Boron dopant- and nitrogen defect-decorated C3N5 porous nanostructure as an efficient sulfur host for lithium-sulfur batteries.

Active site implantation and morphology manipulation are efficient protocols for boosting the electrochemical performance of carbon nitrides. As a promising sulfur host for lithium-sulfur batteries (LSBs), in this study, C3N5 porous nanostructure incorporated with both boron (B) atoms and nitrogen (N) defects was constructed (denoted as ND-B-C3N5) using a two-step strategy, i.e., pyrolysis of the mixture of 3-amino-1,2, 4-triazole and boric acid to obtain B-doped C3N5 porous nanostructure and then KOH etching under hydrothermal condition to generate N defects. The doped B atoms in the C3N5 porous nanostructure are in the form of B-N bonds and grafted B-O bonds. N defects are primarily created at the CN-C positions of the triazine unit, leaving behind some N vacancies and cyano groups. Benefiting from the involvement of B dopants and N defects, the optimized ND-B-C3N5-12 sample exhibits ameliorative conductivity, mass transport, lithium polysulfides (LiPSs) adsorption ability, diffusion of Li+ ions, Li2S deposition capacity, sulfur redox polarization, and a reversible solid-solid sulfur redox process. Consequently, the ND-B-C3N5-12/S cathode delivers accelerated redox performance of polysulfides for LSBs, revealing capacities of 1091 ± 44 and 753 ± 20 mAh/g at 0.2C for the initial and 300th cycles, respectively. The ND-B-C3N5-12/S cathode is also endowed with desired sulfur redox activity and stability at 2C for 1000 cycles, holding an initial discharging capacity of 788 ± 24 mAh/g and a low decay rate of 0.05 % per cycle.

Monitoring and influencing factors of grassland livestock overload in Xinjiang from 1982 to 2020.

It is crucial to estimate the theoretical carrying capacity of grasslands in Xinjiang to attain a harmonious balance between grassland and livestock, thereby fostering sustainable development in the livestock industry. However, there has been a lack of quantitative assessments that consider long-term, multi-scale grass-livestock balance and its impacts in the region. This study utilized remote sensing and empirical models to assess the theoretical livestock carrying capacity of grasslands. The multi-scale spatiotemporal variations of the theoretical carrying capacity in Xinjiang from 1982 to 2020 were analyzed using the Sen and Mann-Kendall tests, as well as the Hurst index. The study also examined the county-level grass-livestock balance and inter-annual trends. Additionally, the study employed the geographic detector method to explore the influencing factors. The results showed that: (1) The overall theoretical livestock carrying capacity showed an upward trend from 1982 to 2020; The spatial distribution gradually decreased from north to south and from east to west. In seasonal scale from large to small is: growing season > summer > spring > autumn > winter; at the monthly scale, the strongest livestock carrying capacity is in July. The different grassland types from largest to smallest are: meadow > alpine subalpine meadow > plain steppe > desert steppe > alpine subalpine steppe. In the future, the theoretical livestock carrying capacity of grassland will decrease. (2) From 1988 to 2020, the average grass-livestock balance index in Xinjiang was 2.61%, showing an overall increase. At the county level, the number of overloaded counties showed an overall increasing trend, rising from 46 in 1988 to 58 in 2020. (3) Both single and interaction factors of geographic detectors showed that annual precipitation, altitude and soil organic matter were the main drivers of spatiotemporal dynamics of grassland load in Xinjiang. The results of this study can provide scientific guidance and decision-making basis for achieving coordinated and sustainable development of grassland resources and animal husbandry in the region.

Construction of N-doped carbon encapsulated Mn2O3/MnO heterojunction for enhanced lithium storage performance.

Owing to high theoretical capacity, low cost and abundant availability, manganese oxides are widely viewed as promising anodes for lithium-ion batteries (LIBs). Nonetheless, their practical application is significantly hindered by poor electrical conductivity, sluggish reaction kinetics and substantial volume change. In this work, an ingenious polypyrrole encapsulation followed by pyrolysis strategy is proposed to produce N-doped carbon encapsulated Mn2O3/MnO heterojunction (Mn2O3/MnO@NC) by using mechanically ground Mn3O4/C3N4 mixture as the precursor. The results show that the selection of precursor plays a pivotal role in the successful preparation of Mn2O3/MnO@NC hybrid. It is revealed that the uniform encapsulation by N-doped carbon significantly enhances the conductivity and structural stability of the final product. Concurrently, the Mn2O3/MnO heterojunction within the resultant hybrid exhibits a unique quantum-dot size, which effectively shortens ion transport pathways and exposes the active sites for lithium storage. Additionally, experimental observations and theoretical calculations demonstrate that the built-in electric fields generated at the interfaces of Mn2O3/MnO heterojunction accelerate the charge transfer and ion diffusion, thereby enhancing the electrochemical reaction kinetics. As a result, the Mn2O3/MnO@NC hybrid displays much enhanced lithium storage performance. Evidently, our work offers a good guidance for the design and synthesis of advanced transition metal oxide/carbon anodes for LIBs.

Bioelectrochemical cascade reaction for energy-saving hydrogen production and innovative Zn-air batteries.

The oxygen evolution reaction (OER) is an important half-reaction in electrochemical hydrogen production (EHP) and rechargeable metal-air batteries. However, the sluggish OER kinetics has seriously impeded their performance. Herein, we report a bioelectrochemical cascade system composed of glucose oxidase (GOx)-functionalized N-doped porous carbon nanofibers to replace OER in EHP and rechargeable Zn-air batteries (ZABs) applications. In this cascade system, GOx catalyzes oxidation of glucose to produce value-added gluconic acid accompanied with the generation of H2O2 under aerobic conditions. The subsequent electrocatalytic oxidation of H2O2 replacing the OER results in an onset voltage below 1.10 V for EHP, and a low charging voltage of 1.35 V as well as a small charging/discharging voltage gap of âˆ¼ 280 mV over 170 h for ZABs in neutral aqueous electrolytes. The advantages of employing the innovative bioelectrochemical cascade reaction are demonstrated in EHP and ZABs, achieving the full utilization of biomass energy in energy-saving electrochemical systems for energy storage and conversion.

3D hierarchical self-supporting Bi2Se3-based anode for high-performance lithium/sodium-ion batteries.

Bi2Se3 is a promising material for anodes in lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs) due to its abundance, easy preparation, and high capacity. However, its practical application is hindered by low conductivity and significant volume variation during cycling, leading to poor rate capability and cycling stability. Herein, a novel composite consisting of Bi2Se3 nanoplates deposited on carbon cloth (CC) and encapsulated by reduced graphene oxide (rGO) has been designed and synthesized. The composite structure combines the advantages of the Bi2Se3 nanoplates, CC substrate, and rGO encapsulation, leading to enhanced electrochemical properties. The physical vapor deposition of Bi2Se3 nanoplates onto CC ensures a high loading of active material, while the rGO encapsulation provides a conductive and stable framework for the composite. This synergistic design allows for improved electron and ion transport, as well as efficient accommodation of the volume changes during cycling. In LIBs, the composite demonstrates a high reversible capacity of 467.5 mAh/g at 0.1 A/g after 120 cycles. Moreover, it displays an outstanding rate capability, delivering a capacity of 398.6 mAh/g at 5.0 A/g. Similarly, in SIBs, the composite maintains a reversible capacity of 375.3 mAh/g at 0.1 A/g over 100 cycles and exhibits a high-rate capacity of 286.3 mAh/g at 5.0 A/g. This work represents a significant step forward in addressing the challenges associated with Bi2Se3 as an anode material, paving the way for the development of high-performance LIBs and SIBs.

Defect-Enriched Graphene Nanoribbons Tune the Adsorption Behavior of the Mediator to Boost the Lactate/Oxygen Biofuel Cell.

Owing to the high efficiency and specificity in moderate conditions, enzymatic biofuel cells (EBFCs) have gained significant interest as a promising energy source for wearable devices. However, the instability of the bioelectrode and the lack of efficient electrical communication between the enzymes and electrodes are the main obstacles. Herein, defect-enriched 3D graphene nanoribbons (GNRs) frameworks are fabricated by unzipping multiwall carbon nanotubes, followed by thermal annealing. It is found that defective carbon shows stronger adsorption energy towards the polar mediators than the pristine carbon, which is beneficial to improving the stability of the bioelectrodes. Consequently, the EBFCs equipped with the GNRs exhibit a significantly enhanced bioelectrocatalytic performance and operational stability, delivering an open-circuit voltage and power density of 0.62 V, 70.7 µW/cm2, and 0.58 V, 18.6 µW/cm2 in phosphate buffer solution and artificial tear, respectively, which represent the high levels among the reported literature. This work provides a design principle according to which defective carbon materials could be more suitable for the immobilization of biocatalytic components in the application of EBFCs.

Effects of drought and climate factors on vegetation dynamics in Central Asia from 1982 to 2020.

Ecological security and ecosystem stability in Central Asia depend heavily on the local vegetation. Vegetation dynamics and the response and hysteresis relationships to climate factors and drought on multiple scales over long time series in the region still need to be further explored. Using the net primary productivity (NPP) values as the vegetation change index of interest, in this study, we analyzed vegetation dynamics in Central Asia from 1982 to 2020 and assessed the responses and time lags of vegetation to climate factors and drought. The results showed that NPP gradually decreased from north to south and from east to west. Vegetation was distributed along both sides of the mountains. The temperatures rose from northeast to southwest, while precipitation gradually increased from southwest to northeast. The proportion of dry and wet years was as follows: normal (56.41%) > slightly dry (28.2%) > slightly humid (15.39%). Precipitation and drought conditions were positively correlated with NPP during the growing season, while temperature was negatively correlated with NPP. Increased spring temperature, precipitation, and drought conditions positively affected vegetation, while sustained summer temperature resulted in suppressed vegetation growth. Autumn vegetation was positively affected by temperature and drought, and precipitation was negatively correlated with autumn vegetation. Increasing winter temperatures promoted vegetation growth. The time lag between NPP and temperature gradually increased from northeast to southwest, and the time lag between NPP and precipitation gradually increased from south to north. Spring temperatures had the greatest beneficial impact on forestlands; summer climatic factors and drought had little effect on shrublands; the autumn climate exhibited small differences in its influence of each plant type; and winter temperatures had the greatest positive effect on grasslands. No time lag effect was found between any of the four vegetation types and precipitation. A one-month lag was found between cultivated lands and temperature; a two-month lag was found between forestlands and temperature; and a one-month lag was found between forestlands and drought and between shrublands and drought. The results can provide a scientific foundation for the sustainable development and management of ecosystems.

Carbon nanorods assembled coral-like hierarchical meso-macroporous carbon as sustainable materials for efficient biosensing and biofuel cell.

Sustainable conversion of renewable biomass into high-performance electrode materials has attracted extensive scientific and technological attention. However, to our knowledge, the potential of biomass derived carbon in biosensors and biofuel cells (BFCs) developments remains to be explored. Herein, the carbon nanorods assembled coral-like hierarchical meso-macroporous carbon (CN-CHMC) was synthesized as a sustainable electrode material to construct biosensor and lactate/air BFC. The CN-CHMC from cucumber (Cucumis sativus) possesses porous structure and plentiful defects, which not only facilitate the effective immobilization of enzymes but also accelerate electron transfer on the bioelectrode surfaces. As an electrochemical lactate biosensor, the CN-CHMC-based biosensor exhibits a wider linear range with lower detection limit (3.6 µM) and higher sensitivities (57.18 and 30.99 µA mM-1 cm-2) compared to carbon nanotube (CNT)-based biosensor. The feasibility of CN-CHMC-based biosensor in practical analysis is demonstrated by detecting lactate contents in real samples. By coupling with bilirubin oxidase-based biocathode, the lactate/air BFC equipped with CN-CHMC reveals a higher output power (112.7 µW cm-2) than that of CNT-based BFC. More interestingly, the lactate/air BFC demonstrates the ability to harvest energy from multi-component samples. The application of CN-CHMC may provide a new avenue to synthesize electrode materials with economical cost and excellent electrochemical activity.

Hybrid catalyst cascade for enhanced oxidation of glucose in glucose/air biofuel cell.

Redox enzymes are capable of harvesting electrical energy from biofuels in high catalytic activity and under mild condition. However, it is difficult to achieve efficient electron transfer and deep oxidation of biofuels simultaneously in a single-enzyme catalytic system. Herein, we report a hybrid catalyst cascade consisting of an organic oxidation catalyst, 2,2,6,6-tetramethyl-1-piperidine N-oxyl (TEMPO), and an enzyme, glucose oxidase (GOx), for electrochemical oxidation of glucose. It is found that TEMPO is capable of mediating electron transfer between the redox center of GOx and the electrode surface. While glucose can be oxidized into glucuronic acid under neutral conditions. Thus, combining GOx and TEMPO, we are able to achieve 4e- electrooxidation of glucose using the hybrid enzymatic and organic cascade (HEOC) system. When coupled with an air-breathing Pt cathode, the resulting glucose/air biofuel cell using the proposed HEOC anode exhibits a maximum power density of 38.1 µW cm-2 with a short-circuit current of 651.4 µA cm-2, which can be attributed to the enhanced energetic efficiency, enabling TEMPO a promising catalyst for glucose oxidation in bioelectronics applications.

DNA derived N-doped 3D conductive network with enhanced electrocatalytic activity and stability for membrane-less biofuel cells.

Enzymes are promising electrocatalysts in many biological processes. We proposed two strategies, co-immobilization and three-dimensional (3D) space design, to strengthen electron transfer (ET). In this research, DNA base and CNT were mixed in an aqueous solution; then the mixture was dried and ground. Finally, the powder was annealed in N2 to obtain DNA derived N-doped 3D conductive network (N-G@CNT). N-G@CNT immobilized mediators on itself through adsorption. Such 3D space structure shows high activity toward a set of critical electrochemical reactions and high-performance in enzymatic biofuel cells (EBFCs). It is found that N-G@CNT conductive network possesses an interconnected porous structure and well-developed porosity. As a result, the membrane-less EBFCs equipped with enzyme/mediator co-immobilization N-G@CNT bioelectrodes were measured in a model 5 mM glucose-containing aqueous solution, human serum, and rabbit whole blood, respectively, which can generate 0.34, 0.078, and 0.15 mW cm-2 power density, respectively. The constant-current discharge method carried out in a model 5 mM glucose-containing aqueous solution shows that the discharge time reached 19 h at a discharge current density of 0.01 mA cm-2. The membrane EBFCs can deliver a high open circuit voltage of 0.68 V, a short-circuit current density of 2 mA cm-2, and a maximum power density of 0.5 mW cm-2.

Deep oxidization of glucose driven by 4-acetamido-TEMPO for a glucose fuel cell at room temperature.

Exploiting suitable oxidation catalysts is of great importance in the development of sugar-based fuel cells (SFCs). Herein, a novel room-temperature glucose/O2 fuel cell (GFC), which employs 4-acetamido-2,2,6,6-tetramethylpiperidin-1-oxyl (ACT) as an anodic electrocatalyst and air-breathing Pt-C as a cathode, is demonstrated. Under room temperature operation, the as-assembled GFCs are capable of delivering a maximum power density of 100 µW cm-2 in the presence of 50 mM glucose. Bulk electrolysis products of glucose identified by mass spectrum and Fourier transform infrared spectroscopy include gluconic acid and glucaric acid, suggesting that the aldehyde and primary hydroxy groups of glucose can be deeply oxidized into carboxyl groups through a 6e- pathway. The deep glucose oxidation capability makes ACT a promising anodic electrocatalyst for SFCs.

Rational design of N-doped CNTs@C3N4 network for dual-capture of biocatalysts in enzymatic glucose/O2 biofuel cells.

Carbonaceous materials are promising electrode materials for enzymatic biofuel cells (EBFCs) due to their excellent electrical conductivity, chemical and physical stability and biocompatibility. Design and preparation of carbon materials with a hollow structure and a rough surface are of great significance for immobilization of enzymes both inside and outside the carbon materials for EBFC applications. We report herein the synthesis of novel carbonaceous materials consisting of bamboo-shaped hollow N-doped carbon nanotubes (N-CNTs) and C3N4 nanosheets (denoted as N-CNTs@C3N4) as electrode materials for dual-capture of enzymes in glucose/O2 EBFCs. The combination of one-dimensional N-CNTs with an open structure and two-dimensional C3N4 nanosheets forms a three-dimensional crosslinking network that significantly enhances the immobilization of enzymes, electrode stability, and mass transfer of substrates, thus boosting the EBFC performance. As a result, EBFCs equipped with N-CNTs@C3N4 can generate a high open circuit potential of 0.93 V and output a maximum power density of 0.57 mW cm-2 at 0.47 V. Additionally, the as-fabricated glucose/O2 EBFCs are capable of directly harvesting energy from various soft drinks, which indicates the promising applications of the N-CNTs@C3N4 nanocomposite as an electrode material for EBFCs.

Human appropriation of net primary production estimates in the Xinjiang grasslands.

The human appropriation of net primary production (HANPP) was developed to estimate the intensity of human activities in natural ecosystems, which is still unclear in the Xinjiang grasslands. Using the Biome-Biogeochemical Cycle (Biome-BGC) grazing model in combination with field data, we assessed the HANPP and explored its spatiotemporal patterns in the Xinjiang grasslands. Our results showed that (1) the HANPP increased from 38 g C/m2/yr in 1979 to 88 g C/m2/yr in 2012, with an average annual increase of 1.47%. The HANPP was 80 g C/m2/yr, which represented 51% of the potential net primary production (NPPpot), and the HANPP efficiency was 70% in this region. (2) The areas with high HANPP values mainly occurred in northern Xinjiang and northwest of the Tianshan Mountains, while areas with low HANPP values mainly occurred in southern Xinjiang and southwest of the Tianshan Mountains. (3) Interannual variations in HANPP and NPPpot were significantly positively correlated (P<0.01). Interannual variations in HANPP efficiency and grazing intensity were negatively correlated (P<0.01). These results can help identify the complex impacts of human activities on grassland ecosystems and provide basic data for grassland management.

Cobalt sulfides/carbon nanohybrids: a novel biocatalyst for nonenzymatic glucose biofuel cells and biosensors.

Exploring high-performance electrocatalysts is of great importance in developing nonenzymatic biofuel cells. Hybrid nanostructures with transition metal compounds and carbon nanomaterials exhibit excellent electrocatalytic activity and have emerged as promising low-cost alternatives for various electrochemical reactions. Herein, we report cobalt sulfide/carbon nanohybrids via a facile synthesis, which have excellent electrocatalytic activity for glucose oxidation and oxygen reduction reaction. The nonenzymatic glucose biofuel cells equipped with cobalt sulfide/carbon nanohybrids deliver a high open circuit voltage of 0.72 V with a maximum open power density of 88 µW cm-2, indicating that cobalt sulfide/carbon nanohybrids are high performance biocatalysts for bioenergy conversion.

Graphene-Embedded Co3O4 Rose-Spheres for Enhanced Performance in Lithium Ion Batteries.

Co3O4 has been widely studied as a promising candidate as an anode material for lithium ion batteries. However, the huge volume change and structural strain associated with the Li+ insertion and extraction process leads to the pulverization and deterioration of the electrode, resulting in a poor performance in lithium ion batteries. In this paper, Co3O4 rose-spheres obtained via hydrothermal technique are successfully embedded in graphene through an electrostatic self-assembly process. Graphene-embedded Co3O4 rose-spheres (G-Co3O4) show a high reversible capacity, a good cyclic performance, and an excellent rate capability, e.g., a stable capacity of 1110.8 mAh g-1 at 90 mA g-1 (0.1 C), and a reversible capacity of 462.3 mAh g-1 at 1800 mA g-1 (2 C), benefitted from the novel architecture of graphene-embedded Co3O4 rose-spheres. This work has demonstrated a feasible strategy to improve the performance of Co3O4 for lithium-ion battery application.

Cystic clear cell papillary renal cell carcinoma: is it related to multilocular clear cell cystic neoplasm of low malignant potential?

AIMS: We report the morphological spectrum of nine cystic clear cell papillary renal cell carcinomas (CCP-RCC). METHODS AND RESULTS: Mean tumour size was 2.1 cm and the stage was pT1a in all cases. The original diagnosis was multilocular clear cell cystic renal neoplasm of low malignant potential (MCCN-LMP) in five and CCP-RCC in four patients. All examples were composed of variably sized cysts lined by one layer of clear cells. Two tumours were exclusively cystic, seven showed tubular formation in the septae and five in which the tubular growth was compact and pseudo-solid. Two tumours had foci of nests and single cells showing similarities to the cellular areas of MCCN-LMP. The tubular/pseudo-solid/nested/single-cells foci formed microscopic nodules with a mean size of 1.8 mm. Three tumours had intracystic micropapillary formation. Cells were of International Society of Urological Pathology (ISUP) grades 1-2/4. In all cases, the neoplastic nuclei were aligned away from the basement membranes at least focally. Tumours were positive for paired box gene 8 (PAX8), carbonic anhydrase IX (CAIX), cytokeratin (CK)7 and CK34BE12 and negative for CD10. CONCLUSIONS: Cystic CCP-RCC is a pattern that should be recognized, as it shows overlapping morphological features with both multilocular cyst and MCCN-LMP. This series raises the question of whether some reported MCCN-LMPs are actually cystic CCP-RCC.

Protein kinase A modulates transforming growth factor-ß signaling through a direct interaction with Smad4 protein.

Transforming growth factor ß (TGFß) signaling normally functions to regulate embryonic development and cellular homeostasis. It is increasingly recognized that TGFß signaling is regulated by cross-talk with other signaling pathways. We previously reported that TGFß activates protein kinase A (PKA) independent of cAMP through an interaction of an activated Smad3-Smad4 complex and the regulatory subunit of the PKA holoenzyme (PKA-R). Here we define the interaction domains of Smad4 and PKA-R and the functional consequences of this interaction. Using a series of Smad4 and PKA-R truncation mutants, we identified amino acids 290-300 of the Smad4 linker region as critical for the specific interaction of Smad4 and PKA-R. Co-immunoprecipitation assays showed that the B cAMP binding domain of PKA-R was sufficient for interaction with Smad4. Targeting of B domain regions conserved among all PKA-R isoforms and exposed on the molecular surface demonstrated that amino acids 281-285 and 320-329 were required for complex formation with Smad4. Interactions of these specific regions of Smad4 and PKA-R were necessary for TGFß-mediated increases in PKA activity, CREB (cAMP-response element-binding protein) phosphorylation, induction of p21, and growth inhibition. Moreover, this Smad4-PKA interaction was required for TGFß-induced epithelial mesenchymal transition, invasion of pancreatic tumor cells, and regulation of tumor growth in vivo.

The value of triple antibody (34ßE12 + p63 + AMACR) cocktail stain in radical prostatectomy specimens with crushed surgical margins.

BACKGROUND: Triple antibody cocktail immunohistochemical staining is routinely used as an ancillary method to establish a diagnosis of prostate cancer in biopsies with small foci of atypical glands. Crush artefact can distort surgical margins in radical prostatectomy specimens, occasionally making it difficult to diagnose a positive margin. AIM: To investigate the ability of a cocktail stain to distinguish carcinoma from benign prostatic glands at the edge of crushed margins in prostatectomy specimens. METHODS: 10 radical prostatectomy specimens with crushed benign glands at the surgical margins, and 20 with crushed margins positive for carcinoma were retrieved from the pathology archives. The latter included 16 (80%) with positive apical margins, 2 (10%) incised intraprostatic margins, and 1 (5%) soft tissue margin. Two-colour triple antibody stain using a cocktail of antibodies against α-methylacyl coenzyme A racemase (AMACR), high molecular weight keratin and p63 was performed on all the selected cases. RESULTS: In 10/10 specimens with crushed benign glands, basal cell staining continued to be detectable, while AMACR staining was negative in all cases (0/10). In the positive margin cases, none of the crushed glands expressed basal cell marker staining (0/20), whereas 14/20 (70%) of the cases showed variable levels of AMACR positivity at the inked margin. CONCLUSION: Two-colour triple antibody cocktail stain is useful in the assessment of most, but not all, surgical margins with crushed artefact in prostatectomy specimens by helping to establish whether glands are malignant or benign.

Role of steroid receptor coactivators in glucocorticoid and transforming growth factor beta regulation of plasminogen activator inhibitor gene expression.

TGFbeta is a major regulator of extracellular matrix deposition and a potent inducer of type-1 plasminogen activator inhibitor (PAI-1) gene expression. We have reported that liganded glucocorticoid receptor (GR) represses TGFbeta transactivation of PAI-1 in Hep3B human hepatoma cells and that it interacts functionally and physically with the C-terminal activation domain of Smad3, a mediator of TGFbeta signaling. The ligand binding domain of GR is required for GR-mediated transrepression, but the GR DNA binding domain and activation function 1 domains are not. We report here that overexpression of steroid receptor coactivator-1 (SRC-1) and GR-interacting protein-1 (GRIP-1) enhanced repression by liganded GR, and by a GR mutant defective in repression. Surprisingly, SRC-1 and GRIP-1 also enhanced TGFbeta-induced activation from the TGFbeta-responsive sequence of the PAI-1 gene by a GR-independent mechanism. Coimmunoprecipitation and mammalian one-hybrid experiments demonstrated that SRC-1 and GRIP-1 interact physically with endogenous Smad3 and functionally with the C-terminal domain of Smad3 to directly enhance transcription. Thus, the GR coactivators, SRC-1 and GRIP-1, act as both corepressors of the glucocorticoid repression of PAI-1 gene transcription, and coactivators of TGFbeta-induced activation of the PAI-1 promoter.

Identification of a putative tumor suppressor gene Rap1GAP in pancreatic cancer.

Human chromosome 1p35-p36 has long been suspected to harbor a tumor suppressor gene in pancreatic cancer and other tumors. We found that expression of rap1GAP, a gene located in this chromosomal region, is significantly down-regulated in pancreatic cancer. Only a small percentage of preneoplastic pancreatic intraductal neoplasia lesions lost rap1GAP expression, whereas loss of rap1GAP expression occurred in 60% of invasive pancreatic cancers, suggesting that rap1GAP contributes to pancreatic cancer progression. In vitro and in vivo studies showed that loss of rap1GAP promotes pancreatic cancer growth, survival, and invasion, and may function through modulation of integrin activity. Furthermore, we showed a high frequency of loss of heterozygosity of rap1GAP in pancreatic cancer. Collectively, our data identify rap1GAP as a putative tumor suppressor gene in pancreatic cancer.