Mitochondrial Calcium Uniporter (MCU) that Modulates Mitochondrial Calcium Uptake and Facilitates Endometrial Cancer Progression through Interaction with VDAC1.

BACKGROUND: Although endometrial cancer represents a frequently diagnosed malignancy of the female reproductive tract, we know very little about the factors that control endometrial cancer. OBJECTIVE: Our study was presented to investigate the function of MCU in endometrial tumorigenesis and the molecular mechanisms involved. METHODS: A total of 94 endometrial cancer patients were recruited into our cohort. MCU and VDAC1 expression was examined in tumor and normal tissues via immunohistochemistry and immunofluorescence. Associations of MCU and VDAC1 expression with clinicopathological characteristics were evaluated. After transfection with shRNA targeting MCU or full-length MCU plasmids, clone formation, wound healing, transwell and MitoTracker Red staining were separately presented in Ishikawa and RL95-2 cells. Moreover, Western blotting or immunofluorescence was utilized to examine the expression of MCU, VDAC1, Na+/Ca2+/Li+ exchanger (NCLX), and ß-catenin under VDAC1 knockdown and/or MCU overexpression or knockdown. RESULTS: MCU and VDAC1 expression were prominently up-regulated in endometrial cancer tissues and were significantly associated with histological grade, depth of myometrial invasion and lymph node status. MCU up-regulation enhanced clone formation, migration, and mitochondrial activity of endometrial cancer cells. The opposite results were investigated when MCU was silenced. MCU or VDAC1 silencing reduced the expression of MCU, VDAC1, NCLX, and ß-catenin. Moreover, VDAC1 knockdown alleviated the promoting effect of MCU overexpression on the above proteins. CONCLUSION: This investigation demonstrated that MCU-induced mitochondrial calcium uptake plays a critical role in endometrial tumorigenesis through interaction with VDAC1.

TGF-ß1 dominates stromal fibroblast-mediated EMT via the FAP/VCAN axis in bladder cancer cells.

BACKGROUND: Bladder cancer is one of the most common malignant tumors of the urinary system and is associated with a poor prognosis once invasion and distant metastases occur. Epithelial-mesenchymal transition (EMT) drives metastasis and invasion in bladder cancer. Transforming growth factor ß1 (TGF-ß1) and stromal fibroblasts, especially cancer-associated fibroblasts (CAFs), are positive regulators of EMT in bladder cancer. However, it remains unclear how TGF-ß1 mediates crosstalk between bladder cancer cells and CAFs and how it induces stromal fibroblast-mediated EMT in bladder cancer. We aimed to investigate the mechanism of TGF-ß1 regulation of stromal fibroblast-mediated EMT in bladder cancer cells. METHODS: Primary CAFs with high expression of fibroblast activation protein (FAP) were isolated from bladder cancer tissue samples. Subsequently, different conditioned media were used to stimulate the bladder cancer cell line T24 in a co-culture system. Gene set enrichment analysis, a human cytokine antibody array, and cytological assays were performed to investigate the mechanism of TGF-ß1 regulation of stromal fibroblast-mediated EMT in bladder cancer cells. RESULTS: Among the TGF-ß family, TGF-ß1 was the most highly expressed factor in bladder cancer tissue and primary stromal fibroblast supernatant. In the tumor microenvironment, TGF-ß1 was mainly derived from stromal fibroblasts, especially CAFs. In stimulated bladder cells, stromal fibroblast-derived TGF-ß1 promoted bladder cancer cell migration, invasion, and EMT. Furthermore, TGF-ß1 promoted the activation of stromal fibroblasts, inducing CAF-like features, by upregulating FAP in primary normal fibroblasts and a normal fibroblast cell line. Stromal fibroblast-mediated EMT was induced in bladder cancer cells by TGF-ß1/FAP. Versican (VCAN), a downstream molecule of FAP, plays an essential role in TGF-ß1/FAP axis-induced EMT in bladder cancer cells. VCAN may also function through the PI3K/AKT1 signaling pathway. CONCLUSIONS: TGF-ß1 is a critical mediator of crosstalk between stromal fibroblasts and bladder cancer cells. We revealed a new mechanism whereby TGF-ß1 dominated stromal fibroblast-mediated EMT of bladder cancer cells via the FAP/VCAN axis and identified potential biomarkers (FAP, VCAN, N-cadherin, and Vimentin) of bladder cancer. These results enhance our understanding of bladder cancer invasion and metastasis and provide potential strategies for diagnosis, treatment, and prognosis.

Evolution of the Microstructure and Mechanical Performance of As-Sprayed and Annealed Silicon Coating on Melt-Infiltrated Silicon Carbide Composites.

In this study, silicon coating was deposited on melt-infiltrated SiC composites using atmospheric plasma spraying and then annealed at 1100 and 1250 °C for 1-10 h to investigate the effect of annealing on the layer. The microstructure and mechanical properties were evaluated using scanning electron microscopy, X-ray diffractometry, transmission electron microscopy, nano-indentation, and bond strength tests. A silicon layer with a homogeneous polycrystalline cubic structure was obtained without phase transition after annealing. After annealing, three features were observed at the interface, namely ß-SiC/nano-oxide film/Si, Si-rich SiC/Si, and residual Si/nano-oxide film/Si. The nano-oxide film thickness was ≤100 nm and was well combined with SiC and silicon. Additionally, a good bond was formed between the silicon-rich SiC and silicon layer, resulting in a significant bond strength improvement from 11 to >30 MPa.

RANKL Promotes Chemotherapy Resistance in Breast Cancer Cells Through STAT3 Mediated Autophagy Induction.

BACKGROUND: This study was to investigate the functional role and mechanism of receptor activator of nuclear factor-kappa B ligand (RANKL) associated autophagy and chemoresistance in breast cancer. MATERIALS AND METHODS: Cell Counting Kit-8 (CCK-8) assay was used to detect the cell viability. Real-time polymerase chain reaction (PCR) was used for determining the relative mRNA levels of key genes and protein expression was assessed by Western blotting. Immunofluorescence was performed to evaluate the changes in the autophagy flux. Short hairpin (shRNA) was used to knockdown the expression of the target genes in breast cancer cells. Based on The Cancer Genome Atlas (TCGA) database, we explored the expression of receptor activator of nuclear factor-kappa B (RANK), autophagy and signal transducer and activator of transcription 3 (STAT3) signaling associated genes and analyzed their correlation with the prognosis of breast cancer patients. RESULTS: The findings showed that receptor activator of nuclear factor-kappa B ligand (RANKL), the ligand of RANK, could effectively enhance the chemoresistance potential of breast cancer cells. Our results showed that RANKL induced autophagy and enhanced the expression of autophagy associated genes in breast cancer cells. The knockdown of RANK suppressed RANKL mediated autophagy induction in these cells. Furthermore, the inhibition of autophagy suppressed RANKL mediated chemoresistance in breast cancer cells. We found STAT3 signaling pathway was involved in RANKL-induced autophagy. Analysis of the expression of RANK, and autophagy and STAT3 signaling associated genes in breast cancer tissues showed that the expression of autophagy and STAT3 signaling associated genes was correlated with the prognosis of breast cancer patients. CONCLUSION: The present study suggests that the RANKL/RANK axis may potentially mediate chemoresistance in breast cancer cells by inducing autophagy through the STAT3 signaling pathway.

Residual Stress Distribution Monitoring and Rehabilitation in Ferromagnetic Steel Rods.

Different means of residual stress distribution monitoring in magnetic rods are illustrated in this paper, through measurements of permeability, magnetoelastic uniformity using two different setups, sound velocity, and eddy currents. The effectiveness of these techniques was assessed through the stress monitoring of the same magnetic rod, suffering residual stresses in two known volumes caused by controlled hammering. Furthermore, rehabilitation has been achieved by means of stress annihilation, achieved by localized induction heating. As a result, the magnetoelastic and sound velocity uniformity measurements are more appropriate for the monitoring of localized residual stresses, while eddy current measurements are useful for the monitoring of the geometrical deformation.

A systematic review on the application of vascular endothelial growth factors in preeclampsia.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) is a disease associated with elevated blood pressure during pregnancy, accounting for 5-10% of all pregnancies, which includes: gestational hypertension, preeclampsia (PE), eclampsia, chronic hypertension with superimposed PE and chronic hypertension. PE is the most prevalent type of HDP that seriously threatens the life and health of mothers and infants. In-depth exploration of the pathogenesis can play an early role in predicting the disease. METHODS: A literature search was conducted in PubMed, Embase, Google Scholar, and other databases in the article. It was investigated by searching for literature published between 1993 and March 2021; the subject terms included-"vascular endothelial growth factor", "preeclampsia", and "pathogenesis". In the article, the inclusion criteria of literature should meet the definition of PE. It was excluded as reviews, case reports, narrative reviews, and publications that lack key information. RESULTS: Vascular endothelial growth factor (VEGF) family factor research provides pivotal value for early clinical prediction of PE. Soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) became a marker for early prediction of PE. Through the included 51 articles, the analysis of VEGF in PE and its pathway factors was summarized to clarify the pathogenesis further and provide innovative ideas for future research directions and clinical diagnosis. DISCUSSION: A systematic review of the VEGF family in the pathogenesis of PE was concluded in the study to find angiogenesis markers of PE from the pathogenesis of the available literature. Therefore, early intervention of clinical diseases could reduce maternal complications and ensure the maximum health of mothers and babies. There are differences in the research results of factors in the VEGF family, and further research is needed to provide accurate clinical evidence.

LncRNA DANCR regulates lymphatic metastasis of bladder cancer via the miR-335/VEGF-C axis.

BACKGROUND: Substantial evidence indicate that long non-coding RNA (lncRNA) and microRNA (miRNA) act as key role in bladder cancer. Differentiation antagonistic ncRNA (DANCR) could be used as a biomarker in the occurrence and development of cancer. This study aims to explore the mechanism of DANCR/miR-335/VEGF-C axis affecting lymphatic metastasis of bladder cancer. METHODS: qRT-PCR detects the expression of DANCR in bladder cancer cell lines (SW780, 5637, T24, UM-UC-3) and normal bladder cell lines (SV-HUC-1), and selects T24 cell lines for subsequent experiments. The expression levels of DANCR, miR-335 and VEGF were measured by qRT-PCR, and the dual luciferase reporter gene verified the targeted regulation of DANCR on miR-335 and miR-335 on VEGF. CCK-8, Transwell and Wound healing assay detect the proliferation, invasion and migration ability of bladder cancer cells, Endothelial cell adhesion assay and Western blot further prove the lymphatic metastasis of bladder cancer. RESULTS: In this study, DANCR was highly expressed in bladder cancer cell lines. Transfection of si-DANCR significantly inhibits the proliferation, migration, invasion and lymphatic metastasis of bladder cancer cells. Dual luciferase assay confirmed that DANCR targets miR-335/VEGF-C. Transfection of miR-335 mimic promotes the proliferation, migration, invasion and lymphatic metastasis of bladder cancer cells, overexpression of DANCR eliminates the promotion of miR-335 mimic on bladder cancer cells. Further experiments proved that inhibition of miR-335 and overexpression of VEGF-C can reverse the inhibitory effect of silencing DANCR on bladder cancer cells. CONCLUSIONS: In bladder cancer, DARCR plays an important role, which regulates the proliferation, migration, invasion and lymphatic metastasis of bladder cancer cells through the miR-335/VEGF-C molecular axis.

Fe/Co-based Bimetallic MOF-derived Co3 Fe7 @NCNTFs Bifunctional Electrocatalyst for High-Efficiency Overall Water Splitting.

Electrocatalytic water splitting to produce hydrogen and oxygen is regarded as one of the most promising methods to generate clean and sustainable energy for replacing fossil fuels. However, the design and development of an efficient bifunctional catalyst for simultaneous generation of hydrogen and oxygen remains extremely challenging yet is critical for the practical implementation of water electrolysis. Here, we report a facile method to fabricate novel N-doped carbon nanotube frameworks (NCNTFs) by the pyrolysis of a bimetallic metal organic framework (MIL-88-Fe/Co). The resultant electrocatalyst, Co3 Fe7 @NCNTFs, exhibits excellent oxygen evolution reaction (OER) activity, achieving 10 mA/cm2 at a low overpotential of just 264 mV in 1 M KOH solution, and 197 mV for the hydrogen evolution reaction. The high electrocatalytic activity arises from the synergistic effect between the chemistry of the Co3 Fe7 and the NCNTs coupled to the novel framework structure. The remarkable electrocatalytic performance of our bifunctional electrocatalyst provides a promising pathway to high-performance overall water splitting and electrochemical energy devices.

Three-Dimensional N-Doped Carbon Nanotube Frameworks on Ni Foam Derived from a Metal-Organic Framework as a Bifunctional Electrocatalyst for Overall Water Splitting.

Rational design of bifunctional, high-performance, and stable non-noble metal-based electrocatalysts for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is of great importance and challenging for the realization of overall water splitting. Metal-organic frameworks (MOFs) have been intensively studied as pyrolyzing precursors to prepare electrocatalysts. However, the aggregation of powder and the low conductivity of polymer binders have limited the applications of powder electrocatalysts. Therefore, the direct growth of MOFs on conductive and porous substrates will be a favorable way to prepare efficient electrocatalysts for electrocatalytic water splitting. Herein, we report a facile strategy for constructing three-dimensional N-doped carbon nanotube frameworks derived from metal-organic framework on Ni foam as a bifunctional electrocatalyst for overall water splitting. The resulting electrocatalyst exhibits excellent stability and high OER and HER activity with rather low overpotentials of 230 and 141 mV at 10 mA/cm2 in 1.0 M KOH, respectively. Specifically, the as-synthesized electrodes were used as both the cathode and anode for overall water splitting with 10 mA/cm2 at a cell voltage of only 1.62 V. The outstanding electrocatalytic performance is mainly attributed to a large number of accessible active sites of Co nanoparticles dispersed by the N-doped carbon nanotubes (CNTs) and the ultra-high surface area of CNT frameworks. The presented strategy offers a novel approach for developing MOF-derived nanocarbon materials on Ni foam for electrocatalysis and electrochemical energy devices.

Grain boundary decohesion by nanoclustering Ni and Cr separately in CrMnFeCoNi high-entropy alloys.

The loss of ductility with temperature has been widely observed in tensile tests of single-phase face-centered cubic structured high-entropy alloys (HEAs). However, the fundamental mechanism for such a ductility loss remains unknown. Here, we show that ductility loss in the CrMnFeCoNi HEA upon deformation at intermediate temperatures is correlated with cracking at grain boundaries (GBs). Nanoclustering Cr, Ni, and Mn separately at GBs, as detected by atom probe tomography, reduces GB cohesion and promotes crack initiation along GBs. We further demonstrated a GB segregation engineering strategy to avoid ductility loss by shifting the fast segregation of principal elements from GBs into preexisting Cr-rich secondary phases. We believe that GB decohesion by nanoclustering multiprincipal elements is a common phenomenon in HEAs. This study not only provides insights into understanding ductility loss but also offers a strategy for tailoring ductility-temperature relations in HEAs.

Sensor to Monitor Localized Stresses on Steel Surfaces Using the Magnetostrictive Delay Line Technique.

In this paper, a new type of force sensor is presented, able to monitor localized residual stresses on steel surfaces. The principle of operation of the proposed sensor is based on the monitoring of the force exerted between a permanent magnet and the under-test steel which is dependent on the surface permeability of the steel providing a non-hysteretic response. The sensor's response, calibration, and performance are described followed by a discussion concerning the applications for steel health monitoring.

[Huanshao Capsules combined with levocarnitine for the treatment of asthenospermia, oligospermia and teratozoospermia].

OBJECTIVE: To observe the clinical effects of Huanshao Capsules (HSC) combined with levocarnitine (LC) on asthenospermia, oligospermia, teratozoospermia, and the semen parameters of the patients. METHODS: This randomized controlled clinical study included 186 infertility patients with spleen and kidney asthenia. We randomly divided them into three groups of equal number and treated them orally with HSC at the dose of 3 capsules tid, LC at 10 ml tid, and HSC+LC, respectively, all for 12 weeks. At 4, 8, and 12 weeks after treatment, we obtained the semen parameters from the patients and compared them among the three groups. RESULTS: Totally, 180 of the patients completed the study, 61 in the HSC, 59 in the LC and 60 in the HSC+LC group. After 12 weeks of medication, the patients of the HSC+LC group showed an increase of 42.77% in the semen volume, 142.37% in sperm concentration, 28.61% in sperm motility, and 24.39% in the percentage of grade a+b sperm and a decrease of 6.27% in the percentage of morphologically abnormal sperm as compared with the baseline (P <0.05). The patients treated with HSC+LC showed significantly more improvement in all the above parameters than those treated with LC alone (P <0.05) as well as in sperm motility and the percentage of progressively motile sperm than those treated with HSC alone (P <0.05). The HSC group exhibited remarkable improvement in the above parameters after treatment as compared with the baseline (P <0.05) and higher semen volume and sperm concentration than the LC group (P <0.05). CONCLUSIONS: Huanshao Capsulescombined with levocarnitinedeserves a wide clinical application as a safe and efficacious therapy forasthenospermia, oligospermia,and teratozoospermia.

Quantum confinement induced ultra-high intensity interfacial radiative recombination in nanolaminates.

Al2O3/ZnO, Al2O3/TiO2, TiO2/ZnO and MgO/ZnO nanolaminates (NLs) were prepared using atomic layer deposition to explore the dependence of luminescence characterization on the sublayer width and constituents. When the ZnO sublayer width is larger than the Bohr radius in Al2O3/ZnO NLs, the UV luminescence arising from ZnO is reduced and even quenched with decreasing the ZnO width due to the nonradiative recombination (NR) caused by the existence of interface states, while for the ZnO width smaller than the Bohr radius, a visible luminescence rather than UV emission is observed and further enhanced with decreasing the ZnO width. It is also found that the visible luminescence needs a certain width of Al2O3 and is extinguished by the replacement of Al2O3 with TiO2. A theoretical model based on the configuration coordination and quantum confinement effect is proposed to understand the physical origin underlying the intriguing optical behaviour. The mechanism has generality and is applicable for other NLs as well, such as Al2O3/TiO2 and MgO/ZnO NLs with ultra-thin sublayers in which similar luminescence enhancements are also observed. This work may provide a promising approach for realizing high performance luminescence with various wavelengths for electro- and photo-luminescence applications in NLs.

Partially Single-Crystalline Mesoporous Nb2 O5 Nanosheets in between Graphene for Ultrafast Sodium Storage.

Partially single-crystalline mesoporous Nb2 O5 nanosheets with orthorhombic structure in between graphene are scalably fabricated via a simple nanocasting method. The well-designed architecture provides numerous open and short channels for fast diffusion of sodium ion and good electronic conductivity, resulting in an enhanced electrochemical performance and a favorable high-rate behavior for sodium storage.