Multiscale embedded printing of engineered human tissue and organ equivalents.

Creating tissue and organ equivalents with intricate architectures and multiscale functional feature sizes is the first step toward the reconstruction of transplantable human tissues and organs. Existing embedded ink writing approaches are limited by achievable feature sizes ranging from hundreds of microns to tens of millimeters, which hinders their ability to accurately duplicate structures found in various human tissues and organs. In this study, a multiscale embedded printing (MSEP) strategy is developed, in which a stimuli-responsive yield-stress fluid is applied to facilitate the printing process. A dynamic layer height control method is developed to print the cornea with a smooth surface on the order of microns, which can effectively overcome the layered morphology in conventional extrusion-based three-dimensional bioprinting methods. Since the support bath is sensitive to temperature change, it can be easily removed after printing by tuning the ambient temperature, which facilitates the fabrication of human eyeballs with optic nerves and aortic heart valves with overhanging leaflets on the order of a few millimeters. The thermosensitivity of the support bath also enables the reconstruction of the full-scale human heart on the order of tens of centimeters by on-demand adding support bath materials during printing. The proposed MSEP demonstrates broader printable functional feature sizes ranging from microns to centimeters, providing a viable and reliable technical solution for tissue and organ printing in the future.

Oncogenic ß-catenin stimulation of AKT2-CAD-mediated pyrimidine synthesis is targetable vulnerability in liver cancer.

CTNNB1, encoding ß-catenin protein, is the most frequently altered proto-oncogene in hepatic neoplasms. In this study, we studied the significance and pathological mechanism of CTNNB1 gain-of-function mutations in hepatocarcinogenesis. Activated ß-catenin not only triggered hepatic tumorigenesis but also exacerbated Tp53 deletion or hepatitis B virus infection-mediated liver cancer development in mouse models. Using untargeted metabolomic profiling, we identified boosted de novo pyrimidine synthesis as the major metabolic aberration in ß-catenin mutant cell lines and livers. Oncogenic ß-catenin transcriptionally stimulated AKT2, which then phosphorylated the rate-limiting de novo pyrimidine synthesis enzyme CAD (carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, dihydroorotase) on S1406 and S1859 to potentiate nucleotide synthesis. Moreover, inhibition of ß-catenin/AKT2-stimulated pyrimidine synthesis axis preferentially repressed ß-catenin mutant cell proliferation and tumor formation. Therefore, ß-catenin active mutations are oncogenic in various preclinical liver cancer models. Stimulation of ß-catenin/AKT2/CAD signaling cascade on pyrimidine synthesis is an essential and druggable vulnerability for ß-catenin mutant liver cancer.

4EBP2-regulated protein translation has a critical role in high-fat diet-induced insulin resistance in hepatocytes.

A high-fat diet (HFD) plays a critical role in hepatocyte insulin resistance. Numerous models and factors have been proposed to elucidate the mechanism of palmitic acid (PA)-induced insulin resistance. However, proteomic studies of insulin resistance by HFD stimulation are usually performed under insulin conditions, leading to an unclear understanding of how a HFD alone affects hepatocytes. Here, we mapped the phosphorylation rewiring events in PA-stimulated HepG2 cells and found PA decreased the phosphorylation level of the eukaryotic translation initiation factor 4E-binding protein 2 (4EBP2) at S65/T70. Further experiments identified 4EBP2 as a key node of insulin resistance in either HFD mice or PA-treated cells. Reduced 4EBP2 levels increased glucose uptake and insulin sensitivity, whereas the 4EBP2_S65A/T70A mutation exacerbated PA-induced insulin resistance. Additionally, the nascent proteome revealed many glycolysis-related proteins translationally regulated by 4EBP2 such as hexokinase-2, pyruvate kinase PKM, TBC1 domain family member 4, and glucose-6-phosphate 1-dehydrogenase. In summary, we report the critical role of 4EBP2 in regulating HFD-stimulated insulin resistance in hepatocytes.

Photoenzymatic Asymmetric Hydroamination for Chiral Alkyl Amine Synthesis.

Chiral alkyl amines are common structural motifs in pharmaceuticals, natural products, synthetic intermediates, and bioactive molecules. An attractive method to prepare these molecules is the asymmetric radical hydroamination; however, this approach has not been explored with dialkyl amine-derived nitrogen-centered radicals since designing a catalytic system to generate the aminium radical cation, to suppress deleterious side reactions such as α-deprotonation and H atom abstraction, and to facilitate enantioselective hydrogen atom transfer is a formidable task. Herein, we describe the application of photoenzymatic catalysis to generate and harness the aminium radical cation for asymmetric intermolecular hydroamination. In this reaction, the flavin-dependent ene-reductase photocatalytically generates the aminium radical cation from the corresponding hydroxylamine and catalyzes the asymmetric intermolecular hydroamination to furnish the enantioenriched tertiary amine, whereby enantioinduction occurs through enzyme-mediated hydrogen atom transfer. This work highlights the use of photoenzymatic catalysis to generate and control highly reactive radical intermediates for asymmetric synthesis, addressing a long-standing challenge in chemical synthesis.

Asymmetric Ion-Pairing Photoredox Catalysis for Stereoselective Cationic Polymerization under Light Control.

By virtue of noninvasive regulations by light, photocontrolled polymerizations have attracted considerable attention for the precision synthesis of macromolecules. However, a cationic polymerization with simultaneous photocontrol and tacticity-regulation remains elusive so far. Herein, we introduce an asymmetric ion-pairing photoredox catalysis strategy that allows for the development of a stereoselective cationic polymerization with concurrent light regulation for the first time. By employing an ion pair catalyst (PC+/*A-) consisting of a photoredox active cation (PC+) and a sterically confined chiral anion (*A-) to deliver the stereochemical control, the cationic polymerization of vinyl ethers can be achieved with photocontrol and high isotactic selectivity (up to 91% m) at a remarkable low catalyst loading (50 ppm).

Loss of OsMATE6 Function Enhances Drought Resistance Without Yield Penalty by Regulating Stomatal Closure in Rice.

Drought is one of the most severe environmental factors limiting plant growth and crop yield, necessitating the identification of genes that enhance drought resistance for crop improvement. Through screening an ethyl methyl sulfonate-mutagenized rice mutant library, we isolated the PEG tolerance mutant 97-1 (ptm97-1), which displays enhanced resistance to osmotic and drought stress, and increased yield under drought conditions. A point mutation in OsMATE6 was identified as being associated with the drought-resistant phenotype of ptm97-1. The role of OsMATE6 in conferring drought resistance was confirmed by additional OsMATE6 knockout mutants. OsMATE6 is expressed in guard cells, shoots and roots and the OsMATE6-GFP fusion protein predominantly localizes to the plasma membrane. Our ABA efflux assays suggest that OsMATE6 functions as an ABA efflux transporter; mutant protoplasts exhibited a slower ABA release rate compared to the wild type. We hypothesize that OsMATE6 regulates ABA levels in guard cells, influencing stomatal closure and enhancing drought resistance. Notably, OsMATE6 knockout mutants demonstrated greater yields under field drought conditions compared to wild-type plants, highlighting OsMATE6 as a promising candidate for improving crop drought resistance.

Deep Learning for Discrimination of Hypertrophic Cardiomyopathy and Hypertensive Heart Disease on MRI Native T1 Maps.

BACKGROUND: Native T1 and radiomics were used for hypertrophic cardiomyopathy (HCM) and hypertensive heart disease (HHD) differentiation previously. The current problem is that global native T1 remains modest discrimination performance and radiomics requires feature extraction beforehand. Deep learning (DL) is a promising technique in differential diagnosis. However, its feasibility for discriminating HCM and HHD has not been investigated. PURPOSE: To examine the feasibility of DL in differentiating HCM and HHD based on T1 images and compare its diagnostic performance with other methods. STUDY TYPE: Retrospective. POPULATION: 128 HCM patients (men, 75; age, 50 years ± 16) and 59 HHD patients (men, 40; age, 45 years ± 17). FIELD STRENGTH/SEQUENCE: 3.0T; Balanced steady-state free precession, phase-sensitive inversion recovery (PSIR) and multislice native T1 mapping. ASSESSMENT: Compare HCM and HHD patients baseline data. Myocardial T1 values were extracted from native T1 images. Radiomics was implemented through feature extraction and Extra Trees Classifier. The DL network is ResNet32. Different input including myocardial ring (DL-myo), myocardial ring bounding box (DL-box) and the surrounding tissue without myocardial ring (DL-nomyo) were tested. We evaluate diagnostic performance through AUC of ROC curve. STATISTICAL TESTS: Accuracy, sensitivity, specificity, ROC, and AUC were calculated. Independent t test, Mann-Whitney U-test and Chi-square test were adopted for HCM and HHD comparison. P < 0.05 was considered statistically significant. RESULTS: DL-myo, DL-box, and DL-nomyo models showed an AUC (95% confidential interval) of 0.830 (0.702-0.959), 0.766 (0.617-0.915), 0.795 (0.654-0.936) in the testing set. AUC of native T1 and radiomics were 0.545 (0.352-0.738) and 0.800 (0.655-0.944) in the testing set. DATA CONCLUSION: The DL method based on T1 mapping seems capable of discriminating HCM and HHD. Considering diagnostic performance, the DL network outperformed the native T1 method. Compared with radiomics, DL won an advantage for its high specificity and automated working mode. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 2.

Theoretical Study on the Effect of Cyano- and Dimethylamine-Group on ESIPT Behavior and Luminescent Properties of Novel Flavone-Based Fluorophore.

Recently, a new fluorescent senor based on 3-hydroxy-2-(naphthalen-2-yl)-4 H-chromen-4-one (HFN) for selective detection of H2Sn was obtained in the experiment (Spectrochim. Acta Part A 271(2022)120962). Based on HFN, three new compounds (HFN1, HFN2 and HFN3) are designed to explore the influences of dimethylamine (-N(CH3)2) and cyano (-CN) groups on the excited-state intramolecular proton transfer (ESIPT) process and luminescent features of HFN. After analyzing the mainly geometrical parameters, electron densities and infrared spectra, we discovered that the intramolecular hydrogen bonds (IHBs) in the target molecules become stronger upon photo-excitation. Introducing -CN or/and -N(CH3)2 groups into HFN indeed influences its ESIPT behavior and luminescent properties. The -N(CH3)2 group enhances IHB, reduces ESIPT barrier and caused absorption/ fluorescence (at T form) peak blue-shift, while the -CN group shows a counterproductive effect. The coincidence of -N(CH3)2 and -CN made the absorption/fluorescent wavelength of HFN red-shift more than single -N(CH3)2 or -CN group does.

Occlusal veneer restoration treatment outcomes of cracked tooth syndrome: A 22.4-month follow-up study.

OBJECTIVES: The aims of this clinical study were to investigate success rate, vital pulp survival rate, tooth survival rate and patient-reported masticatory ability by evaluating the pain symptoms and signs of the cracked teeth as well as Index of Eating Difficulty (IED) and Oral Health Impact Profile-14 (OHIP-14) questionnaire after cracked teeth were restored with occlusal veneers. MATERIALS AND METHODS: 27 cracked teeth of 24 patients with cold and/or biting pains without spontaneous/nocturnal pains were recruited in this study. The cracked teeth were restored with occlusal veneers fabricated by lithium disilicate ceramic. Cold test and biting test were used to evaluate pain signs. IED and OHIP-14 questionnaire were used to evaluate masticatory ability. FDI criteria was used to evaluate restorations. The paired Wilcoxon test was used to analyze significant differences of detection rate of pain signs, OHIP scores and IED grade before and after restorations. Kaplan-Meier survival curve was used to describe the success rate, vital pulp survival rate, and tooth survival rate. RESULTS: 27 cracked teeth were restored with occlusal veneers with average of 22.4-month follow-up. Two cracked teeth had pulpitis and pain signs of the other cracked teeth completely disappeared. OHIP total scores were significantly reduced after treatment. Scores of 'pain', 'occlusal discomfort', 'uncomfortable to eat', 'diet unsatisfactory' and 'interrupted meals' reduced significantly after treatment. After treatment, IED grades of 25 vital teeth were significantly lower than those before treatment. FDI scores of 25 restorations except for 2 teeth with pulpitis were no greater than 2. The 12 months accumulated pulp survival rate of the cracked teeth was 92.6%. The 12 months accumulated tooth survival rate was 100%. The success rate at the latest recall was 92.6%. CONCLUSION: Occlusal veneer restorations with success rate of 92.6% and the same pulp survival rate might be an effective restoration for treating the cracked teeth. CLINICAL RELEVANCE: The occlusal veneer restorations might be an option for treating the cracked teeth when cracks only involve enamel and dentin, not dental pulp.

The influence of neutral MDP-Na salt on dentin bond performance and remineralization potential of etch-&-rinse adhesive.

OBJECTIVES: To investigate the effect of neutral 10-methacryloyloxydecyl dihydrogen phosphate salt (MDP-Na) on the dentin bond strength and remineralization potential of etch-&-rinse adhesive. METHODS: Two experimental etch-&-rinse adhesives were formulated by incorporating 0 wt% (E0) or 20 wt% (E20) neutral MDP-Na into a basic primer. A commercial adhesive, Adper Single Bond 2 (SB, 3 M ESPE), served as the control. Sixty prepared teeth were randomly allocated into three groups (n = 20) and bonded using either one of the experimental adhesives or SB. Following 24 h of water storage, the bonded specimens were sectioned into resin-dentin sticks, with four resin-dentin sticks obtained from each tooth for microtensile bond strength (MTBS) test. Half of the sticks from each group were immediately subjected to tensile loading using a microtensile tester at a crosshead speed of 1 mm/min, while the other half underwent tensile loading after 6-month incubation in artificial saliva (AS). The degree of conversion (DC) of both the control and experimental adhesives (n = 6 in each group) and the adsorption properties of MDP-Na on the dentin organic matrix (n = 5 in each group) were determined using Fourier-transform infrared spectrometry. Furthermore, the effectiveness of neutral MDP-Na in promoting the mineralization of two-dimensional collagen fibrils and the adhesive-dentin interface was explored using transmission electron microscopy and selected-area electron diffraction. Two- and one-way ANOVA was employed to assess the impact of adhesive type and water storage on dentin bond strength and the DC (α = 0.05). RESULTS: The addition of MDP-Na into the primer increased both the short- and long-term MTBS of the experimental adhesives (p = 0.00). No difference was noted in the DC between the control, E0 and E20 groups (p = 0.366). The MDP-Na remained absorbed on the demineralized dentin even after thorough rinsing. The intra- and extra-fibrillar mineralization of the two-dimensional collagen fibril and dentin bond hybrid layer was confirmed by transmission electron microscopy and selected-area electron diffraction when the primer was added with MDP-Na. CONCLUSIONS: The use of neutral MDP-Na results in high-quality hybrid layer that increase the dentin bond strength of etch-&-rinse adhesive and provides the adhesive with remineralizing capability. This approach may represent a suitable bonding strategy for improving the dentin bond strength and durability of etch-&-rinse adhesive.

The OsNLP3/4-OsRFL module regulates nitrogen-promoted panicle architecture in rice.

Rice panicles, a major component of yield, are regulated by phytohormones and nutrients. How mineral nutrients promote panicle architecture remains largely unknown. Here, we report that NIN-LIKE PROTEIN3 and 4 (OsNLP3/4) are crucial positive regulators of rice panicle architecture in response to nitrogen (N). Loss-of-function mutants of either OsNLP3 or OsNLP4 produced smaller panicles with reduced primary and secondary branches and fewer grains than wild-type, whereas their overexpression plants showed the opposite phenotypes. The OsNLP3/4-regulated panicle architecture was positively correlated with N availability. OsNLP3/4 directly bind to the promoter of OsRFL and activate its expression to promote inflorescence meristem development. Furthermore, OsRFL activates OsMOC1 expression by binding to its promoter. Our findings reveal the novel N-responsive OsNLP3/4-OsRFL-OsMOC1 module that integrates N availability to regulate panicle architecture, shedding light on how N nutrient signals regulate panicle architecture and providing candidate targets for the improvement of crop yield.

Untargeted Lipidomics Analysis Unravels the Different Metabolites in the Fat Body of Mated Bumblebee (Bombus terrestris) Queens.

The fat body has important functions in energy, fertility, and immunity. In female insects, mating stimulates physiological, behavioral, and gene expression changes. However, it remains unclear whether the metabolites in the fat body are affected after the bumblebee (Bombus terrestris) queen mates. Here, the ultrastructure and lipid metabolites in fat body of mated queens were compared with those of virgins. The fat body weight of mated bumblebee queens was significantly increased, and the adipocytes were filled with lipid droplets. Using LC-MS/MS-based untargeted lipidomics, 949 and 748 differential metabolites were identified in the fat body of virgin and mated bumblebee queens, respectively, in positive and negative ion modes. Most lipid metabolites were decreased, especially some biomembrane components. In order to explore the relationship between the structures of lipid droplets and metabolite accumulation, transmission electron microscopy and fluorescence microscopy were used to observe the fat body ultrastructure. The size/area of lipid droplets was larger, and the fusion of lipid droplets was increased in the mated queen's fat body. These enlarged lipid droplets may store more energy and nutrients. The observed differences in lipid metabolites in the fat body of queens contribute to understanding the regulatory network of bumblebees post mating.

Correlation between family function and quality of life in patients with atrial fibrillation. / å¿ƒæˆ¿é¢¤åŠ¨æ‚£è€ å®¶åº­åŠŸèƒ½ä¸Žç”Ÿæ´»è´¨é‡çš„ç›¸å ³æ€§.

OBJECTIVES: Many studies have shown that the quality of life for patients with atrial fibrillation (AF) is significantly impaired, but the impact on family function is still unclear. This study aims to evaluate the family function and quality of life in patients with AF using scales, to analyze the correlation between family function and quality of life, and to predict the influencing factors of quality of life. METHODS: A total of 223 patients with AF who were admitted to the Department of Cardiology and General Medicine of the Lanzhou University Second Hospital from January 1, 2021 to May 1, 2022, were selected as research subjects, the general information of patients with AF were collected via a questionnaire, the family function and quality of life were assessed by the Family Assessment Device (FAD) and Atrial Fibrillation Effect on Quality-of-Life (AFEQT) scale. The patients were divided into a non-family functional disorder group and a family functional disorder group on the basis of their FAD scores. The above data were analyzed using SPSS 26.0 statistical software. RESULTS: Among the 223 patients, 64 (28.70%) were in the non-family functional disorder group, and 159 (71.30%) were in the family functional disorder group. The total score of FAD and scores of all dimensions in the family functional disorder group were higher than those in the non-family functional disorder group (all P<0.01). AFEQT total score and symptoms, treatment concerns and daily activities in the non-family functional disorder group were significantly higher than those in the family functional disorder group (all P<0.01). The Pearson linear analysis showed that there was a linear negative correlation between the total score and each dimension of FAD with the total score and each dimension of AFEQT (all P<0.01). The variables with statistical significance in the univariate analysis were included in the multiple linear regression analysis, and the result showed that female, and the problem solving, role, affective involvement, and general functioning dimensions of family function had an impact on the quality of life (all P<0.01). CONCLUSIONS: Most patients with AF have different degrees of family dysfunction. The quality of life in patients with family functional disorder group is generally low. Female, and the problem solving, role, affective involvement, and general functioning of family function have a significant impact on the quality of life in patients with AF. In clinical treatment of AF, attention should be paid to the family function of patients, and family members can be involved in clinical intervention to improve family function and improve the quality of life.

Modulation of Topological Structures and Adsorption Properties of Copper-Tricarboxylate Frameworks Enabled by the Effect of the Functional Group and Its Position.

To push forward the structural development and fully explore the potential utility, it is highly desired but challenging to regulate in a controllable manner the structures and properties of MOFs. In this work, we reported the structural and functional modulation of Cu(II)-tricarboxylate frameworks by employing a strategy of engineering the functionalities and their positions. Two pairs of unsymmetrical biaryl tricarboxylate ligands modified with a methyl group and a pyridinic-N atom at distinct positions were logically designed and synthesized, and their corresponding Cu(II)-based MOFs were solvothermally constructed. Diffraction analyses revealed that the variation of functionalities and their positions furnished three different types of topological structures, which we ascribed to the steric effect exerted by the methyl group and the chelating effect involving the pyridinic-N atom. Furthermore, gas adsorption studies showed that three of them are potential candidates as solid separation media for acetylene (C2H2) purification, with the separation potential tailorable by altering functionalities and their locations. At 106.7 kPa and 298 K, the C2H2 uptake capacity varies from 64.1 to 132.4 cm3 (STP) g-1, while the adsorption selectivities of C2H2 over its coexisting components of CO2 and CH4 fall in the ranges of 3.28-4.60 and 14.1-21.9, respectively.

Hydroxypropylmethylcellulose as a film and hydrogel carrier for ACP nanoprecursors to deliver biomimetic mineralization.

Demineralization of hard tooth tissues leads to dental caries, which cause health problems and economic burdens throughout the world. A biomimetic mineralization strategy is expected to reverse early dental caries. Commercially available anti-carious mineralizing products lead to inconclusive clinical results because they cannot continuously replenish the required calcium and phosphate resources. Herein, we prepared a mineralizing film consisting of hydroxypropylmethylcellulose (HPMC) and polyaspartic acid-stabilized amorphous calcium phosphate (PAsp-ACP) nanoparticles. HPMC which contains multiple hydroxyl groups is a film-forming material that can be desiccated to form a dry film. In a moist environment, this film gradually changes into a gel. HPMC was used as the carrier of PAsp-ACP nanoparticles to deliver biomimetic mineralization. Our results indicated that the hydroxyl and methoxyl groups of HPMC could assist the stability of PAsp-ACP nanoparticles and maintain their biomimetic mineralization activity. The results further demonstrated that the bioinspired mineralizing film induced the early mineralization of demineralized dentin after 24 h with increasing mineralization of the whole demineralized dentin (3-4 µm) after 72-96 h. Furthermore, these results were achieved without any cytotoxicity or mucosa irritation. Therefore, this mineralizing film shows promise for use in preventive dentistry due to its efficient mineralization capability.

Biodegradation of phenol by a highly tolerant strain Rhodococcus ruber C1: Biochemical characterization and comparative genome analysis.

A novel phenol-degrading strain was isolated and identified as Rhodococcus ruber C1. The degradation analysis shows that 1806 mg/L of phenol can be completely degraded by strain C1 within 38 h, and the maximum specific growth rate (µmax=1.527 h-1) and maximum specific phenol degradation rate (qmax=3.674 h-1) indicate its excellent phenol metabolism capability. More importantly, phenol can be degraded by strain C1 in the temperature range of 20-45 °C within 72 h, and with longer degradation time, phenol can be completely degraded even at 10, 15 and 50 °C. The whole genome of strain C1 was sequenced, and a comparative genome analysis of strain C1 with 36 other genomes of Rhodococcus was performed. A remarkable gene family expansion occurred during the evolution of Rhodococcus, and a comprehensive evolutionary picture of Rhodococcus at genomic level was presented. Moreover, the copy number of genes involved in phenol metabolism was compared among genus Rhodococcus, and the results demonstrate high phenol degradation capability of strain C1 at genomic level. These findings suggest that Rhodococcus ruber C1 is a bacterium capable of degrading phenol efficiently in the temperature range of 10-50 °C.

Energy Transfer from CdS QDs to a Photogenerated Pd Complex Enhances the Rate and Selectivity of a Pd-Photocatalyzed Heck Reaction.

This Article describes the design of a colloidal quantum dot (QD) photosensitizer for the Pd-photocatalyzed Heck coupling of styrene and iodocyclohexane to form 2-cyclohexylstyrene. In the presence of 0.05 mol % CdS QDs, which have an emission spectrum that overlaps the absorption spectrum of a key Pd(II)alkyl iodide intermediate, the reaction proceeds with 82% yield for the Heck product at 0.5 mol % loading of Pd catalyst; no product forms at this loading without a sensitizer. A radical trapping experiment and steady-state and transient optical spectroscopies indicate that the QDs transfer energy to a Pd(II)alkyl iodide intermediate, pushing the reaction toward a Pd(I) alkyl radical species that leads to the Heck coupled product, and suppressing undesired ß-hydride elimination directly from the Pd(II)alkyl iodide. Functionalization of the surfaces of the QDs with isonicotinic acid increases the rate constant of this reaction by a factor of 2.4 by colocalizing the QD and the Pd-complex. The modularity and tunability of the QD core and surface make it a convenient and effective chromophore for this alternative mode of cooperative photocatalysis.

Effects of Tetrahydrobiopterin Combined with Nebivolol on Cardiac Diastolic Function in SHRs.

This study aimed to evaluate the effects of combined use of tetrahydrobiopterin (BH4) and nebivolol on cardiac diastolic dysfunction in spontaneously hypertensive rats (SHRs). Twelve-week-old male SHRs were treated with BH4, nebivolol, or a combination of both. Left ventricle function was evaluated, and reactive oxygen species (ROS) production (including dihydroethidium (DHE) and 3-nitrotyrosine (3-NT)), nitric oxide synthase (NOS) activity and the level of NO in myocardial tissue were determined. The expression levels of endothelial NOS (eNOS), phospholamban (PLN), sarcoplasmic reticulum Ca2+ ATPase (SERCA2a), ß3-adrenoceptor, cyclic guanosine monophosphate (cGMP), and protein kinase G (PKG) were assayed. Treatment with BH4, nebivolol, or both reversed the noninvasive indexes of diastolic function, including E/E' and E'/A', and the invasive indexes, including time constant of isovolumic left ventricle (LV) relaxation (tau), -dP/dtmin, -dP/dtmin/LV systolic pressure (LVSP), and LV end-diastolic pressure (LVEDP) in SHRs. mRNA and protein expression levels of eNOS dimer, phosphorylated PLN, SERCA2a, cGMP, and PKG in the myocardium of treated SHRs were significantly up-regulated compared with those in control rats (p < 0.05 or p < 0.01). The expression levels of 3-NT and DHE were reduced in all treated groups (p < 0.05 or p < 0.01). Notably, combined use of BH4 and nebivolol had better cardioprotective effects than monotherapies. BH4 or nebivolol has a protective effect on diastolic dysfunction in SHRs, and BH4 combined with nebivolol may exert a synergistically cardioprotective effect through activation of ß3-adrenoceptor and the NO/cGMP/PKG signaling pathway.

Properties of quantum dots coupled to plasmons and optical cavities.

Quantum electrodynamics is rapidly finding a set of new applications in thresholdless lasing, photochemistry, and quantum entanglement due to the development of sophisticated patterning techniques to couple nanoscale photonic emitters with photonic and plasmonic cavities. Colloidal and epitaxial semiconductor nanocrystals or quantum dots (QDs) are promising candidates for emitters within these architectures but are dramatically less explored in this role than are molecular emitters. This perspective reviews the basic physics of emitter-cavity coupling in the weak-to-strong coupling regimes, describes common architectures for these systems, and lists possible applications (in particular, photochemistry), with a focus on the advantages and issues associated with using QDs as the emitters.

The effect of phospho-peptide on the stability of gold nanoparticles and drug delivery.

BACKGROUND: Gold nanoparticles (AuNPs) have been proposed for many applications in medicine and bioanalysis. For use in all these applications, maintaining the stability of AuNPs in solution by suppressing aggregation is paramount. Herein, the effects of amino acids were investigated in stabilizing AuNPs by rationally designed peptide scaffolds. RESULTS: Compared to other tested amino acids, phosphotyrosine (pY) significantly stabilized AuNPs. Our results indicated that pY modified AuNPs presented a high level of stability in various solutions, and had good biocompatibility. When a pY-peptide was used in stabilizing AuNPs, the phosphate group could be removed by phosphatases, which subsequently caused the aggregation and the cargo release of AuNPs. In vitro study showed that AuNPs formed aggregation in a phosphatase concentration depending manner. The aggregation of AuNPs was well correlated with the enzymatic activity (R2 = 0.994). In many types of cancer, a significant increase in phosphatases has been observed. Herein, we demonstrated that cancer cells treated with pY modified AuNPs in conjunction with doxorubicin killed SGC-7901 cells with high efficiency, indicating that the pY peptide stabilized AuNPs could be used as carriers for targeted drug delivery. CONCLUSION: In summary, pY peptides can act to stabilize AuNPs in various solutions. In addition, the aggregation of pY-AuNPs could be tuned by phosphatase. These results provide a basis for pY-AuNPs acting as potential drug carriers and anticancer efficacy.