Poly(3-Methylthiophene)/Graphene Composite Cathode for Rechargeable Aluminum-Ion Batteries.

To reduce the dependence on traditional fossil energy, developing efficient energy storage systems is urgent. The reserves of aluminum resources in the earth's crust are extremely rich, which makes aluminum-ion batteries a promising competitor of new energy storage devices. Here, we report a poly(3-methylthiophene)/graphene (P3TH/Graphene) composite as the cathode of an aluminum-ion battery. The adjustment of polymer chain spacing by the methyl side chain provides a channel conducive to the transport of large-size AlCl4- complexes. The addition of electron donor groups also changes the electron delocalization characteristics of polymers and improves the specific capacity of the material. At the same time, the in situ composite of graphene can enhance the Π-Π interaction to form a favorable electronic transmission channel. At a current density of 200 mA g-1, the P3TH/Graphene composite showed a specific capacity of ∼150 mA g-1. The flexible structure of the polymer also guarantees the excellent rate capability of the composite.

Primary N2-He gas field formation in intracratonic sedimentary basins.

Helium, nitrogen and hydrogen are continually generated within the deep continental crust1-9. Conceptual degassing models for quiescent continental crust are dominated by an assumption that these gases are dissolved in water, and that vertical transport in shallower sedimentary systems is by diffusion within water-filled pore space (for example, refs. 7,8). Gas-phase exsolution is crucial for concentrating helium and forming a societal resource. Here we show that crustal nitrogen from the crystalline basement alone-degassing at a steady state in proportion to crustal helium-4 generation-can reach sufficient concentrations at the base of some sedimentary basins to form a free gas phase. Using a gas diffusion model coupled with sedimentary basin evolution, we demonstrate, using a classic intracratonic sedimentary basin (Williston Basin, North America), that crustal nitrogen reaches saturation and forms a gas phase; in this basin, as early as about 140 million years ago. Helium partitions into this gas phase. This gas formation mechanism accounts for the observed primary nitrogen-helium gas discovered in the basal sedimentary lithology of this and other basins, predicts co-occurrence of crustal gas-phase hydrogen, and reduces the flux of helium into overlying strata by about 30 per cent because of phase solubility buffering. Identification of this gas phase formation mechanism provides a quantitative insight to assess the helium and hydrogen resource potential in similar intracontinental sedimentary basins found worldwide.

Impaired OTUD7A-dependent Ankyrin regulation mediates neuronal dysfunction in mouse and human models of the 15q13.3 microdeletion syndrome.

Copy number variations (CNVs) are associated with psychiatric and neurodevelopmental disorders (NDDs), and most, including the recurrent 15q13.3 microdeletion disorder, have unknown disease mechanisms. We used a heterozygous 15q13.3 microdeletion mouse model and patient iPSC-derived neurons to reveal developmental defects in neuronal maturation and network activity. To identify the underlying molecular dysfunction, we developed a neuron-specific proximity-labeling proteomics (BioID2) pipeline, combined with patient mutations, to target the 15q13.3 CNV genetic driver OTUD7A. OTUD7A is an emerging independent NDD risk gene with no known function in the brain, but has putative deubiquitinase function. The OTUD7A protein-protein interaction network included synaptic, axonal, and cytoskeletal proteins and was enriched for ASD and epilepsy risk genes (Ank3, Ank2, SPTAN1, SPTBN1). The interactions between OTUD7A and Ankyrin-G (Ank3) and Ankyrin-B (Ank2) were disrupted by an epilepsy-associated OTUD7A L233F variant. Further investigation of Ankyrin-G in mouse and human 15q13.3 microdeletion and OTUD7AL233F/L233F models revealed protein instability, increased polyubiquitination, and decreased levels in the axon initial segment, while structured illumination microscopy identified reduced Ankyrin-G nanodomains in dendritic spines. Functional analysis of human 15q13.3 microdeletion and OTUD7AL233F/L233F models revealed shared and distinct impairments to axonal growth and intrinsic excitability. Importantly, restoring OTUD7A or Ankyrin-G expression in 15q13.3 microdeletion neurons led to a reversal of abnormalities. These data reveal a critical OTUD7A-Ankyrin pathway in neuronal development, which is impaired in the 15q13.3 microdeletion syndrome, leading to neuronal dysfunction. Furthermore, our study highlights the utility of targeting CNV genes using cell type-specific proteomics to identify shared and unexplored disease mechanisms across NDDs.

Clinical Characteristics Predict Recurrence in Borderline Ovarian Tumor Patients with Fertility-Preserving Surgery.

PURPOSE: To identify prognostic factors in patients with borderline ovarian tumor (BOT) and establish and validate a nomogram predicting recurrence in BOT patients treated with fertility-preserving surgery. PATIENTS AND METHODS: Patients with BOT who underwent surgery at two institutions between January 2000 and June 2017 were included and categorized into training and validation cohorts. Univariate log rank test and Cox regression analysis were performed in the training cohort to identify prognostic factors, and a nomogram was developed to predict the recurrence rate. The model was validated by calculating the C-index and drawing the calibration curve and receiver operating curve (ROC). CONCLUSION: In the multivariate Cox regression analysis, practice period, past history of benign ovarian disease, past history of benign breast disease, elevated CA125 levels, elevated CA199 levels, surgical methods, greater omentum resection, FIGO stage, postoperative pregnancy, and re-operation were independently associated with recurrence-free survival (p<0.05). The aforementioned prognostic factors were used to develop a nomogram. The nomogram demonstrated a good ability to predict the risk of recurrence (training cohort C-index: 0.866, validation cohort C-index: 0.920). The calibration curve suggested that the predicted recurrence-free survival was closely related to the actual recurrence. ROC analysis showed that the nomogram had a good discriminatory power with the area under curve between 0.776 and 0.956. The nomogram can predict the 1-, 3-, and 5-year recurrence-free survival of BOT patients undergoing fertility-preserving surgery. The predictive model can help guide surgical plans, postoperative monitoring, and prognostic evaluation of BOT patients.

LncRNA GAS5 regulates migration and epithelial-to-mesenchymal transition in lens epithelial cells via the miR-204-3p/TGFBR1 axis.

Diabetic cataract (DC) is a major ocular complication secondary to diabetes mellitus. The epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) is an important event in DC progression. Long non-coding RNAs (lncRNAs) and microRNAs are involved in various biological processes and disorders. The aim of this study was to investigate the roles of lncRNA growth arrest-specific transcript 5 (GAS5) and microRNA-204-3p (miR-204-3p) deregulation in the pathogenic mechanism of high glucose (HG)-stimulated LECs. The results show that GAS5 was up-regulated, whereas miR-204-3p was down-regulated in anterior lens capsule tissues of DC patients and in HG-treated LECs compared to their controls, respectively. Functional experiments suggest that the lentivirus-mediated depletion of GAS5, as well as overexpression of miR-204-3p, suppressed migration and EMT in HG-treated LECs. Further mechanistic studies revealed that lncRNA GAS5/miR-204-3p/type 1 receptor of transforming growth factor-beta (TGFBR1) has a regulatory role in the process. Collectively, we demonstrated that dysregulation of GAS5 affects lens epithelial cell migration and EMT under HG conditions via the miR-204-3p/TGFBR1 axis. The current findings may provide new insights into the molecular mechanisms of DC development.

The Protective Effect of Cx43 Protein-Mediated Phosphocreatine on Myocardial Ischemia/Reperfusion Injury.

OBJECTIVES: To verify the protective effect of phosphocreatine on myocardium in an ischemic model and the possible mechanism of action. METHODS: The model of myocardial ischemia/reperfusion (I/R) was established by the ligation balloon method. 30 SD rats were randomly divided into three groups, n = 10 in each group. Sham operation group: the coronary artery was not blocked and observed for 120 minutes. The ischemia/reperfusion (I/R) group was given ischemia for 30 minutes and ischemia reperfusion for 90 minutes. Phosphocreatine (PCr) group: after 30 minutes of ischemia, the rats were intraperitoneally injected with PCr (200 mg/kg) for 90 minutes. The animal groups of myocardial ischemia/reperfusion model in vitro were the same as those in vivo. The heart was removed by thoracotomy and washed immediately in H-K buffer solution. Then, the heart was installed on the Langendorff instrument. The concentration of PCr perfusion fluid in the PCr group was 10 mmol/L. The changes in coronary blood flow in isolated myocardium were recorded. The heart rate and electrocardiogram were recorded by RM6240BT. At the end of the experiment, myocardial pathological sections and Cx43 immunofluorescence staining were made, and the contents of malondialdehyde (MDA) in myocardial tissue were detected. RESULTS: Phosphocreatinine treatment improved the myocardial ischemia model, performance in electrocardiogram (ECG) changes (ST segment apparent), and histological changes (decrease in necrotic myocardial cells, inflammatory cell infiltration, and a reduction in myocardial edema). At the same time, MDA decreased, while coronary blood flow and Cx43 expression significantly improved. CONCLUSIONS: Phosphocreatine can improve the electrocardiogram and restore histologic changes in ischemic myocardium and coronary blood flow. The postulated mechanism is by inhibiting the generation of free oxygen radicals and restoring the expression of Cx43 protein.

Identification of significant genes signatures and prognostic biomarkers in cervical squamous carcinoma via bioinformatic data.

BACKGROUND: Cervical squamous cancer (CESC) is an intractable gynecological malignancy because of its high mortality rate and difficulty in early diagnosis. Several biomarkers have been found to predict the prognose of CESC using bioinformatics methods, but they still lack clinical effectiveness. Most of the existing bioinformatic studies only focus on the changes of oncogenes but neglect the differences on the protein level and molecular biology validation are rarely conducted. METHODS: Gene set data from the NCBI-GEO database were used in this study to compare the differences of gene and protein levels between normal and cancer tissues through significant pathway selection and core gene signature analysis to screen potential clinical biomarkers of CESC. Subsequently, the molecular and protein levels of clinical samples were verified by quantitative transcription PCR, western blot and immunohistochemistry. RESULTS: Three differentially expressed genes (RFC4, MCM2, TOP2A) were found to have a significant survival (P < 0.05) and highly expressed in CESC tissues. Molecular biological verification using quantitative reverse transcribed PCR, western blotting and immunohistochemistry assays exhibited significant differences in the expression of RFC4 between CESC and para-cancerous tissues (P < 0.05). CONCLUSION: This study identified three potential biomarkers (RFC4, MCM2, TOP2A) of CESC which may be useful to clarify the underlying mechanisms of CESC and predict the prognosis of CESC patients.

Dual-drug loaded nanoneedles with targeting property for efficient cancer therapy.

BACKGROUND: Since the anticancer drugs have diverse inhibited mechanisms to the cancer cells, the use of two or more kinds of anticancer agents may achieve excellent therapeutic effects, especially to the drug-resistant tumors. RESULTS: In this study, we developed a kind of dual drug [methotrexate (MTX) and 10-hydroxycamptothecine (HCPT)] loaded nanoneedles (DDNDs) with pronounced targeting property, high drug loading and prolonged drug release. The anti-solvent precipitation of the HCPT and MTX modified PEG-b-PLGA (PEG-b-PLGA-MTX, PPMTX) leads to nucleation of nanoneedles with nanocrystalline HCPT as the core wrapped with PPMTX as steric stabilizers. In vitro cell uptake studies showed that the DDNDs revealed an obviously targeting property and entered the HeLa cells easier than the nanoneedles without MTX modification. The cytotoxicity tests illustrated that the DDNDs possessed better killing ability to HeLa cells than the individual drugs or their mixture in the same dose, indicating its good synergistic effect and targeting property. The in vivo studies further confirmed these conclusions. CONCLUSIONS: This approach led to a promising sustained drug delivery system for cancer diagnosis and treatment.

Oleoylethanolamide inhibits α-melanocyte stimulating hormone-stimulated melanogenesis via ERK, Akt and CREB signaling pathways in B16 melanoma cells.

The present study aimed to examine the potential inhibitory activity of oleoylethanolamide (OEA) on α-melanocyte stimulating hormone (α-MSH)-stimulated melanogenesis and the molecular mechanism(s) involved in the process in B16 mouse melanoma cells. Our data demonstrated that OEA markedly inhibited melanin synthesis and tyrosinase activity in α-MSH-stimulated B16 cells. In addition, the expression of melanogenesis-related proteins, such as melanocortin-1 receptor (MC1R), microphthalmia-associated transcription factor (MITF), tyrosinase-related protein-1 (TRP-1) and tyrosinase, was suppressed in a concentration-dependent manner by OEA. In addition, OEA may suppress melanogenesis through a peroxisome proliferator-activated receptor α (PPARα)-independent pathway. Moreover, OEA activated ERK, Akt, p38 pathways and inhibits CREB pathway in α-MSH-stimulated B16 cells. The specific ERK inhibitor PD98059 partly blocked OEA-inhibited melanin synthesis and tyrosinase activity and partly abrogated the OEA-suppressed expression of melanogenic proteins. Furthermore, OEA presented remarkable inhibition on the body pigmentation in the zebrafish model system. Our findings demonstrated that OEA is an effective inhibitor of hyperpigmentation through activation of ERK, Akt and p38 pathways, inhibition of the CREB pathway, and subsequent down-regulation of MITF, TRP-1 and tyrosinase production.