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The hierarchical porous lattice implant with microscopic porosity, which resembles the original human bone structure, has significant potential application value. The microscopic porosity in the hierarchical porous lattice implant plays a crucial role in transporting nutrients and promoting tissue regeneration. However, it is difficult to fabricate microscopic pores smaller than 200 μm by powder bed fusion (PBF) processes due to the limitations of the laser spot size. In this study, the preparation of a hierarchical porous lattice implant with microscopic porosity is proposed by coupling structure design with the high scanning speed - short hatch spacing (HSSH) process formation. The structure-versus-process relationship is used to control the size and distribution of the microscopic pores, which meets the requirements of modulus and high biocompatibility. This proposed process breaks the inherent law where the higher the porosity, the higher the modulus of the lattice for the same lattice type. The modulus and porosity of the hierarchical porous implants could be flexibly tuned over a wide range (0.1–1.8 GPa and 63–84 %, respectively). The microscopic porosity is mainly distributed near the contour of the core rod, and the macroscopic porosity and microscopic porosity are approximately 73.70 % and 8.22 %, respectively. The problem of large errors in fitting the hierarchical porous lattice modulus calculation model according to the Gibson-Ashby equation has been solved. The mechanism of microscopic porosity formation was also analyzed. Furthermore, this method has the advantage of universal applicability, providing a feasible way for the development and application of porous materials.

Purpose: The purpose of this study is to provide an alternative approach to teacher learning on top of the usual practices of listening to experts' lectures and conducting school-based activities among peers in China. A boundary-crossing lesson study (BCLS) through school-university partnership served as an example to illustrate how a class teacher's mindset changed towards her students in equal interactions with university scholars. Design/methodology/approach: With the lenses of action science theory and boundary-crossing learning theory, the study used qualitative research approach to collect and analyze data. One Chinese primary school class teacher from a workshop on narrative action research was selected as the case for this study. Interviewing, observation and document analysis were used to collect data. Data analysis methods included categorization and contextualization of the teacher's mindset change towards her student. Findings: The case teacher, Mrs. Li, collaborated closely in paired teaching with her university partner AP Yu in all the four phases of their BCLS. Each phase was marked with an interactive event such as dialogic illumination, reflexive theorization, embodied conversation, and fusion of teacher and trainer roles. With inspirational trust as a major interactive mechanism, Mrs. Li jumped out of her single-loop learning (changing strategies according to results) to double-loop learning (changing both strategies and values/values). As a result, her mindset changed from attribution to appreciation towards her low-achieving student. Originality/value: This study made contributions in two ways. First, it examined a class teacher's mindset change towards her student, rather than that of subject matter teachers towards their teaching materials and methods. Second, it revealed how reflective interactions in a special kind of BCLS by school teachers and university scholars may promote the teacher's mindset change. The findings further confirm that having differences as boundaries is not enough for teacher learning. For deep learning like Mrs. Li's mindset change, it requires a respectful and inspirational relationship between school teachers and university scholars in the BCLS.

The complex phase transition that occurs during the charge/discharge process leads to poor rate and cycling performance of O3-type NaNi1/3Fe1/3Mn1/3O2(NFM). In this paper, we propose a novel modification strategy for NFM that involves doping its transition metal layer with Ta5+ions of higher valence and stronger binding energy to oxygen than the transition metal. The effects of Ta doping on the crystal structure, transition metal valence states, activation barrier energy, and bandgap of NFM were investigated, and the modification mechanisms were explored. The capacity retention of NFM-Ta0.01 (80.15 %) was higher than that of NFM (35.44 %) after 200 cycles. This improvement is attributable to the strong bonding energy effect of TaO, which stabilized the crystal structure of NFM, delayed the transition of the material from the hexagonal O3 phase to the hexagonal P3 phase beyond 3.2 V, and enhanced the phase transition reversibility of NFM. Moreover, Ta introduction increased the sodium layer spacing and reduced the Na+activation barrier energy of the material from 0.773 to 0.692 eV, and the band gap from 1.7416 to 1.5951 eV, leading to a significant improvement in electronic conductivity. Owing to the synergistic effect of these factors, the discharge capacity of NFM-Ta0.01 at a 5C rate (100.6 mAh g−1) was considerably higher than that of NFM (79.3 mAh g−1). This work presents a proven modification strategy for achieving structurally stable and improved rate performance for NFM.

•Hirschsprung's disease (HD) is a rare congenital digestive tract malformation in children. Knowledge on long non-coding RNAs (lncRNAs) in HD is still limited.•A total of 90 differentially expressed lncRNAs were detected in normal and stenosed intestinal tissue of HD patients.•LINC01579–204, miR-203a-3p, and NEFL are predicted to play important roles in the progression of HD.•LINC01579–204, miR-203a-3p and NEFL had a significant overall predictive ability to identify progression of HD patients.

ABSTRACTPHLPP1 (PH domain and leucine rich repeat protein phosphatase 1) is a newly identified family of Ser/Thr phosphatases that catalyzes the dephosphorylation of a conserved regulatory motif of the AGC kinases resulting in a tumor suppressive function, while CDKN1B/p27 also acts as a tumor suppressor by regulating cell cycle, senescence, apoptosis, and cell motility. Our most recent studies reveal that CDKN1B is required for PHLPP1 abundance, which contributes to the inhibition of carcinogenic arsenite-induced cell malignant transformation through inhibition of RPS6-mediated Hif1atranslation. However, nothing is known about the mechanisms underlying the crosstalk between these 2 key tumor suppressors in intact cells. Here, for the first time to the best of our knowledge, we show that CDKN1B is able to promote PHLPP1 protein translation by attenuating the abundance of Mir6981, which binds directly to the 5ʹuntranslated region (UTR) of Phlpp1mRNA. Further studies indicate that the attenuation of Mir6981expression is due to macroautophagy/autophagy-mediated degradation of Mir6981in an SQSTM1/p62-dependent fashion. Moreover, we have determined that Sqstm1is upregulated by CDKN1B at the level of transcription viaenhancing SP1 protein stability in an HSP90-depdendent manner. Collectively, our studies prove that: 1) SQSTM1 is a CDKN1B downstream effector responsible for CDKN1B-mediated autophagy; 2) by promoting the autophagy-mediated degradation of Mir6981, CDKN1B exerts a positive regulatory effect on PHLPP1 translation; 3) Mir6981suppresses PHLPP1 translation by binding directly to its mRNA 5ʹ-UTR, rather than classical binding to the 3ʹ-UTR. These findings provide significant insight into understanding the crosstalk between CDKN1B and PHLPP1.Abbreviations:ATG: autophagy related; ACTB: actin beta; BAF: bafilomycin; BECN1: beclin 1; Cdkn1b/p27: cyclin-dependent kinase inhibitor 1B; CHX: cycloheximide; DMEM: dulbecco’s modified eagle medium; FBS: fetal bovine serum; GAPDH: glyceraldehyde −3-phosphate dehydrogenase; Hif1a: hypoxia inducible factor 1, alpha subunit; Hsp90: heat shock protein 90; JUN: Jun proto-oncogene, AP1 transcription factor subunit; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MG132: proteasome inhibitor; Mtor: mechanistic target of rapamycin kinase; Phlpp1: PH domain and leucine rich repeat protein phosphatase 1; Phlpp2: PH domain and leucine rich repeat protein phosphatase 2; Pp2c: protein phosphatase 2 C; RPS6: ribosomal protein S6; Sp1: trans-acting transcription factor 1; Sqstm1/p62: sequestosome 1; TUBA: alpha tubulin; 3ʹ-UTR; 3ʹ-untranslated region; 5ʹ-UTR: 5ʹ-untranslated region.

Aggressive prolactin (PRL)-secreting pituitary adenomas that are resistant to conventional therapy with dopamine agonists, surgery, and radiation pose a therapeutic challenge. The mammalian target of rapamycin (mTOR) inhibitor everolimus is approved to treat neuroendocrine tumors (NETs), and cotreatment with the somatostatin receptor ligand octreotide improved median progression-free survival in patients with metastatic pancreatic NETs.

Neurocytoma (NC) is a rare, low-grade tumor of the central nervous system, with a 10-year survival rate of 90% and local control rate of 74%. However, 25% of NCs will be atypical, with an elevated Ki-67 labeling index >2%, and will exhibit a more aggressive course, with a high propensity for local recurrence and/or craniospinal dissemination. Although no standard treatment regimen exists for these atypical cases, adjuvant stereotactic or conventional radiotherapy and/or chemotherapy have been typically offered but have yielded inconsistent results.

ABSTRACTOur previous studies have demonstrated that XIAP promotes bladder cancer metastasis through upregulating RhoGDIβ/MMP-2 pathway. However, the molecular mechanisms leading to the XIAP upregulation was unclear. In current studies, we found that XIAP was overexpressed in human high grade BCs, high metastatic human BCs, and in mouse invasive BCs. Mechanistic studies indicated that XIAP overexpression in the highly metastatic T24T cells was due to increased mRNA stability of XIAP that was mediated by downregulated miR-200c. Moreover, the downregulated miR-200c was due to CREB inactivation, while miR-200c downregulation reduced its binding to the 3’-UTR region of XIAP mRNA. Collectively, our results demonstrate the molecular basis leading to XIAP overexpression and its crucial role in BC invasion.

For the compounds Cmc21-X2As2O (X = Si, Ge, and Sn), the stabilities are verified by the elastic constants and the phonon dispersion spectra. The structural, mechanical, electronic, and optical properties are investigated by using density functional theory (DFT) calculations. For Cmc21-X2As2O, the mechanical strengths in the [100], [010], and [001] directions are studied. Young’s modulus for Cmc21-Ge2As2O is more anisotropic than that of Cmc21-Si2As2O and Cmc21-Sn2As2O. The band structures of Cmc21-Si2As2O and Cmc21-Sn2As2O show that they are indirect-bandgap semiconductors with bandgaps of 2.744 and 2.201 eV, by using the HSE06 hybrid functional. Cmc21-Ge2As2O is a direct narrow-bandgap semiconductor with a bandgap of 2.131 eV. The static dielectric constants of Cmc21-Si2As2O and Cmc21-Sn2As2O in the [001] direction are higher than those in the [100] and [010] directions. The static dielectric constant of Cmc21-Ge2As2O in the [001] direction is lower than those in the [100] and [010] directions.

Pleckstrin homology domain leucine-rich repeat protein phosphatase 2 (PHLPP2) is a tumor suppressor that catalyzes the de-phosphorylation of the AGC kinases, while p27 acts as a tumor suppressor that regulates cell cycle, apoptosis, and cell motility. Our previous studies have identified that PHLPP2 participates in inhibition of transformation of human bronchial epithelial cells following lung carcinogen B[a]P/B[a]PDE exposure. However, nothing was known about the association of p27 with regulation of PHLPP2 expression and the role of PHLPP2 in bladder cancer (BC) invasion. In our current studies, we demonstrated that PHLPP2 inhibited BC invasion through promoting MMP2 degradation via p62-mediated autophagy; and p27 expression was able to stabilize PHLPP2 protein by inhibiting protein degradation of Hsp90, which could directly bind to PHLPP2 and protect it from degradation. More in-depth studies discovered that stabilization of Hsp90 by p27 was mediated by calpain1 proteolysis system, whereas p27 inhibited calpain1 gene transcription by attenuating Jak1/Stat1 cascade in human invasive BC cells. Collectively, we for the first time revealed PHLPP2 downregulation in BCs and its participating in promotion of BC invasion, as well as novel role of p27 and mechanisms underlying its regulation of PHLPP2 protein degradation through Hsp90-dependent manner. Our findings improve our understanding of p27 and PHLPP2 roles and their crosstalk in regulation of BC invasion, which further contributes to improve the current strategy for invasive bladder cancer therapy.

•The two new materials are not researched by others.•The two materials are researched under high pressure.•The band structures show that they present semiconducting character.

•Five potential novel phases of AlAs are proposed.•The electronic properties are calculated by hybrid functional.•Pmn21-AlAs and Pbam-AlAs have direct band gaps.

Ni-rich layered cathodes are considered to be the most suitable high-capacity electrode material for current needs since their reversible capacity of over 200 mAh·g−1and high operating voltage. However, the conventional Ni-rich layered cathodes inevitably go through rapid capacity degradation and poor rate performance. Herein, a designed strategy is proposed that W doping can regulate the electronic structure of NCMA(LiNi0.90Co0.04Mn0.03Al0.03O2) materials, presenting upgraded cyclability and enhanced rate performance. In this study, combined with density functional theory (DFT) calculation and conventional electrochemical measurements, revealed that the dual improvements of electronic and cationic conductivity are the possible reasons for the promoted electrochemical behavior. The bandgap of W-doped cathode material is reduced from 1.3857 to 1.2479 eV, which arises from the increased amount of electrons near Fermi energy after W doping. Such enhancement in electronic conductivity subsequently diminishes the polarization of the electrodes, thus the capacity retention of W-doped material after 100 cycles at 0.5C is greatly improved from 32.3 % to 95.0 %. Meanwhile, the strong WO bond intensifies cationic conductivity, facilitating Li+diffusion. The introduction of W cations expands the thickness of Li slab up to 2.71 Å. Such improvements thereafter lead to a specific capacity of 155 mAh·g−1at 5C. Compared to the pristine sample, W-NCMA cathode displays high potential for EV application.

Neuroendocrine tumors, including carcinoids, are rare and insidiously growing tumors. Related to their site of origin, tumors can be functional, causing various forms of the carcinoid syndrome, owing to the overproduction of serotonin, histamine, or other bioactive substances. They often invade adjacent structures or metastasize to the liver and elsewhere. Treatment includes multimodal approaches, including cytoreductive surgery, locoregional embolization, cytotoxic therapy, peptide receptor radionuclide therapy, and various targeted therapies with goals of symptom relief and control of tumor growth. This article summarizes current and emerging approaches to management and reviews several promising future therapies.

•Two novel structures, t-Sn3P4and o-Sn3P4, are predicted.•The mechanical, electronic and optical properties are analyzed.•The band gap of t-Sn3P4is 0.936 eV, and o-Sn3P4has metallic characteristics.

As transition metal borides have been successfully synthesised, the study of the combination of transition metal and boron is another effective way to investigate the properties of boride. We have predicted the novel phase Amm2-NbB4. Using the Cambridge Serial Total Energy Package (CASTEP) code, we further researched on the mechanical, electronic and optical properties of C2/c- and Amm2-NbB4. It is found that both the phases of NbB4are dynamically and mechanically stable at 0 and 100 GPa. Their Vickers hardness values are both 34 GPa, which indicate that they are hard materials. The band gap of C2/c-NbB4is 0.145 eV, which indicates that it is a semiconductor (or metalloid) at 0 GPa. For the Amm2-NbB4, the band structure without band gap indicates it is a metal at 0 GPa. The optical properties of these two structures are similar. At 0 eV, the real part of dielectric function is 28.8 for C2/c-NbB4, and the real part value for Amm2-NbB4is 43. We hope our work will provide some help to the experimental work about the technology of the material.

•The optical penetration depth of the laser beam into the powder bed is taken into account in this model.•The convective heat flux dominate the heat tranfer in the molten pool, and further decides the shape of molten pool.•Heat accumulation can significantly change the size of the molten pool, but has little effect on the molten pool shape.

Rubidium doped cathode materials RbxLi1.27-xCr0.2Mn0.53O2 (x = 0, 0.01, 0.03 and 0.05) were prepared via a solid state reaction method. The influences of the amount of Rb+ incorporated in the cathodes on the electrochemical performance were investigated in detail. It was found that the initial specific capacity, coulombic efficiency and rate performance were improved by Rb doping. Among the prepared cathode samples, the Rb0.03Li1.24Cr0.2Mn0.53O2 material presented the best results. The material showed an initial discharging capacity of 224.9 mAh*g[?]1, a capacity retention of 98.8% after 50 cycles and excellent high-rate performance of 92.0 mAh*g[?]1 at 5C rate. The improved diffusion coefficient of Li ions in the Rb+ incorporated cathodes was confirmed by electrochemical impedance measurement. The changes in diffusion coefficient are in good accordance with the changes in lattice parameter of c axis obtained from XRD Rietveld refinement. With the increase in Rb concentration, the interlayer spacing increases, then the diffusion of Li ions is enhanced and finally the electrochemical properties is improved. However, when x reaches 0.05, the lattice distorsion happened, c axis begins to shrink, the Li ion diffusion is restricted, and therefore the electrochemical performance is reduced with further increase in Rb concentration.

The Na3V2-xCux(PO4)3/C (x = 0, 0.01, 0.03, 0.05 and 0.07) cathodes have been prepared by ballmilling and spray-drying assisted high-temperature solid-state reaction. The effects of Cu doping on Na3V2(PO4)3/C are characterized by XRD, SEM, XPS, EPR and electrochemical measurements. The results show that the Na3V1.95Cu0.05(PO4)3/C delivers the highest discharge capacity of 90.6 mAh g[?]1 at 50 C and superior cyclic retention of 88.2% after 2000 cycles at 20 C, which could be mainly attributed to the high electronic conductivity (7.2 x 10[?]2 S cm[?]1) and Na ion diffusion coefficient (1.695 x 10[?]12 cm2 s[?]1). The introduction of Cu2+ into the Na3V2(PO4)3/C lattice produces oxygen vacancies with accompanying conduction electrons, which lead to the enhanced electronic conductivity and Na ion diffusion coefficient. Besides, inactive Cu2+ acts as a pillar to reduce the negative effects caused by the volume shrinking/swelling during the Na+ extraction/insertion, resulting in increased cycle stability of the Cu-doped Na3V2(PO4)3 system.

Background Previous studies have failed to investigate the specific effects of advanced age on survival outcomes by considering the Charlson Comorbidity Index (CCI) and age permutation in patients with T1a renal cell carcinoma (T1a RCC) treated by microwave ablation (MWA). Notably, RCC guidelines recommended radiofrequency ablation (RFA) and active surveillance (AS) are both treatment options for elderly T1a RCC, but whether MWA is superior to AS in light of higher heating efficiency and larger ablation zone compared with RFA is not clear. This study aimed to investigate the specific effects of advanced age on survival outcomes of T1a RCC patients stratified by CCI score and indicate better intervention for elderly T1a RCC between MWA and AS.Methods This was a retrospective study. We retrospectively reviewed 237 patients with T1a RCC who had undergone MWA over the last 16 years. Data were analyzed by Cox regression and Landmark analysis. Interaction tests and propensity score matching were used to account for potential biases. We compared the overall survival (OS) and cancer-specific survival (CSS) rates of patients ≥75 years in our study with corresponding figures from 4251 counterparts undergoing AS in published articles.Results Using patients ＜75 years with a CCI ≤2 as a reference, the hazard ratio (HR) and 95% confidence interval (CI) of OS for patients＜75 years with a CCI ≥3, patients ≥75 years with a CCI ≤2, and patients ≥75 years with CCI ≥3, were 2.954 (1.139-7.663), 3.48 (1.487-8.146), and 3.357 (1.162-9.698), respectively. The adverse effect of an age ≥75 years on OS was attenuated in patients with a CCI ≥3. The attenuation lasted for 62.5 months of follow-up (P= .017). Notably, advanced age exerted a protective effect on progression-free survival (PFS) in patients with a CCI ≥3, increasing the 8-year PFS from 67.8% to 100% (P= .049). Relative to 1-, 3-, 5-, and 8-year survival data for patients aged ≥75 undergoing AS, the OS rates for 5-year follow-up were always better in MWA. However, beyond 5 years, the OS rates dropped to levels that were similar to AS.Conclusions Advanced age exerts adverse effects and significantly protective effects on OS and PFS, respectively, in T1a RCC patients with a CCI ≥ 3. According to our study, elderly patients with T1a RCC underwent radical MWA may yield a better medium-term OS relative to AS.

ABSTRACTIsorhapontigenin (ISO) is a new derivative of stilbene isolated from the Chinese herb Gnetum cleistostachyum. Our recent studies have revealed that ISO treatment at doses ranging from 20 to 80 μM triggers apoptosis in multiple human cancer cell lines. In the present study, we evaluated the potential effect of ISO on autophagy induction. We found that ISO treatment at sublethal doses induced autophagy effectively in human bladder cancer cells, which contributed to the inhibition of anchorage-independent growth of cancer cells. In addition, our studies revealed that ISO-mediated autophagy induction occurred in a SESN2 (sestrin 2)-dependent and BECN1 (Beclin 1, autophagy related)-independent manner. Furthermore, we identified that ISO treatment induced SESN2 expression via a MAPK8/JNK1 (mitogen-activated protein kinase 8)/JUN-dependent mechanism, in which ISO triggered MAPK8-dependent JUN activation and facilitated the binding of JUN to a consensus AP-1 binding site in the SESN2promoter region, thereby led to a significant transcriptional induction of SESN2. Importantly, we found that SESN2 expression was dramatically downregulated or even lost in human bladder cancer tissues as compared to their paired adjacent normal tissues. Collectively, our results demonstrate that ISO treatment induces autophagy and inhibits bladder cancer growth through MAPK8-JUN-dependent transcriptional induction of SESN2, which provides a novel mechanistic insight into understanding the inhibitory effect of ISO on bladder cancers and suggests that ISO might act as a promising preventive and/or therapeutic drug against human bladder cancer.

Context:Glucocorticoids are powerful steroid hormones that regulate development, metabolism, and immune response. However, glucocorticoid unresponsiveness or resistance is observed in the treatment of inflammatory, autoimmune, and lymphoproliferative diseases and significantly limits their efficacy.Objective:In Cushing's disease, although some glucocorticoid-mediated suppression of pituitary-derived ACTH is seen, corticotroph tumors exhibit relative resistance to glucocorticoid action. We previously demonstrated that testicular orphan receptor 4 (TR4) binds to the pro-opiomelanocortin (POMC) promoter to induce corticotroph tumor POMC expression and ACTH secretion, and we hypothesized that TR4 may interact with glucocorticoid signaling to modulate POMC expression and action.Results:Here we demonstrate that TR4 abrogates glucocorticoid receptor (GR)- or dexamethasone-mediated POMC and activator protein-1 transrepression in both murine and human pituitary corticotroph tumor cells. Co-immunoprecipitation studies indicate that TR4 and GR interact directly with each other, resulting in TR4-mediated disruption of GR binding to the POMC promoter.Conclusion:These results demonstrate that TR4 binds GR to play an important role in glucocorticoid-directed corticotroph tumor POMC regulation in addition to modulating glucocorticoid actions on other GR targets. Characterization of this pathway may offer important insights into glucocorticoid resistance and may identify a novel approach for the treatment of Cushing's disease and the glucocorticoid-resistant states.

Two new phases of Si8C4and Si4C8with the P42/mnm symmetry are proposed. Using first principles calculations based on density functional theory, the structural, elastic, and electronic properties of Si8C4and Si4C8are studied systematically. Both Si8C4and Si4C8are proved to be mechanically and dynamically stable. The elastic anisotropies of Si8C4and Si4C8are studied in detail. Electronic structure calculations show that Si8C4and Si4C8are indirect semiconductors with the band gap of 0.74 and 0.15 eV, respectively.

This study reports a novel function of p50 in its regulation of SOD2 transcription via an NFκB-independent pathway. p50-regulated FoxO3a phosphorylation and transactivation contributes to SOD2 transcription, and p50–down-regulated PHLPP1 translation via miR190 is responsible for activation of Akt and FoxO3a.

An Nb5+-doped cathodic material, Li1[?]xNbx+yFe1[?]yPO4, was synthesized via the high-temperature solid-state method. The crystal structure, micro-defects and doping ion occupancy of doped LiFePO4 have been studied via the Rietveld crystal structure refinement, HRTEM, EPR and positron annihilation lifetime spectroscopy (PALS) methods. The effect of ion doping on the electrochemical properties was studied by measuring the changes in the electronic localization and structural defects. The results of the Rietveld crystal structure refinement showed that Nb5+ occupied positions on both Li and Fe in [Li0.99[?]xNbx][Fe1[?]yNby]PO4, with an occupancy rate on Fe approximately six times greater than that in the Li position. The HRTEM results indicated that, when Nb5+ was doped into the lattice well, there were no other phases on the grain surface. Furthermore, the EPR results indicated that Nb5+ occupying the Fe position broke the Fe2+-O-Fe2+ electron spin correlation, which distorted the crystal ligand field around Fe2+. The PALS investigation showed that Nb5+ could be doped into the internal LiFePO4 lattice to produce cation vacancy defects. The internal defects and outer electron energy of the cations in the lattice were changed because of the Nb5+ doping, which could improve the electrochemical performance of the material.

Arsenite exposure is associated with an increased risk of human lung cancer. However, the molecular mechanisms underlying the arsenite-induced human lung carcinogenesis remain elusive. In this study, we demonstrated that arsenite upregulates cyclin D1 expression/activity to promote the growth of human bronchial epithelial Beas-2B cells. In this process, the JNKs (c-Jun N-terminal kinases)/c-Jun cascade is elicited. The inhibition of JNKs or c-Jun by chemical or genetic inhibitors blocks the cyclin D1 induction mediated by arsenite. Furthermore, using a loss of function mutant of p85 (p85, a subunit of PI3K) or dominant-negative Akt (DN-Akt), we showed that PI3K and Akt act as the upstream regulators of JNKs and c-Jun in arsenite-mediated growth promotion. Overall, our data suggest a pathway of PI- 3K/Akt/JNK/c-Jun/cylin D1 signaling in response to arsenite in human bronchial epithelial cells.

Abstract: It is widely accepted that the consumption of alcohol may lead to hepatic injuries such as hepatic fibrosis and cirrhosis. However, consumption of Maotai, one of the famous liquors in China, is found to have no obvious relevance with hepatic injury as ordinary white wine does in both epidemiological and histopathological studies. Present study used human hepatoma cell line Hep3B to address the mechanisms involved in the resistance of alcohol-induced hepatic injury by Maotai liquor. We found that exposure of Hep3B cells to Maotai residue without ethanol (MRWE) resulted in the increased GST A1 anti-oxidant responsive element (ARE) transcriptional expression, while MRWE treatment did not affect Nrf-2-dependent transcriptional activity. Those findings were further confirmed at all time points and doses tested, suggesting that GST A1 transcription was regulated by MRWE via an Nrf-2-independent pathway. Consistent with GST A1 induction, the phosphorylation of c-Jun, extracellular signal-regulated kinases (ERKs) and p38 kinase (p38 K), were also observed in MRWE-treated Hep3B cells. Furthermore, pretreatment of cells with either PD98059 (an inhibitor specific for MEK1/2-ERKs pathway) or SB202190 (an inhibitor specific for p38 K) led to a significant decrease in the induction of GST A1 transcriptional expression by MRWE treatment. Our results indicate that certain content in MRWE is able to induce GST A1 ARE transcriptional expression, which may provide protective effects for hepatic cells by antagonizing the oxidative stress derived from ethanol via an ERKs- and p38 K-dependent pathway.

Hepatocellular carcinoma recurrence and metastasis after microwave ablation (MWA) are challenges in the clinic. This study showed that mannose-derived carbon dots (Man-CDs) could effectively capture several “danger signals” (DS) after MWA treatment and then deliver DS specifically to dendritic cells (DCs). This improved delivery of DS to DCs enhanced the processing and presentation of tumor-associated antigens by DCs. The results demonstrated that intratumoral injection of Man-CDs after MWA therapy elicited a potent tumor-specific immune response and finally led to the effective suppression of both primary and distant tumors. MWA + Man-CD treatment could efficiently reject tumor cell rechallenge in vivo. This study demonstrated that Man-CD nanoparticles are effective adjuvants that can improve MWA therapy by eliciting a tumor-specific immune response.

The Na3V2-xCux(PO4)3/C (x = 0, 0.01, 0.03, 0.05 and 0.07) cathodes have been prepared by ballmilling and spray-drying assisted high-temperature solid-state reaction. The effects of Cu doping on Na3V2(PO4)3/C are characterized by XRD, SEM, XPS, EPR and electrochemical measurements. The results show that the Na3V1.95Cu0.05(PO4)3/C delivers the highest discharge capacity of 90.6 mAh g−1at 50 C and superior cyclic retention of 88.2% after 2000 cycles at 20 C, which could be mainly attributed to the high electronic conductivity (7.2 × 10−2S cm−1) and Na ion diffusion coefficient (1.695 × 10−12cm2s−1). The introduction of Cu2+into the Na3V2(PO4)3/C lattice produces oxygen vacancies with accompanying conduction electrons, which lead to the enhanced electronic conductivity and Na ion diffusion coefficient. Besides, inactive Cu2+acts as a pillar to reduce the negative effects caused by the volume shrinking/swelling during the Na+extraction/insertion, resulting in increased cycle stability of the Cu-doped Na3V2(PO4)3system.

Rubidium doped cathode materials RbxLi1.27-xCr0.2Mn0.53O2(x = 0, 0.01, 0.03 and 0.05) were prepared via a solid state reaction method. The influences of the amount of Rb+incorporated in the cathodes on the electrochemical performance were investigated in detail. It was found that the initial specific capacity, coulombic efficiency and rate performance were improved by Rb doping. Among the prepared cathode samples, the Rb0.03Li1.24Cr0.2Mn0.53O2material presented the best results. The material showed an initial discharging capacity of 224.9 mAh·g−1, a capacity retention of 98.8% after 50 cycles and excellent high-rate performance of 92.0 mAh·g−1at 5C rate. The improved diffusion coefficient of Li ions in the Rb+incorporated cathodes was confirmed by electrochemical impedance measurement. The changes in diffusion coefficient are in good accordance with the changes in lattice parameter of caxis obtained from XRD Rietveld refinement. With the increase in Rb concentration, the interlayer spacing increases, then the diffusion of Li ions is enhanced and finally the electrochemical properties is improved. However, when x reaches 0.05, the lattice distorsion happened, c axis begins to shrink, the Li ion diffusion is restricted, and therefore the electrochemical performance is reduced with further increase in Rb concentration.

The structural, mechanical, and electronic properties of the orthorhombic GaN (Pnma-GaN) are investigated at ambient pressure by using first-principles calculations method with the ultrasoft pseudopotential scheme. The elastic constants and phonon calculations reveal Pnma-GaN is mechanically and dynamically stable at ambient pressure. The calculated Young modulus of Pnma-GaN is 170 GPa, which is the three-fifths of wurtzite-GaN. Electronic structure study shows that Pnma-GaN is a direct semiconductor with band gap of 1.847 eV. The anisotropic calculation shows that wurtzite-GaN has a smaller elastic anisotropy than that of Pnma-GaN in Young’s modulus. In addition, when the composition of aluminum increases from 0 to 0.063 in the alloy, the band gap decreases initially and increases afterward for Pnma-Ga1−xAlxN, while, for wurtzite-Ga1−xAlxN, the band gap increases with the increasing composition x. Due to the structural porous feature, Pnma-GaN can also be expected to be a good hydrogen storage material.

An Nb5+-doped cathodic material, Li1−xNbx+yFe1−yPO4, was synthesized via the high-temperature solid-state method. The crystal structure, micro-defects and doping ion occupancy of doped LiFePO4have been studied via the Rietveld crystal structure refinement, HRTEM, EPR and positron annihilation lifetime spectroscopy (PALS) methods. The effect of ion doping on the electrochemical properties was studied by measuring the changes in the electronic localization and structural defects. The results of the Rietveld crystal structure refinement showed that Nb5+occupied positions on both Li and Fe in [Li0.99−xNbx][Fe1−yNby]PO4, with an occupancy rate on Fe approximately six times greater than that in the Li position. The HRTEM results indicated that, when Nb5+was doped into the lattice well, there were no other phases on the grain surface. Furthermore, the EPR results indicated that Nb5+occupying the Fe position broke the Fe2+-O-Fe2+electron spin correlation, which distorted the crystal ligand field around Fe2+. The PALS investigation showed that Nb5+could be doped into the internal LiFePO4lattice to produce cation vacancy defects. The internal defects and outer electron energy of the cations in the lattice were changed because of the Nb5+doping, which could improve the electrochemical performance of the material.

The relationship between the intrinsic structure and transport properties of lithium ions in LiFePO4cathode materials is investigated by molecular dynamics simulations.