Enhancing Chemotherapy of p53‐Mutated Cancer through Ubiquitination‐Dependent Proteasomal Degradation of Mutant p53 Proteins by Engineered ZnFe‐4 Nanoparticles

A significant percentage of human cancers harbor missense mutations in the TP53 gene and express highly stabilized mutant p53 protein (mutp53) with tumor‐promoting gain‐of‐function (GOF) properties. Inducing mutp53 degradation is a viable precision anti‐tumor therapeutic strategy. Based on the previously reported finding that a zinc‐curcumin compound induced mutp53 degradation, a series of ZnFe nanoparticles (ZnFe NPs) are synthesized and it is found that ZnFe‐4, with an Zn:Fe ratio of 1:2, exhibits outstanding mutp53‐degrading capability. ZnFe‐4 induced ubiquitination‐mediated proteasomal degradation of several different mutp53 species, but not the wild‐type p53 protein. Cellular internalization, intracellular Zn++ elevation and increased ROS are all necessary for ZnFe‐4‐induced mutp53 degradation. Degradation of mutp53 by ZnFe‐4, abrogated mutp53‐manifested GOF, leading to increased p21 expression, cell cycle arrest, reduced cell proliferation and cell migration, and cell demise. ZnFe‐4 also sensitized to cisplatin‐elicited killing in p53 S241F ES‐2 ovarian cancer cells, and dramatically improved the therapeutic efficacy of cisplatin in a subcutaneous ES‐2 tumor model. The potential clinical utility of ZnFe‐4 is further demonstrated in an orthotopically‐implanted p53 Y220C patient‐derived xenograft (PDX) breast cancer model. ZnFe‐4 is the first reported mutp53‐degrading nanomaterial, and further materials engineering may lead to the development of zinc‐based nanoparticles with minimal toxicity and maximized mutp53‐degrading capability.     

Tumor Microenvironment-Responsive Nanocarrier Based on VOx Nanozyme Amplify Oxidative Stress for Tumor Therapy

The construction of a novel nanocarrier that can break the redox balance in tumor cell is a promising anti-tumor strategy. Herein, a tumor microenvironment (TME)-responsive nanocarrier VC@Lipo is rationally designed by embedding ultrasmall VO_x nanozyme and photosensitizer chlorin e6 (Ce6) into liposomes. The size of VC@Lipo nanocarrier is ≈35 nm and can be degraded in the weakly acidic environment of TME. The VO_x nanozyme exhibits peroxidase-like activity and generates highly toxic hydroxyl radical ∙OH through Fenton-like reaction and ¹O₂ in the presence of H₂O₂ independent of light, and more ¹O₂ can be generated by the photodynamic effect of Ce6. In addition, the VO_x nanozyme can effectively deplete intracellular overexpressed glutathione (GSH) through redox reactions. In vivo experiments demonstrate that the nanocarrier shows excellent biocompatibility, presents the largest enrichment at the tumor site after 6 h of intravenous injection into mice with the highest tumor inhibition rate of 54.18% after laser irradiation. Compared with the single treatment mode, VC@Lipo shows the best synergistic effect of chemodynamic-photodynamic therapy. This work provides a new paradigm for nanocatalytic therapy of cancer and is expected to provide new ideas for precision medicine in cancer.     

A Chemoimmunotherapy Nanogel Enables Efficient Delivery of Interleukin-2 and Induction of Immunogenic Cell Death for Effective Cancer Therapy

Interleukin-2 (IL-2) is one of the first FDA-approved immunotherapeutics, but its use is limited by toxicity and low efficacy. In addition, all immunotherapies are limited by the immunosuppressive and desmoplastic microenvironment of “immunologically cold” tumors, such as pancreatic ductal adenocarcinoma (PDAC) or hepatocellular carcinoma (HCC) with advanced liver fibrosis. Here, a new chemoimmunotherapy nanogel (IL2-Pt@Nanogel) for dual delivery of IL-2 and the type II immunogenic cell death inducer Pt-NHC that reduces the immunosuppressive phenotype of tumor-associated macrophages and diminishes regulatory T cell infiltration by inducing the production of type I interferon (IFN) by cancer cells is reported. Combining the angiotensin II receptor blocker losartan with IL2-Pt@Nanogel treatment reduces desmoplasia and reprogrammes the microenvironment of PDAC and HCC toward an immunostimulatory one. These effects result in potent anti-tumor efficacy in models of primary and metastatic PDAC and HCC with underlying liver fibrosis. This study presents a strategy for IL-2-based chemoimmunotherapy with the potential for clinical translation to treat solid tumors.     

Multicolored Electrochromism of a Poly{1,4‐bis[2‐(3,4‐ethylenedioxy)thienyl]benzene} Derivative Bearing Viologen Functional Groups

1,4‐Bis[2‐(3,4‐ethylenedioxy)thienyl]‐2,5‐bis[6‐(1′‐butyl‐4,4′‐bipyridyl)hexyloxy]benzene tetrahexafluorophosphate (BEDOTPh‐2V) was synthesized and electropolymerized to form a viologen‐bearing conductive polymer [P(BEDOTPh‐2V)] film on an electrode surface. This polymer exhibits multicolor electrochromic behavior: it is highly transparent light‐blue P(BEDOTPh^1.7+‐2V²⁺) at 1.0 V (vs. Ag/Ag⁺), pale‐bisque P(BEDOTPh^0.6+‐2V²⁺) at 0.1 V, magenta P(BEDOTPh⁰‐2V²⁺) at –0.5 V, purple P(BEDOTPh⁰‐2V ^•+) at –0.9 V, and crimson P(BEDOT⁰‐2V⁰) at –1.4 V. Since both the viologen pendant and the polymer backbone have cathodic coloring characteristics and their redox‐potential ranges do not overlap each other, the dual electrochromic action provides more plentiful electrochromic colors compared to simple poly{1,4‐bis[2‐(3,4‐ethylenedioxy)thienyl]‐2,5‐dialkoxybenzene}.     

Controllable Patterning of Porous MXene (Ti3C2) by Metal-Assisted Electro-Gelation Method

Since discovered in 2011, transition metal carbides or nitrides (MXenes) have attracted enormous attention due to their unique properties. Morphology regulation strategies assembling 2D MXene sheets into 3D architecture have endowed the as-formed porous MXene with a better performance in various fields. However, the direct patterning strategy for the porous MXene into integration with multifunctional and multichannel electronic devices still needs to be investigated. The metal-assisted electro-gelation method the authors propose can directly generate porous-structured MXene hydrogel with a tunable feature. By electrolyzing the sacrificial metal, the released metal cations initiate the electro-gelation process during which electrostatic interactions occur between cations and the MXene sheets. A high spatial resolution down to micro-meter level is achieved utilizing the method, enabling high-performance hydrogels with more complex architectures. Electronics prepared through this metal-assisted electro-gelation process have shown promising applications of the porous MXene in energy and biochemical sensing fields. Energy storage devices with a capacitance at 33.3 mF cm⁻² and biochemical sensors show prominent current responses towards metabolites (sensitivity of H₂O₂: 165.6  µ A mm ⁻¹ cm⁻²; sensitivity of DA: 212 nA  µ m ⁻¹ cm⁻²), suggesting that the metal-assisted electro-gelation method will become a prospective technique for advanced fabrication of MXene-based devices.     

Dual Enzyme Mimics Based on Metal–Ligand Cross-Linking Strategy for Accelerating Ascorbate Oxidation and Enhancing Tumor Therapy

The development of high-efficiency nanozymes is of great significance in the field of nanozymology, because this is one of the prerequisites for the sophisticated performance of nanozymes. Herein, the developed metal–ligand cross-linking strategy engineers porous carbon nanorod supported ultra-small iron carbide nanoparticles that possess excellent oxidase-like and peroxidase-like enzyme activities. The fabricated nanozyme can efficiently accelerate the oxidation of ascorbate (AA) to enhance cancer cells ablation efficacy. Due to the nanozyme having great surface atoms utilization ratio and large specific surface area, the AA can be rapidly and completely autoxidized within 20 min. Mechanism research demonstrates that the nanozyme's first activation of O₂ to generate superoxide free radicals (O₂^•−) via the oxidase-like pathway, then the O₂^•− directly oxidizes AA and produces hydrogen peroxide (H₂O₂). Simultaneously, the H₂O₂ transforms into the toxic hydroxyl radical through the peroxidase-like pathway and induces tumor cell death. Further in vitro and in vivo assays show the significant enhancement of the anti-tumor efficacy through AA oxidation which is catalyzed by the developed nanozyme. It is expected that this work will benefit not only the development of other efficient nanozymes, but also future advances in the field of AA oxidation induced tumor therapy.     

A Self-Assembly Combined Nano-Prodrug to Overcome Gemcitabine Chemo-Resistance of Pancreatic Tumors

Gemcitabine (GEM), as a first-line chemotherapeutics for pancreatic ductal adenocarcinoma (PDAC) treatment, still faces several clinical challenges, restricted by instability in blood circulations, low tumor selectivity, and acquired nature characteristics of chemo-resistance. To solve these challenges, the rational design of combination therapy with GEM and other therapy modalities is imperative. Herein, a small molecular self-assembly nano-prodrug is developed, which can achieve the co-delivery of GEM, Ferrocene and nutlin-3a on the achievement of GEM-induced apoptosis with ferroptosis. In this nano-prodrug, the disulfide linkage not only acts as a GSH-responsive trigger but also plays an important role in self-assembly behavior of nanoparticle that can load nutlin-3a. Interestingly, nutlin-3a plays an important role in both ferroptosis and apoptosis, one is effectively sensitized cells to ferroptosis by inhibiting cystine uptake, and the other is promoted apoptosis by elevating p53 expression. To further enhance the drug tumor accumulation and maintain stability in systemic circulations, this nano-prodrug is then encapsulated into plectin1 receptor-targeting phospholipid micelles (DSPE-PEG-PTP), which displays high selective tumor inhibition and good biosafety on different mice models, especially in orthotopic and patient-derived xenograft (PDX) models. The findings provide new insights into the combination therapy of GEM with ferroptosis for reduced chemo-resistance on PDAC treatment.     

Star-shaped self-assembly of an organic thin film transistor sensor in the presence of Cu2+ and CN− ions

In this study we developed organic thin film transistors (OTFTs) for the sensing of metal ions and anions through the self-assembly of a pentacene/Schiff base pyrene derivative. Our bilayer OTFTs displayed attractive device parameters: an electron mobility (μ) of 0.12 cm² V⁻¹ s⁻¹, a threshold voltage (V_th) of 22.20 V, and a five-orders-of-magnitude on/off ratio. This device was sensitive toward Cu²⁺ among 13 metal cations and toward CN⁻ among nine anions, as measured through changes in the values of V_th and I_off in the presence of Cu²⁺ cations and a change in the value of I_sat in the presence of CN⁻ anions. We observed selectivity toward both of these ions in mixed ion solutions, with sensitivity over different concentrations (from 20 to 350 μM for Cu²⁺; from 100 to 350 μM for CN⁻) as well as in sea water. The pyrene derivative self-assembled through pyrene–pyrene^* coordination in the presence of Cu²⁺ ions; the rods of the pyrene derivative broke into smaller pieces upon formation of benzoxazole rings in the presence of CN⁻ ions, as confirmed using atomic force microscopy and fourier transform attenuated total reflection spectroscopy.     

Alkoxy- and Alkyl-Side-Chain-Functionalized Terpolymer Acceptors for All-Polymer Photovoltaics Delivering High Open-Circuit Voltages and Efficiencies

A new terpolymer acceptor is presented, comprising various ratios of the same dithienothienopyrrolobenzothiadiazole (BTP) core with different side chains—alkoxy side chains (BTPO-IC) and alkyl side chains (BTP-IC)—and thiophene units, for use in all-polymer organic photovoltaics. Devices incorporating binary blends of this terpolymer and the polymer PM6 as the active layer displayed open-circuit voltages (V_OC) that increase linearly upon increasing the molar ratio of BTPO-IC. For example, the optimized device incorporating PM6:PY-0.2OBO (i.e., with 20 mol% of BTPO-IC) (1:1.2 wt.%) blend, with the smallest domain sizes but largest coherence length and combined face-on and edge-on orientation fractions among all blends, have a champion power conversion efficiency (PCE) of 16.7% (V_OC = 0.97 V; J_SC = 25.2 mA cm⁻²; FF = 0.68), whereas the device containing a similar blend ratio of the PM6:PY-OD:PY-OBO ternary blend (1:0.96:0.24 wt.%) displayed a PCE of 8.6% (V_OC = 0.969 V; J_SC = 18.7 mA cm⁻²; FF = 0.48). The device with PM6:PY-0.2OBO displays better thermal stability than the devices with PM6: PY-OD or PY-OBO. Thus, employing terpolymer acceptors with differently functionalized side-chain units can be an effective approach for simultaneously optimizing the aggregation domain and enhancing the PCEs and thermal stabilities of all-polymer devices.     

Exploration of electrochemical properties of zinc antimonate nanoparticles as supercapacitor electrode material

Synthesis and Electrochemical properties of zinc antimonate nanoparticles have been explored and the strategy was to engage zinc antimonate towards supercapacitors. Cyclic voltammetry measurements were done at different sweep rates and the inclusion of two heterovalent metal cations such as Zn²⁺ and Sb⁵⁺ in the nanostructure participates in the electrochemical phenomena thereby exhibiting pseudocapacitance behavior with a significant specific capacitance of 140.8 F/g at the sweep rate of 10 mV/s was achieved. Further, from galvanostatic charge-discharge measurements, it is apparent that the capacitor characteristics were found to be phenomenal in 1 M H₂SO₄ electrolyte with good electrochemical constancy over 500 cycles with an incredible capacity retention of 100% at a current density of 1 A/g respectively. The results suggest that the obtained zinc antimonate could be a promising, inexpensive and electrochemically active candidate in supercapacitor application.     

Efficient enhancement of second order nonlinear optical response by complexing metal cations in conjugated 7-substituted coumarin

Most of the coumarins have been found useful as non-linear optical chromophores. The four novel water-soluble coumarin-based compounds (OC6, NC6, OC7, and NC7) and the metallic compounds of NC7 with different metal cations (Na⁺, K⁺, Mg²⁺, Ca²⁺, Fe²⁺, and Zn²⁺) have been investigated by carrying out density functional theory (DFT). Our DFT calculations revealed that the second-order nonlinear optical properties have a pronounced enhancement by means of the introduction of π-conjugatd electron donor (dimethylamino phenyl alkynyl) in 7-position of the coumarin ring and metal cations, especially for transition metals. The further investigations of the larger first hyperpolarizability (β_tot) reveal that the NC7*Fe²⁺ and NC7*Zn²⁺ present the larger values as 1.151 × 10⁻²⁷ and 1.083 × 10⁻²⁷ esu owing to the lower transition energies and larger oscillator strengths of crucial electronic transitions. Moreover, time-dependent DFT results show that the large intramolecular charge transfers exist in the NC7*Fe²⁺ and NC7*Zn²⁺. In addition, the natural bond orbital analysis demonstrated that the second-order stabilization energies is from the lone pair (LP) orbital on O atom to the LP* orbital of metal cations interaction correlate with the O-Mⁿ⁺ atomics distance. On the other hand, the atoms in molecules analysis showed that the O-Mⁿ⁺ interactions can be characterized by the presence of a bond critical point (BCP) and the O-Fe²⁺ and O-Zn²⁺ interactions have partially ionic and partially covalent bonds rather than an electrostatic character for O-Mⁿ⁺ (Na⁺, K⁺, Mg²⁺ and Ca²⁺). In addition, the delocalization indices of O-Mⁿ⁺ bonds correlate reasonably well with electron density, kinetic and potential energy densities in these complexes. Thus, we hope this research will introduce a new relation between the structure and the property of chromophore nonlinear optical activity.     

High‐Performance Organic Heterojunction Phototransistors Based on Highly Ordered Copper Phthalocyanine/para‐Sexiphenyl Thin Films

High‐performance organic heterojunction phototransistors are fabricated using highly ordered copper phthalocyanine (CuPc) and para ‐sexiphenyl (p ‐6P) thin films. The p ‐6P thin film plays an important role on the performance of CuPc/p ‐6P heterojunction phototransistors. It acts as a molecular template layer to induce the growth of highly ordered CuPc thin film, which dramatically improves the charge transport and decreases the grain boundaries. On the other hand, the p ‐6P thin film can form an effective heterojunction with CuPc thin film, which is greatly helpful to enhance the light absorption and photogenerated carriers. Under 365 nm ultraviolet light irradiation, the ratio of photocurrent and dark current and photoresponsivity of CuPc/p ‐6P heterojunction phototransistors reaches to about 2.2 × 10⁴ and 4.3 × 10² A W^?1, respectively, which are much larger than that of CuPc phototransistors of about 2.7 × 10² and 7.3 A W^?1, respectively. A detailed study carried out with current sensing atomic force microscopy proves that the photocurrent is predominately produced inside the highly ordered CuPc/p ‐6P heterojunction grains, while the photocurrent produced at the boundaries between grains can be neglected. The research provides a good method for fabricating high‐performance organic phototransistors using a combination of molecular template growth and organic heterojunction.     

A 10 b 120 MS/s 108 mW 0.18 μm CMOS ADC with a PVT-insensitive current reference

This paper proposes a 10 b 120 MS/s CMOS ADC with a PVT-insensitive current reference. The designed current reference shows a mean temperature drift of 35.2 ppm/°C in the temperature range from −25 to 100°C and a supply rejection of 1.1%/V between 1.6 and 2.0 V. The prototype ADC fabricated in a 0.18 μm 1P6M CMOS technology demonstrates a measured DNL and INL of 0.18LSB and 0.53LSB with a maximum SNDR and SFDR of 53 and 68 dB at 120 MS/s. The ADC with an active chip area of 1.8 mm² consumes 108 mW at 120 MS/s and 1.8 V while the proposed on-chip current reference consumes 0.35 mW with a die area of 0.02 mm².     

Eco-Friendly and Highly Efficient Light-Emission Ferroelectric Scintillators by Precise Molecular Design

Hybrid manganese halide has attracted much attention in the field of environment friendly ferroelectric and photo-responsive multifunctional materials. Here, the highly efficient photoluminescent inorganic framework MnBr₄²⁻ is utilized to conceive and synthesize a series of hybrid manganese bromide compounds [RQ]₂MnBr₄ by introducing precisely designed quasi-spherical cations [RQ]⁺ (R  =  H, Me, Et, FEt, Q  =  quinuclidine). The accurate and effective modification of cations not only achieves the satisfactory ferroelectricity, but also enhances the photoluminescence quantum yield from 38.7% to 83.65%. Moreover, [FEtQ]₂MnBr₄ shows a highly efficient X-ray scintillator performance, including a large range of linear response to X-ray dose rate from 0.3 to 414.2  μ Gy_air s⁻¹, a high light yield of 34 438 photons per MeV, and a low detection limit of 258 nGy_air s⁻¹. This work provides an efficient strategy for the preparation of hybrid manganese halide ferroelectrics with highly efficient light-emission and X-ray detection.     

A Novel High-Entropy Perovskite Electrolyte with Improved Proton Conductivity and Stability for Reversible Protonic Ceramic Electrochemical Cells

Reversible protonic ceramic electrochemical cells (R-PCECs) are emerging as highly efficient energy conversion devices, operating below 650 °C. The primary challenge in advancing R-PCECs lies in developing efficient and stable proton-conducting electrolytes capable of withstanding the chemical instability caused by common contaminants like CO₂ and H₂O. Herein, a novel high-entropy perovskite oxide (HEPO) material is introduced, incorporating six equimolar B-site cations (BaHf_1/6Sn_1/6Zr_1/6Ce_1/6Y_1/6Yb_1/6O_3-δ, BHSZCYYb). The total conductivity of BHSZCYYb outperforms that of the examined HEPO electrolytes and other reported HEPO variants. Additionally, superior chemical stability of BHSZCYYb is observed when exposed to CO₂. Utilizing the microwave-assisted sintering method, an R-PCEC with BHSZCYYb electrolyte is successfully fabricated. This cell exhibits a maximum power density of 1.151 W cm⁻² (650 °C) in fuel cell mode and a current density of 2.326 A cm⁻² at 1.3 V (650 °C) in electrolysis cell mode. These results represent the highest-reported values for R-PCECs employing HEPO electrolytes to date and provide valuable insights into the development and advancement of HEPOs, holding great promise for achieving high-performance R-PCECs.     

3D Hollow Porous Radio-Granular Hydrogels for SPECT Imaging-Guided Cancer Intravascular Brachytherapy

Radioactive microspheres have shown excellent therapeutic effects in the treatment of advanced hepatocellular carcinoma (HCC) due to indiscriminate embolization and killing of tumor cells. However, limitations such as unstable loading, in vivo reflux, and untrackable radioactive microspheres restrict their clinical applicability. Herein, a novel injectable lutetium-177-labeled 3D hollow porous radio-granular hydrogels with a double-cross-linked network (¹⁷⁷Lu-3D-HPGH) are synthesized via microfluidics combined with ultraviolet photo-cross-linking technology is reported. The radiolabeling efficiency of ¹⁷⁷Lu-3D-HPGH can reach 97.85%. The 3D hollow porous radio-granular hydrogels exhibited uniform, controllable size, radio-theranostics, and excellent underwater adhesion properties, avoiding unwanted radiation damage to non-target organs. Particularly, the extended X-ray absorption fine structure combined with the density functional theory calculation revealed the mechanism of 3D-HPGH loading with ¹⁷⁷Lu through Lu-N/O coordination. Furthermore, rabbit orthotopic kidney and liver tumor models are used to verify the excellent embolization performance, radionuclide loading stability, anti-reflux characteristics, anti-tumor effect, and biosafety of ¹⁷⁷Lu-3D-HPGH. Briefly, this facile, green, and safe synthesis strategy provides a superior choice for intravascular brachytherapy of HCC and has great application value and transformative potential in clinical diagnosis and treatment.     

Charge transport properties and microstructure of polythiophene/polyfluorene blends

We present a combined charge transport and X-ray diffraction study of blends based on regioregular poly(3-hexylthiophene) (P3HT) and the polyfluorene co-polymer poly((9,9-dioctylfluorene)-2,7-diyl-alt-[4,7-bis(3-hexylthien-5-yl)-2,1,3-benzothiadiazole]-2′,2′′-diyl) (F8TBT) that are used in efficient all-polymer solar cells. Hole mobility is observed to increase by nearly two orders of magnitude from less than 10^?7 cm² V^?1 s^?1 for as spin-coated blends to 6 × 10^?6 cm² V^?1 s^?1 for blends annealed at 453 K at a field of 2.7 × 10⁵ V/cm, but still significantly below the time-of-flight mobility of unblended P3HT of 1.7 × 10^?4 cm² V^?1 s^?1. The hole mobility of the blends also show a strong negative electric-field dependence, compared with a relatively flat electric-field dependence of unblended P3HT, suggestive of increased spatial disorder in the blends. X-ray diffraction measurements reveal that P3HT/F8TBT blends show a phase separation of the two components with a crystalline part attributed to P3HT and an amorphous part attributed to F8TBT. In as-spun and mildly annealed blends, the measured d-values and relative intensities of the 100, 200 and 300 P3HT peaks are noticeably different to unblended P3HT indicating an incorporation of F8TBT in P3HT crystallites that distorts the crystal structure. At higher anneal temperatures the blend d-values approach that of unblended P3HT suggesting a well separated blend with pure P3HT crystallites. P3HT crystallite size in the blend is also observed to increase with annealing from 3.3 to 6.1 nm, however similar changes in crystallite size are observed in unblended P3HT films with annealing. The lower mobility of P3HT/F8TBT blends is attributed not only to increased P3HT structural disorder in the blend, but also due to the blend morphology (increased spatial disorder). Changes in hole mobility with annealing are interpreted in terms of the need to form percolation networks of P3HT crystallites within an F8TBT matrix, with a possible contribution due to the intercalation of F8TBT in P3HT crystallites acting as defects in the as-prepared state.     

Resident holes and electrons at organic/conductor and organic/organic interfaces: An electron paramagnetic resonance investigation

A number of organic/conductor and organic/organic interfaces have been examined by EPR spectroscopy to ascertain the areal concentration of organic ions at the interface. Organic hole transport materials such as NPB and TAPC at an interface with MoO_x are found to have areal concentrations on the order of 10¹⁴ cations per cm². C₆₀ at an interface with MoO_x creates ≈10¹³ cations per cm² depending on the roughness of the substrate. However, C₆₀ at an interface with Mg or Ag produces only about 4 × 10¹² anions per cm². Ion concentrations are generally in accord with the energy levels (adiabatic IP, EA etc) of the two materials at a given interface.     

Drosha蛋白在胰腺癌组织中的表达及其临床意义

目的:探讨胰腺癌组织中Drosha蛋白表达状况及其临床意义。方法:收集胰腺癌样本85例及对应癌旁组织53例,采用HE和免疫组化法检测胰腺癌组织标本中Drosha蛋白的表达并分析其与临床病理因素之间的关系。采用定量PCR方法检测Drosha基因表达。结果:胰腺癌组织中Drosha的表达阳性率为72.9%(62/85),而相应癌旁Drosha表达阳性率为100%(53/53),两者表达差异有统计学意义(P=0.000),Drosha蛋白在胰腺癌中的阳性强度平均积分值由10.3分降至2.3分。Drosha蛋白的表达与肿瘤的分期(c2=19.2,P=0.0003)、分级(c2=10.8,P=0.013)、淋巴结转移(c2=23.6,P=0.00003)等密切相关。与对应癌旁组织相比,Drosha基因在胰腺癌组织中表达下调(P=0.000)。结论:Drosha蛋白在胰腺癌组织中表达下降,Drosha可能在胰腺癌的发生、发展中具有重要作用。     

New triphenylamine-based poly(amine-imide)s with carbazole-substituents for electrochromic applications

A new carbazole-derived triphenylamine-containing diimide-diacid monomer (5), 4,4′-bis(trimellitimido)-4″-N-carbazolytriphenylamine, is prepared by the condensation of 4,4′-diamino-4″-N-carbazolytriphenylamine (4) and two molar equivalents of trimellitic anhydride (TMA). A series of new poly(amide-imide)s (PAIs) 7a–7d with carbazole-substituted triphenylamine units are prepared by direct polymerization from the new diimide-diacid (5) and various aromatic diamines (6a–6d). The PAIs shows high glass transition temperature between 269 and 297 °C, and high 5% weight loss temperature between 526 and 561 °C under nitrogen environment. Cyclic voltammograms of the PAIs films, which are casted onto the indium–tin oxide (ITO)-coated glass substrate, exhibit two reversible oxidation redox couples at 1.05–1.08 V and 1.38–1.46 V under an anodic sweep. The PAI-7a film reveals excellent stability of electrochromic characteristics for the radical cations generated, changing color from original pale yellowish neutral form to the green and then to dark blue oxidized forms. Furthermore, the anodically coloring of PAI-7a shows high coloration efficiency (CE = 205 cm²/C), high contrast of optical transmittance change (ΔT = 80% at 776 nm) and long-term redox reversibility.