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Cancer cells entail metabolic adaptation and microenvironmental remodeling to survive and progress. Both calcium (Ca2+) flux and Ca2+-dependent signaling play a crucial role in this process, although the underlying mechanism has yet to be elucidated. Through RNA screening, we identified one long noncoding RNA (lncRNA) named CamK-A (lncRNA for calcium-dependent kinase activation) in tumorigenesis. CamK-A is highly expressed in multiple human cancers and involved in cancer microenvironment remodeling via activation of Ca2+-triggered signaling. Mechanistically, CamK-A activates Ca2+/calmodulin-dependent kinase PNCK, which in turn phosphorylates IκBα and triggers calcium-dependent nuclear factor κB (NF-κB) activation. This regulation results in the tumor microenvironment remodeling, including macrophage recruitment, angiogenesis, and tumor progression. Notably, our human-patient-derived xenograft (PDX) model studies demonstrate that targeting CamK-A robustly impaired cancer development. Clinically, CamK-A expression coordinates with the activation of CaMK-NF-κB axis, and its high expression indicates poor patient survival rate, suggesting its role as a potential biomarker and therapeutic target.
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Carcinogênese/genética , Neoplasias/genética , RNA Longo não Codificante/genética , Microambiente Tumoral/genética , Sinalização do Cálcio/genética , Proteína Quinase Tipo 1 Dependente de Cálcio-Calmodulina/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Macrófagos/metabolismo , Macrófagos/patologia , NF-kappa B/genética , Neoplasias/patologia , Fosforilação , Transdução de Sinais/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Notch has been implicated in human cancers and is a putative therapeutic target. However, the regulation of Notch activation in the nucleus remains largely uncharacterized. Therefore, characterizing the detailed mechanisms governing Notch degradation will identify attractive strategies for treating Notch-activated cancers. Here, we report that the long noncoding RNA (lncRNA) BREA2 drives breast cancer metastasis by stabilizing the Notch1 intracellular domain (NICD1). Moreover, we reveal WW domain containing E3 ubiquitin protein ligase 2 (WWP2) as an E3 ligase for NICD1 at K1821 and a suppressor of breast cancer metastasis. Mechanistically, BREA2 impairs WWP2-NICD1 complex formation and in turn stabilizes NICD1, leading to Notch signaling activation and lung metastasis. BREA2 loss sensitizes breast cancer cells to inhibition of Notch signaling and suppresses the growth of breast cancer patient-derived xenograft tumors, highlighting its therapeutic potential in breast cancer. Taken together, these results reveal the lncRNA BREA2 as a putative regulator of Notch signaling and an oncogenic player driving breast cancer metastasis.
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Neoplasias da Mama , Neoplasias Pulmonares , RNA Longo não Codificante , Humanos , Feminino , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Ubiquitinação , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Neoplasias Pulmonares/genética , Neoplasias da Mama/genética , Receptor Notch1/genética , Receptor Notch1/metabolismoRESUMO
Meningiomas are the most common primary intracranial tumors and account for nearly 30% of all nervous system tumors. Approximately half of meningioma patients exhibit neurofibromin 2 (NF2) gene inactivation. Here, NF2 was shown to interact with the endoplasmic reticulum (ER) calcium (Ca2+) channel inositol 1,4,5-trisphosphate receptor 1 (IP3R1) in IOMM-Lee, a high-grade malignant meningioma cell line, and the F1 subdomain of NF2 plays a critical role in this interaction. Functional assays indicated that NF2 promotes the phosphorylation of IP3R (Ser 1756) and IP3R-mediated endoplasmic reticulum (ER) Ca2+ release by binding to IP3R1, which results in Ca2+-dependent apoptosis. Knockout of NF2 decreased Ca2+ release and promoted resistance to apoptosis, which was rescued by wild-type NF2 overexpression but not by F1 subdomain deletion truncation overexpression. The effects of NF2 defects on the development of tumors were further studied in mouse models. The decreased expression level of NF2 caused by NF2 gene knockout or mutation affects the activity of the IP3R channel, which reduces Ca2+-dependent apoptosis, thereby promoting the development of tumors. We elucidated the interaction patterns of NF2 and IP3R1, revealed the molecular mechanism through which NF2 regulates IP3R1-mediated Ca2+ release, and elucidated the new pathogenic mechanism of meningioma-related NF2 variants. Our study broadens the current understanding of the biological function of NF2 and provides ideas for drug screening of NF2-associated meningioma.
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Apoptose , Sinalização do Cálcio , Cálcio , Receptores de Inositol 1,4,5-Trifosfato , Neoplasias Meníngeas , Meningioma , Animais , Humanos , Camundongos , Cálcio/metabolismo , Linhagem Celular Tumoral , Retículo Endoplasmático/metabolismo , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Receptores de Inositol 1,4,5-Trifosfato/genética , Neoplasias Meníngeas/metabolismo , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/genética , Meningioma/metabolismo , Meningioma/patologia , Meningioma/genética , Neurofibromina 2RESUMO
AUXIN/INDOLE-3-ACETIC ACIDs are transcriptional repressors for auxin signalling. Aux/IAAs of Arabidopsis thaliana display some functional redundancy. The IAA3/SHY2 clade (IAA1, IAA2, IAA3 and IAA4) show strong sequence similarity, but no higher-order mutants have been reported. Here, through CRISPR/Cas9 genome editing, we generated loss-of-function iaa1/2/3/4 mutants. The quadruple mutants only exhibited a weak phenotype. Thus, we additionally knocked out IAA7/AXR2 and IAA16, which are coexpressed with IAA1/2/3/4. Remarkably, under white light control conditions, the iaa1/2/3/4/7/16 mutants exhibited a shade avoidance-like phenotype with over-elongated hypocotyls and petioles and hyponastic leaves. The sextuple mutants were highly sensitive to low light intensity, and the hypocotyl cells of the mutants were excessively elongated. Transcriptome profiling and qRT-PCR analyses revealed that the sextuple mutation upregulated IAA19/MSG2 and IAA29, two shared shade/auxin signalling targets. Besides, genes encoding cell wall-remodelling proteins and shade-responsive transcription regulators were upregulated. Using dual-luciferase reporter assays, we verified that IAA2/IAA7 targeted the promoters of cell wall-remodelling genes to inhibit their transcription. Our work indicates that the IAA1/2/3/4/7/16 gene set is required for the optimal integration of auxin and shade signalling. The mutants generated here should be valuable for exploring the complex interactions among signal sensors, transcription activators and transcription repressors during hormone/environmental responses.
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OBJECTIVE: To retrospectively analyze the clinical characteristics of 193 Chinese patients with McCune-Albright syndrome (MAS). METHODS: By using keywords "McCune-Albright syndrome", "Albright syndrome", or " fibrous dysplasia " as the search terms, 193 cases of MAS reported in China from January 1990 to November 2022 from the Wanfang data, CNKI, VIP, PubMed, and Embase databases were obtained, and their clinical data was retrospectively analyzed. Intergroup comparisons were carried out by using t test, Mann-Whitney U test, and X2 test. RESULTS: The 193 MAS patients had included 42 males and 151 females, with the median first-visit age of females being younger than males. The typical triad group had accounted for 46.1% of patients, and the middle first-visit and diagnosis age was younger than the atypical group. The primary reason for first-visit in males of MAS was fibrous dysplasia (FD), whilst that in females of MAS was peripheral precocious puberty (PPP). FD has occurred in 84.5% of the patients, with an average age of onset age being 6.1 years old, and 90% was ≤ 16 years of age. Endocrine hyperfunction was found in 79.3% of the patients, with a higher proportion in females compared with males (P < 0.05). Pituitary involvement was seen in 21.8% of the patients, and the incidence of craniofacial FD and cranial nerve compression was significantly higher in those with elevated growth hormone (GH) than without (P < 0.05). Café-au-Lait Spots were noted in 86.5% of the patients, and 28.3% (28/99) had located on the different side of FD. CONCLUSION: Most MAS patients had atypical manifestations and multi-systemic involvement. It is more common and occurs earlier in females. The most common reasons for initial diagnosis in male and female patients were FD and PPP, respectively. Patients with elevated GH should be examined for cranial nerve compression.
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Displasia Fibrosa Poliostótica , Humanos , Displasia Fibrosa Poliostótica/genética , Masculino , Feminino , Criança , Adolescente , China , Pré-Escolar , Adulto , Estudos Retrospectivos , Adulto Jovem , Lactente , Povo Asiático/genética , Pessoa de Meia-Idade , População do Leste AsiáticoRESUMO
Pathological scarring resulting from traumas and wounds, such as hypertrophic scars and keloids, pose significant aesthetic, functional and psychological challenges. This study provides a comprehensive transcriptomic analysis of these conditions, aiming to illuminate underlying molecular mechanisms and potential therapeutic targets. We employed a co-expression and module analysis tool to identify significant gene clusters associated with distinct pathophysiological processes and mechanisms, notably lipid metabolism, sebum production, cellular energy metabolism and skin barrier function. This examination yielded critical insights into several skin conditions including folliculitis, skin fibrosis, fibrosarcoma and congenital ichthyosis. Particular attention was paid to Module Cluster (MCluster) 3, encompassing genes like BLK, TRPV1 and GABRD, all displaying high expression and potential implications in immune modulation. Preliminary immunohistochemistry validation supported these findings, showing elevated expression of these genes in non-fibrotic samples rich in immune activity. The complex interplay of different cell types in scar formation, such as fibroblasts, myofibroblasts, keratinocytes and mast cells, was also explored, revealing promising therapeutic strategies. This study underscores the promise of targeted gene therapy for pathological scars, paving the way for more personalised therapeutic approaches. The results necessitate further research to fully ascertain the roles of these identified genes and pathways in skin disease pathogenesis and potential therapeutics. Nonetheless, our work forms a strong foundation for a new era of personalised medicine for patients suffering from pathological scarring.
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Cicatriz Hipertrófica , Queloide , Humanos , Cicatriz Hipertrófica/genética , Cicatriz Hipertrófica/terapia , Cicatriz Hipertrófica/metabolismo , Queloide/genética , Queloide/terapia , Queratinócitos/metabolismo , Fibroblastos/metabolismo , Miofibroblastos/metabolismoRESUMO
Quasi-one-dimensional (quasi-1D) van der Waals crystal fibrous red phosphorus (RP) exhibits pronounced in-plane optical anisotropy, positioning it as a potential candidate for polarization-related micro-nano devices. Unfortunately, a comprehensive investigation into the complex refractive index of fibrous RP and the structure-activity relationship connecting the distinctive quasi-1D structure with optical anisotropy is currently deficient. Herein, we have collectively determined the complex refractive index of the fibrous RP flakes within the ab-plane through Kramers-Kronig (KK) analysis and theoretical calculation. Notably, the maximum birefringence of fibrous RP reaches 0.642@475â nm with an absolute extinction coefficient of only 0.08, superior to the reported traditional optical crystals and the emerging low-dimensional materials as well. The remarkable birefringence can be attributed to the synergistic influence of the large electronic dipole polarizability, anisotropic electron density distribution and the distortion of stereochemically active lone pair (SCALP). This work demonstrates the potential of fibrous RP for polarization-sensitive devices, illuminating possibilities to exploit novel giant birefringent crystals based on the structure-activity relationship.
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The lead-free hybrid perovskite piezoelectrics possess advantages of easy processing, light weight, and low-toxicity over inorganic ceramics. However, the lack of understanding in structure-property relationships hinders exploration of new molecular piezoelectric crystals with excellent performances. Herein, by introducing chiral α-phenylethylammonium (α-PEA+ ) cations into bismuth-based hybrid halides, centimeter-sized (R-α-PEA)4 Bi2 I10 and (S-α-PEA)4 Bi2 I10 single crystals with a superior piezoelectric voltage coefficient g22 of 309 mV m N-1 , are obtained. Structural rigidity in crystals leads to a remarkable electrostrictive coefficient Q22 of 25.8 m4 C-2 , nearly 20 times higher than that of poly(vinylidene fluoride) (PVDF), which is beneficial to improve piezoelectricity with the synergistic effect of chirality. Moreover, the as-grown crystals show outstanding phase stability from 173 K to ≈470 K. This work suggests a design strategy based on rigidity and chirality to exploit novel piezoelectrics among hybrid metal halides.
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The growth of high-quality halide perovskite single crystals is imperative to study their intrinsic physical properties and to realize high-performance optoelectronic devices. Here, a room-temperature solvent evaporation-induced crystallization (RTSEIC) method is reported based on Le Chatelier's principle, which provides a general strategy to grow halide perovskite single crystals including 3D, 2D, 1D, and 0D, and either hybrid or all-inorganic halide perovskites. Taking 2D n-BA2 PbBr4 (n-BA = butylammonium) as an example, the room-temperature crystallization kinetics is demonstrated. The centimeter-sized n-BA2 PbBr4 single crystals exhibit an extremely small full width at half maximum (FWHM) of 0.024° in (0 0 2) plane rocking curve and a small trap density of 2.74 × 1010 cm-3 . The superior crystalline quality endows the n-BA2 PbBr4 single crystal ultraviolet photodetectors with recorded performance among reported n-BA2 PbBr4 ultraviolet photodetectors, demonstrating a detectivity reaching 1.8 × 1013 Jones, a fast response time of 55 µs and a high on-off ratio of 104 . The low-cost, simple, general, and efficient RTSEIC method is anticipated to promote the blossoming of halide perovskites single crystals.
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In view of the significance of circular RNA (circRNA) in multiple carcinogeneses, our study focused on circ_0060937 and investigated its function and molecular mechanism in lung cancer. Quantitative real-time PCR (qPCR) and western blot assays were applied for expression analysis of circ_0060937, miR-1304-5p, LAD1, and several marker proteins. Functional experiments, including colony formation assay, EdU assay, transwell analysis, sphere formation assay, and flow cytometry experiment, were conducted for cell behavior analysis. The putative binding relationship between circ_0060937 and miR-1304-5p was validated by dual-luciferase reporter experiment and pull-down analysis. Animal models were established to ascertain the role of circ_0060937. Upregulation of circ_0060937 was shown in lung cancer tissues and cell lines. Circ_0060937 downregulation repressed A549 and H1299 cell proliferative, migratory, invasive, and sphere formation abilities, and circ_0060937 absence also decelerated tumorigenesis in animal models. Circ_0060937 bound to miR-1304-5p to positively regulate LAD1 expression. The inhibitory effects of circ_0060937 absence on A549 and H1299 cell malignant behaviors were largely reversed by miR-1304-5p inhibition or LAD1 overexpression, hinting that circ_0060937 affected lung cancer progression via modulating the miR-1304-5p/LAD1 axis. Circ_0060937 downregulation decreased the expression of LAD1 by releasing miR-1304-5p to effectively repress lung cancer cell growth and in vivo tumorigenesis.
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Neoplasias Pulmonares , MicroRNAs , Animais , Neoplasias Pulmonares/genética , Carcinogênese , Linhagem Celular , Movimento Celular , Proliferação de Células , MicroRNAs/genéticaRESUMO
Mitochondrial DNA (mtDNA) mutations result in a variety of genetic diseases. As an emerging therapeutic method, mtDNA editing technology recognizes targets more based on the protein and less on the nucleic acid. Although the protein recognition type mtDNA editing technology represented by zinc finger nuclease technology, transcription activator like effector nuclease technology and base editing technology has made some progress, the disadvantages of complex recognition sequence design hinder further popularization. Gene editing based on nucleic acid recognition by the CRISPR system shows superiority due to the simple structure, easy design and modification. However, the lack of effective means to deliver nucleic acids into mitochondria limits application in the field of mtDNA editing. With the advances in the study of endogenous and exogenous import pathways and the deepening understanding of DNA repair mechanisms, growing evidence shows the feasibility of nucleic acid delivery and the broad application prospects of nucleic acid recognition type mtDNA editing technology. Based on the classification of recognition elements, this article summarizes the current principles and development of mitochondrial gene editing technology, and discusses its application prospects.
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Genes Mitocondriais , Ácidos Nucleicos , Edição de Genes , Mitocôndrias/genética , DNA Mitocondrial/genética , TecnologiaRESUMO
BACKGROUND: Circular RNAs (circRNAs) have shown pivotal regulatory roles in the pathology of non-small cell lung cancer (NSCLC). However, the role of circ_0000463 in NSCLC progression and its associated molecular mechanism remain to be illustrated. METHODS: Cell proliferation ability was analyzed by colony formation assay and 5-ethynyl-2'-deoxyuridine (EdU) assay. Cell migration and invasion abilities were assessed by scratch test and transwell invasion assay. Flow cytometry was employed to analyze cell apoptotic rate. The interaction between microRNA-924 (miR-924) and circ_0000463 or solute carrier family 1 member 5 (SLC1A5) was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The uptake of glutamine and the production of glutamate and α-ketoglutarate were analyzed using their corresponding kits. Xenograft model in vivo was established to analyze the role of circ_0000463 in tumor growth. RESULTS: Circ_0000463 expression was elevated in NSCLC tissues and cell lines. Circ_0000463 knockdown suppressed the proliferation, migration, and invasion and promoted the apoptosis of NSCLC cells. Circ_0000463 acted as a molecular sponge for miR-924, and circ_0000463 interference-mediated anti-tumor effects were largely reversed by the silence of miR-924 in NSCLC cells. miR-924 interacted with the 3' untranslated region (3'UTR) of SLC1A5, and SLC1A5 overexpression largely overturned miR-924 overexpression-mediated anti-tumor effects in NSCLC cells. Moreover, circ_0000463 absence suppressed the glutamine metabolism of NSCLC cells by targeting miR-924/SLC1A5 axis. Circ_0000463 knockdown suppressed xenograft tumor growth in vivo. CONCLUSION: Circ_0000463 absence suppressed the malignant behaviors and glutamine metabolism of NSCLC cells through mediating miR-924/SLC1A5 axis.
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Sistema ASC de Transporte de Aminoácidos/genética , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs/genética , Antígenos de Histocompatibilidade Menor/genética , RNA Circular/genética , Animais , Apoptose/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Glutamina/metabolismo , Humanos , Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Ternary hybrid perovskite solid solutions have shown superior optoelectronic properties and better stability than their ABX3 simple perovskite counterparts under ambient conditions. However, crystal growth and identification of the accurate composition of these complex crystalline compounds remain challenging, and their stability under extreme conditions such as in highly moist atmosphere is unknown. Herein, large-size (up to 2â cm) single crystals of ternary perovskite 0.80FAPbI3 â x'FAPbBr3 â y'CsPbI3 (x'+y'=0.20) are grown. An elemental analysis method based on wavelength dispersive X-ray fluorescence is proposed to determine their accurate compositions. Among these single crystals, the composition with y'=0.12 shows the best moisture stability at 90 % relative humidity for 15â days. Other components with richer or poorer Cs+ ions undergo different phase segregation behaviours. The performance and stability of photodetectors based on these single crystals are tested. This work offers a deeper insight into phase stability of ternary hybrid perovskite solid solution crystals in highly moist atmosphere.
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CD133 (AC133/prominin-1) has been identified as a stem cell marker and a putative cancer stem cell marker in many solid tumors. Its biologic function and molecular mechanisms remain largely elusive. Here, we show that a fly mutant for prominin-like, a homolog of mammalian CD133, shows a larger body size and excess weight accompanied with higher fat deposits as compared with the wild type. The expression levels of prominin-like are mediated by ecdysone signaling where its protein levels increase dramatically in the fat body during metamorphosis. Prominin-like mutants exhibit higher Drosophila insulin-like peptide 6 (di lp6) levels during nonfeeding stages and increased Akt/ Drosophila target of rapamycin (dTOR) signaling. On an amino acid-restricted diet, prominin-like mutants exhibit a significantly larger body size than the wild type does, similar to that which occurs upon the activation of the dTOR pathway in the fat body. Our data suggest that prominin-like functions by suppressing TOR and dilp6 signaling to control body size and weight. The identification of the physiologic function of prominin-like in Drosophila may provide valuable insight into the understanding of the metabolic function of CD133 in mammals.-Zheng, H., Zhang, Y., Chen, Y., Guo, P., Wang, X., Yuan, X., Ge, W., Yang, R., Yan, Q., Yang, X., Xi, Y. Prominin-like, a homolog of mammalian CD133, suppresses di lp6 and TOR signaling to maintain body size and weight in Drosophila.
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Antígeno AC133/metabolismo , Tamanho Corporal , Peso Corporal , Proteínas de Drosophila/antagonistas & inibidores , Drosophila melanogaster/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Somatomedinas/antagonistas & inibidores , Antígeno AC133/genética , Animais , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Mutação , Receptores Proteína Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases/metabolismo , Transdução de Sinais , Somatomedinas/genética , Somatomedinas/metabolismoRESUMO
Doping has been a reliable way to improve the properties of black phosphorus (BP). However, a uniform and large amount of doping in BP remains a challenge. Herein, the synthesis of tellurium-doped black phosphorus (Te-doped BP) single crystals with high crystalline quality is achieved by the chemical vapor transport reaction method. The synthetic route enables a uniform and relatively large amount (up to 0.5% atomic ratio) of Te-doping in BP single crystals. The electrocatalytic oxygen evolution reaction (OER) properties of few-layer Te-doped BP nanosheets prepared by liquid exfoliation were also investigated for the first time. Electrochemical tests demonstrated that the OER onset-potential of undoped and Te-doped BP nanosheets was 1.63 and 1.49 V, respectively. The result implies that doping provides an effective route to enhance the electrochemical OER performance of BP.
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A systematic cytotoxicity study of layered black phosphorus (BP) is urgently needed before moving forward to its potential biomedical applications. Herein, bulk BP crystals are synthesized and exfoliated into layered BP with different lateral size and thickness. The cytotoxicity of as-exfoliated layered BP is evaluated by a label-free real-time cell analysis technique, displaying a concentration-, size-, and cell type-dependent response. The IC50 values can vary by 40 and 30 times among the BP sizes and cell types, respectively. BP-1 with the largest lateral size and thickness has the highest cytotoxicity; whereas the smallest BP-3 only shows moderate toxicity. The sensitivity of three tested cell lines follows the sequence of 293T > NIH 3T3 > HCoEpiC. Two possible mechanisms for BP to induce cytotoxicity are proposed and verified: (1) the generation of intracellular reactive oxygen species (ROS) is detected by a ROS sensitive probe using the inverted fluorescence microscopy and flow cytometry; (2) the interaction of layered BP and model cell membrane is examined by quartz crystal microbalance with dissipation, illustrating the disruption of cell membrane integrity especially by the largest BP-1. This systematic study of BP's cytotoxicity will shed light on its future biomedical and environmental applications.
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Sobrevivência Celular/efeitos dos fármacos , Fósforo/farmacologia , Animais , Citometria de Fluxo , Células HEK293 , Humanos , Camundongos , Microscopia de Fluorescência , Células NIH 3T3 , Fósforo/químicaRESUMO
Few-layer black phosphorus, also known as phosphorene, is a new two-dimensional material which is of enormous interest for applications, mainly in electronics and optoelectronics. Herein, we for the first time employ phosphorene for directing the self-assembly of asymmetric polystyrene-block-polymethylmethacrylate (PS-b-PMMA) block copolymer (BCP) thin film to form the perpendicular orientation of sub-10 nm PS nanopore arrays in a hexagonal fashion normal to the interface. We experimentally demonstrate that none of the PS and PMMA blocks exhibit preferential affinity to the phosphorene-modified surface. Furthermore, the perpendicularly-oriented PS nanostructures almost stay unchanged with the variation of number of layers of few-layer phosphorene nanoflakes between 15-30 layers. Differing from the neutral polymer brushes which are widely used for chemical modification of the silicon substrate, phosphorene provides a novel physical way to control the interfacial interactions between the asymmetric PS-b-PMMA BCP thin film and the silicon substrate. Based on our results, it is possible to build a new scheme for producing sub-10 nm PS nanopore arrays oriented perpendicularly to the few-layer phosphorene nanoflakes. Furthermore, the nanostructural microdomains could serve as a promising nanolithography template for surface patterning of phosphorene nanoflakes.
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(Pb,La)(Zr,Sn,Ti)O3 (PLZST) single crystals with their chemical composition located at the tetragonal antiferroelectric region are grown via the flux method in a PbO-PbF2-B2O3 mixture. Segregation of the Ti4+ component in the as-grown crystals is observed due to the strong affinity between the oxygen anion and Ti4+ ions. The critical electric field of the antiferroelectric to ferroelectric phase transition is determined to be about 0.5 kV mm-1. The electric field induced ferroelectric phase transforms back into the antiferroelectric phase at a depolarization temperature of 125 °C. Anisotropy of the harvested energy density and electrocaloric behaviors are achieved for the [100], [110] and [111]-oriented PLZST crystals. Based on the thermodynamic theory approach, all the abovementioned behaviors originate from the anisotropic total entropy change. Enhanced electrocaloric strength (0.3 K mm kV-1) and the harvested energy density of 0.62 J cm-3 are obtained in the [111]-oriented PLZST crystals. Our results demonstrate the competence of PLZST single crystals for cooling devices and pyroelectric energy harvesting and provide new opportunities to improve energy harvesting density and electrocaloric properties via the anisotropic structural layout, which make the PLZST crystals attractive for solid state cooling devices and energy conversion technologies.
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The liver is able to regenerate itself in response to partial hepatectomy or liver injury. This is accomplished by a complex network of different cell types and signals both inside and outside the liver. Bile acids (BAs) are recently identified as liver-specific metabolic signals and promote liver regeneration by activating their receptors: Farnesoid X Receptor (FXR) and G-protein-coupled BA receptor 1 (GPBAR1, or TGR5). FXR is a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors. FXR promotes liver regeneration after 70% partial hepatectomy (PHx) or liver injury. Moreover, activation of FXR is able to alleviate age-related liver regeneration defects. Both liver- and intestine-FXR are activated by BAs after liver resection or injury and promote liver regeneration through distinct mechanism. TGR5 is a membrane-bound BA receptor and it is also activated during liver regeneration. TGR5 regulates BA hydrophobicity and stimulates BA excretion in urine during liver regeneration. BA signaling thus represents a novel metabolic pathway during liver regeneration. This article is part of a Special Issue entitled: Nuclear receptors in animal development.