Caffeic acid alleviates cerebral ischemic injury in rats by resisting ferroptosis via Nrf2 signaling pathway.

There are few effective and safe neuroprotective agents for the treatment of ischemic stroke currently. Caffeic acid is a phenolic acid that widely exists in a number of plant species. Previous studies show that caffeic acid ameliorates brain injury in rats after cerebral ischemia/reperfusion. In this study we explored the protective mechanisms of caffeic acid against oxidative stress and ferroptosis in permanent cerebral ischemia. Ischemia stroke was induced on rats by permanent middle cerebral artery occlusion (pMCAO). Caffeic acid (0.4, 2, 10 mg·kg-1·d-1, i.g.) was administered to the rats for 3 consecutive days before or after the surgery. We showed that either pre-pMCAO or post-pMCAO administration of caffeic acid (2 mg·kg-1·d-1) effectively reduced the infarct volume and improved neurological outcome. The therapeutic time window could last to 2 h after pMCAO. We found that caffeic acid administration significantly reduced oxidative damage as well as neuroinflammation, and enhanced antioxidant capacity in pMCAO rat brain. We further demonstrated that caffeic acid down-regulated TFR1 and ACSL4, and up-regulated glutathione production through Nrf2 signaling pathway to resist ferroptosis in pMCAO rat brain and in oxygen glucose deprivation/reoxygenation (OGD/R)-treated SK-N-SH cells in vitro. Application of ML385, an Nrf2 inhibitor, blocked the neuroprotective effects of caffeic acid in both in vivo and in vitro models, evidenced by excessive accumulation of iron ions and inactivation of the ferroptosis defense system. In conclusion, caffeic acid inhibits oxidative stress-mediated neuronal death in pMCAO rat brain by regulating ferroptosis via Nrf2 signaling pathway. Caffeic acid might serve as a potential treatment to relieve brain injury after cerebral ischemia. Caffeic acid significantly attenuated cerebral ischemic injury and resisted ferroptosis both in vivo and in vitro. The regulation of Nrf2 by caffeic acid initiated the transcription of downstream target genes, which were shown to be anti-inflammatory, antioxidative and antiferroptotic. The effects of caffeic acid on neuroinflammation and ferroptosis in cerebral ischemia were explored in a primary microglia-neuron coculture system. Caffeic acid played a role in reducing neuroinflammation and resisting ferroptosis through the Nrf2 signaling pathway, which further suggested that caffeic acid might be a potential therapeutic method for alleviating brain injury after cerebral ischemia.

Associations of dietary oxidative balance score with femur osteoporosis in postmenopausal women: data from the National Health and Nutrition Examination Survey.

We used data from the NHANES to explore associations of DOBS with femur BMD and osteoporosis in postmenopausal women. We found that DOBS was positively associated with femur BMD and negatively associated with the risk of osteoporosis in postmenopausal women. PURPOSE: The study aimed to investigate the relationship between dietary oxidative balance score (DOBS) and the risk of osteoporosis in American postmenopausal women. METHODS: A total of 3043 participants were included in this study. The linear relationship between DOBS and femur BMD was evaluated using a weighted multivariate linear regression model. The association between DOBS and the risk of osteoporosis was assessed using a weighted logistic regression model, with odds ratios (ORs) and 95% confidence intervals (CIs) calculated. Moreover, the relationship was further characterized through smooth curve fitting (SCF) and weighted generalized additive model (GAM) analysis. RESULTS: After adjusting for all covariates, the weighted multivariable linear regression models showed a positive correlation between DOBS and femur BMD. Moreover, the weighted logistic regression model demonstrated that compared to the first tertile of DOBS, the highest tertile of DOBS was significantly associated with a lower risk of osteoporosis, with ORs of 0.418 (95% CI, 0.334, 0.522) for individuals under the age of 70 and 0.632 (95% CI, 0.506, 0.790) for individuals aged 70 or above. Similar trends were also observed in SCF and GAM models. CONCLUSION: The present study indicated that postmenopausal women with a higher DOBS have a lower risk of femur osteoporosis. This finding may highlight the potential protective role of an antioxidant-rich diet for the bones of the postmenopausal population. Moreover, DOBS may also be a valuable tool in identifying individuals with osteoporosis. Screening and early intervention for osteoporosis may be essential for postmenopausal women with low DOBS.

A feasible protocol to profile bile acids in dried blood spots from rats using a UHPLC-MS/MS method combining a surrogate matrix.

Dried blood spot (DBS) sampling is a promising method for microliter blood sample collection with the advantages of convenient transportation, storage and clinical operations. However, it is challenging to develop an analytical protocol to determine endogenous metabolites, such as bile acids (BAs) in DBSs, due to the low-blood-volume character of DBSs and the complex features of filter paper. Herein, we developed a method of fast ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) to profile and quantify BAs in DBSs. The pretreatment methods were optimized and a two-step solvent addition method, where a small amount of water was firstly added to moisten the DBS and then methanol was added, showed high extraction efficiency for multiple BAs in DBSs. The UHPLC-MS/MS conditions were optimized and 35BAs in different types could be profiled with good resolution and quantified with acceptable precision and accuracy. Preparation of a DBS surrogate matrix without endogenous BAs has been well developed using rat erythrocytes in BSA solution and showed good performance on both the signal suppression/enhancement percentage and parallelism assessment evaluation of three different stable-isotope-labeled (SIL) BAs. The established protocol was successfully applied to profile BAs in DBSs of intrahepatic cholestasis model and healthy control rats with good repeatability. To our knowledge, it is the first time that 35 BAs in DBSs could be well profiled and an appropriate DBS surrogate matrix has been developed. This protocol presents future-oriented applications of DBSs for relevant preclinical studies to profile BAs and probe biomarkers.

Effects of different cladding materials on orbital angular momentum modes propagating in photonic crystal fibers.

With the development of orbital angular momentum (OAM) photonic crystal fibers (PCFs) for more efficient communication, fiber claddings are important to the performance. In this paper, the influence of S i O 2 and four new optical materials, which are amethyst, SSK2, SF11, and LaSF09, as cladding materials, on the OAM mode characteristics is studied based on a common PCF for OAM transmission. In addition, the effective index difference, dispersion, confinement loss, and other properties of OAM modes transmitted in the five materials are derived by the finite element method. After in-depth analysis, universal rules can be obtained as guidelines for optimization of PCF in the future for improving the efficiency of optical fiber communication. Through chart analysis, it can be concluded that when materials of high effective refractive indices are used as cladding materials for PCF, the dispersion, nonlinear coefficient, confinement loss, mode purity, and other properties are significantly improved. Lower dispersion and confinement loss are more conducive to long-distance communication transmission. The decrease in nonlinear coefficient represents a better effect in suppressing nonlinear effects, and the increase in numerical aperture and mode purity respectively improves the transmission efficiency and stability of OAM communication. These conclusions provide universal rules for high-quality communication in the future.

Pixel-Domain Just Noticeable Difference Modeling with Heterogeneous Color Features.

With the rapidly emerging user-generated images, perception compression for color image is an inevitable mission. Whilst in existing just noticeable difference (JND) models, color-oriented features are not fully taken into account for coinciding with HVS perception characteristics, such as sensitivity, attention, and masking. To fully imitate the color perception process, we extract color-related feature parameters as local features, including color edge intensity and color complexity, as well as region-wise features, including color area proportion, color distribution position and color distribution dispersion, and inherent feature irrelevant to color content called color perception difference. Then, the potential interaction among them is analyzed and modeled as color contrast intensity. To utilize them, color uncertainty and color saliency are envisaged to emanate from feature integration in the information communication framework. Finally, color and uncertainty saliency models are applied to improve the conventional JND model, taking the masking and attention effect into consideration. Subjective and objective experiments validate the effectiveness of the proposed model, delivering superior noise concealment capacity compared with start-of-the-art works.

Electronic and Spintronic Open-Shell Macromolecules, Quo Vadis?

Open-shell macromolecules (i.e., polymers containing radical sites either along their backbones or at the pendant sites of repeat units) have attracted significant attention owing to their intriguing chemical and physical (e.g., redox, optoelectronic, and magnetic) properties, and they have been proposed and/or implemented in a wide range of potential applications (e.g., energy storage devices, electronic systems, and spintronic modules). These successes span multiple disciplines that range from advanced macromolecular chemistry through nanoscale structural characterization and on to next-generation solid-state physics and the associated devices. In turn, this has allowed different scientific communities to expand the palette of radical-containing polymers relatively quickly. However, critical gaps remain on many fronts, especially regarding the elucidation of key structure-property-function relationships that govern the underlying electrochemical, optoelectronic, and spin phenomena in these materials systems. Here, we highlight vital developments in the history of open-shell macromolecules to explain the current state of the art in the field. Moreover, we provide a critical review of the successes and bring forward open opportunities that, if solved, could propel this class of materials in a meaningful manner. Finally, we provide an outlook to address where it seems most likely that open-shell macromolecules will go in the coming years. Our considered view is that the future of radical-containing polymers is extremely bright and the addition of talented researchers with diverse skills to the field will allow these materials and their end-use devices to have a positive impact on the global science and technology enterprise in a relatively rapid manner.

High-Spin (S = 1) Blatter-Based Diradical with Robust Stability and Electrical Conductivity.

Triplet ground-state organic molecules are of interest with respect to several emerging technologies but usually show limited stability, especially as thin films. We report an organic diradical, consisting of two Blatter radicals, that possesses a triplet ground state with a singlet-triplet energy gap, ΔEST ≈ 0.4-0.5 kcal mol-1 (2J/k ≈ 220-275 K). The diradical possesses robust thermal stability, with an onset of decomposition above 264 °C (TGA). In toluene/chloroform, glassy matrix, and fluid solution, an equilibrium between two conformations with ΔEST ≈ 0.4 kcal mol-1 and ΔEST ≈ -0.7 kcal mol-1 is observed, favoring the triplet ground state over the singlet ground-state conformation in the 110-330 K temperature range. The diradical with the triplet ground-state conformation is found exclusively in crystals and in a polystyrene matrix. The crystalline neutral diradical is a good electrical conductor with conductivity comparable to the thoroughly optimized bis(thiazolyl)-related monoradicals. This is surprising because the triplet ground state implies that the underlying π-system is cross-conjugated and thus is not compatible with either good conductance or electron delocalization. The diradical is evaporated under ultra-high vacuum to form thin films, which are stable in air for at least 18 h, as demonstrated by X-ray photoelectron and electron paramagnetic resonance (EPR) spectroscopies.

Long noncoding RNA OVAAL enhances nucleotide synthesis through pyruvate carboxylase to promote 5-fluorouracil resistance in gastric cancer.

5-Fluorouracil (5-FU) is widely used in gastric cancer treatment, yet 5-FU resistance remains an important clinical challenge. We established a model based on five long noncoding RNAs (lncRNA) to effectively assess the prognosis of gastric cancer patients; among them, lncRNA OVAAL was markedly upregulated in gastric cancer and associated with poor prognosis and 5-FU resistance. In vitro and in vivo assays confirmed that OVAAL promoted proliferation and 5-FU resistance of gastric cancer cells. Mechanistically, OVAAL bound with pyruvate carboxylase (PC) and stabilized PC from HSC70/CHIP-mediated ubiquitination and degradation. OVAAL knockdown reduced intracellular levels of oxaloacetate and aspartate, and the subsequent pyrimidine synthesis, which could be rescued by PC overexpression. Moreover, OVAAL knockdown increased sensitivity to 5-FU treatment, which could be reversed by PC overexpression or repletion of oxaloacetate, aspartate, or uridine. OVAAL overexpression enhanced pyrimidine synthesis to promote proliferation and 5-FU resistance of gastric cancer cells, which could be abolished by PC knockdown. Thus, OVAAL promoted gastric cancer cell proliferation and induced 5-FU resistance by enhancing pyrimidine biosynthesis to antagonize 5-FU induced thymidylate synthase dysfunction. Targeting OVAAL-mediated nucleotide metabolic reprograming would be a promising strategy to overcome chemoresistance in gastric cancer.

Mitochondrial Oxidative Phosphorylation Complex Regulates NLRP3 Inflammasome Activation and Predicts Patient Survival in Nasopharyngeal Carcinoma.

We previously reported that tumor inflammasomes play a key role in tumor control and act as favorable prognostic markers in nasopharyngeal carcinoma (NPC). Activated inflammasomes frequently form distinguishable specks and govern the cellular secretion of IL-1ß. However, we know little about the biological and biochemical differences between cells with and without apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) speck formation. In this study, we used proteomic iTRAQ analysis to analyze the proteomes of NPC cells that differ in their ASC speck formation upon cisplatin treatment. We identified proteins that were differentially over-expressed in cells with specks, and found that they fell into two Gene ontology (GO) pathways: mitochondrial oxidative phosphorylation (OxPhos) and ubiquinone metabolism. We observed up-regulation of various components of the OxPhos machinery (including NDUFB3, NDUFB8 and ATP5B), and subsequently found that these changes lead to mitochondrial ROS (mtROS) production, which promotes the formation and activation of NLRP3 inflammasomes and subsequent pyroptosis. In NPC patients, better local recurrence-free survival was significantly associated with high-level expression of NDUFB8 (p = 0.037) and ATP5B (p = 0.029), as examined using immunohistochemistry. However, there were no significant associations between the expression of NDUFB8 and ATP5B with overall survival of NPC patients. Together, our results demonstrate that up-regulated mitochondrial OxPhos components are strongly associated with NLRP3 inflammasome activation in NPC. Our findings further suggest that high-level expression of OxPhos components could be markers for local recurrence and/or promising therapeutic targets in patients with NPC.

Thermoelectric Performance of Lead-Free Two-Dimensional Halide Perovskites Featuring Conjugated Ligands.

Sn-based halide perovskites are promising for thermoelectric (TE) device applications because of their high electrical conductivity as well as the low thermal conductivity associated with their soft lattices. However, conventional three-dimensional Sn-based perovskites are not stable under typical TE device operating conditions. Here, we report a stable two-dimensional Sn-based perovskite for thermoelectric energy conversion by incorporating bulky conjugated ligands. We demonstrate a thin film with a large power factor of 5.42 ± 3.07 (average) and 7.07 (champion) µW m-1 K-2 at 343 K with an electrical conductivity of 5.07 S cm-1 and a Seebeck coefficient of 118.1 µV K-1. Importantly, these thin films show excellent operational stability (i.e., for over 100 h) at 313 K. This work suggests that the novel hybrid two-dimensional perovskites are a promising platform for thermoelectric energy conversion applications.

Cancellous bone allograft is comparable to fibular strut allograft for augmentation in three- or four-part proximal humeral fractures.

BACKGROUND: Bone grafts have been used for augmentation and improving stability of reduced fractures in proximal humeral fractures. The aim of this study was to analyze the clinical and radiological outcomes after the use of cancellous bone allografts (CAs) for augmentation in 3- or 4-part proximal humeral fractures, and compare with fibular strut allografts (FAs). METHODS: Between November 2016 and February 2018, 55 patients, followed for at least 1 year, with 3- or 4-part proximal humeral fractures fixed with locking plates were included and grouped according to the type of allograft bone used for augmentation. In this retrospective analysis, we assessed and compared the clinical and radiological outcomes of the 2 groups, using the visual analog scale score, the Constant-Murley score (CMS), the disability of the arm, shoulder, and hand (DASH) score, the range of movement, neck-shaft angle (NSA), humeral head height (HHH), and the changes of NSA and HHH, as well as recording any complications. The repeatedly measured clinical and radiological outcomes were analyzed by linear mixed models. The differences in outcomes between groups at the final follow-up were compared using Student's t test. RESULTS: There were 28 patients in the CA group and 27 patients in the FA group with an average follow-up of 14.5 months. The mean age of all patients was 64 (36-86). Nonsignificant group effects were observed on CMS (ß = -8.792, P = .216), DASH (ß = 1.329, P = .094), NSA (ß = 1.432, P = .752), and HHH (ß = 1.660, P = .628). At the final follow-up, the patients in the CA group showed no significant differences in visual analog scale (1.8 vs. 2.2, P = .276), CMS (81.5 vs. 75.4, P = .072), and DASH (11.0 vs. 13.5, P = .235) scores compared with the FA group. There were no significant differences in the change of NSA (6 vs. 4, P = .387) or HHH (1 vs. 2, P = .261). CONCLUSIONS: Patients with 3- or 4-part proximal humeral fractures treated with locking plates combined with CAs have good clinical and radiographic outcomes, similar to those treated with FAs.

EFLA 945 restricts AIM2 inflammasome activation by preventing DNA entry for psoriasis treatment.

Psoriasis is a chronic inflammatory skin disease that affects about 2% of the general population. Activation of the Absent in Melanoma 2 (AIM2) inflammasome is crucial for immune defense, but it can also cause inflammatory and autoimmune diseases, including psoriasis. We currently lack an AIM2 inflammasome inhibitor that could be used therapeutically. Here, we show that EFLA 945, a safe product of red grape vine leaf extracts, can restrict AIM2 inflammasome activation. Mechanistically, EFLA945 prevents DNA entry into THP-1-derived macrophages, and thereby inhibits cytoplasmic DNA-dependent apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization, caspase-1 activation, and the secretion of interleukin (IL)-1ß and IL-18. The major phytochemicals of EFLA 945, resveratrol and peonidin 3-O-glucoside (P3G), appear to be the potential bioactive compounds responsible for its ability to restrict AIM2-dependent IL-1ß secretion. Importantly, in an in vivo mouse model, EFLA 945 attenuates imiquimod (IMQ)-induced psoriasis-related pro-inflammatory responses in topical psoriatic skin, including caspase-1 activation, IL-1ß maturation, and IL-17 production, and decreases the severity of psoriasis. Together, these results demonstrate that the safe natural product, EFLA 945, can restrict the AIM2 inflammasome activation through preventing DNA entry and may prove beneficial for treating psoriasis.

4,5 caffeoylquinic acid and scutellarin, identified by integrated metabolomics and proteomics approach as the active ingredients of Dengzhan Shengmai, act against chronic cerebral hypoperfusion by regulating glutamatergic and GABAergic synapses.

Dengzhan Shengmai (DZSM) is a proprietary Chinese medicine for remarkable curative effect as a treatment of cerebrovascular diseases, such as chronic cerebral hypoperfusion (CCH) and dementia based on evidence-based medicine, which have been widely used in the recovery period of ischemic cerebrovascular diseases. The purpose of this study was to investigate the active substances and mechanism of DZSM against CCH. Integrative metabolomic and proteomic studies were performed to investigate the neuroprotective effect of DZSM based on CCH model rats. The exposed components of DZSM in target brain tissue were analysed by a high-sensitivity HPLC-MS/MS method, and the exposed components were tested on a glutamate-induced neuronal excitatory damage cell model for the verification of active ingredients and mechanism of DZSM. Upon proteomic and metabolomic analysis, we observed a significant response in DZSM therapy from the interconnected neurotransmitter transport pathways including glutamatergic and GABAergic synapses. Additionally, DZSM had a significant regulatory effect on glutamate and GABA-related proteins including vGluT1 and vIAAT, suggested that DZSM could be involved in the vesicle transport of excitatory and inhibitory neurotransmitters in the pre-synaptic membrane. DZSM could also regulated the metabolism of arachidonic acid (AA), phospholipids, lysophospholipids and the expression of phospholipase A2 in post-synaptic membrane. The results of glutamate-induced neuronal excitatory injury cell model experiment for verification of active ingredients and mechanism of DZSM showed that there are five active ingredients, and among them, 4,5 caffeoylquinic acid (4,5-CQA) and scutellarin (SG) could simultaneously affect the GABAergic and glutamatergic synaptic metabolism as well as the related receptors, the NR2b subunit of NMDA and the α1 subunit of GABAA. The active ingredients of DZSM could regulate the over-expression of the NMDA receptor, enhance the expression of the GABAA receptor, resist glutamate-induced neuronal excitatory damage, and finally maintain the balance of excitatory and inhibitory synaptic metabolism dominated by glutamate and GABA. Furtherly, we compared the efficacy of DZSM, 4,5-CQA, SG and the synergistic effect of 4,5-CQA and SG, and the results showed that all the groups significantly improved cell viability compared with the model group (p < 0.001). The western blot results showed that DZSM, 4,5-CQA, SG and 4,5-CQA/SG co-administration groups could significantly regulate the expression of receptors (GABAA α1 and NR2b subunit of NMDA) and synaptic-related proteins, such as Sv2a, Syp, Slc17a7, bin1 and Prkca, respectively. These results proved DZSM and its active ingredients (4,5-CQA and SG) had the effect of regulating glutamatergic and GABAergic synapses. Finally, membrane potential FLIPR assay of 4,5-CQA and SG was used for GABRA1 activity test, and it was found that the two compounds could increase GABA-induced activation of GABRA1 receptor (GABA 10 µM) in a dose-dependent manner with EC50 value of 48.74 µM and 29.77 µM, respectively. Manual patch clamp method was used to record NMDA NR1/NR2B subtype currents, and scutellarin could cause around 10 % blockade at 10 µM (p＜0.05 compared with the control group). These studies provided definitive clues of the mechanism for the neuroprotective effect of DZSM for CCH treatment and the active compounds regulating glutamatergic and GABAergic synapses. Additionally, 4,5-CQA and SG might be potential drugs for the treatment of neurodegenerative disease related to CCH.

Cbl Negatively Regulates NLRP3 Inflammasome Activation through GLUT1-Dependent Glycolysis Inhibition.

Activation of the nod-like receptor 3 (NLRP3) inflammasomes is crucial for immune defense, but improper and excessive activation causes inflammatory diseases. We previously reported that Cbl plays a pivotal role in suppressing NLRP3 inflammasome activation by inhibiting Pyk2-mediated apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization. Here, we showed that Cbl dampened NLRP3 inflammasome activation by inhibiting glycolysis, as demonstrated with Cbl knockout cells and treatment with the Cbl inhibitor hydrocotarnine. We revealed that the inhibition of Cbl promoted caspase-1 cleavage and interleukin (IL)-1ß secretion through a glycolysis-dependent mechanism. Inhibiting Cbl increased cellular glucose uptake, glycolytic capacity, and mitochondrial oxidative phosphorylation capacity. Upon NLRP3 inflammasome activation, inhibiting Cbl increased glycolysis-dependent activation of mitochondrial respiration and increased the production of reactive oxygen species, which contributes to NLRP3 inflammasome activation and IL-1ß secretion. Mechanistically, inhibiting Cbl increased surface expression of glucose transporter 1 (GLUT1) protein through post-transcriptional regulation, which increased cellular glucose uptake and consequently raised glycolytic capacity, and in turn enhanced NLRP3 inflammasome activation. Together, our findings provide new insights into the role of Cbl in NLRP3 inflammasome regulation through GLUT1 downregulation. We also show that a novel Cbl inhibitor, hydrocortanine, increased NLRP3 inflammasome activity via its effect on glycolysis.

High expression of LASS2 is associated with unfavorable prognosis in patients with ovarian cancer.

Homo sapiens longevity assurance homolog 2 of yeast LAG1 (LASS2), is a gene isolated from a human liver complementary DNA library. In this study, we found that LASS2 protein level was positively related to International Federation of Gynecology and Obstetrics (FIGO) stage and LASS2-negative tumors showed significant association with longer disease-free survival (DFS) and overall survival (OS) in ovarian cancer patients. The heterogeneous expression of LASS2 had been exhibited in diverse ovarian cancer cells. A significantly lower messenger RNA (mRNA) and protein level of LASS2 was seen in 3AO cell compared with those in other types of ovarian cancer cells. Meanwhile, the mRNA and protein levels of LASS2 in ES-2 and NIH:OVCAR-3 cells were obviously higher. LASS2 overexpression in 3AO cell could promote migration, invasion, and metastasis abilities in vitro and in vivo, while LASS2 knockdown in ES-2 and NIH:OVCAR-3 cells had the opposite effects. The oncogenic capacity of LASS2 in ovarian cancer may be mediated by increased expression of YAP/TAZ. It is indicated that lowering the expression of LASS2 is likely to serve as an unprecedented approach for the treatment of ovarian cancer.

Low expression of CRISP3 predicts a favorable prognosis in patients with mammary carcinoma.

The discovery of cysteine-rich secretory protein 3 (CRISP3) has been made in human neutrophils for the first time. Cloning of the complementary DNA (cDNA) for CRISP3 was performed from a cDNA library of human bone marrow. In patients with mammary carcinoma, we found that lower expression of CRISP3 was connected to a significantly improved DFS (disease-free survival) and OS (overall survival). Furthermore, the CRISP3 protein level was significantly associated with negative ANXA1 protein level. In addition, the heterogeneous expression of CRISP3 had been exhibited in diverse mammary carcinoma cells. A significant higher mRNA and the protein level of CRISP3 were seen in T-47D as well as SK-BR-3 cells compared with those in other types of mammary carcinoma cells. Knockdown of CRISP3 in T-47D or SK-BR-3 cells resulted in the weakened migration or invasion abilities. Furthermore, CRISP3 knockdown significantly inhibited the ERK1/2 MAPK signaling pathway in T-47D or SK-BR-3 cells. Research results indicated that the lowering in the expression of CRISP3 is likely to serve as an unprecedented approach for the treatment of mammary carcinoma.

Low expression of ENC1 predicts a favorable prognosis in patients with ovarian cancer.

Ectodermal-neural cortex 1 (ENC1) belongs to a member of the kelch family of genes. It is an actin-binding protein and plays a pivotal role in neuronal and adipocyte differentiation. Here, we found that lower expression of ENC1 in the ovarian cancer patients was associated with favorable prognosis. In addition, ENC1 was heterogeneously expressed in various ovarian cancer cells. The messenger RNA and protein expression levels of ENC1 in HO-8910PM and NIH:OVCAR-3 cells were obviously higher than that in the other types of ovarian cancer cells. Knockdown of ENC1 in HO-8910PM or NIH:OVCAR-3 cells could significantly increase the reactive oxygen species levels, resulting in inhibition of in vitro proliferation, migration, and invasion. Our findings suggest that decreasing expression of ENC1 may be a new approach that can be used for ovarian cancer treatment.

High expression of glutamate-ammonia ligase is associated with unfavorable prognosis in patients with ovarian cancer.

Glutamate-ammonia ligase (GLUL), which is also called GS (glutamine synthetase), is the enzyme that catalyzes the synthesis of glutamine from glutamate and ammonia in an ATP-dependent reaction. Here, we found higher expression of GLUL in the ovarian cancer patients was associated with worse disease-free survival (DFS) and overall survival (OS). In addition, GLUL was heterogeneously expressed in various ovarian cancer cells. The mRNA and protein expression levels of GLUL in NIH:OVCAR-3 and ES-2 cells were obviously higher than that in the other types of ovarian cancer cells. Knockdown of GLUL in NIH:OVCAR-3 or ES-2 cells could significantly decrease the proliferation ability. Furthermore, GLUL knockdown markedly inhibited the p38 MAPK signaling pathway in NIH:OVCAR-3 or ES-2 cells. Our findings suggest that decreasing expression of GLUL may be a new approach that can be used for ovarian cancer treatment.

Assembly of Multifold Helical Polyoxometalate-Based Metal-Organic Frameworks as Anode Materials in Lithium-Ion Batteries.

For exploring the multifold helical fabrication of polyoxometalate (POM)-based hybrid compounds, four POM-based crystalline compounds with different meso-helices, H3[Ag27(trz)16(H2O)6][SiW12O40]2·5H2O (1), H[Ag27(trz)16(H2O)4][PW12O40]2·2H2O (2), [Ag23(trz)14(H2O)2][HSiW12O40] (3), and [Ag23(trz)14(H2O)2][PW12O40] (4), were successfully isolated by using the delicate 1,2,3-triazole ligand and silver ions in this work. Crystal analysis reveals that compounds 1 and 2 and compounds 3 and 4 are isomorphous and display 2-/4-fold mixed meso-helices and simple 2-fold meso-helices, respectively. In addition, due to the reversible multielectron redox behavior and electron storage functions of POMs, compounds 1 and 3 were studied as anode materials in lithium-ion batteries (LIBs). Compounds 1 and 3 show very high lithiation capacities (1356 and 1140 mAh g-1, respectively) in the initial cycle, which are much higher than those of (NBu4)4[SiW12O40] and commercial graphite at the current density of 100 mA g-1. More importantly, both compounds also show good stable performance after 100 cycles.

Metformin depresses overactivated Notch1/Hes1 signaling in colorectal cancer patients with type 2 diabetes mellitus.

The function of metformin in colorectal cancer (CRC) patients with diabetes mellitus (DM) remains a controversial topic because studies are increasingly focusing on epidemiologic features. We examined Notch1/Hes1 signaling in CRC with DM (DM-CRC) and investigated alterations in signaling caused by metformin treatment. For this purpose, information on pathological characteristics was collected from each patient. The proliferation of epithelium labeled with proliferating cell nuclear antigen and the differentiation of goblet cells were investigated using immunohistochemistry and periodic acid-Schiff staining, respectively. The factors involved in Notch1/Hes1 signaling were detected using qRT-PCR and western blot. In our study, we found that lymphatic metastasis, pTNM staging, and the carcinoembryonic antigen level were significantly different between groups. The depth of crypts and the rate of proliferating cell nuclear antigen-positive cells were distinctly higher in DM-CRC and patients who were managed with insulin. Moreover, the goblet cell differentiation rate was decreased in DM-CRC. The expression of Dll1, Notch1, Math1, and RBP-Jκ was increased in DM-CRC, whereas the expression of Dll4 and Hes1 was decreased in this group in normal tissue. In CRC tissue, the expression of Dll1 and Notch1 was clearly higher than that in DM-CRC. Furthermore, the trend in these changes was aggravated with insulin management and alleviated with metformin treatment. In conclusion, the abnormal cell proliferation and differentiation observed in DM-CRC are correlated with overactivated Notch1/Hes1 signaling, which is potentially relieved by metformin treatment.