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We investigate the ground-state phases and phase transitions of extended Bose–Hubbard ladder by using the dynamical cluster-Gutzwiller mean-field(CGMF) approach. Unlike the single-site Gutzwiller mean-field (SGMF) theory, the intracluster hopping and NN interaction terms are undecoupled, while the intercluster hopping and NN interaction terms are decoupled in the CGMF method. Therefore, the system generates the novel quantum phases and quantum phase transitions. In addition to the conventional superfluid (SF) and Mott insulator (MI) phases, we also find the loophole insulator (LI) phase, three kinds of the charge density wave (CDW) phases, i.e., the integer-CDW, half-integer-CDW and CDW-II phases, and two kinds of the supersolid (SS) phases, i.e., the SS-I and SS-II phases. The density distributions of the ground-state phases are also discussed. The Z 2 reflection of two chains is broken by the intracluster NN interaction, the density distributions of the L -chain and R -chain of the CDW-II and SS-II phases show the characteristic of interleaving each other. [ABSTRACT FROM AUTHOR]

The present study aimed to evaluate the potential of the monocyte to red blood cell count ratio (MRR), the neutrophil to red blood cell count ratio (NRR), the lymphocyte to red blood cell count ratio (LRR) and the product of lymphocyte count and albumin concentration (LA) for the diagnosis of lung cancer. The cases of 216 patients with newly diagnosed lung cancer and 184 healthy volunteers were retrospectively analysed. The MRR and NRR were found to be higher in patients with lung cancer compared with those in healthy controls, while the LRR and LA were lower. The receiver operating characteristic curve analysis revealed that of the four markers, the MRR and LA yielded a higher area under the curve (AUC) (MRR: AUC, 0.810; 95% CI, 0.768-0.847; and LA: AUC, 0.721; 95% CI, 0.674-0.764). The combination of MRR, LA, carcinoembryonic antigen (CEA) and cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) achieved the highest diagnostic value when compared with other single or combined markers (AUC, 0.882; 95% CI, 0.846-0.912; sensitivity, 81.9%; specificity, 81.0%). As the disease progressed, the MRR tended to increase, while LA exhibited a decreasing trend. Binary logistic regression analysis revealed an increase in the MRR, as well as in CEA and CYFRA21-1 concentrations, and a decrease in the LA, which could all be possible risk factors for lung cancer. Differences in the MRR and LA between patients with early stage (IA-IIIA) lung cancer and healthy controls were observed. Further analysis revealed that the MRR also exhibited the potential to detect early stage (IA-IIIA) lung cancer in the model. The present findings demonstrated that the MRR and LA may be used as auxiliary biomarkers for the diagnosis of lung cancer and could partly indicate disease progression. [ABSTRACT FROM AUTHOR]

Abstract: We propose a robust scheme to prepare entangled states among two 87Rb Bose–Einstein Condensates (BECs) via a stimulated Raman adiabatic passage (STIRAP) technique. The atomic spontaneous radiation, the cavity decay, and the fiber loss are efficiently suppressed by engineering an adiabatic passage. The simulation also shows that we can generate this entanglement state with high fidelity. [Copyright &y& Elsevier]

Osteoporosis is a complex disease that affects >10 million people in the United States and results in 1.5 million fractures annually. In addition, the high prevalence of osteopenia (low bone mass) in the general population places a large number of people at risk for developing the disease. In an effort to identify genetic factors influencing bone density, we characterized a family that includes individuals who possess exceptionally dense bones but are otherwise phenotypically normal. This high-bone-mass trait (HBM) was originally localized by linkage analysis to chromosome 11q12-13. We refined the interval by extending the pedigree and genotyping additional markers. A systematic search for mutations that segregated with the HBM phenotype uncovered an amino acid change, in a predicted β-propeller module of the low-density lipoprotein receptor-related protein 5 (LRP5), that results in the HBM phenotype. During analysis of >1,000 individuals, this mutation was observed only in affected individuals from the HBM kindred. By use of in situ hybridization to rat tibia, expression of LRP5 was detected in areas of bone involved in remodeling. Our findings suggest that the HBM mutation confers a unique osteogenic activity in bone remodeling, and this understanding may facilitate the development of novel therapies for the treatment of osteoporosis. [ABSTRACT FROM AUTHOR]

Withanolides are a group of naturally occurring C 28 steroids based on an ergostane skeleton. They have a high degree of polyoxygenation, and the abundance of O -functional groups has enabled various natural alterations to both the carbocyclic skeleton and the side chain. Consequently, these molecules have intricate structural features that lead to their highly varied display of biological activities including anticancer, anti-inflammatory, and immunomodulating properties. Despite being intriguing leads for further discovery research, synthetic access to the withanolides remains highly challenging-compounds for current biological research are mainly isolated from plants, often inefficiently. Here, we report the divergent synthesis of 11 withanolides in 12 to 20 steps, enabled by a gram-scale route and a series of late-stage functionalizations, most notably a bioinspired photooxygenation-allylic hydroperoxide rearrangement sequence. This approach enables further biological research disconnected from a reliance on minute quantities of the parent natural products or their simple derivatives.

Einstein-Podolsky-Rosen (EPR) steering is commonly shared among multiple observers by utilizing unsharp measurements. Nevertheless, their usage is restricted to local measurements and does not encompass all nonlocal measurement-based cases. In this work, a method for finding beneficial local measurement settings has been expanded to include nonlocal measurement cases. This method is applicable for any bipartite state and offers benefits even in scenarios with a high number of measurement settings. Using the Greenberger-Horne-Zeilinger state as an illustration, we show that employing unsharp nonlocal measurements can activate the phenomenon of steering sharing in contrast to using local measurements. Furthermore, our findings demonstrate that nonlocal measurements with unequal strength possess a greater activation capability compared to those with equal strength. Our activation method generates fresh concepts for conservation and recycling quantum resources., (© 2024. The Author(s).)

An increased interest to expand three-dimensional chemical space for the design of new materials and medicines has created a demand for isosteric replacement groups of commonly used molecular functionality. The structural and chemical properties of chiral S(VI) functional groups provide unique spatial and electronic features compared with their achiral sulfur- and carbon-based counterparts. Manipulation of the S(VI) centre to introduce structural variation with stereochemical control has remained a synthetic challenge. The stability of sulfonimidoyl fluorides and the efficiency of sulfur fluorine exchange chemistry has enabled the development of the enantiopure bifunctional S(VI) transfer reagent t-BuSF to overcome current synthetic limitations. Here, we disclose a reagent platform that serves as a chiral sulfur fluorine exchange template for the rapid asymmetric synthesis of over 70 sulfoximines, sulfonimidoyl fluorides and sulfonimidamides with excellent enantiomeric excess and good overall yields. Furthermore, the practical utility of the bifunctional S(VI) transfer reagent was demonstrated in the syntheses of enantiopure pharmaceutical intermediates and analogues., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The 1,2,3-triazole coordinated ruthenium carbene complexes (TA-Ru) were reported for the first time as a new class of modified Grubbs catalyst to achieve challenging olefin metathesis at higher temperatures without catalyst decomposition. Previously reported N-tethered Ru-carbene complexes all suffered from rapid cis/trans isomerization, causing significantly reduced catalyst reactivity. These new TA-Ru complexes hold the active trans -dichloro conformation even at 80 °C, allowing effective olefin metathesis for challenging substrates. With this new TA-Ru catalyst, cross-metathesis (CM), ring-closing metathesis (RCM) and dynamic covalent chemistry (DCvC) were achieved. Excitingly, the reactivity of TA-Ru prevails all previously reported N-coordinated Ru-carbene precatalysts, Grubbs II, and Hoveyda-Grubbs, making the TA-Ru a transformative catalytic system in olefin catalysis., Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests.

Objective: This study aims at assessing the potential benefits of observation of monocyte-to-albumin ratio (MAR) and neutrophil percentage-to-hemoglobin ratio (NPHR) in the detection of non-small cell lung cancer (NSCLC)., Methods: This study retrospectively involved 195 NSCLC patients and 204 healthy volunteers. The correlations between the clinicopathological characteristics of NSCLC and the two ratios including MAR and NPHR were assessed. The diagnostic efficiency of NSCLC patients by MAR and NPHR, alone or in combination with carcinoembryonic antigen (CEA), was assessed by receiver operating characteristic (ROC) curve. The risk factors for NSCLC were analyzed with binary logistic regression., Results: Compared to healthy controls, the levels of MAR and NPHR in NSCLC patients were elevated. MAR and NPHR were related to clinicopathologic characteristics and increased significantly along with the progression of NSCLC. The area under the curve (AUC) for 95% confidence interval (95% CI) of MAR and NPHR in the diagnosis of NSCLC was 0.812 (0.769-0.854) and 0.724 (0.675-0.774), respectively. The combination of MAR, NPHR, and CEA achieved the highest diagnostic utility compared to each individually or combined markers (AUC, 0.86; 95% CI, 0.824-0.896; sensitivity, 72.8%; specificity, 87.3%). Further analysis showed that MAR combined with NPHR presented the potential to detect early-stage (IA-IIB) NSCLC (AUC, 0.794; 95% CI, 0.743-0.845; sensitivity, 55.1%; specificity, 87.7%). The result indicated that MAR and NPHR might be risk factors for NSCLC., Conclusion: MAR and NPHR could be novel and effective auxiliary indexes in the detection of NSCLC, especially when combined with CEA., Competing Interests: The authors did not report any exist potential conflict of interest associate with this study., (© 2023 Zhao et al.)

SNAIL is a key transcriptional regulator in embryonic development and cancer. Its effects in physiology and disease are believed to be linked to its role as a master regulator of epithelial-to-mesenchymal transition (EMT). Here, we report EMT-independent oncogenic SNAIL functions in cancer. Using genetic models, we systematically interrogated SNAIL effects in various oncogenic backgrounds and tissue types. SNAIL-related phenotypes displayed remarkable tissue- and genetic context-dependencies, ranging from protective effects as observed in KRAS- or WNT-driven intestinal cancers, to dramatic acceleration of tumorigenesis, as shown in KRAS-induced pancreatic cancer. Unexpectedly, SNAIL-driven oncogenesis was not associated with E-cadherin downregulation or induction of an overt EMT program. Instead, we show that SNAIL induces bypass of senescence and cell cycle progression through p16 INK4A -independent inactivation of the Retinoblastoma (RB)-restriction checkpoint. Collectively, our work identifies non-canonical EMT-independent functions of SNAIL and unravel its complex context-dependent role in cancer., (© 2023. The Author(s).)

Synthetic lethality is a genetic interaction that results in cell death when two genetic deficiencies co-occur but not when either deficiency occurs alone, which can be co-opted for cancer therapeutics. Pairs of paralog genes are among the most straightforward potential synthetic-lethal interactions by virtue of their redundant functions. Here, we demonstrate a paralog-based synthetic lethality by targeting vaccinia-related kinase 1 (VRK1) in glioblastoma (GBM) deficient of VRK2, which is silenced by promoter methylation in approximately two thirds of GBM. Genetic knockdown of VRK1 in VRK2-null or VRK2-methylated cells resulted in decreased activity of the downstream substrate barrier to autointegration factor (BAF), a regulator of post-mitotic nuclear envelope formation. Reduced BAF activity following VRK1 knockdown caused nuclear lobulation, blebbing, and micronucleation, which subsequently resulted in G2-M arrest and DNA damage. The VRK1-VRK2 synthetic-lethal interaction was dependent on VRK1 kinase activity and was rescued by ectopic expression of VRK2. In VRK2-methylated GBM cell line-derived xenograft and patient-derived xenograft models, knockdown of VRK1 led to robust tumor growth inhibition. These results indicate that inhibiting VRK1 kinase activity could be a viable therapeutic strategy in VRK2-methylated GBM., Significance: A paralog synthetic-lethal interaction between VRK1 and VRK2 sensitizes VRK2-methylated glioblastoma to perturbation of VRK1 kinase activity, supporting VRK1 as a drug discovery target in this disease., (©2022 The Authors; Published by the American Association for Cancer Research.)

Six new halogenated butenolides, tongalides A-C ( 1 - 3 ) and their acetylated congeners ( 4 - 6 ), were isolated from an extract of the Antarctic rhodophyte Delisea sp. that displayed significant antibiotic activity. The structures of the compounds were determined by analysis of data acquired by spectroscopic and spectrometric techniques including NMR, HRESIMS, optical rotation, and X-ray diffraction studies. The newly isolated compounds were assayed for antibacterial activity, but exhibited no growth inhibition of ESKAPE pathogens. The extract bioactivity was attributed to the previously reported Z -acetoxyfimbrolide A also isolated from the extract, providing further evidence that the exocyclic double bond is essential to the antibacterial activity of the structurally related fimbrolide class of metabolite.

Mind wandering has been argued to be beneficial for breaking through mental impasses, which leads to better creative performance upon a second attempt (i.e., the incubation effect). However, the evidence is inconsistent. Different from the propensity for mind wandering that has been the focus of past studies, in this study we further examined the role of diversity (i.e., non-repetitiveness of mind wandering respective to its content) and types of mind wandering along the dimensions of intentionality and awareness during incubation when engaging in a 0-back task (a mind wandering-prone condition) and a focused-breathing practice (a mindfulness-induced condition). We proposed that diversity rather than the propensity for mind wandering was crucial for post-incubation divergent creativity and that mindfulness induction would be a more effective way to elicit the incubation effect because it should result in fewer but more diverse mind-wandering incidents than engaging in a mind wandering-prone task. We conducted an experiment with a between-participant variable (incubation tasks: mind wandering-prone, mindfulness-induced, and no incubation). As predicted, the mindfulness-induced group (N = 30) outperformed the control group (N = 31) on flexibility for the unusual uses task measuring divergent thinking after incubation, but the mind wandering-prone group (N = 29) did not outperform the control group. In addition, the diversity of mind wandering and the tendency toward intentional mind wandering predicted the magnitude of incubation effects on flexibility and originality, respectively. Theoretical and practical implications are discussed., Competing Interests: The authors have declared that no competing interests exist.

A new class of stable four-coordinated benzotriazole-borane compounds was developed via gold-catalyzed alkyne hydroboration. The application of polymeric (BH 2 CN) n reagent gave the formation of cyano-amine-boranes (CAB) complexes with less basic N-heterocyclic amines and anilines. Various new CABs were investigated in catalytic hydroboration to synthesize N-B cycles. The 1,2,3-benzotriazoles were identified as the only feasible N-source, giving the four coordinated borane N-B cycles (BTAB) in excellent yields (up to 90%) with good functional group tolerability. This new class of polycyclic N-B compounds showed excellent stability toward acid, base, high temperature, and photo-irradiation. The facile synthesis, excellent stability, strong and tunable fluorescence emission make BTAB interesting new fluorescent probes for future chemical and biological applications., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Extending the structural hierarchy and complexity through small-molecular self-assembly is a powerful way to obtain large discrete, functional molecular architecture. A hydrogen-bonded supramolecular organic framework (H S OF) with nanometer-size pores is constructed in a solid state with simple guanosine-monomer self-assembly. To extend the hierarchy of the G-quartet self-assembly to a higher order thanthatofthetraditionalG-quadruplex,H-bondacceptorsontheC-8 position of guanosine are introduced to establish inter-quadruplex linkage via H bonding to N(2)-H B from the neighboring G-quartet. After screening different C-8 substitution groups and various synthesis conditions, H S OF-G1a' is obtained by solvent evaporation under diluted condition. Single-crystal X-ray structure reveals that cubic repeating units formed by G 8 are the supermolecule secondary building block (SBU) with large pores (d=34A). To our knowledge, this is the first G-quartet self-assembly with an organized structure beyond cylindrical G-quadruplexes., Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests.

Various robust, crystalline, and porous organic frameworks based on in situ-formed imine-linked oligomers were investigated. These oligomers self-assembled through collaborative intermolecular hydrogen bonding interactions via liquid-liquid interfacial reactions. The soluble oligomers were kinetic products with multiple unreacted aldehyde groups that acted as hydrogen bond donors and acceptors and directed the assembly of the resulting oligomers into 3D frameworks. The sequential formation of robust covalent linkages and highly reversible hydrogen bonds enforced long-range symmetry and facilitated the production of large single crystals, with structures that were unambiguously determined by single-crystal X-ray diffraction. The unique hierarchical arrangements increased the steric hindrance of the imine bond, which prevented attacks from water molecules, greatly improving the stability. The multiple binding sites in the frameworks enabled rapid sequestration of micropollutant in water., (© 2021 Wiley-VCH GmbH.)

Systematic investigations were performed with various substituted groups at C8 purine and ribose. A series of isoG analogs, C8-phenyl substituted isoG were synthesized and applied for Cs + coordination. The structural proximity between purine and ribose limited pentaplex formation for C8-phenyl substituted isoG derivatives. Based on this observation, deoxy isoG derivative with modification on ribose ( tert -butyldimethylsilyl ether) was applied to assemble with the Cs + cation. Critical solvent (CDCl 3 and CD 3 CN) and anion (BPh 4 - , BARF - , and PF 6 - ) effects were revealed, leading to the controllable formation of various stable isoG pentaplexes, including singly charged decamer, doubly charged decamer, and 15-mer, etc. Finally, the X-ray crystal structure of [isoG 20 Cs 3 ] 3+ (BARF - ) 3 was successfully obtained, which is the first example of multiple-layer deoxy isoG binding with the Cs + cation, providing solid evidence of this new isoG ionophore beyond two-layer sandwich self-assembly., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Here we report the first example of alkyne trifunctionalization through simultaneous construction of C-C, C-O, and C-N bonds via gold catalysis. With the assistance of a γ-keto directing group, sequential gold-catalyzed alkyne hydration, vinyl-gold nucleophilic addition, and gold(III) reductive elimination were achieved in one pot. Diazonium salts were identified as both electrophiles (N source) and oxidants (C source). Vinyl-gold(III) intermediates were revealed as effective nucleophiles toward diazonium, facilitating nucleophilic addition and reductive elimination with high efficiency. The rather comprehensive reaction sequence was achieved with excellent yields (up to 95%) and broad scope (>50 examples) under mild conditions (room temperature or 40 °C).

Purpose: To investigate the antitumor efficacy of pingyangmycin (PYM) in combination with anti-PD-1 antibody and determine the capability of PYM to induce immunogenic cell death (ICD) in cancer cells., Methods: The murine 4T1 breast cancer and B16 melanoma models were used for evaluation of therapeutic efficacy of the combination of PYM with anti-PD-1 antibody. The ELISA kits were used to quantify the ICD related ATP and HMGB1 levels. The Transwell assay was conducted to determine the chemotaxis ability of THP-1 cell in vitro. The flow cytometry was used to measure reactive oxygen species level and analyze the ratio of immune cell subsets., Results: PYM induced ICD in murine 4T1 breast cancer and B16 melanoma cells and increased the release of nucleic acid fragments that may further promote the monocytic chemotaxis. In the 4T1 murine breast cancer model, PYM alone, anti-PD-1 antibody alone, and their combination suppressed tumor growth by 66.3%, 16.1% and 77.6%, respectively. PYM markedly enhanced the therapeutic efficacy of anti-PD-1 antibody against 4T1 breast cancer. The calculated CDI (coefficient of drug interaction) indicated synergistic effect. Evaluated by graphic analysis, the nucleated cells intensity in the femur bone marrow remained unchanged. Histopathological observations revealed no noticeable toxico-pathological changes in the lung and various organs, indicating that the PYM and anti-PD-1 antibody combination exerted enhanced efficacy at well-tolerated dosage level. By the combination treatment, a panel of immunological changes emerged. The ratio of CD3 + cells, NK cells and NKT cells increased and Tregs decreased in peripheral blood. The DCs increased in the spleen. Prominent changes occurred in tumor infiltrating lymphocytes. The ratio of CD8 + cells increased, while that of CD4 + cells decreased; however, the ratio of CD3 + cells remained unchanged, implying that certain immunological responses emerged in the tumor microenvironment. PYM alone could also increase CD8 + cells and reduce CD4 + cells in tumor infiltrating lymphocytes., Conclusions: The studies indicate that PYM, as an ICD inducer with mild myelosuppression effect, may enhance the therapeutic efficacy of anti-PD-1 antibody in association with tumor infiltrating CD8 + T cell augmentation.

Porous materials with open metal sites have been investigated to separate various gas mixtures. However, open metal sites show the limitation in the separation of some challenging gas mixtures, such as C 2 H 2 /CO 2 . Herein, we propose a new type of ultra-strong C 2 H 2 nano-trap based on multiple binding interactions to efficiently capture C 2 H 2 molecules and separate C 2 H 2 /CO 2 mixture. The ultra-strong acetylene nano-trap shows a benchmark Q st of 79.1 kJ mol -1 for C 2 H 2 , a record high pure C 2 H 2 uptake of 2.54 mmol g -1 at 1×10 -2  bar, and the highest C 2 H 2 /CO 2 selectivity (53.6), making it as a new benchmark material for the capture of C 2 H 2 and the separation of C 2 H 2 /CO 2 . The locations of C 2 H 2 molecules within the MOF-based nanotrap have been visualized by the in situ single-crystal X-ray diffraction studies, which also identify the multiple binding sites accountable for the strong interactions with C 2 H 2 ., (© 2021 Wiley-VCH GmbH.)

An electrochemical approach in promoting directed C-H alkynylation with terminal alkyne via iridium catalysis is reported. This work employed anodic oxidation of Ir(III) intermediate (characterized by X-ray crystallography) to promote reductive elimination, giving the desired coupling products in good yields (up to 95%) without the addition of any other external oxidants. This transformation is suitable for various directing groups with H 2 as the only by-product, which warrants a high atom economy and practical oxidative C-C bond formation under mild conditions., Competing Interests: The authors claim no competing financial interest.

A synergistic gold/iron catalytic system was developed for sequential alkyne hydration and vinyl gold addition to aldehydes or ketones. Fe(acac) 3 was identified as an essential co-catalyst in preventing vinyl gold protodeauration and facilitating nucleophilic additions. Effective C-C bond formation was achieved under mild conditions (r.t.) with excellent regioselectivity and high efficiency (1% [Au], up to 95% yields). Extending reaction scope to intramolecular fashion achieved successful macrocyclization (16-31 ring sizes) with excellent yields (up to 90%, gram-scale) without extended dilution (0.2 M), which highlighted the great potential of this new crossed-aldol strategy in challenging target molecule synthesis., Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests.

Silver nanowires with high yield, uniform size and high aspect ratio were successfully synthesized by a simple and effective polyol method under low temperature and quiescent conditions, adopting CuCl2·2H2O as the nucleation control agent for the first time. The synthesized silver nanowires were characterized by X-ray powder diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and UV-Vis diffuse reflectance spectroscopy (DRS). The results indicate that the silver nanowires were composed of face-centered cubic structure of pure metallic silver with high crystallinity. And the silver nanowires have an average length of 80~100 μm and an average diameter of 40~80 nm. Thus, the aspect ratio of the nanowires was greater than 1000. In addition, the influence on the morphology and structure of the silver nanowires were investigated for reaction temperature, mole ratio of PVP:AgNO3, molecular weight of PVP and mole ratio of control agent CuCl2 · 2H2O:AgNO3. Finally, the optimum reaction condition were obtained for the preparation of the silver nanowires with high aspect ratio.

The present study examines how a person's working memory capacity (WMC) and awareness of change in context influences modulating inhibitory control. Context was manipulated by changing the predictive validity of a prime to a following target (i.e., the proportion of prime repetition) across three phases in a single-prime negative priming task. The prime was a distractor for the following target when the proportion was 25% (in the first and third phases) and a useful cue when the proportion rose to 75% (in the second phase). Participants' WMCs were measured and whether they were aware of the change of the prime-repetition proportion was determined in interviews at the end of the experiment. We found that when the stimulus-onset asynchrony (SOA) was short (Experiment 1), participants aware of the change of prime-repetition proportion showed a null negative priming effect when the contingency increased from 25% to 75%, and then rebooted the effect when it decreased back to 25%, thus indicating an ability to modulate inhibitory control as context varied. In contrast, the unaware participants kept inhibiting primes all the time. When SOA was long (Experiment 2), participants with awareness even showed a positive priming effect when the prime-repetition proportion increased. Surprisingly, participants' WMCs did not matter except for the conscious strategy used in the long-SOA condition. This is the first study simultaneously investigating how WMC and awareness can affect people's ability to modulate inhibitory control and reveals that awareness plays a more direct role in such modulation than does WMC., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Overexpression of EGFR and MMP-2 plays an essential role in the initiation and progression of non-small-cell lung carcinoma (NSCLC). In this study, a novel format of EGFR/MMP-2 bi-targeted fusion protein Ec-LDP-TIMP2 and its enediyne-integrated analogue Ec-LDP(AE)-TIMP2 have been prepared by genetic engineering and molecular reconstitution. The Ec-LDP(AE)-TIMP2 comprises endogenous inhibitor of matrix metalloproteinase 2 (TIMP2), EGF-derived oligopeptide (Ec), lidamycin apoprotein (LDP), and the extremely potent cytotoxic enediyne (AE). By tissue microarray, Ec-LDP-TIMP2 showed high binding intensity and selectivity to human NSCLC specimens as compared with the matched non-cancerous tissues. By in vivo imaging, Ec-LDP-TIMP2 displayed prominent tumor-specific distribution in human NSCLC H460 xenograft. Particularly, Ec-LDP(AE)-TIMP2 inhibited tumor growth of H460 xenograft in athymic mice more striking. At doses of 0.2 and 0.4mg/kg, Ec-LDP(AE)-TIMP2 suppressed tumor growth by 74% and 89%, respectively. No histopathological changes were found in various organs of treated animals, suggesting that the effective dosage was tolerated. In summary, the ligand-based and enediyne-integrated fusion protein displaying extremely potent cytotoxicity might be highly effective for NSCLC therapy and useful as a carrier for drug delivery., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: To investigate the possible contribution of GDNF in matrix-degrading, cell-adhesion during perineural invasion (PNI) of salivary adenoid cystic carcinoma (ACC)., Methods: Totally 42 ACCs and 5 normal salivary tissues were included in the present study．Immunohistochemical staining SP method was used to detect the expression of GDNF,MMP-9,NF-κB,integrin β1 in ACC specimens and normal salivary tissues. Statistical analysis was performed using SPSS16.0 software package. RESULTS：GDNF was strongly expressed in ACC tumor cells and nerve fibers adjacent to ACC tumor cells. NF-κB, MMP-9, integrin β1 were positively expressed in ACC cell cytoplasm, integrin β1 was also found in ACC cell membrane, and NF-κB in nuclei occasionally. The positive expression rate was 69.05%（29/42）,66.67%（28/42）,61.90%（26/42）, respectively. The differences between the expression of NF-κB, MMP-9, integrinβ1 in PNI group and non-PNI group were significant (P=0.005,P=0.011,P=0.001, respectively). Expression of NF-κB, MMP-9, integrin β1 was correlated to that of GDNF(r=0.443, P=0.003; r=0.401, P=0.009; r=0.535, P=0.000, respectively). Expression of MMP-9 and integrin β1 was positively correlated to that of NF-κB(r=0.501, P=0.001; r=0.429, P=0.005). Expression of MMP-9 was correlated positively to that of integrin β1 (r=0.381, P=0.013). CONCLUSIONS：GDNF may increase the matrix-degrading and cell-adhesion of ACC in the process of PNI. NF-κB, MMP-9 and integrin β1 involve in ACC cells invading nerves.

Objective: To investigate the effect on adhesion and motion capbilities of adenoid cystic carcinoma (ACC), by detecting the expression of nerve growth factor (NGF), E-cadherin (E-cad) and S100A4 and the clinical significance in ACC tissues and analyzing the relationships between them with perineural invasion (PNI)., Methods: The expression of NGF, E-cad and S100A4 in ACC was detected with the way of immunohistochemistry SP, and then analyzing the expression level of them in different pathological types and histological regions in statistical ways on the basis of their relation with clinical and pathological parameters., Results: The expression of NGF and S100A4 in PNI group [88% (23/26) and 77% (20/26)], was higher than that in NPNI group (8/16 and 7/16, P < 0.05), and a positive correlation between them was identified in PNI group (r = 0.316, P < 0.05). However the E-cad expression was lower in PNI group [31% (8/26), P < 0.05]. On the other hand it suggested a negative correlation with NGF (r = 0.385, P < 0.05) as well as that with S100A4 (r = -0.612, P = 0.000). The expression level of NGF in fasciculus [83% (25/30)] has significant deviation compared with it in distant tumor tissues [47% (14/30), P < 0.05]., Conclusions: In the PNI process of ACC, NGF plays important parts but not the only factor. It can increase the expression and activity of S100A4 but decrease E-cad expression through binding with its receptor. Thus, adhesion abilities of tumor cells was weakened and motional abilities was strengthen.

Alpha-synuclein (alpha-SYN) is one of the major components of intracellular fibrillary aggregates in the brains of a subset of neurodegenerative disorders. Although alpha-SYN expression has been found in developing mouse brain, a detailed distribution during mouse-embryonic development has not been made. Here we describe the expression pattern of alpha-SYN during the development of mice from E9.5 to P0 by immunohistochemistry (IHC). As a result, alpha-SYN was detected as early as E9.5. During the embryonic stages, alpha-SYN was dynamically expressed in several regions of the brain. In the neocortex, expression was detected in the marginal zone (MZ) in the early stages and was later condensed in the MZ and in the subplate (SP); in the cerebellum, expression was initially detected in the deep cerebellar nuclei (DCN) and was later condensed in the Purkinje cells. These spatio-temporal expression patterns matched the neuronal migratory pathways and the formation of the synapse connections. Additionally, alpha-SYN was detected in the sensory systems, including the nasal mucosa, the optic cup, the sensory ganglia, and their dominating nerve fibers. Furthermore, the nuclear location of alpha-SYN protein was found in developing neurons in the early stages, and later it was mostly found in the non-nuclear compartments. This finding was further confirmed by Western blot analysis. These results suggest that alpha-SYN may be involved not only in the migration of neurons and in the synaptogenesis of the central nervous system (CNS) but also in the establishment of the sensory systems. The nuclear location of alpha-SYN may hint at an important function in these events.

The tumor suppressor phosphatase and tensin homologue (PTEN) is a protein and lipid phosphatase. PTEN mutations have been associated with a large number of human cancers. To understand the physiological role of PTEN in the brain and its relationship to Akt in ischemic injury, we first investigated the localization of PTEN immunoreactivity in the brains of normal adult rats using immunohistochemistry. We then detected the modulation of PTEN and p-Akt following transient global ischemia by Western blot and immunohistochemistry analyses. Our observation of normal brains showed that PTEN was heterogeneously distributed in the cytoplasm, nuclei, and processes in different regions. It was shown immunohistochemically that PTEN was distributed differentially in rat brain, with the highest levels in the anterior olfactory nucleus, cerebral cortex, amygdaloid nucleus, hippocampus, Purkinje's cells, and several nuclei in the basal ganglia, thalamus, midbrain, and pons. After global cerebral ischemia, PTEN and p-Akt immunoreactivities were increased in the cerebral cortex. This was accompanied by the nuclear translocation of p-Akt. Double-labeling experiments revealed that PTEN and p-Akt were most likely localized to neurons. These results suggest a role for PTEN in normal adult brain and that the PTEN/Akt pathway may be involved in neuronal survival or plasticity after ischemic injury.

Homeobox protein engrailed-2 (EN-2), is a subtype of the homeoprotein transcription factors of EN family. It can be transported between cells in culture by unconventional secretion and internalization mechanisms. When internalized, it can activate the transcription or translation. EN-2 had been considered to be an important transcriptional factor during the embryonic development , it involved in the regulation of anteroposterior polarity. In recent years, much more functions of EN-2 are revealed. It controls synaptic choice as well as axon projections; and there are some relationships between EN-2 and Parkinson's disease. Furthermore, EN-2 is thought to be a candidate oncogene in human breast cancer and a candidate gene of Autism Spectrum Disorder. The structure, distribution, function and regulation of EN-2 as well as the relationships between EN-2 and some diseases are reviewed in the present article.

Objective: To evaluate the effect of gilding technique on the release of element from copper-based alloy post-core exposed to artificial saliva., Methods: The quantities of nickel ion and copper ion released from common copper-based alloy post-core (control group), blasting gilding copper-based alloy post-core (blasting group) and burnishing gilding Copper-based alloy post-core (burnishing group) in artificial saliva after 1 month,3 months,6 months and 8 months of exposure were measured with atomic absorption spectrophotometer. The tooth tissues were stripped off at the eighth month and the oxygenization on the surface of the posts were observed., Results: There was a significant difference of element release of nickel between the gilding groups and the control group at the sixth and eighth month. There was a significant difference of element release of copper between the gilding groups and the control group at the third, sixth and eighth month. The quantities of element released from the gilding groups were fewer than those from the control groups. The release of nickel and copper ions increased with the length of exposure significantly after three month of exposure. The element release from the control groups increased more rapidly than the gilding groups. The surface of the post-core in the control groups were all oxygenized while those in the gilding groups had been oxygenized only near the margins of the cores and the upper 1/3 part of the post with uncontinuous and relatively thin layers., Conclusion: Gilding surface treatment can decrease the release of nickel and copper ions from copper based-alloy post-core and the surface oxygenization, which will improve the biocompatibility of the core.

Objective: To assess the effect of the thickness of periodontal ligament on the fracture resistance of root and post-core system., Methods: Forty-five simulated roots in the same length, taper and diameter were made of polymethacrylate (PMMA). Then the wax patterns of post-cores were cast. Soft lining material was used to simulated periodontal ligament. And each specimen was embedded in acrylic resin and then fixed in a special jig on the universal load-testing machine. A compressive load was applied at a 90-degree angle to the long axis of the core until fracture, at a crosshead speed of 1 mm/min. The maximum of load and the displacement were recorded., Results: The mean values of load in root and post-core system were 148.033 N, 161.889 N, 168.667 N, 181.589 N, 194.622 N, and the mean values of displacement were 1.965 mm, 2.837 mm, 3.327 mm, 3.927 mm, 5.326 mm., Conclusion: The fracture resistance and displacement of root and post-core system with the same quality and altitude periodontal ligament are associated with the thickness of periodontal ligament when the range of thickness is from 0.2 mm to 1.0 mm.