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Objective: Try to create a dose gradient function (DGF) and test its effectiveness in reducing radiation induced lung injury in breast cancer radiotherapy., Materials and Methods: Radiotherapy plans of 30 patients after breast-conserving surgery were included in the study. The dose gradient function was defined as DGH=VDVp3, then the area under the DGF curve of each plan was calculated in rectangular coordinate system, and the minimum area was used as the trigger factor, and other plans were triggered to optimize for area reduction. The dosimetric parameters of target area and organs at risk in 30 cases before and after re-optimization were compared., Results: On the premise of ensuring that the target dose met the clinical requirements, the trigger factor obtained based on DGF could further reduce the V5, V10, V20, V30 and mean lung dose (MLD) of the ipsilateral lung in breast cancer radiotherapy, P < 0.01. And the D2cc and mean heart dose (MHD) of the heart were also reduced, P < 0.01. Besides, the NTCPs of the ipsilateral lung and the heart were also reduced, P < 0.01., Conclusion: The trigger factor obtained based on DGF is efficient in reducing radiation induced lung injury in breast cancer radiotherapy.

This study aims to develop a trigger operator based on the Overlap Volume Histogram (OVH) and examined its effectiveness in enhancing plan quality to minimize radiation-induced lung injury in postoperative radiotherapy for breast cancer. This trigger operator was applied for plan re-optimization to the previous Volumetric Modulated Arc Therapy (VMAT) plans of 16 left breast conserving surgery cases. These cases were categorized into a Contiguous Group (CG) and a Separated Group (SG) based on the relative position between the target and the Left-Lung (L-Lung). We investigated the changes in Vx, mean dose, and Normal Tissue Complication Probability (NTCP) values of organs-at-risk (OARs) before and after using the trigger operator. The Pairwise Sample T test was employed to evaluate the differences in indices between the two groups before and after optimizations. The trigger operator effectively initiated plan re-optimization. The values of V5, V10, V20, V30, and V40 of the L-Lung, as well as the mean dose of the heart, all decreased after re-optimization. The Pairwise Sample T test results showed statistically significant differences in the V20, V30, and V40 of the L-Lung in the CG (P < 0.01), and in the V5, V10, V20, V30, and V40 of the L-Lung in the SG (P < 0.01). Our findings suggest that the proposed trigger operator can improve plan quality, thereby reducing radiation-induced lung injury in postoperative radiotherapy for breast cancer., (© 2023. The Author(s).)

The employee organizational citizenship behavior for the environment (OCBE) contributes to the improvement of the organization's environment, its study is increasing in number. However, the psychological mechanism of promoting employee OCBE is still a missing link. Drawing on the theory of social information processing, this study seeks to establish the impact of green transformational leadership on employee OCBE and the mediating role of green organizational climate in this nexus. In addition, we have integrated environmental concerns to better explain the impact of this differentiation. The results show that: green transformational leadership has a significant positive impact on employee OCBE, and green organizational climate has a mediating effect on the impact of green transformational leadership on employee OCBE. Furthermore, environmental concern not only has a positive moderating effect on the influence of green transformational leadership on green organizational climate, but also positively moderates the impact of the influence of green transformational leadership on employee OCBE. This paper reveals the internal psychological mechanism of improving employee OCBE and provides ideas for promoting the sustainable development of enterprises., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu and Yu.)

Based on the career construction model of adaptation, this study explores the impact of core self-evaluations on career adaptability, with the mediating role of protean career attitudes and moderating role of meritocratic beliefs. The results of the questionnaire survey on 1000 Chinese college students show that: (1) core self-evaluations positively predicted college students' career adaptability; (2) protean career attitudes mediated the relationship between core self-evaluations and career adaptability; (3) meritocratic beliefs not only moderated the effect protean career attitudes have on career adaptability but also moderated the indirect influence of core self-evaluations on career adaptability through protean career attitudes. These results extend the existing antecedent studies on career adaptability and demonstrate the importance of combining self-mobility beliefs (protean career attitudes) with social mobility beliefs (meritocratic beliefs) in the process of core self-evaluations affecting career adaptability. In conclusion, we hope to further develop the theory of career construction and provide more suggestions for college consultants and students., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Du, Yu, Luo and Liu.)

Career planning and career decision are important tasks for college students. The process may be affected by career stress, career exploration, and future work self, with some students facing career indecision. Combining both construction career and proactive motivation model, this study investigated the relationships between career stress, career exploration, future work self, career planning and career indecision among 1,012 Chinese college students using the Structure equation model (SEM) to test the proposed mediation model. Results show that career stress negatively predicts career planning, while career exploration positively predicts career planning. The mediating role of future work self has on career stress and career exploration's effects on both career planning and career indecision was verified. Moreover, the study also found future work self's positive effects on both career planning and career indecision in Chinese college students. Finally, the study's theoretical and practical significance and implications are discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Yu and Liu.)

Job-search is considered as a developmental task for college students to move from campus to workplace. Based on the self-determination theory, 859 Chinese college students were selected as the study sample and hierarchical regression analysis was used to explore the perseverance of effort and consistency of interest on job-search intensity and clarity. The survey showed that the perseverance of effort has a significant positive effect on the job-search intensity, while it has no significant positive effect on job-search clarity. Consistency of interest has a significant negative effect on job-search intensity and a significant positive effect on job-search clarity. Theoretical and practical implications are discussed and the directions for future research are outlined in this study., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yu, Yuan, Liu and He.)

In this work, a novel sustained released system (VCSB-Zn(II)) for zinc supplements was built by vanillin-chitosan Schiff base (VCSB) chelated with Zn 2+ to improve the zinc trace element utilization ratio. Samples were characterized by FT-IR, 1 H NMR, XRD, SEM, and TGA. The results showed that VCSB exhibited a more excellent chelation capacity of Zn 2+ than chitosan. The chelation capacity of VCSB was about 1.7 times more than that of chitosan, corresponding to 50.96 mg/g and 29.91 mg/g, respectively. Furthermore, VCSB-Zn(II) showed excellent sustained released performance at simulated gastric fluid because of the acid slow-dissolving ability. And the higher the CN content of VCSB, the higher the cumulative release rate (R i ) of Zn 2+ , the highest R i reached 77.81%. The sustained released curves were described by the first-order and Korsmeyer-Peppas equation, which described the Zn 2+ sustained released performance caused by the dissolution of VCSB-Zn(II) and Fick diffusion. This Zn 2+ sustained released system shows great potential in the application in the field of trace elements supplements for animals., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Intelligence is innate, but grit is something everyone can develop. Grit not only enables students to stick to their goals, but also to persevere even when they fail. Career adaptability is an important concept in vocational education of college students, which is a person engaged in some work, must have a certain physical and psychological quality. Base on the self-regulation theory, this study investigated the relationship between grit and career adaptability of Chinese college student based on the self-regulatory processes. We surveyed 839 Chinese college students and tested a self-regulation model. As expected, grit was related to greater career adaptability via greater career exploration and decision self-efficacy, positive affect, and goal commitment. These findings not only broaden the theoretical framework for the effect of grit on career adaptability, but also open up a new horizon for improving college students' career adaptability in practice., Competing Interests: The authors declare that the submitted work was carried out in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Yu, Mei, Liu, Li and Luo.)

Hepatocellular carcinoma is one of the most common malignant tumors in China and is also a major cause of cancer deaths worldwide. Recent advances in immunotherapy have identified new treatments in which immunotherapy can be combined with antiangiogenic therapy. We report a case of hepatocellular carcinoma with a tumor thrombus at the inferior vena cava-right atrium junction and multiple lung metastases after a multiple-course treatment. Treatment with sintilimab in combination with sorafenib led to a partial remission and immune-related hepatitis.

In order to deepen the understanding of the personality antecedents of students' career decidedness, this study, based on social cognitive career theory and career development theory, examined the effect of proactive personality on career decidedness as well as the mediating mechanism and moderating factors in this process. The results of the survey of 783 Chinese college students showed that proactive personality was positively related to career decidedness via career exploration, and anticipated regret moderated the relationship between proactive personality and career exploration significantly. Both theoretical and practical implications are discussed at the end of this research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yu, Luo, Liu, Li, Li and Mei.)

Purpose: The purpose of the present study was to evaluate the feasibility of using 4-dimensional computed tomography (4DCT)-ventilation-weighted dose analysis to predict radiation-induced pneumonia probability (RIPP)., Methods and Materials: The study population for this retrospective analysis included 16 patients with stage III lung cancer. Each patient's 4DCT images, including end-inhale and end-exhale sequences, were used for the deformable image registration, and the Hounsfield units (HU) density-change was used to calculate the ventilation. A previously established equation was used to convert the original dose (OD) D 0, i in the lungs in the original plan (OP) to the weighted-dose (WD) D w, i in the weighted plan (WP). The patients were divided into 2 groups, one with radiation-induced pneumonia (RIP), and one without. The Spearman correlation analysis was used to analyze the correlation of RIP with ΔV 20 (ΔV x = V w, x in the WP - V 0, x in the OP), ΔMLD (ΔMLD = mean lung dose (MLD) in the WP - MLD in the OP), and ΔV 5 ., Results: The results showed that 5 of the 16 patients were suffering from acute RIP, 4 of which had higher ΔV 20 and ΔMLD values than the rest of the patients. The results of the Spearman correlation analysis for those 4 patients were as follows: RIP vs. ΔV 20 , r = 0.5123; RIP vs. ΔMLD, r = 0.5119; RIP vs. ΔV 5 , r = 0.1904., Conclusions: The 4DCT-ventilation-based weighted-dose analysis showed some correlation between RIPP and both ΔV 20 and ΔMLD, when comparing the weighted-dose and the conventional dose-volume histogram (DVH) analyses., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

In recent years, there have been advancements in traditional patterns of tumor therapy with the adoption of immunotherapy. Its application with or without other combined regimens has attracted attention from clinicians. Sintilimab (Tyvyt®), a highly selective fully human IgG4 monoclonal antibody, blocks the binding site of programmed cell death protein 1 (PD-1), thereby, inhibiting the interaction between PD-1 and its ligands (PD-L1/2) to restore the endogenous anti-tumor T cell responses. Sintilimab has been proven to be clinically beneficial in multiple solid tumor therapies. Combination therapy and monotherapy have shown potential and encouraging anti-tumor efficacy with controllable and acceptable toxicities. The combination therapy is more likely to be a novel and promising therapeutic option. This study provides an overview of the status of sintilimab-based clinical trials in various solid tumors.

Objectives: To test the effectiveness of quantitative linear-quadratic-based (qLQB) model on evaluating irradiation-induced liver injury (ILI) and establish the relation between the damaged ratio/percent (DRP) in qLQB model and normal tissue complication probility (NTCP)., Materials and Methods: We established the qLQB model to calculate the ratio/percent (RP) between damaged cell/functional subunit (FSU) and entire cell/FSU of liver for radiation dose response, tested the qLQB against the Lyman-Kutcher-Burman (LKB) model, and established relation between the RP and NTCP through analyzing the dose of 32 patients with cancer of abdominal cavity who were treated with radiation therapy at our department. Based on varied α/β and varied parameters for NTCP, we put the calculated results into varied arrays for the next analysis. We named the 2 groups of RPs: RP1 (α/β = 3.0, α = 0.03) and RP2 (α/β = 8.0, α = 0.26), and named the 2 groups of NTCPs: NTCP1 (n = 0.32, m = 0.15, TD50(1) = 4000 cGy) and NTCP2 (n = 1.10, m = 0.28, TD50(1) = 4050 cGy)., Results: Spearman correlation analysis was used to analyze the correlations among the groups, the results were as follows: RP1 vs NTCP1, rs = 0.83827, p < 0.0001; RP1 vs NTCP2, rs = 0.83827, p < 0.0001; RP2 vs NTCP2, rs = 0.79289, p < 0.0001; and RP2 vs NTCP1, rs = 0.79289, p < 0.0001., Conclusions: There is a significant correlation between RP value and NTCP for evaluating ILI, and there is no difference between qLQB model and LKB model on evaluating ILI., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Evidence suggests that built environment characteristics affect older adults' travel activity behaviors, e.g., walking and cycling, which have well-established health benefits. However, the relationship between urban greenery and walking behaviors remains unclear, partly due to methodological limitation. Previous studies often measured urban greenery from a bird's eye perspective, which may mismatch with the pedestrian's perception from the street. In this study, we measured greenery view index from eye-level streetscape photos retrieved from Baidu Street View, an online mapping service provider. Walking behaviors of 180 older adults in six neighborhoods were collected from questionnaires. We also measured land use diversity, pedestrian-oriented design (street connectivity), and population density-the three Ds of the built environment. Results show that street greenery view index contributes to walking time of older adults, suggesting street greenery should be taken into design consideration to promote walking behaviors of older adults.

E2F transcription factors (E2Fs) were found to be related with cell activities and disease progression among a variety of different tumors, including regulating cell division and cell proliferation. In the analysis, it aimed to focus on transcriptional and survival information of E2Fs in gastric cancer (GC) from Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier plotter, cBioPortal, Database for Annotation, Visualization and Integrated Discovery (DAVID), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and Oncomine databases. It was found that the expression of E2F1/2/3/5/7/8 in GC tissues was obviously higher than the normal. Of interest, none of the E2Fs was related with pathological stages. Nevertheless, high expression of E2F2/3/5/7/8 was related with better survival data, except E2F6 regarding shorter first-progression (FP) survival. High expression levels of E2F2/5/7/8 have significant correlations with overall survival (OS) in patients with intestinal and diffuse GC, and this prognostic value is not affected by gender. Oppositely, the lower level of E2F1/4 illustrated superior survival data. Moreover, increased expression of E2F1 in GC tissues might play an important role in the development of GC. Collectively, E2F1 could be a potential therapeutic target for patients with GC. E2F1/2/3/5/7/8 might be original prognostic predictors of GC., (© 2020 The Authors.)

Objective: To explore the efficacy and sensitivity of 3D gamma analysis and bio-mathematical model for cervical cancer in detecting dose changes caused by dose-calculation-grid-size (DCGS)., Methods: 17 patients' plans for cervical cancer were enrolled (Pinnacle TPS, VMAT), and the DCGS was changed from 2.0 mm to 5.0 mm to calculate the planned dose respectively. The dose distribution calculated by DCGS = 2.0 mm as the "reference" data set (RDS), the dose distribution calculated by the rest DCGS as the"measurement"data set (MDS), the 3D gamma passing rates and the (N) TCPs of the all structures under different DCGS were obtained, and then analyze the ability of 3D gamma analysis and (N) TCP model in detecting dose changes and what factors affect this ability., Results: The effect of DCGS on planned dose was obvious. When the gamma standard was 1.0 mm, 1.0 and 10.0%, the difference of the results of the DCGS on dose-effect could be detected by 3D gamma analysis (all p value < 0.05). With the decline of the standard, 3D gamma analysis' ability to detect this difference shows weaker. When the standard was 1.0 mm, 3.0 and 10.0%, the p value of > 0.05 accounted for the majority. With DCGS = 2.0 mm being RDS, ∆gamma-passing-rate presented the same trend with ∆(N) TCPs of all structures except for the femurs only when the 1.0 mm, 1.0 and 10.0% standards were adopted for the 3D gamma analysis., Conclusions: The 3D gamma analysis and bio-mathematical model can be used to analyze the effect of DCGS on the planned dose. For comparison, the former's detection ability has a lot to do with the designed standard, and the latter's capability is related to the parameters and calculated accuracy instrinsically.

In experiments with univalent target stimuli, task-switching costs can be eliminated if participants are unaware of the task rules and apply cue-target-response associations. However, in experiments with bivalent target stimuli, participants show task-switching costs. Participants may exhibit switch costs even when no task rules are provided in the instructions because they can infer the task rules. We tested this prediction by controlling the meaningfulness of cues and targets and therefore the ability to apply the task rules in 2 groups of participants. We compared the performance of Chinese and non-Chinese participants, who responded to Chinese numerals in an odd/even and high/low number task. In Experiment 1, Chinese participants, who knew Chinese characters and understood the task rules, showed task-switching costs. Non-Chinese participants on the other hand, who did not know Chinese characters, exhibited no switch costs. They applied a "target-first" strategy which means that they processed the target stimulus before the cue. In Experiment 2, we confirmed the absence of task-switching costs in Chinese participants using traditional Chinese numerals as target stimuli. Further, to determine how the target-first strategy affects switch costs, we manipulated the sequence of cue and target presentations. We conclude that task-switching costs can be eliminated more easily than previously thought, even for bivalent stimuli. The occurrence of task-switching costs depends on the approach used by participants and this may answer the puzzling question why humans typically do show task-switching costs whereas pigeons and monkeys do not. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Applying categorization rules narrows attention toward the relevant features of a target and helps participants to ignore the irrelevant features of the target. This is called the shielding function of categorization rules. Here we explored the limitation of the shielding function in two task-switching experiments. In Experiment 1, we assigned each target a single digital numeral as an additional feature in addition to conventional bivalent features as in the previous task-switching experiments with bivalent tasks. In the first two stages of Experiment 1, half of the participants learned the numeral-response associations and the other half used an alternative numeral-categorization rule to infer the response. Without participants applying conventional task-switching rules, the switching costs disappeared. Moreover, when participants performed tasks by numeral-response associations the bivalent features interfered with response retrieval and caused response-congruency effects, whereas when participants applied the numeral-categorization rule, the bivalent features were shielded away and thereby the response-congruency effects disappeared. In the third stage, in which all participants applied task-switching rules by discriminating between bivalent features (i.e., filling and orientations), we found task-switching costs and response-congruency effects. In Experiment 2, new bivalent features produced stronger interference compared to Experiment 1. As a consequence, participants in both the association group and the numeral-categorization rule group showed significant response-congruency effects in the first two stages, where task-switching rules were not introduced. It follows that the shielding function of categorization rules has limits-strong interference from bivalent features can break down the shielding function. In addition, participants in the association group showed task-switching costs without being informed about the task-switching rules. We propose that strong proactive interference can produce task-switching costs even without the use of task-switching rules.

In task-switching experiments with bivalent target stimuli, conflicts during response selection give rise to response-congruency effects. Typically, participants respond more slowly and make more errors in trials with incongruent targets that require different responses in the two tasks, compared to trials with congruent targets that are associated with the same response in both tasks. Here we investigate whether participants show response-congruency effects when task rules are not made explicit. In two experiments, we assigned task-irrelevant features to each bivalent target. When participants were instructed to apply the task rules, they showed significant task-switching costs as well as response-congruency effects. Importantly, when the same participants did not know the task rules and responded without applying the task rules, they showed response-congruency effects but no switch costs. The significant congruency effects suggest that associations between bivalent target features and responses can be formed passively, even when participants do not follow the task rules and use task-irrelevant target features to make a response.

The structural, mechanical, elastic anisotropic, and electronic properties of Pbca -XN (X = C, Si, Ge) are investigated in this work using the Perdew-Burke-Ernzerhof (PBE) functional, Perdew-Burke-Ernzerhof for solids (PBEsol) functional, and Ceperly and Alder, parameterized by Perdew and Zunger (CA-PZ) functional in the framework of density functional theory. The achieved results for the lattice parameters and band gap of Pbca -CN with the PBE functional in this research are in good accordance with other theoretical results. The band structures of Pbca -XN (X = C, Si, Ge) show that Pbca -SiN and Pbca -GeN are both direct band gap semiconductor materials with a band gap of 3.39 eV and 2.22 eV, respectively. Pbca -XN (X = C, Si, Ge) exhibits varying degrees of mechanical anisotropic properties with respect to the Poisson's ratio, bulk modulus, shear modulus, Young's modulus, and universal anisotropic index. The (001) plane and (010) plane of Pbca -CN/SiN/GeN both exhibit greater elastic anisotropy in the bulk modulus and Young's modulus than the (100) plane., Competing Interests: The authors declare no conflict of interest.

The structural, mechanical, anisotropic, electronic and thermal properties of Si, Si 0.667 Ge 0.333 , Si 0.333 Ge 0.667 and Ge in P 4₂/ ncm phase are investigated in this work. The calculations have been performed with an ultra-soft pseudopotential by using the generalized gradient approximation and local density approximation in the framework of density functional theory. The achieved results for the lattice constants and band gaps of P 4₂/ ncm -Si and P 4₂/ ncm -Ge in this research have good accordance with other results. The calculated elastic constants and elastic moduli of the Si, Si 0.667 Ge 0.333 , Si 0.333 Ge 0.667 and Ge in P 4₂/ ncm phase are better than that of the Si, Si 0.667 Ge 0.333 , Si 0.333 Ge 0.667 and Ge in P 4₂/ mnm phase. The Si, Si 0.667 Ge 0.333 , Si 0.333 Ge 0.667 and Ge in P 4₂/ ncm phase exhibit varying degrees of mechanical anisotropic properties in Poisson's ratio, shear modulus, Young's modulus, and universal anisotropic index. The band structures of the Si, Si 0.667 Ge 0.333 , Si 0.333 Ge 0.667 and Ge in P 4₂/ ncm phase show that they are all indirect band gap semiconductors with band gap of 1.46 eV, 1.25 eV, 1.36 eV and 1.00 eV, respectively. In addition, we also found that the minimum thermal conductivity κ min of the Si, Si 0.667 Ge 0.333 , Si 0.333 Ge 0.667 and Ge in P 4₂/ ncm phase exhibit different degrees of anisotropic properties in (001), (010), (100) and (01¯0) planes., Competing Interests: The authors declare no conflict of interest.

Human bone marrow-derived stromal cells (hBMSC) are multi-potent stem cells that can differentiate into osteogenic and adipogenic lineages. Adiponectin (APN) is an adipocyte-derived hormone that modulates a series of metabolic processes. Recent studies revealed a relationship between APN and bone regeneration, though the underlying mechanism was not fully examined. Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a tumor suppressor and a therapeutic target for the metabolic syndrome. Its deletion mutants increase osteoblast activity and bone mineral density. Both APN and PTEN are involved in osteogenic differentiation. However, whether PTEN is involved in APN-induced bone metabolism remains unclear. This project was designed to study whether PTEN was involved in APN-mediated osteogenesis of hBMSCs. We found that APN downregulated PTEN expression and that both it and an inhibitor of PTEN (SF1670) increased the expression of osteogenic markers such as osteocalcin, alkaline phosphatase, and runt-related transcription factor-2 in APN-treated hBMSCs. Our results suggested that APN enhanced osteogenic differentiation of hBMSCs in vitro partially by inhibiting PTEN expression. APN could be a therapeutic agent in tissue regeneration engineering and bone regeneration by inhibiting PTEN expression and then promoting the osteogenic differentiation of hBMSCs., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Structural, mechanical, electronic properties, and stability of boron nitride (BN) in Pnma structure were studied using first-principles calculations by Cambridge Serial Total Energy Package (CASTEP) plane-wave code, and the calculations were performed with the local density approximation and generalized gradient approximation in the form of Perdew-Burke-Ernzerhof. This BN, called Pnma -BN, contains four boron atoms and four nitrogen atoms buckled through sp ³-hybridized bonds in an orthorhombic symmetry unit cell with Space group of Pnma . Pnma -BN is energetically stable, mechanically stable, and dynamically stable at ambient pressure and high pressure. The calculated Pugh ratio and Poisson's ratio revealed that Pnma -BN is brittle, and Pnma -BN is found to turn brittle to ductile (~94 GPa) in this pressure range. It shows a higher mechanical anisotropy in Poisson's ratio, shear modulus, Young's modulus, and the universal elastic anisotropy index A U . Band structure calculations indicate that Pnma -BN is an insulator with indirect band gap of 7.18 eV. The most extraordinary thing is that the band gap increases first and then decreases with the increase of pressure from 0 to 60 GPa, and from 60 to 100 GPa, the band gap increases first and then decreases again.

Triple-negative breast cancer is a high-risk breast cancer with poor survival rate. To date, there is a lack of targeted therapy for this type of cancer. One unique phenomenon is that inflammatory breast cancer is frequently triple negative. However, it is still ambiguous how inflammation influences triple-negative breast cancer growth and responding to chemotherapy. Herein, we investigated the levels of inflammation-associated enzyme, iNOS, in 20 triple-negative breast cancer patients' tumors, and examined its correlation with patients' responses to platinum-based neoadjuvant chemotherapy. Our studies showed that triple-negative breast cancer patients with attenuated iNOS levels in tumor cells after treatment showed better responses to platinum-based neoadjuvant chemotherapy than other triple-negative breast cancer patients. Our further in vitro studies confirmed that induction of proper levels of NO increased the resistance to cisplatin in triple-negative MDA-MB-231 cells. Our data suggest that aberrant high level of iNOS/NO are associated with less effectiveness of platinum-based neoadjuvant chemotherapy in triple-negative breast cancer. Therefore, we propose to monitor iNOS levels as a new predictor for triple-negative breast cancer patient's response to platinum-based neoadjuvant chemotherapy. Moreover, iNOS/NO is considered as a potential target for combination therapy with platinum drugs for triple-negative breast cancer.

The authors have isolated and characterized a novel serine palmitoyltransferase (SPT)-like gene in marine Emiliania huxleyi virus (EhV-99B1). The open-reading frame (ORF) of EhV99B1-SPT encoded a protein of 496 amino acids with a calculated molecular mass of 96 kDa and Ip 6.01. The results of sequence analysis showed that there was about 31%-45% identity in amino acid sequence with other organisms. The maximum likelihood phylogenetic tree suggested that the EhV99B1-SPT gene possibly horizontally transferred from the eukaryote. Hydrophobic profiles of deduced amino acid sequences suggested a hydrophobic, globular and membrane-associated protein with five transmembrane domains (TMDs) motifs. Several potential N-linked glycosylation sites were presented in SPT. These results suggested that EhV99B1-SPT was an integral endoplasmic reticulum membrane protein. Despite lower sequence identity, the secondary and three-dimensional structures predicted showed that the "pocket" structure element composed of 2 α -helices and 4 β -sheets was the catalytic center of this enzyme, with a typical conserved "TFTKSFG" active site in the N-terminal region and was very close to those of prokaryotic organisms. However, the N-terminal domain of EhV99B1-SPT most closely resembled the LCB2 catalysis subunit and the C-terminal domain most closely resembled the LCB1 regulatory subunit of other organisms which together formed a spherical molecule. This "chimera" was highly similar to the prokaryotic homologous SPT. For a functional identification, the EhV99B1-LCB2 subunit gene was expressed in Escherichia coli , which resulted in significant accumulation of new sphingolipid in E. coli cells., (© The Chinese Society of Oceanography and Springer-Verlag Berlin Heidelberg 2012.)

Reactive astrogliosis is a prominent neuropathologic feature of manganism, a neurodegenerative disorder caused by excessive accumulation of manganese (Mn) in the basal ganglia. Activation of astrocytes has been linked to neuronal injury in manganism resulting from overproduction of inflammatory mediators, including tumor necrosis factor-alpha (TNFalpha), interferon-gamma (IFNgamma), interleukin-1beta (IL-1beta), and nitric oxide (NO), but the signaling mechanisms by which Mn regulates these factors remain poorly understood. We previously reported that Mn enhances production of NO in activated astrocytes that promotes apoptosis in cocultured neuronal cells by a mechanism involving the transcription factor nuclear factor-kappaB (NF-kappaB) (Liu et al., 2005). Because NF-kappaB-dependent expression of inducible nitric oxide synthase (NOS2) can be antagonized by the nuclear orphan receptor peroxisome proliferator-activated receptor-gamma (PPARgamma), we postulated that a novel agonist of this receptor, 1,1-bis(3'-indolyl)-1-(p-trifluoromethylphenyl)methane (cDIM1), would suppress expression of NOS2 in astrocytes and protect cocultured neuronal cells from apoptosis. Submicromolar concentrations of cDIM1 potently suppressed production of NO and expression of NOS2 in cultured astrocytes exposed to Mn and IFNgamma/TNFalpha and prevented apoptosis in cocultures of differentiated PC12 cells, but this neuroprotective effect was lost in the absence of astrocytes. By using fluorescence reporter and chromatin immunoprecipitation (ChIP) assays, we found that cDIM1 prevented activation of NF-kappaB in astrocytes by a mechanism involving stabilization of the nuclear corepressor 2 (NCoR2) on the proximal NF-kappaB binding site of the NOS2 promoter. These data suggest that PPARgamma may be an effective target for limiting inflammatory activation of astrocytes during neurologic injury., ((c) 2007 Wiley-Liss, Inc.)

Developmental nicotine exposure has been implicated in the association between maternal smoking and adverse outcomes in offspring. The 3rd trimester of human pregnancy is equivalent to the 1st postnatal week in rodents; both are periods of active brain growth during which nicotinic acetylcholine receptors are transiently upregulated. Chronic neonatal nicotine (CNN; 6 mg/kg/day) from postnatal Days 1 to 7 was given orally to rat pups to evaluate long-term behavioral effects. Males and females were tested as adolescents or as young adults. CNN significantly decreased center time, ambulatory behavior, and rearing in the open-field test and decreased the number of entrances and time spent in the open arm of the elevated plus-maze in both sexes and ages. CNN did not change performance in the T maze or in the water maze in adult males or females. Motor coordination was not altered. In summary, CNN had long-term effects on anxiety-like behavior but did not affect spatial learning and memory functions. This finding is particularly important when evaluating the benefits of nicotine-replacement therapies during human pregnancies, which may improve smoking cessation rates but could result in long-term behavioral consequences.

Chronic exposure to excessive manganese (Mn) is the cause of a neurodegenerative movement disorder, termed manganism, resulting from degeneration of neurons within the basal ganglia. Pathogenic mechanisms underlying this disorder are not fully understood but involve inflammatory activation of glial cells within the basal ganglia. It was postulated in the present studies that reactive astrocytes are involved in neuronal injury from exposure to Mn through increased release of nitric oxide. C57Bl/6 mice subchronically exposed to Mn by intragastric gavage had increased levels of Mn in the striatum and displayed diminutions in both locomotor activity and striatal DA content. Mn exposure resulted in neuronal injury in the striatum and globus pallidus, particularly in regions proximal to the microvasculature, indicated by histochemical staining with fluorojade and cresyl fast violet. Neuropathological assessment revealed marked perivascular edema, with hypertrophic endothelial cells and diffusion of serum albumin into the perivascular space. Immunofluorescence studies employing terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (DUTP)-biotin nick-end labeling revealed the presence of apoptotic neurons expressing neuronal nitric oxide synthase (NOS), choline acetyltransferase, and enkephalin in both the striatum and globus pallidus. In contrast, soma and terminals of dopaminergic neurons were morphologically unaltered in either the substantia nigra or striatum, as indicated by immunohistochemical staining for tyrosine hydroxylase. Regions with evident neuronal injury also displayed increased numbers of reactive astrocytes that coexpressed inducible NOS2 and localized with areas of increased neuronal staining for 3-nitrotyrosine protein adducts, a marker of NO formation. These data suggest a role for astrocyte-derived NO in injury to striatal-pallidal interneurons from Mn intoxication.

Neuronal injury in manganism is accompanied by activation of astroglia within the basal ganglia that is thought to increase production of inflammatory mediators such as nitric oxide (NO). The present studies postulated that astroglial-derived NO mediates neuronal apoptosis induced by manganese (Mn) and pro-inflammatory cytokines. Pheochromocytoma (PC12) cells differentiated with nerve growth factor (NGF) were co-cultured with primary astrocytes and exposed to Mn and tumor necrosis factor-alpha (TNF-alpha) plus interferon-gamma (IFN-gamma). Mn enhanced cytokine-induced expression of inducible nitric oxide synthase (NOS2, EC 1.14.13.39) and production of NO in astrocytes that correlated with apoptosis in co-cultured neurons, as determined by caspase activity, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL), and nuclear morphology. Apoptosis in PC12 neurons required the presence of astrocytes and was blocked by overexpression of a phosphorylation-deficient mutant of IkappaBalpha (S32/36A) in astrocytes that prevented induction of NOS2. Pharmacologic inhibition of NOS2 with (+/-)-2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT) significantly reduced neuronal apoptosis, and the addition of low concentrations of the NO donor, S-nitroso-N-acetylpenicillamine (SNAP), to neurons cultured without astrocytes was sufficient to recover the apoptotic phenotype following exposure to Mn and TNF-alpha/IFN-gamma. It is concluded that Mn- and cytokine-dependent apoptosis in PC12 neurons requires astroglial-derived NO and NF-kappaB-dependent expression of NOS2.

Neuronal injury in manganese neurotoxicity (manganism) is thought to involve activation of astroglial cells and subsequent overproduction of nitric oxide (NO) by inducible nitric oxide synthase (NOS2). Manganese (Mn) enhances the effects of proinflammatory cytokines on expression of NOS2 but the molecular basis for this effect has not been established. It was postulated in the present studies that Mn enhances expression of NOS2 through the cis-acting factor, nuclear factor kappaB (NF-kappaB). Exposure of C6 glioma cells to lipopopolysaccharide (LPS) resulted in increased expression of NOS2 and production of NO that was dramatically potentiated by Mn and was blocked through overexpression of mutant IkappaBalpha (S32/36A). LPS-induced DNA binding of p65/p50 was similarly enhanced by Mn and was decreased by mutant IkappaBalpha. Phosphorylation of IkappaBalpha was potentiated by Mn and LPS and was not blocked by U0126, a selective inhibitor of ERK1/2. Mn decreased mitochondrial membrane potential and increased matrix calcium, associated with a rise in intracellular reactive oxygen species (ROS) that was attenuated by the mitochondrial-specific antioxidant, MitoQ. Blocking mitochondrial ROS also attenuated the enhancing effect of Mn on LPS-induced phosphorylation of IkappaBalpha and expression of NOS2, suggesting a link between Mn-induced mitochondrial dysfunction and activation of NF-kappaB. Overexpression of a dominant-negative mutant of the NF-kappaB-interacting kinase (Nik) prevented enhancement of LPS-induced phosphorylation of IkappaBalpha by Mn. These data indicate that Mn augments LPS-induced expression of NOS2 in C6 cells by increasing mitochondrial ROS and activation of NF-kappaB.