Tuning ferroelectric phase transition temperature by enantiomer fraction.

Tuning phase transition temperature is one of the central issues in phase transition materials. Herein, we report a case study of using enantiomer fraction engineering as a promising strategy to tune the Curie temperature (TC) and related properties of ferroelectrics. A series of metal-halide perovskite ferroelectrics (S-3AMP)x(R-3AMP)1-xPbBr4 was synthesized where 3AMP is the 3-(aminomethyl)piperidine divalent cation and enantiomer fraction x varies between 0 and 1 (0 and 1 = enantiomers; 0.5 = racemate). With the change of the enantiomer fraction, the TC, second-harmonic generation intensity, degree of circular polarization of photoluminescence, and photoluminescence intensity of the materials have been tuned. Particularly, when x = 0.70 - 1, a continuously linear tuning of the TC is achieved, showing a tunable temperature range of about 73 K. This strategy provides an effective means and insights for regulating the phase transition temperature and chiroptical properties of functional materials.

Halogen Substitution Regulates High Temperature Dielectric Switch in Lead-Free Chiral Hybrid Perovskites.

Hybrid metal halides (HMHs) based phase transition materials have received widespread attention due to their excellent performance and potential applications in energy harvesting, optoelectronics, ferroics, and actuators. Nevertheless, effectively regulating the properties of phase transitions is still a thorny problem. In this work, two chiral lead-free HMHs (R-3FP)2 SbCl5 (1; 3FP=3-fluoropyrrolidinium) and (R-3FP)2 SbBr5 (2) were synthesized. By replacing the halide ions in the inorganic skeleton, the phase transition temperature of 2 changes with an increase of about 20 K, compared with 1. Meanwhile, both compounds display reversible dielectric switching properties. Through crystal structure analysis and Hirshfeld surface analysis, their phase transitions are ascribed to the disorder of the cations and deformation of the inorganic chains.

Curcumin inhibits the invasion and migration of pancreatic cancer cells by upregulating TFPI-2 to regulate ERK- and JNK-mediated epithelial-mesenchymal transition.

PURPOSE: Pancreatic cancer (PC) is one of the most deadly human malignancies. Curcumin is a natural polyphenolic compound with wide-ranging pharmacological effects. Growing evidence suggests that curcumin has anticancer activity against PC, but the mechanism remains incompletely elucidated. This study aimed to investigate the effects and mechanisms of curcumin on the invasion and migration of PC cells. METHODS: Effect of curcumin on tissue factor pathway inhibitor (TFPI)-2 mRNA expression in PC cells was initially identified using qRT-PCR. Cytotoxicity of curcumin was assessed with MTT assays and IC50 was calculated. Involvement of ERK and JNK pathways, as well as protein expression of TFPI-2 and epithelial-mesenchymal transition (EMT)-related markers, were detected using immunoblotting. Invasion and migration of PC cells were examined using Transwell assays. TFPI-2 expression was manipulated by transfection with siRNA and shRNA. Rescue assays were used to validate the effect of curcumin on cell invasion and migration via TFPI-2. RESULTS: Curcumin increased the expression of TFPI-2 mRNA and protein in PC cells and attenuated cell invasion and migration. Curcumin also inhibited ERK and JNK pathways and EMT in PC cells. Knockdown of TFPI-2 partially reversed the inhibition of ERK and JNK pathways and EMT by curcumin. Mechanistically, curcumin upregulated TFPI-2, thereby inhibiting the ERK and JNK pathways, leading to the inhibition of EMT in PC cells. CONCLUSION: Collectively, curcumin inhibits ERK- and JNK-mediated EMT through upregulating TFPI-2, which in turn suppresses the migration and invasion of PC cells. These findings provide new insights into the antitumor mechanism of curcumin.

Chemically Asymmetric Polymers Manipulate the Crystallization of Two-Dimensional Covalent Organic Frameworks to Synthesize Processable Nanosheets.

Nanosheets derived from two-dimensional covalent organic frameworks (2D COFs) are increasingly desirable in various fields. While breakthroughs in the chemical and physical delamination of 2D COFs are rising, precisely regulating the growth of the COF nanosheets has not been realized yet. Herein, we report an effective strategy of polymer-manipulated crystallization to accurately control the growth of COF nanosheets. Chemically asymmetric polyvinylpyrrolidone (PVP) is developed as the manipulator that selectively interacts with the aldehydes and (100) facet to induce anisotropic growth of COFs. The number of PVP constitutional units determines this specific interaction, leading to molecularly thin but thickness-controllable nanosheets with excellent dispersity. We process these nanosheets into robust A4-sized membranes for ultraselective molecular separation. The membrane intercalated with long-chain PVP demonstrates largely improved performance, surpassing the reported COF membranes. This work reports a strategy for anisotropically crystallizing 2D COFs to yield processable nanosheets toward practical applications.

A Two-Dimensional Hybrid Lead Bromide Ferroelectric Semiconductor with an Out-of-Plane Polarization.

A two-dimensional (2D) organic-inorganic hybrid perovskite (OIHP) material with out-of-plane ferroelectricity is the key to the miniaturization of vertical-sandwich-type ferroelectric optoelectronic devices. However, 2D OIHP ferroelectrics with out-of-plane polarization are still scarce, and effective design strategies are lacking. Herein, we report a novel 2D Dion-Jacobson perovskite ferroelectric semiconductor synthesized by a rigid-to-flexible cationic tailoring strategy, achieving an out-of-plane polarization of 1.7 µC/cm2 and high photoresponse. Integrating out-of-plane ferroelectricity with excellent photoelectric properties affords a promising platform to investigate ferroelectricity-related effects in vertical optoelectronic devices.

Tumorigenic and immunological roles of Heat shock protein A2 in pancreatic cancer: a bioinformatics analysis.

OBJECTIVE: Heat shock protein A2 has been reported to be tightly associated with tumorigenesis and tumor progression. This study aimed to determine the oncogenic and immunological roles of Heat shock protein A2 in pancreatic cancer by bioinformatics. METHODS: Expression of Heat shock protein A2 in tumorous and normal specimens of pancreatic cancer was analyzed using the Cancer Genome Atlas and the Cancer Genome Atlas + Genotype-Tissue Expression data sets, respectively. Relationships of Heat shock protein A2 expression with immune infiltrates in pancreatic cancer were assessed. Heat shock protein A2-associated coexpressed genes in pancreatic cancer were obtained, followed by the implementation of enrichment analysis. RESULTS: The data demonstrated that Heat shock protein A2 was significantly overexpressed in tumorous samples compared with normal samples. Heat shock protein A2 expression was remarkably positively interrelated with CD8+ T cell, neutrophil, dendritic cell, and macrophage, but not with CD4+ T and B cells. Heat shock protein A2 expression was markedly positively relevant to both cancer-associated fibroblast and endothelial cell. Enrichment data revealed that Heat shock protein A2 was intimately involved in the tumorigenesis and progression of pancreatic cancer. CONCLUSION: Heat shock protein A2 is upregulated in pancreatic cancer and is closely associated with tumor immunity and aggressive progression.

Tumorigenic and immunological roles of Heat shock protein A2 in pancreatic cancer: a bioinformatics analysis

SUMMARY OBJECTIVE: Heat shock protein A2 has been reported to be tightly associated with tumorigenesis and tumor progression. This study aimed to determine the oncogenic and immunological roles of Heat shock protein A2 in pancreatic cancer by bioinformatics. METHODS: Expression of Heat shock protein A2 in tumorous and normal specimens of pancreatic cancer was analyzed using the Cancer Genome Atlas and the Cancer Genome Atlas + Genotype-Tissue Expression data sets, respectively. Relationships of Heat shock protein A2 expression with immune infiltrates in pancreatic cancer were assessed. Heat shock protein A2-associated coexpressed genes in pancreatic cancer were obtained, followed by the implementation of enrichment analysis. RESULTS: The data demonstrated that Heat shock protein A2 was significantly overexpressed in tumorous samples compared with normal samples. Heat shock protein A2 expression was remarkably positively interrelated with CD8+ T cell, neutrophil, dendritic cell, and macrophage, but not with CD4+ T and B cells. Heat shock protein A2 expression was markedly positively relevant to both cancer-associated fibroblast and endothelial cell. Enrichment data revealed that Heat shock protein A2 was intimately involved in the tumorigenesis and progression of pancreatic cancer. CONCLUSION: Heat shock protein A2 is upregulated in pancreatic cancer and is closely associated with tumor immunity and aggressive progression.

Upregulated HSPA2 predicts early relapse of pancreatic cancer after surgery.

BACKGROUND: Heat shock protein A2 (HSPA2) is known to relate to the pathogenesis and progress of cancer. This study aimed to investigate the connection between HSPA2 and early postsurgical relapse of pancreatic cancer (PC). METHODS: Expression of HSPA2 in 85 pairs of cancerous and matched noncancerous samples was determined by immunostaining method. The relationship between HSPA2 expression and early postsurgical recurrence was assessed using logistic regression. The performance and potential application of HSPA2 expression to predict early postsurgical recurrence was evaluated by receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA). RESULTS: HSPA2 expression in tumor specimens was markedly elevated compared with non-tumor specimens. Logistic regression analysis indicated that HSPA2 upregulation was an independent risk marker for early postsurgical recurrence of PC. ROC curve analysis and DCA demonstrated that both the area under the curve (AUC) and the net benefit of HSPA2 expression were higher than those of other clinicopathologic features in predicting early postsurgical relapse of PC. The combination of HSPA2 expression with other malignant clinicopathologic characteristics had greater AUC and net benefit relative to them alone in predicting early postsurgical recurrence. CONCLUSIONS: Upregulated HSPA2 independently predicts early postsurgical recurrence of PC and has superior predictive performance and potential application value when combined with malignant clinicopathologic features. Our findings reveal that HSPA2 is a promising predictor for early postoperative relapse of PC.

Overexpressed HSPA2 correlates with tumor angiogenesis and unfavorable prognosis in pancreatic carcinoma.

Heat shock-related 70-kDa protein 2 (HSPA2) is known to correlate with tumor development and progression. This work aimed to determine the expression and prognostic roles of HSPA2 in pancreatic carcinoma. Tumor and their corresponding non-tumor tissues were obtained from 80 patients with pancreatic carcinoma. HSPA2 expression in tumor and non-tumor tissues was evaluated by immunohistochemistry. Expression of vascular endothelial growth factor (VEGF) and CD31 in tumor tissues were also evaluated by immunostaining. The relationships of HSPA2 with clinicopathological data, tumor angiogenesis and prognosis were analyzed. The results showed that HSPA2 expression was significantly elevated in tumor tissues compared with adjacent non-tumor tissues (P < 0.05). High HSPA2 expression was significantly associated with aggressive clinicopathological characteristics. HSPA2 staining was positively correlated with VEGF (r = 0.466, P < 0.001) and microvessel density (MVD) (r = 0.366, P = 0.001) in tumor tissues. Patients with high HSPA2 expression showed worse relapse-free survival (RFS) (P < 0.001) and overall survival (OS) (P < 0.001) than those with low HSPA2 expression. Multivariate analysis indicated that high HSPA2 expression was an independent predictor for poor RFS (P < 0.001) and OS (P = 0.001). Taken together, overexpressed HSPA2 is correlated with tumor angiogenesis and poor prognosis in pancreatic carcinoma. HSPA2 may play an important role in tumor progression, and serve as a potential biomarker for the prediction of adverse prognosis in pancreatic carcinoma.

Sulfotyrosine dipeptide: Synthesis and evaluation as HIV-entry inhibitor.

Human immunodeficiency virus type 1 (HIV-1) is responsible for the worldwide AIDS pandemic. Due to the lack of prophylactic HIV-1 vaccine, drug treatment of the infected patients becomes essential to reduce the viral load and to slow down progression of the disease. Because of drug resistance, finding new antiviral agents is necessary for AIDS drug therapies. The interaction of gp120 and co-receptor (CCR5/CXCR4) mediates the entry of HIV-1 into host cells, which has been increasingly exploited in recent years as the target for new antiviral agents. A conserved co-receptor binding site on gp120 that recognizes sulfotyrosine (sTyr) residues represents a structural target to design novel HIV entry inhibitors. In this work, we developed an efficient synthesis of sulfotyrosine dipeptide and evaluated it as an HIV-1 entry inhibitor.

Anticancer activity of Honokiol against lymphoid malignant cells via activation of ROS-JNK and attenuation of Nrf2 and NF-κB.

PURPOSE: To evaluate the effect of Honokiol (HK) in the ROS-JNK pro-apoptotic pathway and NF-κB, Nrf2 anti-apoptotic pathways, in order to seek a possible explanation for its anticancer efficacy. METHODS: The Raji and Molt4 cell lines were utilized for the determination of anticancer activity against lymphoid malignant cells. BALB/C nude mice, weighing 18-20g each and aged 4-5 weeks, were procured from the central animal house facility. For establishing non-Hodgkin lymphoma in BALB/C, the nude mice were subcutaneously administered 1×10(7) Raji cells, suspended in 0.2 mL sterile PBS on the back. The mice were then randomly divided into 3 groups (6 mice in each group). HK cytotoxicity was determined using the colorimetric MTT assay. RESULTS: In colorimetry-based MTT assay, the cytotoxicity of HK was determined at different time intervals, in lymphoid malignant Raji and Molt4 cell lines. HK exhibited prominent cytotoxicity against Raji cell lines with IC50 of 0.092 ± 0.021 µM. In Molt4 cells, the administration of HK caused significant cytotoxicity with IC50 of 0.521 ± 0.115 µM. The treatment of HK caused significant increase in the activity of reactive oxygen species (ROS) in Raji cells at various time intervals. Moreover, the level of NF-κB was significantly reduced in the presence of HK, which could be easily understood by a decreased level of p-65. Furthermore, in the presence of ROS inhibitor NAC (10mM) for 24 hrs, the JNK pathway was markedly activated, together with inhibition of NF-κB activity and a reduced level of Nrf2 expression. To further confirm the in vitro results by in vivo activity, HK was observed to inhibit the proliferation of Raji cells in vivo, which might be attributable to its inhibitory effect against the progression of the tumor (p<0.05). CONCLUSION: The present study suggests that HK causes considerable induction of apoptosis in lymphoid malignant cells, both in vitro and in vivo, whereas the generation of ROS might serve as an underlying mechanism for inducing apoptosis.

Evolution of Src Homology 2 (SH2) Domain to Recognize Sulfotyrosine.

Protein tyrosine O-sulfation is considered as the most common type of post-translational tyrosine modification in nature and plays important roles in extracellular biomolecular interactions. To facilitate the mapping, biological study, and medicinal application of this type of post-translational modification, we seek to evolve a small protein scaffold that recognizes sulfotyrosine with high affinity. We focused our efforts on the engineering of the Src Homology 2 (SH2) domain, which represents the largest class of known phosphotyrosine-recognition domain in nature and has a highly evolvable binding pocket. By using phage display, we successfully engineered the SH2 domain to recognize sulfotyrosine with high affinity. The best mutant, SH2-60.1, displayed more than 1700 fold higher sulfotyrosine-binding affinity than that of the wild-type SH2 domain. We also demonstrated that the evolved SH2 domain mutants could be used to detect sulfoprotein levels on the cell surface. These evolved SH2 domain mutants can be potentially applied to the study of protein tyrosine O-sulfation with proper experimental designs.

Inhibiting Hexamer Disassembly of Human UDP-Glucose Dehydrogenase by Photoactivated Amino Acid Cross-Linking.

The enzyme UDP-glucose dehydrogenase (UGDH) catalyzes the reaction of UDP-glucose to UDP-glucuronate through two successive NAD(+)-dependent oxidation steps. Human UGDH apoprotein is purified as a mixture of dimeric and hexameric species. Addition of substrate and cofactor stabilizes the oligomeric state to primarily the hexameric form. To determine if the dynamic conformations of hUGDH are required for catalytic activity, we used site-specific unnatural amino acid incorporation to facilitate cross-linking of monomeric subunits into predominantly obligate oligomeric species. Optimal cross-linking was achieved by encoding p-benzoyl-l-phenylalanine at position 458, normally a glutamine located within the dimer-dimer interface, and exposing the enzyme to long wavelength ultraviolet (UV) radiation in the presence of substrate and cofactor. Hexameric complexes were purified by gel filtration chromatography and found to contain significant fractions of dimer and trimer (approximately 50%) along with another 10% higher-molecular mass species. The activity of the cross-linked enzyme was reduced by almost 60% relative to that of the un-cross-linked UGDH mutant, and UV exposure had no effect on the activity of the wild-type enzyme. These results support a model for catalysis in which the ability to dissociate the dimer-dimer interface is as important for maximal enzyme function as has been previously shown for the formation of the hexamer.

Fine-tuning interaction between aminoacyl-tRNA synthetase and tRNA for efficient synthesis of proteins containing unnatural amino acids.

By using a directed evolution approach, we have identified aminoacyl-tRNA synthetase variants with significantly enhanced activity for the incorporation of unnatural amino acids into proteins in response to the amber nonsense codon in bacteria. We demonstrated that the optimization of anticodon recognition of tRNA by aminoacyl-tRNA synthetase led to improved incorporation efficiency that is unnatural amino acid-specific. The findings will facilitate the creation of an optimized system for the genetic incorporation of unnatural amino acids in bacteria.

Factors related to the time to cryptorchidism surgery--a nationwide, population-based study in Taiwan.

BACKGROUND/PURPOSE: Current guidelines recommend that the optimal timing for cryptorchidism surgery is by the age of 12 months. This study investigated the trend of surgical timing and examined the factors associated with time to surgery for cryptorchidism in Taiwan by using a nationwide, population-based database. METHODS: The present study utilized the Longitudinal Health Insurance Database 2005, a subset of the National Health Insurance Research Database, which contains data on all paid medical benefit claims over the period 1997-2007 for a subset of 1 million beneficiaries randomly drawn from 22.72 million individuals enrolled in the National Health Insurance program in 2005. We analyzed the timing of surgery in boys younger than 18 years with diagnosis of cryptorchidism. RESULTS: We identified 547 boys who underwent surgery under 18 years of age. Approximately 79.2% of study participants received surgery after the age of 12 months. A multivariate analysis showed that several factors were significantly associated with time to surgery: age of the physician making the diagnosis, age of the surgeon performing the surgery, age of the patient at the first diagnosis of cryptorchidism, and number of previous clinic visits with the diagnosis of cryptorchidism and urbanization level of the patient's residence. CONCLUSION: A surprisingly high rate (79.2%) of all study participants underwent surgery beyond the optimal timing. Certain doctor and patient factors were associated with time to cryptorchidism surgery. Improving the alertness and education of parents and specialists may lead to earlier surgeries.

Molecular recognition of sulfotyrosine and phosphotyrosine by the Src homology 2 domain.

We study molecular recognition of two closely resembling posttranslational modification products, phosphotyrosine (pTyr) and sulfotyrosine (sTyr). The differences in charge, size, and binding geometry of pTyr and sTyr are the main recognition elements. Protein engineering can be applied to alter the specificity and strength of the recognition.

Sediment sources of Yan'gou watershed in the Loess Hilly region China under a certain rainstorm event.

At present the large scale vegetation restoration and intensive oil exploiting had brought huge influence on local environment in Yan'an region. the sediment yield data form series experiment plots and hydrological monitoring station in the Yan'an watershed after one rainfall event on July 2, 2005, which included sediment from different land uses (crop-land plot, vegetation plots, hard road surface) and 3 types roads(mountain-road brunches, mountain-road, and mountain-transport way) has been analyzed. Results showed that the erosion intensity of the 3 type roads was respectively 500 t/km(2), 3163 t/km(2), and 13500 t/km(2). The sediment from cropland and grass, shrub land was within 6-184 t/km(2). It stated that sediment from road area which only covered 1% of total area accounted for 42.3% of the total sediment yield, far beyond that from other uses of land. Sediment from grass-land and shrub-land, which covered 70.5% of watershed area, shared 26.7% of the total sediment. The further analysis showed that the 41.2% of total sediment could be detained by re-vegetation. On the contrary, that road constructing brought heavy sediment which offset the benefit of vegetation restore by 58.4%. the suggestion were to adjust our strategy from slope management to the road erosion mitigation Many studies have confirmed it is an important measure to return the steep slope farming land to green, and to restore vegetation in line with local conditions to prevent soil erosion in the Loess Plateau [1, 2]. To implement the measure in western region, the researches on "Grain for Green", returning farmland to forest and grassland, has become popular [3, 4]. Many scholars studied the effects of farming land and trees and grass land on soil water storage [2, 5]. Tang Keli stated that the slope land for farming was the main source of the sediment in Yellow river, and the maximum gradient slope for farming land use was 25° [6]. Many authorities not only pointed out that a far-reaching influence of land-use changes on the distribution of sediment source area but also put forward some new ideas about returning farming to green in Loess Plateau [7, 8]. However, we were still not sure the contribution of returning farmland to forest and grassland on reducing sediment yield of the valley and known it was difficult to identify its contribution to the total sediment yield. Analysis on the contribution of the stream channel and slope sediment yield had some results already [9, 10]. It was still too early to make clear the relationship between the sediment sources changes of the valley and the management. At present, Ecological restoration in the Loess Plateau caused the sediment form the slope land declining [3]. Due to human economic activities, the mountain road developed rapidly, it is inevitable that road erosion has been intensified [11]. A. Rijsdijk and LA Bruijnzeel (1991), [12] based the valley Konto observation, pointed out that although the rural road in the area accounts for only 3% of the area, but the impact on the sediment of this area was tremendous. Nyssen J, Moneryersons J. et al (2002) [13] also think that road without protection is one of the main sources of sediment. Many kinds of protective measures have great importance to the road erosion control. So attentions were paid to the study on the protection all kind of roads. Then what will happen to the soil erosion of the watershed, driven by the vegetation restoration and new road construction? What will happen to the proportion of sediment quality from slope land, road area and gully? A correct understanding of the sediment sources pattern of the typical watershed is of great significance on assessment the roles of vegetation to slope management and the roles of prevention the linear path erosion.

Metabolic syndrome associated with reduced lower urinary tract symptoms in middle-aged men receiving health checkup.

OBJECTIVE: To investigate the impact of metabolic syndrome on lower urinary tract symptoms in a sample of middle-aged men receiving a health checkup. METHODS: Subjects aged 45 years or older who voluntarily underwent a medical checkup were enrolled. Participant demographics and health history were collected by a self-administered questionnaire. All participants were stratified into 2 groups by the presence of metabolic syndrome, as defined according to the updated National Cholesterol Education Program's Adult Treatment Panel III. Prostate volume and prostate-specific antigen levels were used for subgroup analysis. RESULTS: During January through December of 2010, 708 subjects with a mean age of 55.6 ± 9.72 years were enrolled into the study. Compared to the nonmetabolic syndrome group, the metabolic syndrome group had lower total international prostatic symptoms score (7.89 ± 6.63 vs 6.85 ± 6.52, P = .05) and lower severity of weak urinary stream (1.24 ± 1.60 vs 0.95 ± 1.50, P = .021). In the higher prostate volume group (prostate volume ≥ 30 mL), total international prostatic symptoms score, storage score, and urinary frequency, urgency and incomplete emptying were lower in men vs those without metabolic syndrome (all P < .05). The negative association between voiding score, severity of lower urinary tract symptoms, and metabolic syndrome became particularly pronounced as the number of metabolic syndrome factors increased (P for trend < .01). CONCLUSION: We confirmed that metabolic syndrome had favorable effects on lower urinary tract symptoms, including voiding and storage symptoms in healthy middle-aged men. This beneficial effect was most significant in men with enlarged prostate and/or high prostate specific antigen levels.