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Purpose: Lung cancer (LC) and breast cancer (BC) are the most common causes of brain metastases (BMs). Time from primary diagnosis to BM (TPDBM) refers to the time interval between initial LC or BC diagnosis and development of BM. This research aims to identify clinical, molecular, and therapeutic risk factors associated with shorter TPDBM. Methods: We retrospectively reviewed all diagnosed LC and BC patients with BM at Harbin Medical University Cancer Hospital from 2016 to 2020. A total of 570 patients with LC brain metastasis (LCBM) and 173 patients with breast cancer brain metastasis (BCBM) patients who met the inclusion criteria were enrolled for further analysis. BM free survival time curves were generated using Kaplan–Meier analyses. Univariate and multivariate Cox regression analyses were applied to identify risk factors associated with earlier development of BM in LC and BC, respectively. Results: The median TPDBM was 5.3 months in LC and 44.4 months in BC. In multivariate analysis, clinical stage IV and M1 stage were independent risk factors for early development of LCBM. LC patients who received chemotherapy, targeted therapy, pulmonary radiotherapy, and pulmonary surgery had longer TPDBM. For BC patients, age ≥ 50 years, Ki67 ≥ 0.3, HER2 positive or triple‐negative breast cancer subtype, advanced N stage, and no mastectomy were correlated with shorter TPDBM. Conclusions: This single‐institutional study helps identify patients who have a high risk of developing BM early. For these patients, early detection and intervention could have clinical benefits. [ABSTRACT FROM AUTHOR]

High‐entropy alloys (HEAs) materials, as promising nanomaterials, have garnered significant attention from researchers due to their excellent performance in the field of hydrogen evolution reaction (HER). The four core effects of HEAs, including the high‐entropy effect, severe lattice distortion effect, sluggish diffusion effect, and cocktail effect, are pivotal in underpinning their remarkable mechanical and thermodynamic properties. Nevertheless, the intricate geometric and electronic structures of HEAs make their catalytic mechanisms exceptionally complex and challenging to decipher. In particular, a thorough analysis of the underlying factors responsible for the outstanding catalytic activity, selectivity, and the ability to maintain stable hydrogen production, even at high current densities, in HEAs is lacking. To provide a systematic exploration of the design and application of HEAs in HER systems, this review commences with an examination of the physicochemical properties of HEAs. It covers a wide range of topics, including the synthesis methods of HEAs, and the major reaction mechanisms of HERs, and presents innovative methods and approaches for designing HEAs specifically in the context of HERs. [ABSTRACT FROM AUTHOR]

The work focuses on the optimization of management strategies of energy supply chain in oil–gas enterprises to find out the optimal management strategy and overcome the fragility of the traditional energy supply system. Back propagation neural network (BPNN) is applied to energy supply predicting and energy security early warning in oil–gas enterprises, and the security early warning system is designed based on the auxiliary cognitive system. The security early warning system is used to predict the peak value of oil and gas supply, and then the detection performances and the data security transmission performances of different models are compared and analysed. Finally, a comprehensive evaluation model for security management of oil–gas supply chain based on the neural network is established. It is found that compared with convolutional neural network (CNNs), the improved BPNN model algorithm proposed shows increased accuracy by 5.4%, reduced model training time and test time, and improved accuracy and recall rate. The accuracy, recall rate, and F1 value of the proposed model are 88.48%, 75.88%, and 96.21%, respectively, which were obviously higher than those of the CNN. It suggests that the improved security management model of oil–gas supply chain shows better recognition and prediction accuracy. Based on the quantitative and qualitative analysis results, the optimization suggestions for management strategies in oil–gas enterprises are put forward, which is of strategic significance for improving the security of oil–gas supply. [ABSTRACT FROM AUTHOR]

Objective: To describe a novel method of medial fixation of titanium mesh with a right‐angled screwdriver for orbital floor and maxillary reconstruction and to compare the reconstruction outcome of orbital floor reconstruction with modified and traditional methods. Methods: The data of 23 patients who underwent maxillectomy and orbital floor defect reconstruction by individualized titanium mesh in Peking University School and Hospital of Stomatology between 2018 and 2021 were retrospectively reviewed. While eight patients received modified orbital floor reconstruction with titanium mesh and angled screwdriver (group A), 15 patients received traditional orbital floor reconstruction (group B). The contact area with buccal flap for titanium mesh in groups A and B was calculated. Titanium mesh deformation, fracture or exposure was recorded. Postoperative ophthalmic function and success of esthetic restoration were assessed. Results: Mean follow‐up was for 15.7 months (range, 9–22 months). The contact area with buccal flap for the modified titanium mesh in group A (13.11 ± 1.41 cm2) was significantly less than that of the traditional titanium mesh in group B (21.83 ± 1.23 cm2; p <.05). The exposure of titanium mesh occurred in two patients in group B. The self‐evaluation of facial symmetry for 23 patients showed no significant difference between group A (7.75 ± 0.71) and group B (6.68 ± 1.30; p >.05). No specific complications were reported. Conclusion: We propose a novel method of zygomatic medial fixation of titanium mesh with a right‐angled screwdriver for orbital floor and maxillary reconstruction, which has the potential to prevent the postoperative exposure of titanium mesh. Level of Evidence: Level III (Retrospective comparative study). [ABSTRACT FROM AUTHOR]

Objective: To explore whether MRI‐visible enlarged perivascular spaces (EPVS) are associated with migraine and may serve as a predictor of migraine. Then further explore its correlation with migraine chronification. Methods: A total of 231 participants (healthy control [HC] = 57, episodic migraine [EM] = 59, chronic migraine [CM] = 115) were included in this case–control study. A 3T MRI device and the validated visual rating scale were used to assess the grades of EPVS in centrum semiovale (CSO), midbrain (MB), and basal ganglia (BG). Comparisons between the two groups were made using the chi‐square or Fisher's exact tests to initially determine whether high‐grade EPVS were associated with migraine and migraine chronification. A multivariate logistic regression model was constructed to further investigate the role of high‐grade EPVS in migraine. Results: The prevalence of high‐grade EPVS in CSO and MB were significantly higher in patients with migraine than in HCs (CSO: 64.94% vs. 42.11%, P = 0.002; MB: 55.75% vs. 29.82%, P = 0.001). Subgroup analysis showed no statistical difference between patients with EM and CM (CSO: 69.94% vs. 62.61%, P = 0.368; MB: 50.85% vs. 58.26%, P = 0.351). Individuals with high‐grade EPVS in CSO (odds ratio [OR]: 2.324; 95% confidence interval [CI]: 1.136–4.754; P = 0.021) and MB (OR: 3.261; 95% CI: 1.534–6.935; P = 0.002) were more likely to suffer from migraine. Interpretation: This case–control study showed that high‐grade EPVS in CSO and MB in clinical practice with the underlying mechanism of dysfunction of the glymphatic system could be a predictor of migraine, but no significant correlation had been found with migraine chronification. [ABSTRACT FROM AUTHOR]

Objective: This meta‐analysis aimed to determine the effect of mindfulness interventions on nurses' levels of depression and anxiety. Design: Meta‐analysis of randomised controlled trials. Methods: The following Chinese and English databases were searched: PubMed, Embase, Cochrane Library, Web of Science, and China National Knowledge Internet (CNKI). The retrieval period was from database construction to 30 March 2022. Two researchers screened the relevant literature and extracted the data. After a cross‐check, data were input into Stata version 16.0 for meta‐analysis. Results: Twelve randomised controlled trials from 2017 to 2021 were included, which involved 807 subjects (405 and 402 in the intervention and control groups, respectively). Meta‐analysis results showed that nurses' anxiety reduced by mindfulness‐based interventions was significantly higher compared to that of the control group (SMD = 0.91, 95% CI: 0.27–1.55, p < 0.05). Furthermore, an 8‐week mindfulness‐based intervention (SMD = 1.43, 95% CI: 0.61–2.24) reduced the level of anxiety significantly more compared to a 4‐week intervention (SMD = 1.03, 95% CI: 0.36–1.71). Mindfulness‐based interventions were better compared to conventional intervention to reduce the level of depression (SMD = 1.02, 95% CI: 0.42–1.61, p < 0.05), and an 8‐week mindfulness intervention (SMD = 1.81, 95% CI: 0.78–2.84) reduced the level of depression significantly more compared to a 4‐week intervention (SMD = 0.82, 95% CI: 0.29–1.35). Since limited studies had interventions longer than 8 weeks, results on longer mindfulness interventions in reducing nurses' anxiety and depression are inconclusive. In conclusion, mindfulness intervention for 8 weeks or less can significantly reduce nurses' anxiety and depression levels. Patient or Public Contribution: None. [ABSTRACT FROM AUTHOR]

Remarkable exertions are directed to reveal and understand topographic cues that induce cell mechanical sensitive responses including lineage determination. Extracellular matrix (ECM) is the sophisticated ensemble of diverse factors offering the complicated cellular microenvironment to regulate cell behaviors. However, the functions of only a few of these factors are revealed; most of them are still poorly understood. Herein, the focus is on understanding the curved structure in ECM network for regulating stem cell mechanotransduction. A curved nanofiber network mimicking the curved structure in ECM is fabricated by an improved electrospinning technology. Compared with the straight fibers, the curved fibers promote cell bridge formation because of the cytoskeleton tension. The actomyosin filaments are condensed near the curved edge of the non‐adhesive bridge in the bridging cells, which generates higher myosin‐II‐based intracellular force. This force drives cell lineage commitment toward osteogenic differentiation. This study enriches and perfects the knowledge of the effects of topographic cues on cell behaviors and guides the development of novel biomaterials. [ABSTRACT FROM AUTHOR]

Introduction: Combined forceps and cryoprobe biopsy during bronchoscopy are increasingly used. However, the adult standard cuffed endotracheal tube (SCETT) is can be limited by general anaesthesia and neuromuscular blockade. An adult uncuffed endotracheal tube (UCETT) might provide simple and safe airway support in stable patients during forceps and cryoprobe biopsy under spontaneous respiration. Methods: A retrospective review of stable patients undergoing forceps and cryoprobe biopsy was performed. They were divided into a UCETT group (N = 33) and a SCETT group (N = 27). The primary technical outcome was the successful intubation and completion of bronchoscopy. The primary safety outcome was the incidence of desaturation events. Recovery time and side effects were also recorded. Results: UCETTs and SCETTs were successfully inserted, and bronchoscopic procedures were completed in all patients. Only 3/33 (9.1%) patients in the UCETT group exhibited a drop of SPO2 < 90% during the bronchoscopy, compared to 2/27 (7.4%) patients in the SCETT group (P = 0.545). Patients recovered faster in the UCETT group than those in the SCETT group. Major bleeding, laryngospasm and major arrhythmias did not occur in either group. Incidences of sinus tachycardia, incidences of vomiting, minor and moderate bleeding and premature atrial contractions were not significantly different between the two groups. Nausea occurred in 5/33 (15.2%) patients in the UCETT group, compared to 11/27 (40.7%) in the SCETT group. Conclusion: This study suggests that UCETT under spontaneous respiration can provide satisfactory airway support and a shorter recovery time in stable patients; thus, it may be an option to assist forceps and cryoprobe biopsy. [ABSTRACT FROM AUTHOR]

Fertility is a significant concern among adolescent and young adult (AYA) cancer survivors and their caregivers, especially after their completion of cancer treatment programs. Concerns about fertility affect not only cancer patients' psychological well‐being, but also all aspects of their medical treatments, including treatment protocol, decision‐making, and treatment adherence. In this scoping review, the PubMed, CINAHL, Web of Science, Embase, CNKI, and Wanfang electronic databases were searched according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis Extension for Scoping Reviews. The searches identified 669 articles, 54 of which met the inclusion criteria. Reviewers extracted the data on the study characteristics, measurements, positive factors, negative factors, and additional themes. This scoping review included studies from 10 countries. Most studies were quantitative using a cross‐sectional design. The prevalence of reproductive concerns among AYA cancer survivors ranged from 44% to 86%, and 28% to 44% of the survivors experienced moderate to severe concerns. The specific implementation of fertility consultation, including timing, consult frequency, and content, deserves ongoing exploration. [ABSTRACT FROM AUTHOR]

Background: Lung cancer (LC) is one of the most common cancers and a leading cause of cancer‐related deaths worldwide. In many pathological conditions, particularly in the tumor microenvironment, cells and tissues frequently exist in a hypoxic state. Here, we evaluated Itchy E3 ubiquitin protein ligase (ITCH) expression in LC cells following hypoxia treatment. Methods: LC cell lines were treated with hypoxic condition. Cell migration, invasion, inflammation, reactive oxygen species (ROS) production, and apoptosis of LC cells were determined by wound healing assay, Transwell invasive assay, ELISA, DCFH‐DA staining, and flow cytometry, respectively. qPCR and WB were used to determine the expression of ITCH and TXNIP. Co‐IP was performed to assess the interaction between ITCH and TXNIP. Results: ITCH expression was downregulated in LC cells under hypoxic conditions. Next, LC cells were subjected to hypoxic conditions and changes in cell viability and metastasis were determined. Hypoxic conditions resulted in increased migration and invasion abilities of LC cells. Intracellular reactive oxygen species (ROS) production, inflammation, and apoptosis were also promoted by hypoxia. We found that ITCH overexpression led to the proteasomal degradation of thioredoxin‐interacting protein (TXNIP), whereas the expression of the ITCH C830A mutant did not affect TXNIP levels in LC cells. The gain‐of‐function experiment demonstrated that migration, invasion, ROS generation, inflammation, and apoptosis of hypoxia‐conditioned LC cells were ameliorated by ITCH overexpression, whereas the ITCH C830A mutant did not cause any changes in these phenotypes. Furthermore, the contribution of TXNIP knockdown and ITCH overexpression to the hypoxia‐induced features in LC cells with ITCH C830A was found to be similar. Conclusion: Our results suggest a novel mechanism underlying the changes in ITCH‐mediated malignant phenotypes of hypoxia‐conditioned LC cells via TXNIP. [ABSTRACT FROM AUTHOR]

Aims: Circular RNAs have been reported to play key roles in the progression of various cancers, including gliomas. The present study was designed to investigate the role of hsa_circ_0072309 in autophagy and temozolomide (TMZ) sensitivity in glioblastoma (GBM). Methods: The effect of hsa_circ_0072309 on autophagy and TMZ sensitivity were examined by GFP‐RFP‐LC3, transmission electron microscopy(TEM), flow cytometry, Western blot, and immunofluorescence. The mechanism of hsa_circ_0072309 regulating p53 signaling pathway was analyzed using Western blot, IP, and rescue experiments. Results: Low hsa_circ_0072309 expression predicts poor prognosis for glioma patients. The regulation of hsa_circ_0072309 on autophagy and TMZ sensitivity depends on the status of p53. Hsa_circ_0072309 promoted autophagy by p53 signaling pathway and enhanced sensitivity of glioblastoma to temozolomide (TMZ) in p53 wild‐type GBM, but not in p53 mutant GBM. Hsa_circ_0072309 inhibits p53 ubiquitination and increases the stability of p53 protein in the context of p53 wild‐type. MiR‐100 mediates hsa_circ_0072309 regulating p53. P53 inhibitor or autophagy inhibitor could reverse the effect of hsa_circ_0072309 on TMZ sensitivity in p53 wild‐type GBM. Conclusions: This study revealed a function of hsa_circ_0072309 promoting autophagy by p53 signaling pathway and enhancing TMZ sensitivity. These findings demonstrated that hsa_circ_0072309 may be a potential and promising target in designing the treatment strategy for GBM. [ABSTRACT FROM AUTHOR]

Regulatory T lymphocyte (Treg) homing reactions mediated by G protein‐coupled receptor (GPCR)–ligand interactions play a central role in maintaining intestinal immune homeostasis by restraining inappropriate immune responses in the gastrointestinal tract. However, the origin of Treg homing to the colon remains mysterious. Here, we report that the C10ORF99 peptide (also known as CPR15L and AP57), a cognate ligand of GPR15 that controls Treg homing to the colon, originates from a duplication of the flanking CDHR1 gene and is functionally paired with GPR15 in amniotes. Evolutionary analysis and experimental data indicate that the GPR15–C10ORF99 pair is functionally conserved to mediate colonic Treg homing in amniotes and their expression patterns are positively correlated with herbivore diet in the colon. With the first herbivorous diet in early amniotes, a new biological process (herbivorous diet short‐chain fatty acid‐C10ORF99/GPR15‐induced Treg homing colon immune homeostasis) emerged, and we propose an evolutionary model whereby GPR15–C10ORF99 functional pairing has initiated the first colonic Treg homing reaction in amniotes. Our findings also highlight that GPCR–ligand pairing leads to physiological adaptation during vertebrate evolution. SYNOPSIS: The GPR15–C10ORF99 pair is functionally conserved to mediate colonic Treg homing in amniotes. Their expression patterns are positively correlated with herbivore diet, suggesting that this functional pairing initiates the first colonic Treg homing reaction in amniotes. C10ORF99 originated via duplication of the flanking CDHR1 gene and is functionally paired with GPR15 in amniotes.The GPR15–C10ORF99 pair is functionally conserved to mediate the first colonic Treg homing reaction in amniotes.GPR15–C10ORF99 expression patterns in the colon correlate with an herbivore diet in amniotes. [ABSTRACT FROM AUTHOR]

Lung cancer is the most common cause of cancer‐related deaths. Moreover, exploring efficient tumor‐killing drugs is urgently needed. In our study, several derivative compounds of myricetin were synthesized and tested. Experiments on non‐small cell lung cancer (NSCLC) showed that S4‐2‐2 (5,7‐dimethoxy‐3‐(4‐(methyl(1‐(naphthalen‐2‐ylsulfonyl)piperidin‐4‐yl)amino)butoxy)‐2‐(3,4,5‐trimethoxyphenyl)‐4H‐chromen‐4‐one) had the strongest effect on A549 cell inhibition across all compounds. Furthermore, S4‐2‐2‐treated A549 cells were also suppressed when transplanted into immunodeficient mice. Particularly, we found that the migration and invasiveness of A549 cells became suppressed upon treatment with S4‐2‐2. Furthermore, the compound significantly induced cell apoptosis, but did not affect the cell cycle of A549 cells. Finally, we revealed that S4‐2‐2 inhibited the biological function of NSCLC cells by regulating the protein process in the endoplasmic reticulum, and then by inducing the expression of apoptosis‐related proteins. Taken together, S4‐2‐2 was shown to act as a potential molecular inhibitor of A549 cells. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most aggressive glioma, and is prone to develop resistance to chemotherapy and radiotherapy; hence, patients with glioblastoma have a high recurrence rate and a low 1‐year survival rate. In addition, the pathogenesis of glioblastoma is complex and largely unknown, and the available treatments are limited. Here, we uncovered a fundamental role of DYRK1A in regulating NFATC1 in GBMs. We found that DYRK1A was highly expressed in glioma and glioblastoma cells, and its expression was positively correlated with that of NFATC1. Moreover, inhibition of DYRK1A promoted NFATC1 degradation in GBM cells and sharply reduced the transactivation of NFATC1, not only by decreasing the expression of NFATC1‐targeted genes, but also by reducing the luciferase activity, and vice versa. However, DYRK1A had the opposite effect on NFATC2. Most importantly, our data suggest that DYRK1A inhibition reduces glioblastoma migration. Polypeptides derived from the DYRK1A‐targeted motif of NFATC1, by competitively blocking DYRK1A kinase activity on NFATC1, clearly destabilized NFATC1 protein and impaired glioblastoma migration. We propose that the recovery of NFATC1 stability is a key oncogenic event in a large proportion of gliomas, and pharmacological inhibition of DYRK1A by polypeptides could represent a promising therapeutic intervention for GBM. [ABSTRACT FROM AUTHOR]

The development of highly efficient electrocatalysts toward the oxygen evolution reaction is imperative for advancing water splitting technology to generate clean hydrogen energy. Herein, a two dimensional (2D) nanosheet ammonium cobalt phosphate hydrate (NH4CoPO4·H2O) catalyst based on the earth‐abundant non‐noble metal is reported. When used for the challenging alkaline saline water electrolysis, the NH4CoPO4·H2O catalyst with the optimal thickness of 30 nm achieves current densities of 10 and 100 mA cm−2 at the record low overpotentials of 252 and 268 mV, respectively, while maintaining remarkable stability during the alkaline saline water oxidation at room temperature. X‐ray absorption fine spectra reveal that the activation of Co (II) ions (in NH4CoPO4·H2O) to Co (III) species constructs the electrocatalytic active sites. The 2D nanosheet morphology of NH4CoPO4·H2O provides a larger active surface area and more surface‐exposed active sites, which enable the nanosheet catalyst to facilitate the alkaline freshwater and simulated seawater oxidation with excellent activity. The facile and environmentally‐benign H2O‐mediated synthesis route under mild condition makes NH4CoPO4·H2O catalyst highly feasible for practical manufacturing. In comparison with noble metals, this novel electrocatalyst offers a cost‐effective alternative for economic saline water oxidation to advance water electrolysis technology. [ABSTRACT FROM AUTHOR]

Introduction: Our objectives were to compare the single‐line and two‐line methods of cervical length measurement in the first trimester of pregnancy and to evaluate the potential value of the first trimester cervical length measured by the two methods in predicting spontaneous preterm birth. Material and methods: This was a prospective study in singleton pregnancies at 11+0 to 13+6 weeks of gestation. Cervical length was measured by two methods: (i) a linear distance between the two ends of the glandular area around the endocervical canal (single‐line method) and (ii) a sum of a linear distance from the internal os to the greatest cervical curvature and a linear distance from this point of the cervix to the external os (two‐line method). The screening performance of the first trimester cervical length measured by the two different methods for the prediction of spontaneous preterm delivery was assessed by receiver‐operating characteristics (ROC) curve analysis. The areas under the ROC (AUROC) were compared by De Long test. Results: A total of 1484 consecutive singleton pregnancies were included in this study. Spontaneous preterm delivery at <37 and <32 weeks occurred in 75 cases (5.1%) and 12 cases (0.8%), respectively. The median cervical length measured by the single‐line method was significantly shorter than that by the two‐line method (33.5 vs 36.5 mm, p <.001). Compared with the term delivery group, the median cervical length measured by the two‐line method was shorter in women with spontaneous delivery at <32 weeks of gestation (36.5 vs 33.6 mm, p <.01). No significant difference in the median cervical length measured by the single‐line method was detected between the spontaneous preterm delivery and term delivery groups. Receiver‐operating‐characteristic curves demonstrated that cervical length measured by the two‐line method achieved better performance in predicting spontaneous delivery at <32 weeks compared with the single‐line method (AUROC: 0.72 vs 0.61, p <.01). Conclusions: We have demonstrated that the first trimester cervical length, measured by the two‐line approach, holds promise as a potential screening tool for early spontaneous preterm delivery. [ABSTRACT FROM AUTHOR]

In this work, an amorphous ZnO was coated on LiNi0.6Co0.2Mn0.2O2 (NCM) using a sol‐gel strategy method. The NCM coated with 1 wt.% ZnO and a thickness of about 3 nm exhibits an improved cycling performance, accompanied by a lower capacity fading (from 194.8 to 133.8 mAh g−1, i.e., 68%) than that of the pristine one (i.e., only 34%) after 300 cycles at 0.2 C. The cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) indicate that the ZnO coating can improve extraction/insertion of Li+ and inhibit the increase in impedance of the NCM cathode material. This approach may benefit the performance improvement of the Ni‐rich cathode materials in Lithium‐ion batteries (LIBs). [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to investigate the differences in shear-wave sonoelastography (SWS) scores between the different parts of cervix, explore the association between the cervical SWS scores with cervical length and evaluate repeatability of the measurement of cervical SWS scores.Material and Methods: This was a prospective study performed in women with singleton pregnancy at 11-13+6 (n = 676), 16-20+6 (n = 364), 21-24+6 (n = 338) and 28-32+6 weeks (n = 304). The SWS scores were obtained at the inner, middle and external parts of the cervix, using a transvaginal ultrasound approach.Results: The SWS scores of the inner cervix were significantly higher than the measurements acquired at the middle and external parts (all P < .001). At 21-24+6 and 28-32+6 weeks, most regions of interest demonstrated a very weak positive correlation with cervical length (r = .125 to r = .299). In comparison with nulliparous women, parous women without prior preterm birth had higher SWS scores of the inner and middle parts of the cervix at 16-20+6 and 21-24+6 weeks. All regions of interest showed good intra- and inter-observer agreement.Conclusions: The assessment of the cervical SWS scores is highly reproducible. The stiffness of the cervix demonstrates a gradient that decreases from the inner part to the external part and a very weak positive correlation with cervical length. [ABSTRACT FROM AUTHOR]

Aims: Painful diabetic neuropathy (PDN) is a refractory complication of diabetes. The study aimed to investigate the role of α‐lipoic acid (ALA) on the regulation of transient receptor potential vanilloid‐1 (TRPV1) in dorsal root ganglion (DRG) neurons of rats with diabetes. Methods: Whole‐cell patch‐clamp recordings were employed to measure neuronal excitability in DiI‐labeled DRG neurons of control and streptozotocin (STZ)‐induced diabetic rats. Western blotting and immunofluorescence assays were used to determine the expression and location of NF‐κBp65 and TRPV1. Results: STZ‐induced hindpaw pain hypersensitivity and neuronal excitability in L4‐6 DRG neurons were attenuated by intraperitoneal injection with ALA once a day lasted for one week. TRPV1 expression was enhanced in L4‐6 DRGs of diabetic rats compared with age‐matched control rats, which was also suppressed by ALA treatment. In addition, TRPV1 and p65 colocated in the same DRG neurons. The expression of p65 was upregulated in L4‐6 DRGs of diabetic rats. Inhibition of p65 signaling using recombinant lentiviral vectors designated as LV‐NF‐κBp65 siRNA remarkably suppressed TRPV1 expression. Finally, p65 expression was downregulated by ALA treatment. Conclusion: Our findings demonstrated that ALA may alleviate neuropathic pain in diabetes by regulating TRPV1 expression via affecting NF‐κB. [ABSTRACT FROM AUTHOR]

Background: This study aimed to overexpress or silence connexin 43 (Cx43) and A‐kinase anchoring protein 95 (AKAP95) in human A549 cells to explore their effects on cyclins and on G1/S conversion when the interrelationship of Cx43, AKAP95, and cyclin E1/E2 changes. Methods: The study mainly used Western blot analysis and Co‐immuno precipitation to detect the target protein in Cx43/AKAP95 over expressed human A549 cells, and the relationship of proteins Cx43, AKAP95 and Cyclin E during G1‐S phase was explored with qualitative and quantitative analysis. Results: The overexpression of Cx43 inhibited the expression of cyclin D1 and E1 by accelerating their degradation and reduced the Cdk2 activity that blocked the DNA transcription activity. However, the overexpression of AKAP95 increased the expression of cyclin D1 and E1 and inhibited their degradation, and enhanced the Cdk2 activity that promoted the DNA transcription activity. Cx43 and AKAP95 competitively bound to cyclin E1/E2, and the competitive binding affected the Cdk2 activity, Rb phosphorylation, DNA transcription activity, and G1/S conversion. Conclusions: This study showed that the expression of ERK1/2, PKA, and PKB increased when BEAS‐2B cells were treated with PDGF‐BB, suggesting that ERK1/2, PKA, and PKB might be involved in the binding of AKAP95 with cyclin E, or the separation of AKAP95 from Cx43 from cyclin E1/E2. The specific mechanism underlying this process still needs further exploration. [ABSTRACT FROM AUTHOR]

Immunoglobulin heavy chain variable region (IGHV) mutational status has been an important prognostic factor for chronic lymphocytic leukemia (CLL) for decades. Patients with unmutated IGHV (≥98% identity to the germline sequence) have inferior prognosis and tend to carry unfavorable genetic markers compared to those with mutated IGHV (<98% identity to the germline sequence). However, 98% as the cutoff for IGHV mutational status is a mathematical choice and remains controversial. We have previously reported distinct IGHV repertoire features between Chinese and western CLL populations. Here, we retrospectively studied 595 Chinese CLL patients to determine the best cutoff value for IGHV in Chinese CLL population. Using 1% as the interval for IGHV identity, we divided the studied cohort into seven subgroups from 95% to 100%. Briefer time to first treatment (TTFT) and overall survival (OS) were observed in cases with ≥98% compared to those with <98%, while the differences were obscure within subgroups ≥98% (98%‐98.99%, 99%‐99.99%, and 100%) and <98% (<94.99%, 95%‐95.99%, 96%‐96.99%, and 97%‐97.99%). Multivariate analysis confirmed the independent prognostic value of 98% being the cutoff for IGHV identity in terms of both TTFT and OS. All the prognostic factors, including del(17p13), del(11q22.3), TP53 mutation, MYD88 mutation, NOTCH1 mutation, SF3B1 mutation, CD38, ZAP‐70, Binet staging, gender, and β2‐microglobulin, were significantly different in distribution between group <98% and group ≥98%, but not among subgroups 98%‐98.99%, 99%‐99.99%, and 100%. In conclusion, 98% is the optimal cutoff of IGHV identity for the prognosis evaluation of Chinese CLL patients. [ABSTRACT FROM AUTHOR]

Quaking homolog (QKI) is a member of the RNA‐binding signal transduction and activator of proteins family. Previous studies showed that QKI possesses the tumour suppressor activity in human cancers by interacting with the 3'‐untraslated region (3'‐UTR) of various gene transcripts via the STAR domain. This study first assessed the association of QKI‐6 expression with clinicopathological and survival data from bladder cancer patients and then investigated the underlying molecular mechanisms. Bladder cancer tissues (n = 223) were subjected to immunohistochemistry, and tumour cell lines and nude mice were used for different in vitro and in vivo assays following QKI‐6 overexpression or knockdown. QKI‐6 down‐regulation was associated with advanced tumour TNM stages and poor patient overall survival. QKI‐6 overexpression inhibited bladder cancer cell growth and invasion capacity, but induced tumour cell apoptosis and cell cycle arrest. Furthermore, ectopic expression of QKI‐6 reduced tumour xenograft growth and expression of proliferation markers, Ki67 and PCNA. However, knockdown of QKI‐6 expression had opposite effects in vitro and in vivo. QKI‐6 inhibited expression of E2 transcription factor 3 (E2F3) by directly binding to the E2F3 3'‐UTR, whereas E2F3 induced QKI‐6 transcription by binding to the QKI‐6 promoter in negative feedback mechanism. QKI‐6 expression also suppressed activity and expression of nuclear factor‐κB (NF‐κB) signalling proteins in vitro, implying a novel multilevel regulatory network downstream of QKI‐6. In conclusion, QKI‐6 down‐regulation contributes to bladder cancer development and progression. [ABSTRACT FROM AUTHOR]

The article offers information on the role of the vesicle-associated membrane proteins (VAMPs) and the plant growth materials to regulate the Brassinosteroids (BRs) BRI1 plasma membrane targeting to control plant growth in Arabidopsis. It discusses Brassinosteroids as the bioactive steroid molecules that act as plant hormones. It mentions the SYP22, plant growth hormone for overexpressing transgenic plants.

Red blood cell distribution width (RDW), which measures the range of variation of red blood cell volume, has been explored as a prognostic factor in multiple types of cancer. However, the role of RDW in mantle cell lymphoma (MCL), a rare type of non‐Hodgkin lymphoma with poor outcomes, remains to be determined. Therefore, we investigated the prognostic role of RDW in MCL. We found that 21 of 76 MCL patients (27.6%) had an abnormally elevated RDW (>15.7%). Abnormally elevated RDW was significantly associated with presence of B symptoms (P = 0.0020), elevated lactate dehydrogenase (LDH) (P = 0.0010), higher leukocyte count (P = 0.0345), higher simplified Mantle Cell International Prognostic Index (sMIPI) (P = 0.0194), and lower level of hemoglobin (Hb) (P < 0.0001). It was marginally associated with increased C‐reactive protein (P = 0.0862). RDW was significantly correlated with Hb level (r2 = 0.42) and LDH level (r2 = 0.19). 15.8% was determined as the best cutoff of RDW in predicting the survival outcome by the X‐tile software. Survival analysis revealed that high RDW (>15.8%) predicted shorter progression‐free survival (PFS) (hazards ratio [HR]: 3.14; P = 0.0005) and shorter overall survival (OS) (HR: 4.04; P < 0.0001). High RDW independently predicted both shorter PFS (P = 0.0493) and OS (P = 0.0118). RDW also improved the prognostic stratification based on sMIPI. In conclusion, our study identified RDW as a novel prognostic factor of clinical feasibility in the prognostication of MCL. [ABSTRACT FROM AUTHOR]

Summary: P0 protein of some polerovirus members can target ARGONAUTE1 (AGO1) to suppress RNA silencing. Although P0 harbors an F‐box‐like motif reported to be essential for interaction with S phase kinase‐associated protein 1 (SKP1) and RNA silencing suppression, it is the autophagy pathway that was shown to contribute to AGO1 degradation. Therefore, the role of P0–SKP1 interaction in silencing suppression remains unclear.We conducted global mutagenesis and comparative functional analysis of P0 encoded by Brassica yellows virus (BrYV) (P0Br).We found that several residues within P0Br are required for local and systemic silencing suppression activities. Remarkably, the F‐box‐like motif mutant of P0Br, which failed to interact with SKP1, is destabilized in vivo. Both the 26S proteasome system and autophagy pathway play a role in destabilization of the mutant protein. Furthermore, silencing of a Nicotiana benthamiana SKP1 ortholog leads to the destabilization of P0Br. Genetic analyses indicated that the P0Br–SKP1 interaction is not directly required for silencing suppression activity of P0Br, but it facilitates stability of P0Br to ensure efficient RNA silencing suppression. Consistent with these findings, efficient systemic infection of BrYV requires P0Br.Our results reveal a novel strategy used by BrYV for facilitating viral suppressors of RNA silencing stability against degradation by plant cells. [ABSTRACT FROM AUTHOR]

The voltage violation phenomenon can be very prominent in the condition of dispersed wind power (DWP) widely integrated into network, which affects the safe operation during integration and effective consumption of wind power. In this study, a self-discipline control strategy of DWP is proposed to solve the voltage violation problem with high penetration. First, the influence of system voltage after the DWP integrated into network is analysed, which raises the feasibility of self-discipline control strategy. Then, according to the proposed strategy, the object of optimisation model is designed to better the voltage quality of the grid connection point of wind power generator and to maximise the active power outputs of wind power. Considering the non-linear and multivariable characteristics of the optimisation model, this study used the particle swarm optimisation to obtain the reactive power and active power regulations of wind power. Finally, the proposed algorithm is tested and analysed on the IEEE 33-node distribution system, and verified by a practical project. The results show that the self-discipline control strategy can effectively eliminate the voltage violation caused by the DWP integration. Moreover, the wind power can be fully utilised. [ABSTRACT FROM AUTHOR]

The microstructure evolution and growth behavior of the Al2O3/Y3Al5O12(YAG)/ZrO2 ternary eutectic ceramics during directional solidification were well investigated. During directional solidification of the Al2O3/YAG/ZrO2 ternary eutectic ceramics, {112¯0} Al2O3 paralleled with {001}ZrO2 while they did not parallel with {001}YAG at the same time in the competitive growth stage. All of the interfaces parallel to each other finally. The area percentage of the Al2O3/ZrO2 and YAG/ZrO2 interfaces are 40.4 ± 0.2% and 30.8 ± 0.1%, respectively, higher than that of the Al2O3/YAG (28.8 ± 0.2%). The content of Al2O3 and YAG phases are 39.9% and 41.1%, respectively, almost double of that of ZrO2. The interfaces of Al2O3/ZrO2 and YAG/ZrO2 are shorter and more dispersed than that of the Al2O3/YAG. It was found that the interfacial energy of Al2O3/ZrO2 and YAG/ZrO2 interfaces are lower than that of Al2O3/YAG. It can be concluded that interfacial energy plays a decisive role in affecting the crystallographic orientation and interfaces distribution in the Al2O3/YAG/ZrO2 eutectic since the interfaces of Al2O3/ZrO2 and YAG/ZrO2 with lower interfacial energy can be formed more easily during directional solidification. Therefore, the contents of Al2O3/ZrO2 and YAG/ZrO2 interfaces are higher. This study can provide theoretical guidance for interface design of multi‐phase materials. [ABSTRACT FROM AUTHOR]

Abstract: The highly efficient charge generation and transport is realized by simply stacking several 1,4,5,8,9,11‐hexa‐azatriphenylene hexacarbonitrile (HAT‐CN)/4,4′,4″‐tris(N‐3‐methylphenyl‐N‐phenylamino) triph‐enylamine (m‐MTDATA) organic heterojunctions in series. Mechanism analysis confirms that the highly effective charge transport property benefits from the efficient charge generation and recombination processes at the HAT‐CN/m‐MTDATA interfaces. It is found that the efficient multialternating organic heterojunctions can be used not only as hole and electron transporters to supply large charge injection, but also as excellent charge generation layer (CGL) to fabricate high‐performance tandem organic light‐emitting diodes (OLEDs). The resulting red phosphorescent OLEDs by simultaneously using the multialternating organic heterojunctions as hole and electron transporters realize the power efficiency (PE) of 36.7 lm W−1, current efficiency (CE) of 28.0 cd A−1, and external quantum efficiency (EQE) of 15.4%, whereas the PE, CE, and EQE, respectively, reach 37.1 lm W−1, 56.0 cd A−1, and 31.8% when simultaneously using the multialternating organic heterojunctions as hole and electron transporters and CGL to fabricate tandem red phosphorescent OLEDs, indicating the validity of the multialternating organic heterojunctions as the charge generator and transporters. The results provide us a totally new way of fabricating high‐performance OLEDs. [ABSTRACT FROM AUTHOR]

Abstract: Because of the exclusion for the patients more than 75 years (very elderly patients) in many clinical trials of esophageal cancer (EC), there is no consensus on prognosis and treatment for this population. We aim to evaluate the outcomes and aging‐related prognostic factors of definitive radiotherapy (RT) for very elderly EC patients. We retrospectively analyzed 149 very elderly EC patients consecutively treated between January 2015 and June 2016 by definitive intensity‐modulated radiotherapy (IMRT) with or without chemotherapy. The clinical outcome and toxicities were assessed, and the potential prognostic factors, such as nutritional risk index (NRI) and neutrophil–lymphocyte ratio (NLR), were analyzed statistically. The median follow‐up time for survivors was 22.5 months. The 2‐year overall survival (OS), local–regional failure‐free survival (LRFFS), and distant metastasis‐free survival (DMFS) were 51.6%, 54.7%, and 85.2%, respectively. Independent predictors for poorer OS were higher American Joint Committee on Cancer (AJCC) stage, lower NRI, and higher NLR value before RT. Meanwhile, the total dose (cutoff value 60 Gy) of planning gross tumor volume (PGTV) and chemotherapy was also identified as independent prognostic indicator for LRFFS and DMFS, respectively. 72 patients had treatment failure and 58 (80.6%), 6 (8.3%), and 18 (25.0%) patients had experienced local, regional, and distant failure, respectively. Few severe toxicities were observed. The conservative definitive RT with modern technique was effective for very elderly EC patients in short term with low rate and tolerable toxicities. Local residue or recurrence was the most common failure pattern. The aging‐related prognostic factors concerned nutrition and immune, such as NRI and NLR before RT, should be considered for use in future clinical practice. [ABSTRACT FROM AUTHOR]

Abstract: Aims/Introduction: Patients with diabetes frequently develop orthostatic hypotension (OH). The present study was designed to examine the relationship of blood pressure (BP) circadian rhythms and outcomes in diabetes with OH. Materials and Methods: In the present study, 173 inpatients with type 2 diabetes were enrolled. Patients were divided into an OH group and a non‐OH group according to the BP changes detected in the supine and standing position. Then, 24‐h ambulatory BP was monitored. Patients were followed up for an average of 45 ± 10 months post‐discharge. Outcomes – death and major adverse cardiac and cerebrovascular events, including heart failure, myocardial infarction and stroke – were recorded. Results: There were 61 patients (35.26%) in the OH group and 112 patients (64.74%) in the non‐OH group. In the OH group, the night‐time systolic BP and night‐time diastolic BP were higher, the blood BP rhythms were predominantly of the riser type (67.21%). OH was as an independent marker of riser type circadian rhythm (adjusted odds ratio 4.532, 95% confidence interval 2.579–7.966). In the OH group, the incidence rates of mortality, and major adverse cardiac and cerebrovascular events were increased significantly compared with those in the non‐OH group (11.48 vs 2.68%, P = 0.014; 37.70 vs 8.93%, P < 0.01). Conclusions: In patients who had type 2 diabetes diagnosed with OH, the BP circadian rhythm usually showed riser patterns, and they had increased rates of mortality, and major adverse cardiac and cerebrovascular events. [ABSTRACT FROM AUTHOR]

Background This study was conducted to investigate the exchange protein directly activated by c AMP ( Epac1), PDE4, and PKC expression in breast cancer tissues, and the correlation between these proteins and AKAP95, Cx43, cyclin D2, and cyclin E1. Methods PV-9000 two-step immunohistochemistry was used to analyze protein expression. Results The positive rate of Epac1 protein expression in breast cancer tissues (58%) was higher than in para-carcinoma tissues (10%) ( P < 0.05). There were no significant differences in the positive rates of PDE4 and PKC expression between breast cancer and para-carcinoma tissues ( P > 0.05). The positive expression rate of PDE4 was higher in the P53 protein positive group compared to the P53 negative group ( P < 0.05). Correlations between Epac1 and cyclin D2, PDE4 and cyclin D2, AKAP95 and PKC, Cx43 and PKC, and cyclin D2 and PKC proteins were observed ( P < 0.05). Conclusion Epac1 expression in breast cancer tissues was increased, suggesting that the protein may be involved in the development of breast cancer. Correlations between Epac1 and cyclin D2, PDE4 and cyclin D2, AKAP95 and PKC, Cx43 and PKC, and cyclin D2 and PKC proteins suggested synergistic effects among these proteins in the development of breast cancer. [ABSTRACT FROM AUTHOR]

We numerically predict the microstructure properties of ceramic membranes and the coupling effects of microstructure properties and layer thickness on the strength and permeance of ceramic membranes. It is found that particle size is the most important factor, followed by thickness and finally by microstructure parameters. The general design principle for strength and permeance are [ABSTRACT FROM AUTHOR]

In social insects, the efficiency of exploitation of resources and colony defence are mediated by chemical communication. In colonies dependent on nutritionally limited resources, corpses represent both a food resource and a risk of pathogens. Because this risk vs. reward changes with time after death, behavioural plasticity in the response to corpses would be advantageous. How social insects regulate this trade-off remains unknown., We conducted quantitative behavioural bioassay and chemical analysis to study corpse management in the eastern subterranean termite, Reticulitermes flavipes. We hypothesized that R. flavipes responds differently towards corpses with prolonged post-mortem time, and this behavioural plasticity is mediated by the dynamic change in death cues., We show that R. flavipes uses a post-mortem signalling system that depends on an early death cue that stimulates corpse retrieval and cannibalism, and late death cues that stimulate recruitment and burial. A blend of 3-octanone and 3-octanol is released immediately after death, with the alcohol (possibly in conjunction with the ketone) playing a clear role as a death cue. This cue enables the colony to recycle nutrients before decomposition occurs and before risk of pathogens increases. The accumulation of late death cues, decomposition products shared by diverse arthropods, elicits a behavioural switch from cannibalism to burial., The ability to detect and respond to the dead is vital to group-living animals. Our study reveals a behavioural shift in corpse management triggered by the interplay of an early death cue and late death cues, which balances risks and rewards associated with corpses. The post-mortem chemical communication highlights the adaptation of a social insect to its ecological niche. [ABSTRACT FROM AUTHOR]

3D microbatteries hold great promise as on-board energy supply systems for microelectronic devices. The construction of 3D microbatteries relies on the development of film deposition techniques that can enable coatings of uniform electrode and electrolyte materials in high-aspect-ratio substrates. Here, a 3D FePO4 on carbon nanotubes (CNTs@FePO4) structure is fabricated by coating FePO4 on CNTs/carbon paper substrate using atomic layer deposition. Compared to FePO4 on a planar substrate, the 3D CNTs@FePO4 electrode exhibits significantly increased areal capacity and excellent rate capability for lithium-ion and sodium-ion storage. The 3D CNTs@FePO4 maintains areal capacities of 64 and 33 μAh cm−2 after 180 cycles for lithium-ion batteries (LIBs) and sodium-ion batteries, which are 16 and 33 times higher than those of planar FePO4 electrode, respectively. Moreover, hybrid 3D CNTs@FePO4@Li3PO4 structure is fabricated by coating Li3PO4 solid-state electrolyte on 3D CNTs@FePO4. The CNTs@FePO4@Li3PO4 electrode shows stable cycling performance in LIBs. Hard X-ray photoemission spectroscopy analysis demonstrates that the Li3PO4 coating prevents the formation of undesirable LiF in the solid-electrolyte interphase layer, which is believed to be responsible for the performance degradation in CNTs@FePO4. This work paves the way to building reliable 3D nanostructured electrode and electrolyte architectures for high areal capacity microbatteries. [ABSTRACT FROM AUTHOR]

Atomic layer deposition (ALD) is considered as a powerful technique to synthesize novel electrode materials for lithium-ion batteries (LIBs), because not only the compositions can be specifically designed to achieve higher battery performances, but also the materials can be deposited on various substrates for different purposes. Herein, a novel design of active material/electrolyte mixture electrode, i.e., titanium dioxide/lithium phosphate (TLPO) nanocomposite, has been successfully developed by ALD and deposited on carbon nanotube substrates (CNTs@TLPO) at 250 °C, by combining the ALD recipes of TiO2 and lithium phosphate (LPO). In the nanocomposite, TiO2 forms anatase nanocrystals, embedded in a matrix of amorphous lithium phosphate. CNTs@TLPO has been examined as an anode material for LIBs, exhibiting a similar electrochemical response as anatase TiO2 in the cyclic voltammetry testing. CNTs@TLPO presents an outstanding capacity of 204 mA h g−1 upon 200 cycles in charge and discharge cycling measurements, as well as a significantly improved rate capability compared with ALD deposited TiO2 on CNTs without LPO ALD cycles. This work shows that the in situ addition of solid-state electrolyte (e.g., lithium phosphate), which introduces higher Li+ ionic conductivity, is an efficient way to achieve high-performance electrode materials for LIBs by ALD. [ABSTRACT FROM AUTHOR]

Objective To examine if mice with focal cortical dysplasia ( FCD) develop spontaneous epileptic seizures and, if so, determine the key electroencephalography ( EEG) features. Methods Unilateral single freeze lesions to the S1 region ( SFLS1R) were made in postnatal day 0-1 pups to induce a neocortical microgyrus in the right cortical hemisphere. Continuous 24-h recordings with intracranial EEG electrodes and behavioral tests were performed in adult SFLS1R and sham-control mice to assess neurologic status. Results A high percentage of adult SFLS1R animals (89%, 40/45) exhibited at least one or more spontaneous nonconvulsive seizure events over the course of 24 h. Of these animals, 60% (27/45) presented with a chronic seizure state that was persistent throughout the recording session, consisting of bursts of rhythmic high-amplitude spike-wave activities and primarily occurring during periods of slow-wave sleep. In comparison, none of the control, age-matched, mice (0/12) developed seizures. The epileptic discharge pattern closely resembled a pattern of continuous spike-waves during slow-wave sleep ( CSWS) of the human syndrome described as an electrical status epilepticus during slow-wave sleep ( ESES). Key findings in the SFLS1R model indicated that the observed CSWS (1) were more prevalent in female (18/23) versus male (9/22, p < 0.05), (2) were strongest in the right S1 region although generalized to other brain regions, (3) were associated with significant cognitive and behavioral deficits, (4) were temporarily alleviated by ethosuximide treatment or optogenetic activation of cortical γ-aminobutyric acid ( GABA)ergic neurons, and (5) theta and alpha band rhythms may play a key role in the generalization of spike-wave activities. Significance This is the first report of an in vivo animal FCD model that induces chronic spontaneous electrographic brain seizures. Further characterization of the abnormal oscillations in this mouse model may lead to a better understanding of the mechanisms of CSWS/ ESES. [ABSTRACT FROM AUTHOR]

How sensory information is processed within olfactory cortices is unclear. Here, we examined long-range circuit wiring between different olfactory cortical regions of acute mouse brain slices using a channelrhodopsin-2 (ChR2)-based neuronal targeting approach. Our results provide detailed information regarding the synaptic properties of the reciprocal long-range monosynaptic glutamatergic projections ( LRMGP) between and within anterior piriform cortex ( aPC), posterior piriform cortex ( pPC), and lateral entorhinal cortex ( LEC), thereby creating a long-range inter- and intracortical circuit diagrams at the level of synapses and single cortical neurons. Our results reveal the following information regarding hierarchical intra- and intercortical organizations: (i) there is massive bottom-up (i.e., rostral-caudal) excitation within the LRMGP accompanied with strong feedforward ( FF) inhibition; (ii) there are convergent FF connections onto LEC from both aPC and pPC; (iii) feedback ( FB) intercortical connections are weak with a significant fraction of presumptive silent synapses; and (iv) intra and intercortical long-range connections lack layer specificity and their innervation of interneurons are stronger than neighboring pyramidal neurons. The elucidation of the distinct hierarchical organization of long-range olfactory cortical circuits paves the way for further understanding of higher order cortical processing within the olfactory system. [ABSTRACT FROM AUTHOR]

GABAergic terminals of chandelier cells exclusively innervate the axon initial segment (AIS) of excitatory neurons. Although the anatomy of these synapses has been well-studied in several brain areas, relatively little is known about their physiological properties. Using vesicular -aminobutyric acid transporter-channelrhodopsin 2-enhanced yellow fluorescence protein (VGAT-ChR2-YFP)-expressing mice and a novel fibreoptic 'laserspritzer' approach that we developed, we investigated the physiological properties of axo-axonic synapses (AASs) in brain slices from the piriform cortex (PC) of mice. AASs were in close proximity to voltage-gated Na+ (NaV) channels located at the AIS. AASs were selectively activated by a 5 µm laserspritzer placed in close proximity to the AIS. Under a minimal laser stimulation condition and using whole-cell somatic voltage-clamp recordings, the amplitudes and kinetics of IPSCs mediated by AASs were similar to those mediated by perisomatic inhibitions. Results were further validated with channelrhodopsin 2-assisted circuit mapping (CRACM) of the entire inhibitory inputs map. For the first time, we revealed that the laserspritzer-induced AAS-IPSCs persisted in the presence of TTX and TEA but not 4-AP. Next, using gramicidin-based perforated patch recordings, we found that theGABA reversal potential (EGABA)was-73.6±1.2mV when induced at the AIS and -72.8 ± 1.1 mV when induced at the perisomatic site. Our anatomical and physiological results lead to the novel conclusions that: (1) AASs innervate the entire length of the AIS, as opposed to forming a highly concentrated cartridge, (2) AAS inhibition suppresses action potentials and epileptiform activity more robustly than perisomatic inhibitions, and (3) AAS activation alone can be sufficient to inhibit action potential generation and epileptiform activities in vitro. [ABSTRACT FROM AUTHOR]

Prostate cancer is a leading cause of cancer-related mortality in men worldwide and there is a lack of effective treatment options for advanced (metastatic) prostate cancer. Currently, limited knowledge is available concerning the role of long non-coding RNAs in prostate cancer metastasis. In this study, we found that long non-coding RNA H19 (H19) and H19-derived microRNA-675 (miR-675) were significantly downregulated in the metastatic prostate cancer cell line M12 compared with the non-metastatic prostate epithelial cell line P69. Upregulation of H19 in P69 and PC3 cells significantly increased the level of miR-675 and repressed cell migration; however, ectopic expression of H19 in M12 cells could not increase the level of miR-675 and therefore had no effect on cell migration. Furthermore, we found that the expression level of either H19 or miR-675 in P69 cells was negatively associated with the expression of transforming growth factor b induced protein (TGFBI), an extracellular matrix protein involved in cancer metastasis. Dual luciferase reporter assays showed that miR-675 directly bound with 30UTR of TGFBI mRNA to repress its translation. Taken together, we show for the first time that the H19-miR-675 axis acts as a suppressor of prostate cancer metastasis, which may have possible diagnostic and therapeutic potential for advanced prostate cancer. [ABSTRACT FROM AUTHOR]

Objectives: Abnormal activation of NF‐κB signalling is a major mechanism of apoptosis resistance in glioblastoma multiforme (GBM). Therefore, better understanding of the regulation of NF‐κB signalling has a significant impact for GBM therapy. Here, we uncovered a critical role of the small GTPase RND3 in regulating the p65 subunit of NF‐κB and NF‐κB signalling in GBM. Materials and methods: Human GBM samples, GBM cells and a human orthotopic GBM‐xenografted animal model were used. The mechanisms of RND3 in regulation of NF‐κB signalling and GBM cell apoptosis were examined by luciferase assay, quantitative PCR, immunostaining, immunoblotting, immunofluorescence, coimmunoprecipitation, TUNEL staining, JC‐1 analysis and flow cytometry. Results: Overexpression of RND3 led to reduced p65 activity in GBM‐cultured cells and a GBM animal model, indicating that the NF‐κB pathway is negatively regulated by RND3 in GBM. Mechanistically, we found that RND3 bound p65 and promoted p65 ubiquitination, leading to decreased p65 protein levels. Furthermore, RND3 enhanced cleaved caspase 3 levels and promoted apoptosis in GBM cells, and RND3 expression was positively correlated with cleaved caspase 3 and IL‐8 in human GBM samples. The effect of RND3 on promoting apoptosis disappeared when p65 ubiquitination was blocked by protease inhibitor carfilzomib or upon co‐expression of ectopic p65. Conclusions: RND3 binds p65 protein and promotes its ubiquitination, resulting in reduced p65 protein expression and inhibition of NF‐κB signalling to induce GBM cell apoptosis. [ABSTRACT FROM AUTHOR]

Summary Wood formation, which occurs mainly through secondary xylem development, is important not only for supplying raw material for the ‘ligno‐chemical’ industry but also for driving the storage of carbon. However, the complex mechanisms underlying the promotion of xylem formation remain to be elucidated. Here, we found that overexpression of Auxin‐Regulated Gene involved in Organ Size (ARGOS) in hybrid poplar 84 K (Populus alba × Populus tremula var. glandulosa) enlarged organ size. In particular, PagARGOS promoted secondary growth of stems with increased xylem formation. To gain further insight into how PagARGOS regulates xylem development, we further carried out yeast two‐hybrid screening and identified that the auxin transporter WALLS ARE THIN1 (WAT1) interacts with PagARGOS. Overexpression of PagARGOS up‐regulated WAT1, activating a downstream auxin response promoting cambial cell division and xylem differentiation for wood formation. Moreover, overexpressing PagARGOS caused not only higher wood yield but also lower lignin content compared with wild‐type controls. PagARGOS is therefore a potential candidate gene for engineering fast‐growing and low‐lignin trees with improved biomass production. [ABSTRACT FROM AUTHOR]

Background This study examined the expression of exchange protein directly activated by c AMP1 ( Epac1), PDE4, and PKC in esophageal cancer tissues, and analyzed the association of each protein with the pathological parameters of the samples. Methods Epac1, PDE4, and PKC protein expression was evaluated by PV-9000 two-step immunohistochemical techniques in 51 esophageal cancer specimens and 10 para-carcinoma tissues. Results The positive expression rates of Epac1 and PKC in esophageal cancer tissues (62.7% and 68.6%, respectively) were higher compared to those in para-carcinoma tissues (20% and 20%, respectively) ( P < 0.05). The positive expression rate of PDE4 in esophageal cancer tissues (54.1%) was higher than in para-carcinoma tissues (30%), ( P > 0.05). Epac1, PDE4, and PKC protein expression levels were not associated with the extent of tumor differentiation and/or lymph node metastasis ( P > 0.05). Epac1 protein expression levels correlated with PDE4, PKC, and AKAP95 protein expression levels. In addition, there was a correlation between PKC and Cx43 protein levels ( P < 0.05). Conclusion The expression rates of Epac1, PDE4, and PKC protein in esophageal cancer tissues were significantly higher compared to the rates in para-carcinoma tissues, suggesting an association between these proteins and the development and progression of esophageal cancer. The correlations between these proteins also revealed that they may exert a synergistic effect during the development of esophageal cancer. [ABSTRACT FROM AUTHOR]