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.

NKAIN1, as an oncogene, promotes the proliferation and metastasis of breast cancer, affecting its prognosis.

Na, K-ATPase interaction (NKAIN) is a transmembrane protein family, which can interact with Na, K-ATPase ß1 subunit. NKAIN1 plays an important role in alcohol-dependent diseases such as endometrial and prostate cancers. However, the relationship between NKAIN1 and human breast cancer has not been studied. Hence, this study aimed to explore the relationship between NKAIN1 expression and breast cancer. Data used in this study were mainly from the Cancer Genome Atlas, including differential expression analysis, Kaplan-Meier survival analysis, receiver operating characteristic curve analysis, multiple Cox regression analysis, co-expression gene analysis, and gene set enrichment analysis. Analyses were performed using reverse transcription-quantitative polymerase chain reaction, western blot analysis, and immunohistochemistry on 46 collected samples. The knockdown or overexpression of NKAIN1 in vitro in MCF-7 and MDA-MB-231 cell lines altered the proliferation and migration abilities of tumor cells. In vivo experiments further confirmed that NKAIN1 knockdown effectively inhibited the proliferation and migration of cancer cells. Therefore, our study identified NKAIN1 as an oncogene that is highly expressed in breast cancer tissues. The findings highlight the potential of NKAIN1 as a molecular biomarker of breast cancer.

Unprecedented Spatial Manipulation and Transformation of Dynamic Thermal Radiation Based on Vanadium Dioxide.

Reconfigurable infrared (IR) materials have widespread applications in thermal management and smart IR concealment. Although various reconfigurable IR materials can be customized by positive or negative differential VO2-based resonators, their insightful mechanism remains unknown. Here, we comprehensively investigate the fundamental design rule of reconfigurable thermal radiation between positive and negative differential thermal radiation properties for the first time. Importantly, the skin depth of VO2 film in the metal state is investigated to clarify the transformation from positive to negative differential thermal radiation properties, and the critical thickness is further derived, providing important guidance in designing the reconfigurable thermal radiation regulator. Furthermore, the reconfigurable multistate thermal images had been presented into one plate. The resulting emittance variation (△ε8-14 µm) of the VO2-based resonator can change from 0.61 to -0.53, which consummates the ability for diverse demands such as infrared concealment, thermal illusion, and thermal management. This work constitutes a promising and universal route toward designing whole smart devices and may create new scientific and technological opportunities for platforms that can benefit from reconfigurable electromagnetic manipulation.

Research and experiment on global path planning for indoor AGV via improved ACO and fuzzy DWA.

In order to obtain an optimal trajectory for indoor AGV, this paper combined an improved ACO and fuzzy DWA (IACO-DWA) algorithm, which can provide an optimal path with collision-free under higher optimization efficiency. The highlights of this paper are detailed as follows: Firstly, an improved adaptive pseudo-random transition strategy is adopted in the state transition probability with an angle factor. A reward and punishment mechanism is introduced in the pheromone updating strategy, then a path optimization strategy called IACO is proposed for the more optimized path. Secondly, IDWA adopted three fuzzy controllers of direction, security and adjustment coefficients through evaluating directional and safety principles, then improving the angular velocity by processing the linear velocity with linear normalization. By adapting to the changes of the environment, the IDWA parameters can be dynamically adjusted to ensure the optimal running speed and reasonable path of AGV. Thirdly, aiming to deal with the path-planning problem in complex environments, we combined IACO with IDWA, the hybrid algorithm involves dividing the globally optimal path obtained from IACO planning into multiple virtual sub-target points. IDWA completes the path planning by switching between these local target points, thereby improving the efficiency of the path planning. Finally, simulations is verified by Matlab and experiment results on the QBot2e platform are given to verify IACO-DWA algorithm's effectiveness and high performance.

GREB1L overexpression is associated with good clinical outcomes in breast cancer.

BACKGROUND: Breast cancer is the most common malignant tumor among women worldwide. GREB1L is a protein-coding gene. Previous studies have shown that GREB1L plays a vital role in lung and gastric adenocarcinoma. Currently, there is no relevant report about its role in breast cancer. METHODS: The Cancer Genome Atlas database was used to compare the expression level of GREB1L between tumor and normal tissues. The TISIDB website was used for prognosis analysis. The LinkedOmics database was used to predict the potential biological mechanism of GREB1L in breast cancer. Immunohistochemistry was used to detect the GREB1L expression level in breast tissue. Western blotting was used to detect the GREB1L expression level in cell lines. Transwell assays, CCK-8 cell proliferation assays, and colony formation assays were used to detect the migration, invasion, proliferation, and colony formation abilities of cells. Subcutaneous xenograft models were used to detect the in vivo tumor formation abilities of cells. RESULTS: GREB1L is highly expressed in breast cancer tissues and breast cancer cells. KEGG enrichment analysis suggested that GREB1L participates in the regulation of the Hedgehog signaling pathway; changes in GREB1L expression affected the migration and invasion abilities of MCF7 and MDA-MB-231 cells. Although changes in GREB1L expression did not affect their proliferation and colony formation abilities in vitro and in vivo, they affected the expression of tumor metastasis-related genes in vivo. The overexpression of GREB1L in breast cancer predicted a favorable prognosis. CONCLUSION: These results showed that GREB1L is involved in the development of breast cancer, and it may be a potential molecular marker for predicting the prognosis of breast cancer.

Glycolysis-based drug delivery nanosystems for therapeutic use in tumors and applications.

Tumor cells are able to use glycolysis to produce energy under hypoxic conditions, and even under aerobic conditions, they rely mainly on glycolysis for energy production, the Warburg effect. Conventional tumor therapeutic drugs are unidirectional, lacking in targeting and have limited therapeutic effect. The development of a large number of nanocarriers and targeted glycolysis for the treatment of tumors has been extensively investigated in order to improve the therapeutic efficacy. This paper reviews the research progress of nanocarriers based on targeting key glycolytic enzymes and related transporters, and combines nanocarrier systems with other therapeutic approaches to provide a new strategy for targeted glycolytic treatment of tumors, providing a theoretical reference for achieving efficient targeted treatment of tumors.

Layered Double Hydroxide-Loaded miR-30a for the Treatment of Breast Cancer In Vitro and In Vivo.

MicroRNAs (miRNAs) play an essential role in cancer therapy, but the disadvantages of its poor inherent stability, rapid clearance, and low delivery efficiency affect the therapeutic efficiency. Loading miRNAs by nanoformulations can improve their bioavailability and enhance therapeutic efficiency, which is an effective miRNA delivery strategy. In this study, we synthesized layered double hydroxides (LDH), which are widely used as carriers of drugs or genes due to the characteristics of good biocompatibility, high loading capacity, and pH sensitivity. We loaded the suppressor oncogene miR-30a on LDH nanomaterials (LDH@miR-30a) and determined the mass ratio of miRNA binding to LDH by agarose gel electrophoresis. LDH@miR-30a was able to escape the lysosomal pathway and was successfully phagocytosed by breast cancer SKBR3 cells and remained detectable in the cells after 24 h of co-incubation. In vitro experiments showed that LDH@miR-30a-treated SKBR3 cells showed decreased proliferation and cell cycle arrest in the G0/G1 phase and LDH@miR-30a was able to regulate the epithelial-mesenchymal transition (EMT) process and inhibit cell migration and invasion by targeting SNAI1. Meanwhile, in vivo experiments showed that nude mice treated with LDH@miR-30a showed a significant reduction in their solid tumors and no significant impairment of vital organs was observed. In conclusion, LDH@miR-30a is an effective drug delivery system for the treatment of breast cancer.

Establishment and validation of a nomogram to predict structural incomplete response in papillary thyroid carcinoma patients: a retrospective study.

OBJECTIVE: To identify risk factors related to structural incomplete response (SIR) in papillary thyroid carcinoma (PTC) and develop a nomogram for PTC patients. METHODS: In this respective study, clinical, ultrasonic, and pathological data of PTC patients treated at our institute between 2016 and 2020 were analyzed. Patients were randomly split into training and validation sets at a ratio of 7:3. Multivariate Cox regression analysis was conducted to determine independent prognostic factors. On the basis of these factors, a nomogram was built to predict SIR. P value, concordance index, calibration plots and decision curve analysis were used to evaluate the model. RESULTS: Multivariate Cox regression analysis showed that BRAF V600E status, lymph node metastasis, sex, tumor size, margin, and surgical procedure were independent prognostic factors. In the validation set, the concordance index of the nomogram was 0.774 (95% confidence interval: 0.703-0.845). Calibration plots at 3 and 5 years showed no apparent difference between predicted SIR probability and the actual SIR proportion. Additionally, the nomogram had good net clinical benefit according to the decision curve analysis compared with cases that were treat-all or treat-none. CONCLUSION: We build a nomogram to predict individualized outcomes and help postoperative surveillance in PTC patients.

DPP4 Is a Potential Prognostic Marker of Thyroid Carcinoma and a Target for Immunotherapy.

DPP4 (dipeptidyl peptidase 4) is expressed in many cancers, but the relationship between DPP4 and thyroid carcinoma (THCA) is incompletely understood. We aim to explore the expression of DPP4 in THCA and the correlation between DPP4 expression with the prognosis of THCA and antitumor immunity. We systematically analyzed data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO) databases and explored DPP4 expression, its impact on prognosis, and its relationship with antitumor immunity in THCA. Next, we collected 18 pairs of fresh THCA and adjacent paracancerous tissues and performed RT-qPCR to validate the DPP4 mRNA level. Concurrently, immunohistochemistry (IHC) analysis was performed on 12 pairs of paraffin-embedded tissues of medullary thyroid carcinoma (MTC) and paracancerous tissues to validate the DPP4 protein level. Bioinformatics analysis showed that DPP4 mRNA expression in THCA was significantly higher than that in paracancerous tissues (p < 0.01). DPP4 was expressed at the highest levels in MTC than in other pathological types. The DPP4 expression level was different between groups with different clinical characteristics. The higher the DPP4 expressed in THCA, the lower the disease-free survival (DFS) was (HR = 1.8, p=0.048). DPP4 was significantly correlated with immune cell infiltration and immune response and was positively associated with 21 immune checkpoint genes (ICGs) in THCA (p < 0.05). The results of RT-qPCR showed that the relative mRNA expression of DPP4 was significantly upregulated in 18 THCA tissues compared to that in paracancerous tissues (p=0.011). IHC results showed that the DPP4 protein level was higher in 12 MTC tissues than in paracancerous tissues (p=0.011). In conclusion, DPP4 is a potential prognostic marker of THCA and may become an effective target for immunotherapy.

Design of stapled peptide-based PROTACs for MDM2/MDMX atypical degradation and tumor suppression.

Rationale: Although stapled peptides offer a powerful solution to overcome the susceptibility of linear peptides to proteolytic degradation and improve their ability to cross membranes, an efficient and durable disease treatment strategy has not yet been developed due to the inevitable elimination of peptide inhibitors and rapid accumulation of target proteins. Methods: Herein we developed stapled peptide-based proteolysis-targeting chimeras (SP-PROTACs), that simultaneously exhibited improved cellular uptake and proteolytic stability attributed to the stapled peptides, and efficient target protein degradation promoted by the PROTACs. Based on the PMI peptide with dual specificity for both MDM2 and MDMX, a series of SP-PROTACs were designed. Results: Among them, the optimized SPMI-HIF2-1 exhibited similar binding affinity with MDM2 and MDMX but obviously higher helical contents, improved proteolytic stability, better cellular permeability, and a better pharmacokinetic profile compared with its linear counterpart. Importantly, SPMI-HIF2-1 could effectively kill cancer cells and inhibit tumor progression in subcutaneous and orthotopic colorectal cancer xenograft models through simultaneously promoting the atypical degradation of both MDM2 and MDMX and durable p53 activation. An FP-based binding assay and structural modeling analysis of the ternary complex suggested that SPMI-HIF2-1 simultaneously bound with the target protein and E3 ligase. Conclusion: Our findings not only provide a new class of anticancer drug candidates, but also bridge the gap and reduce the physical distance between peptides and PROTACs.

VO2-Based Infrared Radiation Regulator with Excellent Dynamic Thermal Management Performance.

Dynamic thermal management materials attract fast-increasing interest due to their adaptability to changing environments and greater energy savings as compared to static materials. However, the high transition temperature and the low emittance tunability of the vanadium dioxide (VO2)-based infrared radiation regulators limit their practical applications. This study addresses these issues by proposing a smart infrared radiation regulator based on a Fabry-Pérot cavity structure (VO2/HfO2/Al), which is prepared by high-power impulse magnetron sputtering (HiPIMS) and has the potential for large-scale production. Remarkably, the outstanding emittance tunability reaches 0.51, and the phase transition temperature is lowered to near a room temperature of 27.5 °C by tungsten (W) doping. In addition, a numerical thermal management power of 196.3 W/m2 (at 8-14 µm band) can be obtained from 0 to 60 °C. As a proof-of-concept, the demonstrated capabilities of the VO2 infrared radiation regulator show great potentials in a wide range of applications for the thermal management of buildings and vehicles.

Using 3-dimensional ultrasound islice technology for the diagnosis of developmental dysplasia of the hip.

OBJECTIVES: This study aimed to investigate the reliability of 3-dimensional (3D) ultrasound in screening for developmental dysplasia of the hip (DDH) by comparing the results with those of 2-dimensional (2D) ultrasound. METHODS: One hundred five infants who were younger than 6 months were enrolled in this study. All of the infants underwent 2D and 3D ultrasound scanning for DDH by novices and experts, and the images were graded by a lead expert. The scanning time and image grades were analyzed by Student t tests (P < .05). The consistency of the α angle measurement between the novices and experts was evaluated by the intraclass correlation coefficient (ICC). RESULTS: The 105 infants included 34 boys and 71 girls. On 2D scanning, there was agreement between the experts about the correct diagnosis, whereas in the novice group, 41 infants had misdiagnoses. There were no misdiagnoses with 3D scanning in either group. In the novice group, the mean image grades ± SD were 4.2 ± 1.3 (2D ultrasound) and 8.1 ± 0.7 (3D ultrasound; P < .05). In the expert group, the mean image grades were 7.4 ± 1.0 (2D ultrasound) and 8.2 ± 1.0 (3D ultrasound; P < .05). There was no statistically significant difference between the groups in the grades for 3D ultrasound (P = .83). The scanning time for 3D ultrasound was shorter than that for 2D ultrasound in both groups (P < .05). In the novice group, the ICC of the α angle between the 2D and 3D ultrasound results was 0.34, and in the expert group, it was 0.92. The ICCs were 0.35 and 0.84, respectively when comparing 2D and 3D ultrasound results in the groups. CONCLUSIONS: Three-dimensional ultrasound required less time and showed greater inter-rater reliability than 2D ultrasound for detecting DDH.

Clinical value of ultrasonic imaging in diagnosis of hypopharyngeal cancer with cervical lymph node metastasis.

Clinical value of ultrasonic imaging in diagnosis of hypopharyngeal cancer with cervical lymph node metastasis was investigated. Eighty-nine patients who were diagnosed with hypopharyngeal cancer in Qilu Hospital of Shandong University (Qingdao) from January 2014 to June 2016 were retrospectively analyzed. Sixty-eight patients were diagnosed with hypopharyngeal cancer with cervical lymph node metastasis by pathological sections. Twenty-one patients did not have cervical lymph node metastasis. All the patients were diagnosed by palpation and ultrasound. The lymph node ultrasound images were quantified by computer, and the long/short diameter ratio, the maximum systolic velocity, blood flow resistance of the metastatic and non-metastatic patients were compared. The diagnostic efficacy of palpation and ultrasound was analyzed in the diagnosis of hypopharyngeal cancer with cervical lymph node metastasis. A correlation analysis was carried out between the image features of ultrasound and lymph node metastasis. The long/short diameter ratio, maximum systolic velocity and resistance index of patients with lymph node metastasis were significantly higher than those without lymph node metastasis, with a significant difference (P<0.05). Forty-one patients were diagnosed with lymph node metastasis by palpation, fifty-nine patients were diagnosed with lymph node metastasis by ultrasound. The sensitivity and diagnostic coincidence rate of ultrasound in diagnosis of hypopharyngeal cancer with cervical lymph node metastasis were significantly higher than those of palpation (P<0.05). Statistically significant differences were observed in lymph node internal echo types, medullary echo characteristics, envelope definition, and blood flow distribution characteristics between the metastasis group and the non-metastasis group (P<0.05). Lymph node internal echo was heterogeneous. There was no medulla, and the disordered blood flow in the lymph node predicted lymph node metastasis. Preoperative ultrasound has a high diagnostic value in diagnosis of hypopharyngeal cancer with cervical lymph node metastasis. The diagnostic results of preoperative ultrasound can be used as a reference for the diagnosis and treatment of hypopharyngeal cancer with cervical lymph node metastasis.

Ultrasound classification and clinical analysis of ovarian pregnancy: A study of 12 cases.

OBJECTIVE: To evaluate the clinical significance of preoperative ultrasound diagnosis and classification of ovarian pregnancy (OP). METHODS: The ultrasonographic reports, medical records, and operative summaries were reviewed for twelve women with a confirmed diagnosis of OP. According to the ultrasonographic appearance, OP was classified into two types. For every type, we analyzed the possibility and clinical significance of preoperative ultrasound diagnosis, combining with its clinical manifestations and treatments. RESULTS: According to sonographic features, twelve cases of OP can be classified into ruptured type (n = 6) and unruptured type (n = 6), the latter was subclassified into embryo sac type (n = 2) and non-homogeneous mass type (n = 4). All the unruptured OP have the characteristic solid hyperechoic rings or masses, and 66.7% (4/6) were correctvly diagnosed by preoperative ultrasound. No characteristic ultrasonogram was detected in ruptured OP which were all diagnosed as ruptured ectopic pregnancy (EP) or corpus luteum by preoperative ultrasound. The diagnostic and surgical procedures of four cases diagnosed by preoperative ultrasound were all laparoscopy and removal of the gestational products, and their average hemoperitoneum, operation time, hospital days was 313 ± 278 ml, 57 ± 9 min, and 4.25 ± 0.5days, respectively. While ruptured OP cases (6 cases diagnosed at first visit and 1 underdiagnosed but ruptured after 6 days), the diagnostic procedures was laparoscopy(3/7) or laparotomy(4/7), the surgical procedure was removal of the gestational products(2/7), wedge resection(3/7), or adenexectomy(2/7), and their average hemoperitoneum, operation time, and hospital days was 1914 ± 1059 ml, 93 ± 17 min, and 5.9 ± 1.3days, respectively. CONCLUSIONS: Ultrasound plays a significant role in diagnosis of OP, and part of the unruptured OP based on the typical sonographic characteristics could be correctly diagnosed by an experienced sonographer, this is beneficial and effective in terms of the risk of patient's operation and life. Whereas ruptured OP were generally diagnosed as ruptured EP or corpus luteum because there were no characteristic ultrasound manifestations.