrospectively investigated newly diagnosed cases of MBNs from our laboratory to investigate mutation landscapes in Chinese patients with MBNs and to combine mutational information and machine learning (ML) into clinical applications for MBNs, especially for subtype classification. Methods: Samples from the Catalogue Of Somatic Mutations In Cancer (COSMIC) database were collected for ML model construction and cases from our laboratory were used for ML model validation. Five repeats of 10-fold cross-validation Random Forest algorithm was used for ML model construction. Mutation detection was performed by NGS and tumor cell size was confirmed by cell morphology and/or flow cytometry in our laboratory. Results: Totally 849 newly diagnosed MBN cases from our laboratory were retrospectively identified and included in mutational landscape analyses. Patterns of gene mutations in a variety of MBN subtypes were found, important to investigate tumorigenesis in MBNs. A long list of novel mutations was revealed, valuable to both functional studies and clinical applications. By combining gene mutation information revealed by NGS and ML, we established ML models that provide valuable information for MBN subtype classification. In total, 8895 cases of 8 subtypes of MBNs in the COSMIC database were collected and utilized for ML model construction, and the models were validated on the 849 MBN cases from our laboratory. A series of ML models was constructed in this study, and the most efficient model, with an accuracy of 0.87, was based on integration of NGS testing and tumor cell sizes. Conclusions: The ML models were of great significance in the differential diagnosis of all cases and different MBN subtypes. Additionally, using NGS results to assist in subtype classification of MBNs by method of ML has positive clinical potential.

Multi-omics data integration reveals the molecular network of dysregulation IQGAP2-mTOR promotes cell proliferation.

IQGAP2 as a tumor suppressor gene can influence cell proliferation in multiple tumor cell lines. However, the regulation network of cell proliferation resulting solely from the deficiency of IQGAP2 in cells was still unclear. Here, we integrated transcriptome, proteome, and phosphoproteome analyses to investigate the regulatory network of cell proliferation in IQGAP2 knockdown HaCaT and HEK293 cells. Our findings revealed that the dysregulation of the IQGAP2-mTOR molecular network led to increased cell proliferation. We demonstrated that IQGAP2 knockdown enhanced the phosphorylation levels of AKT and S6K, leading to increased cell proliferation. Additionally, we found that AKT and mTOR inhibitors partially rescued abnormal cell proliferation by reducing hyperphosphorylation. Our data suggest a potential connection between the mTOR signaling pathway and aberrant cell proliferation in IQGAP2 knockdown cells. These findings offer a new therapeutic strategy for patients with IQGAP2 deficiency.

Integrative analyses of ferroptosis and immune related biomarkers and the osteosarcoma associated mechanisms.

Osteosarcoma (OS) is the most common primary malignant bone tumor with high metastatic potential and relapse risk. To study the regulatory mechanism of the OS microenvironment, a complex regulatory network involving the ferroptosis- and immune response-related genes remains to be established. In the present study, we determined the effect of a comprehensive evaluation system established on the basis of ferroptosis- and immune-related genes on the immune status, related biomarkers, prognosis, and the potential regulatory networks underlying OS based on the TARGET and Gene Expression Omnibus databases that contain information on OS patients by bioinformatics analyses. We first characterized individual ferroptosis scores and immune scores through gene set variation analysis (GSVA) against TARGET-OS datasets. We then identified differentially expressed genes by score groups. Weighted gene co-expression network analysis was performed to identify the most relevant ferroptosis-related and immune-related gene modules, which facilitated the identification of 327 ferroptosis gene and 306 immune gene candidates. A 4-gene (WAS, CORT, WNT16, and GLB1L2) signature was constructed and valuation using the least absolute shrinkage and selection operator-Cox regression models to effectively predict OS prognosis. The prediction efficiency was further validated by GSE39055. We stratified patients based on the prognostic scoring systems. Eight hub genes (namely CD3D, CD8A, CD3E, IL2, CD2, MYH6, MYH7, and MYL2) were identified, and TF-miRNA target regulatory networks were constructed. Furthermore, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, gene set enrichment analysis, and GSVA were used to determine the signature's potential pathways and biological functions, which showed that the hub genes were enriched in ferroptosis-associated biological functions and immune-associated molecular mechanisms. Thereafter, we investigated the proportion and infiltration extent of 22 infiltrating immune cells by using CIBERSORT, which revealed significant subgroup differences in CD8 + T cells, M0 macrophages, and M2 macrophages. In conclusion, we determined a new ferroptosis-related and immune-related gene signature for predicting OS patients' prognosis and further explored the ferroptosis and immunity interactions during OS development, which provides insights into the exploration of molecular mechanisms and targeted therapies in patients with OS.

Establishing an RNA fusions panel in soft tissue sarcoma with clinical validation.

The diagnosis and classification of soft tissue sarcomas (STS) remain challenging because of the rarity and overlapping morphologic manifestations of diverse STS subtypes. Characteristic gene fusions are commonly detected in STS and represent useful diagnostic markers. This study established and validated a custom-designed RNA sequencing panel that identified 64 gene fusions in STS. The analytical performance validation yielded excellent accuracy, with 100% (95% CI, 94.40%-100%) sensitivity and 93.33% (95% CI, 68.05%-99.83%) specificity. Clinical performances were further confirmed with 145 clinical formalin-fixed and paraffin-embedded (FFPE) samples from STS patients. Fusions were detected in 40% of samples (58/145). The common fusions SS18-SSX family, EWSR1-related fusions, COL1A1-PDGFB, FOXO1-associated fusions, and FUS-associated fusions were identified in corresponding STS subtypes. The RNA panel detected specific fusions in several cases where no conclusive diagnosis can be made based on the morphology and immunohistochemistry results. Data collected in this study demonstrate that the RNA fusions panel can better classify STS subtypes and serve as a good supplement for histopathology, exhibiting a great potential for the STS precise diagnosis.

Tunable resonance of a graphene-perovskite terahertz metasurface.

The combination of graphene and perovskite has received extensive research attention because its photoelectric properties are excellent for the dynamic manipulation of light-matter interactions. Combining graphene and perovskite with a metasurface is expected to effectively improve the metasurface device's performance. Here, we report a terahertz graphene-perovskite metasurface with a tunable resonance. Under 780 nm laser excitation, the device's THz transmission is significantly reduced, and the Fano resonance mode can be manipulated in multiple dimensions. We verify the experimental results using a finite-difference time-domain (FDTD) simulation. Graphene and perovskite interact strongly with the metasurface, resulting in a short-circuit effect, which significantly weakens the resonance intensity of the Fano mode. The photoinduced conductivity enhancement intensifies the short-circuit effect, reducing the THz transmission and resonance intensity of the Fano mode and causing the resonance frequency to redshift. Finally, we provide a reference value for applications of hybrid metasurface-based optical devices in a real environment by investigating the effect of moisture on device performance.

ACR Appropriateness Criteria® Osteoporosis and Bone Mineral Density: 2022 Update.

Osteoporosis constitutes a significant public health risk. An estimated 10.2 million adults in the United States >50 years of age have osteoporosis, a systemic condition that weakens the bones increasing the susceptibility for fractures. Approximately one-half of women and nearly one-third of men >50 years of age will sustain an osteoporotic fracture. These fractures are associated with a decrease in quality of life, diminished physical function, and reduced independence. Dual-energy X-ray absorptiometry (DXA) is the primary imaging modality used to screen for osteoporosis in women >65 years of age and men >70 years of age. DXA may be used in patients <65 years of age to evaluate bone mass density if there are additional risk factors. In certain situations, vertebral fracture assessment and trabecular bone score may further predict fracture risk, particularly in patients who are not yet osteoporotic but are in the range of osteopenia. Quantitative CT is useful in patients with advanced degenerative changes in the spine. Given the proven efficacy of pharmacologic therapy, the role of imaging to appropriately identify and monitor high-risk individuals is critical in substantially reducing osteoporosis-associated morbidity and mortality, and reducing the considerable cost to the health care system. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Establishment of early diagnosis models for cervical precancerous lesions using large-scale cervical cancer screening datasets.

BACKGROUND: Human papilloma virus (HPV) DNA test was applied in cervical cancer screening as an effective cancer prevention strategy. The viral load of HPV generated by different assays attracted increasing attention on its potential value in disease diagnosis and progression discovery. METHODS: In this study, three HPV testing datasets were assessed and compared, including Hybrid Capture 2 (n = 31,954), Aptima HPV E6E7 (n = 3269) and HPV Cobas 4800 (n = 13,342). Logistic regression models for diagnosing early cervical lesions of the three datasets were established and compared. The best variable factor combination (VL + BV) and dataset (HC2) were used for the establishment of six machine learning models. Models were evaluated and compared, and the best-performed model was validated. RESULTS: Our results show that viral load value was significantly correlated with cervical lesion stages in all three data sets. Viral Load and Bacterial Vaginosis were the best variable factor combination for logistic regression model establishment, and models based on the HC2 dataset performed best compared with the other two datasets. Machine learning method Xgboost generated the highest AUC value of models, which were 0.915, 0.9529, 0.9557, 0.9614 for diagnosing ASCUS higher, ASC-H higher, LSIL higher, and HSIL higher staged cervical lesions, indicating the acceptable accuracy of the selected diagnostic model. CONCLUSIONS: Our study demonstrates that HPV viral load and BV status were significantly associated with the early stages of cervical lesions. The best-performed models can serve as a useful tool to help diagnose cervical lesions early.

Development and Validation of Nomograms to Assess Risk Factors and Overall Survival Prediction for Lung Metastasis in Young Patients with Osteosarcoma: A SEER-Based Study.

Background: To establish two nomograms to quantify the diagnostic factors of lung metastasis (LM) and their role in assessing prognosis in young patients with LM osteosarcoma. Methods: A total of 618 osteosarcoma young patients from 2010 to 2015 were included from the Surveillance, Epidemiology, and End Results (SEER) database. Another 131 patients with osteosarcoma from local hospitals were also collected as an external validation set. Patients were randomized into training sets (n = 434) and validation sets (n = 184) with a ratio of 7:3. Univariate and multivariate logistic regression analyses were used to identify the risk factor for LM and were used to construct the nomogram. Risk variables for the overall survival rate of patients with LM were evaluated by Cox regression. Another nomogram was also constructed to predict survival rates. The results were validated using bootstrap resampling and retrospective research on 131 osteosarcoma young patients from 2010 to 2019 at three local hospitals. Results: There were 114 (18.45%) patients diagnosed as LM at initial diagnosis. The multivariate logistic regression analysis suggested that T stage, N stage, and bone metastasis were independent risk factors for LM in newly diagnosed young osteosarcoma patients (P < 0.001). The ROC analysis revealed that area under the curve (AUC) values were 0.751, 0.821, and 0.735 in the training set, internal validation set, and external validation set, respectively, indicating good predictive discrimination. The multivariate Cox proportional hazard regression analysis suggested that age, surgery, chemotherapy, primary site, and bone metastasis were prognostic factors for young osteosarcoma patients with LM. The time-dependent ROC curves showed that the AUCs for predicting 1-year, 2-year, and 3-year survival rates were 0.817, 0.792, and 0.815 in the training set and 0.772, 0.807, and 0.804 in the internal validation set, respectively. As for the external validation set, the AUCs for predicting 1-year, 2-year, and 3-year survival rates were 0.787, 0.818, and 0.717. Conclusions: The nomograms can help clinicians strengthen their personal decision-making and can improve the prognosis of osteosarcoma patients.

Chelator Iminodisuccinic Acid Regulates Reactive Oxygen Species Accumulation and Improves Maize (Zea mays L.) Seed Germination under Pb Stress.

To explore the effects of iminodisuccinic acid (a chelating agent) on maize (Zea mays L.) seed germination under lead (Pb) stress, we comparatively analyzed the effects of applying different concentrations of iminodisuccinic acid (0, 5, 20, and 100 mmol·dm-3) and combined an addition of exogenous substances regulating reactive oxygen species production on maize seed germination, seedling growth, H2O2 content, NADPH oxidase activity, and antioxidant enzyme activities under Pb-stressed and Pb-free conditions. Iminodisuccinic acid (100 mmol·dm-3) significantly delayed seed germination under normal germination conditions and alleviated the inhibitory effects of Pb stress (20 mmol·dm-3) on seed germination. Under normal conditions (without Pb stress), the iminodisuccinic acid-induced inhibition of seed germination was enhanced by treatment with dimethylthiourea (a specific scavenger of reactive oxygen species) or diphenyleneiodonium chloride (a specific inhibitor of NADPH oxidase), but diminished by treatment with H2O2, CaCl2, diethyldithiocarbamic acid (a specific inhibitor of superoxide dismutase), or aminotriazole (a specific inhibitor of catalase). Under Pb stress, iminodisuccinic acid partially eliminated the excessive H2O2 accumulation, improved superoxide dismutase and catalase activity, and weakened the high NADPH oxidase activity. In addition, Ca2+ chelation may be essential for maintaining the reactive oxygen species' balance and improving seed germination and seedling growth by iminodisuccinic acid supplementation in maize under Pb stress. The proposed iminodisuccinic acid supplementation-based method improved maize seed germination in Pb-polluted soil.

Integrative analyses of immune-related biomarkers and associated mechanisms in coronary heart disease.

Various studies showed that the effect of immune activation is pro-atherogenic and coronary heart disease (CHD) should therefore be considered an autoimmune disease. This study aimed to identify potential immune-related biomarkers, pathways, and the potential regulatory networks underlying CHD. Differentially expressed genes (DEGs) between CHD and control samples were determined by analyzing GSE71226 and GSE9128. The overlapping differential expression immune-related genes (DE-IRGs) for CHD were identified by analyzing the ImmPort database and two GEO databases. A total of 384 DE-IRGs were identified. Subsequently, comprehensive enrichment analyses suggested that DE-IRGs were enriched in immune-related pathways, including autoimmune thyroid disease, the intestinal immune network for IGA production, and downstream signaling events of B cell receptors. The signature of DE-IRGs was validated using an external independent dataset GSE20681 (AUC = 0.875). Furthermore, we conducted protein-protein interaction network analysis and identified eight hub genes, which were most enriched in regulation of defense response, NF-κB signaling pathway, regulation of JNK cascade, and regulation of cytokine production. Moreover, networks of miRNAs-mRNAs and transcription factors (TFs)-mRNA underlying the integrated data were established, involving eight miRNAs and 76 TF-targeting hub genes. Ultimately, 17 SNPs in miRNA-mediated gene networks were identified. We screened potential immune-related genes in CHD and constructed miRNA-mRNA-TF and SNP-miRNA networks, which not only provide inspired insights into the occurrence and the molecular mechanisms of CHD but also lay a foundation for targeting potential biomarkers using immunotherapy and for understanding the molecular mechanisms of CHD.

Graphene-based terahertz bias-driven negative-conductivity metasurface.

A graphene-based terahertz negative-conductivity metasurface based on two types of unit cell structures is investigated under the control of an external bias voltage. Electrical characterization is conducted and verification is performed using a finite-difference time-domain (FDTD) and an optical-pump terahertz (THz)-probe system in terms of simulation and transient response analysis. Owing to the metal-like properties of graphene, a strong interaction between the metasurface and monolayer graphene yields a short-circuit effect, which considerably weakens the intensity of the resonance mode under passive conditions. Under active conditions, graphene, as an active load, actively induces a negative-conductivity effect, which enhances the THz transmission and recovers the resonance intensity gradually because of the weakening of the short-circuit effect. The resulting resonance frequency shows a blue shift. This study provides a reference value for combining graphene exhibiting the terahertz bias-driven negative-conductivity effect with metasurfaces and its corresponding applications in the future.

High expression of N-type calcium channel indicates a favorable prognosis in gliomas.

For the diagnosis and prognosis of glioma, the development of prognostic biomarkers is critical. The N-type calcium channel, whose predominant subunit is encoded by calcium voltage-gated channel subunit alpha1 B (CACNA1B), is mostly found in the nervous system and is closely associated with neurosensory functions. However, the link between the expression of CACNA1B and glioma remains unknown. We used ONCOMINE to explore the differences in CACNA1B expression among different cancers. We then conducted survival analysis and COX analysis using TCGA_LGG and TCGA_GBM datasets, which were divided into CACNA1Bhigh and CACNA1Blow based on the median. We examined the differences in other favorable prognostic markers or clinical characteristics between CACNA1Bhigh and CACNA1Blow using t tests. Differentially expressed genes were identified, and KEGG pathway enrichment was performed. We compared the expression of methyltransferases and analyzed the differentially methylated regions. Immunohistochemistry results were retrieved from the Human Protein Atlas database for validation purposes. CACNA1B was expressed at lower levels in gliomas, and, for the first time, we found that high expression of CACNA1B in gliomas predicts a good prognosis. Other favorable prognostic markers, such as isocitrate dehydrogenase mutation, 1p/19q codeletion, and O6-methylguanine-DNA methyltransferase promoter methylation, were increased in tandem with high expression of CACNA1B. Differentially expressed genes were enriched in multiple pathways related to cancer progression and aberrant epigenetic alterations were significantly associated with CACNA1B. High expression of N-type calcium channels indicates a favorable prognosis for gliomas. This study provides a better understanding of the link between gliomas and N-type calcium channels and may offer guidance for the future treatment of gliomas.

One-Step Preparation of Adhesive Composite Hydrogels through Fast and Simultaneous In Situ Formation of Silver Nanoparticles and Crosslinking.

In this study, a series of gelatin/silver nanoparticles (AgNPs) composite hydrogels are prepared for the first time through the facile in situ formation of AgNPs. AgNPs, which are formed by reducing Ag+ using dopamine-conjugated gelatins. These can simultaneously crosslink gelatin molecules, thus generating three-dimentional and porous hydrogels. The gelation time and pore sizes of these composite hydrogels can be controlled by controlling the feeding concentration of AgNO3 and weight content of gelatin in water, respectively. The feeding concentration of AgNO3 also has an effect on the equilibrium swelling ratio of the hydrogels. Moreover, these composite hydrogels, with a controllable gelation time and in situ forming ability, exhibit good adhesive properties and can be used as drug-release depots.

Methylation quantitative locus rs3758653 in the DRD4 gene is associated with duration from first heroin exposure to addiction.

Opioid addiction is a chronic brain disease with a high heritability. However, the genetic underpinnings remain uncertain. DNA methylation is involved in the adaptive changes in neuroplasticity after prolonged drug use. The dopamine receptor D4 (DRD4) has an essential role in the reward processes associated with addictive drugs. To further elucidate the potential role and mechanism of the DRD4 gene variants in heroin addiction, we detected the methylation level of 46 CpG sites in the promoter region and the genotypes of three SNPs in the DRD4 gene. Correlations between the SNPs and methylation levels of the CpG sites, i.e., the analysis of methylation quantitative trait loci (mQTLs) was conducted. Following the identification of mQTLs that are unique in the heroin addiction group, we performed an association study between the mQTLs and traits of heroin addiction. Our results revealed that there were several correlations of SNPs rs3758653 and rs11246226 with the methylation levels of some CpG sites in the DRD4 gene. Among these SNP-CpG pairs, rs3758653-DRD4_04, rs3758653-DRD4_05, rs3758653-DRD4_13 and rs3758653-DRD4_03 were unique in the heroin addiction group. Moreover, we found that mQTL rs3758653 was associated with duration from first heroin exposure to addiction, and the expression level of the DRD4 gene in human brain regions of the frontal cortex and hippocampus. Our findings suggested that some mQTLs in the genome may be associated with traits of opioid addiction through implicating the processes of DNA methylation and gene expression.

Inhibition of miR-1224 suppresses hypoxia/reoxygenation-induced oxidative stress and apoptosis in cardiomyocytes through targeting GPX4.

We have focused on the underlying role of miR-1224 in cardiomyocyte injury stimulated by hypoxia/reoxygenation (H/R). In the current study, the rat cardiomyocyte cell line H9C2 was used to construct a H/R cell model to validate the cardioprotective effects of miR-1224. Data from the dual-luciferase assay revealed that the glutathione peroxidase 4 (GPX4) was a direct target of miR-1224. Expression of miR-1224, determined using qRT-PCR, was remarkably increased while that of GPX4 protein, evaluated via western blotting, was significantly decreased in cardiomyocytes in response to H/R exposure. ROS generation, superoxide dismutase (SOD) activity, concentrations of malondialdehyde (MDA) and 4-hydroxy aldehydes (4-HNE), and H9C2 cell apoptosis were further evaluated following overexpression of miR-1224 or silencing of GPX4 in H9C2 cells. H9C2 cells under H/R conditions displayed increased synthesis of ROS, along with overexpression of miR-1224 and downregulation of GPX4. SOD activity was significantly decreased while concentrations of MDA and 4-HNE were markedly increased under H/R injury conditions. In addition, miR-1224 mimic or GPX4 siRNA plasmids dramatically enhanced H/R-mediated apoptosis, Bax expression and caspase-3 activity, with a concomitant reduction in Bcl-2 expression. Conversely, inhibition of miR-1224 exerted suppressive effects on oxidative stress and apoptosis in H9C2 cells under H/R conditions. Interestingly, silencing of GPX4 attenuated the negative effects of miR-1224 inhibition. Our results suggested that inhibition of miR-1224 caused resistance to H/R and diminished oxidative stress in vitro through targeting of GPX4.

Knockdown of cell division cycle-associated protein 4 expression inhibits proliferation of triple negative breast cancer MDA-MB-231 cells in vitro and in vivo.

Cell division cycle-associated protein 4 (CDCA4), also known as SEI-3/hematopoietic progenitor protein, is a target gene of transcription factor E2F and represses E2F-dependent transcriptional activation and cell proliferation. The present study investigated the effects of CDCA4 knockdown on the regulation of triple negative breast cancer (TNBC) cell proliferation in vitro and in vivo. Human TNBC MDA-MB-231 cells were subjected to CDCA4 expression knockdown using a lentiviral vector carrying CDCA4 or a negative control short hairpin RNA, and reverse transcription-quantitative polymerase chain reaction, MTT cell viability, cell growth, flow cytometric apoptosis, cell cycle and nude mouse tumorigenesis assays were conducted. The knockdown of CDCA4 expression effectively inhibited the growth of MDA-MB-231 cells by promoting apoptosis in vitro. Additionally, CDCA4 expression knockdown suppressed nude mouse tumor cell xenograft formation and growth in vivo. In conclusion, the data from the present study supported the hypothesis that CDCA4 may be involved in regulating human TNBC progression, and that targeting CDCA4 expression could be useful as a novel strategy in future TNBC treatment.

Towards basic ionic liquid-based hybrid membranes as hydroxide-conducting electrolytes under low humidity conditions.

We have developed basic ionic liquid-based hybrid membranes with ionic liquid modified zeolitic imidazolate frameworks (ZIFs) as fillers, aiming to enhance the electrochemical and physical properties of the membrane.