Search

In this study, the effect of pulsed electric field (PEF) on apparent morphology and molecular structure of shell-like ferritin obtained from horse spleen was determined by circular dichroic (CD), fluorescence spectroscopy, Raman spectroscopy, cold field emission scanning electron microscopy (CF-SEM) and transmission electron microscopy (TEM), and verified by molecule dynamics (MD) simulation. After PEF treatment, the α-helix content of the samples reached a minimum value at 10 kV/cm, which indicated that the ferritin structure has been partially unfolded. However, the α-helix content peaked again after resting for 2 h at 25 ± 1 °C. This indicated that the PEF-treated ferritin tended to restore its original spherical morphology probably owing to the reversible assembly characteristic of ferritin. In addition, microstructure analysis revealed that ferritin particles aggregated after PEF treatment. Therefore, PEF treatment could induce the "exposure" of hydrophobic amino acids and conversion of disulfide bond configuration, and consequently, regulate the internal cavity stability of ferritin. The research will be beneficial to expand the application of PEF treatment in the modification of protein structure, and provide a theoretical basis for the application of ferritin as a carrier of bioactive molecules in food.

Bismuth-Yttrium Oxide Bi3YO6 (BYO) is well-known among researchers for its potential applications in different fields but its use as an electrode for asymmetric supercapacitor (ASC) has not yet been discussed and uncovered. As high energy and power densities could be well achieved with the aid of optimum potential. In the current scenario, BYO is used as an electrode material for ASCs for the first time. The material is prepared by a solid-state reaction method and its structural, morphological, and electrochemical properties have been explored by using different characterization tools. Structural analysis declared the flourite based structure of BYO having a cubic phase without any visible impurity. In a morphological analysis, a mesoporous thin film with a high surface area (~ 36.6 m2 g−1) with a narrow pore width of (~ 5–18 nm) has been observed. The as-prepared BYO employed as an electrode material for SCs delivers a high specific capacitance of (388 F g−1 at 100 m Vs−1 in the three-electrode system) with excellent cycling stability (5% loss after 6000 cycles). Essentially, an ASC is assembled using BYO and rGO as a positive and negative electrodes operating in a stable and wide potential window up to 2.2 V. Moreover, a high energy density of 11 Wh kg−1 along with a power density of 648 W kg−1 is obtained and maintained a high power density of 888 W kg−1 with the downfall of energy density to 3.7 Wh kg−1. The results prove electrode material as an alternative promising candidate for ASCs.

The development of new nanocarriers with desired degradability and targeted ability is of great significance for efficient drug delivery. In this work, a monodisperse hollow structured MnO2 (H-MnO2) with a mesoporous shell is prepared and functionalized for efficient targeted drug delivery. The highly monodisperse H-MnO2 with a uniform morphology was obtained by in situ growing MnO2 on solid silica nanoparticles and subsequently removing the silica core. Then, the H-MnO2 is successively modified with polyethylene glycol and targeted molecule folate (FA). The resultant H-MnO2-FA shows excellent colloidal stability and high drug-loading content (∼58.2%) of the antitumor drug doxorubicin hydrochloride (DOX). The H-MnO2-FA possesses acid-responsive T1-weighted magnetic resonance imaging ability. The pH-dependent biodegradation behavior of H-MnO2-FA is directly observed in vitro and confirmed by in vivo imaging, which is expected to favor the potential clearance of this hollow structured nanocarrier and eliminate its long-term toxicity. In addition, the DOX-loaded H-MnO2-FA also demonstrates excellent cancer cell-killing effect and tumor inhibition efficacy.

Purpose As radiation therapy is widely used for the management of pancreatic cancer, identifying novel targets to improve the radiosensitivity of cancer cells is beneficial. Rosiglitazone, a specific peroxisome proliferator-activated receptor γ (PPARγ) agonist, has an inhibitory effect on various types of cancer cells. The purpose of this paper is to investigate the effect of rosiglitazone on the radiosensitivity of pancreatic cancer cells and the potential mechanism. Materials and methods PPARγ expression in pancreatic cancer and adjacent tissues was evaluated using immunohistochemistry analysis. The viability, migration and invasion ability of PANC1 and PaTu8988 cells were detected using MTT assay, scratch-wound assay and transwell invasion assay. The effect of rosiglitazone on radiosensitivity of the cells was determined using the clonogenic assay. PANC1 cells were inoculated into BALB/c mice to establish tumors. Microarray was used to investigate changes of genes involved. Results Higher PPARγ expression was demonstrated in pancreatic cancer tissues compared with para-carcinoma tissues. Rosiglitazone inhibited the cell viability and enhanced the radiation-induced anti-migration and anti-invasion effect. Rosiglitazone potentiated the radiosensitivity of pancreatic cancer cells and PANC1 xenografts. Microarray analysis revealed that rosiglitazone plus radiation altered the expression of multiple genes and affected multiple pathways. Conclusion Rosiglitazone enhances the radiosensitivity of human pancreatic cancer cells in vitro and in vivo via complex mechanisms.

This study aimed to investigate the effects of heat waves and ozone on hypertensive rats. Heat wave and ozone pollution were simulated on the Shanghai Meteorological and Environmental Animal Exposure System. Eighteen hypertensive rats were randomly divided into a control group, an ozone group, and a heat wave plus ozone group. The experimental groups were transferred to the exposure system for exposure to the ozone and heat wave plus ozone. After exposure, blood samples were collected from the abdominal aorta, and the hearts were harvested in all groups. The concentrations of inflammatory factors, vasomotion factors, cardiovascular risk factors, oxidative stress and thrombosis factors and heat stress factors in heart tissue were measured in each rat. Ozone exposure and heat wave plus ozone exposure increased the levels of inflammatory factors, thrombosis factors, vasomotion factors and cardiovascular risk factors, except for HDL-C, which was reduced. Moreover, experimental exposure increased the heat stress factors and oxidative stress, except for SOD, which was decreased. These data demonstrated that both ozone exposure and heat wave plus ozone exposure could adversely affect hypertensive rats, and that heat wave may enhance the toxic effect of ozone exposure.

Lactate dehydrogenase C4 (LDH-C4) as a cancer/testis antigen (CTA) is abnormally expressed in some malignant tumors. However, the expression and clinical significance of LDH-C4 in breast cancer (BC) has not been characterized.We determined LDHC mRNA expression in serum and serum-derived exosomes of BC patients by quantitative RT-PCR. We also evaluated the protein expression of LDH-C4 in BC tissues using high-throughput tissue microarray analysis and immunohistochemistry.Our results showed high mRNA expression level of LDHC in serum and serum-derived exosomes of BC patients. The LDHC level in serum and exosomes could distinguish BC cases from healthy individuals based on their AUCs of 0.9587 and 0.9464, respectively. Besides, the LDHC level in exosomes of BC patients associated with tumor size, and positively correlated with HER2 and Ki-67 expressions (all with P 0.05). Serum and exosomal level of LDHC negatively correlated with medical treatment and positively with the recurrence of BC. Survival analysis showed that LDH-C4 expression negatively correlated with BC prognosis.Serum and exosomal LDHC may be an effective indicator for the diagnosis, efficacy evaluation, and monitoring the recurrence of BC. LDH-C4 may act as a biomarker that predicts BC prognosis.

Effect of the impurity in Cu2O nanowire on the degradation of methyl orange under light irradiation in dark circumstances was investigated. Here, we present the fabrication of Cu2O nanowires at different temperatures (110, 130, 150, 170, and 190 °C) by a facile hydrothermal route. Meanwhile, at the synthesis temperature of 110–150 °C, the major impurity in Cu2O nanowires was Cu4O3, and a new Cu impurity was introduced in the Cu2O nanowires as the synthesis temperature increased from 170 to 190 °C. Overall, as the synthesis temperature increases from 110 to 190 °C, the total impurity decreases in Cu2O nanowires. The fast degradation rate in dark circumstances has been achieved in Cu2O nanowires for all synthesis temperatures, which can be attributed to the Cu2+ in the Cu4O3 impurity of Cu2O nanowires. This result shows that the Cu2O nanowires obtained at the synthesis temperature of 150 °C have the fastest degradation rate for both under light irradiation and in dark circumstances. It has been found that under light irradiation, the Cu impurity in Cu2O nanowires plays a vital role in the degradation of methyl orange. In the current scenario, different impurity contents influence the catalyst activity of Cu2O nanowires under the visible light or dark, respectively.

Transition metal dichalcogenides (TMDs) such as MoS 2 have emerged as promising candidates for replacement of Pt-based catalysts for HER. However, the poor conductivity of TMDs hinders the electron-transfer process and thus limit the HER performance. Assembling TMDs with conductive supports such as graphene has been demonstrated as an efficient way to improve HER performance. Furthermore, compared with its crystalline counterpart, amorphous molybdenum sulfide (a-MoS x ) is believed to possess better activity toward HER. Up to now, some preparation methods have been proposed to synthesize a-MoS x , including electrochemical deposition, wet-chemical synthesis and thermolysis. However, these synthesis approaches still suffer from one or more of the following drawbacks, such as solvent toxicity, high- temperature processing and time- and labor-consuming. A strategy that overcomes all of the above-mentioned problems is still highly desirable.

Ionizing radiation and radioactive materials have been widely used in industry, medicine, science and military. The efficacy of radiotherapy and adverse effects of normal tissues are closed related to cellular radiosensitivity. Molecular mechanisms underlying radiosensitivity are of significance to tumor cell radiosensitization as well as normal tissue radioprotection. 5,6,7,8-Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide synthases (NOS) and aromatic amino acid hydroxylases, and its biosynthesis involves de novo biosynthesis and a pterin salvage pathway. In this review we overview the role of BH4 metabolism in modulating radiosensitivity. BH4 homeostasis determines the role of NOS, affecting the production of nitric oxide (NO) and oxygen free radicals. Under conditions of oxidative stress, such as UV-radiation and ionizing radiation, BH4 availability is diminished due to its oxidation, which subsequently leads to NOS uncoupling and generation of highly oxidative free radicals. On the other hand, BH4/NOS axis facilitates vascular normalization, a process by which antiangiogenic therapy corrects structural and functional flaws of tumor blood vessels, which enhances radiotherapy efficacy. Therefore, BH4/NOS axis may serve as an angel or a devil in regulating cellular radiosensitivity. Finally, we will address future perspectives, not only from the standpoint of perceived advances in treatment, but also from the potential mechanisms. These advances have demonstrated that it is possible to modulate cellular radiosensitivity through BH4 metabolism.

Regional iron accumulation and α‐synuclein (α‐syn) spreading pathology within the central nervous system are common pathological findings in Parkinson's disease (PD). Whereas iron is known to bind to α‐syn, facilitating its aggregation and regulating α‐syn expression, it remains unclear if and how iron also modulates α‐syn spreading. To elucidate the influence of iron on the propagation of α‐syn pathology, we investigated α‐syn spreading after stereotactic injection of α‐syn preformed fibrils (PFFs) into the striatum of mouse brains after neonatal brain iron enrichment. C57Bl/6J mouse pups received oral gavage with 60, 120, or 240 mg/kg carbonyl iron or vehicle between postnatal days 10 and 17. At 12 weeks of age, intrastriatal injections of 5‐µg PFFs were performed to induce seeding of α‐syn aggregates. At 90 days post‐injection, PFFs‐injected mice displayed long‐term memory deficits, without affection of motor behavior. Interestingly, quantification of α‐syn phosphorylated at S129 showed reduced α‐syn pathology and attenuated spreading to connectome‐specific brain regions after brain iron enrichment. Furthermore, PFFs injection caused intrastriatal microglia accumulation, which was alleviated by iron in a dose‐dependent way. In primary cortical neurons in a microfluidic chamber model in vitro, iron application did not alter trans‐synaptic α‐syn propagation, possibly indicating an involvement of non‐neuronal cells in this process. Our study suggests that α‐syn PFFs may induce cognitive deficits in mice independent of iron. However, a redistribution of α‐syn aggregate pathology and reduction of striatal microglia accumulation in the mouse brain may be mediated via iron‐induced alterations of the brain connectome.

Radon exposure is known to be the second most frequent cause followed by tobacco exposure for lung cancer development. In lung cancer development, microRNAs (miRNAs) play an important role in regulating various target genes associated with this disease. It is well-established that apoptosis is involved in the elimination of cancer cells. However, the mechanisms underlying chronic radon exposure induced miRNAs regulation attributed to result in carcinogenesis and subsequent activation of apoptosis is not completely understood. The aim of this study was thus to examine chronic low level radon exposure on lung miRNAs as a model for carcinogenesis induction and subsequent activation of apoptosis using human bronchial epithelial BEAS-2B cells. Quantitative real-time PCR (qRT-PCR) and flow cytometry were used to determine the miR-34a gene expression and apoptotic rate in BEAS-2B cells. Data demonstrated that chronic radon exposure up-regulated the expressions of miR-34a and enhanced cellular apoptosis in a time-dependent manner. Western blot analysis demonstrated that overexpression of the gene miR-34a enhanced apoptotic rate and elevated proapoptotic Bax protein expression accompanied by decreased protein expressions of antiapoptotic Bcl-2 and PARP-1. It is noteworthy that the apoptotic rate was elevated in BEAS-2B cells transfected with mi-R34a mimic but reduced in mi-R34a inhibitor-transfected cells. Evidence thus indicates that chronic exposure to radon produced up-regulation of miR-34a gene which subsequently enhanced apoptosis in BEAS-2B cells. The observed consequences following chronic radon exposure leading to carcinogenesis appear to involve activation of miR-34a gene.

The nanocomposites of gold nanoparticles/reduced graphene oxide (AuNPs/rGO) have attracted a lot of attention due to their excellent synergic properties. However, a green and low-cost synthesis method without suffering from solvent toxicity, labor-consuming, or high-temperature processes is still highly desirable. In this work, we demonstrated the preparation of AuNPs/rGO nanocomposite films by a one-step dual reduction of graphene oxide (GO) and chloroauric acid (HAuCl4) using argon (Ar) plasma. The oxygen functional groups on GO anchored the Au ions and the electrons generated in Ar plasma reduce these ions into metallic Au. By controlling the time of plasma treatment and concentration of HAuCl4 precursor, the size and density of AuNPs on GO can be widely tuned. The underlying mechanism for the size- and density-tunability was also discussed. The AuNPs/rGO nanocomposite films were used as Raman substrates and achieved strongly enhanced signals with excellent reproducibility and stability. The nanocomposites were also successfully applied to the catalytical reduction of toxic 4-nitrophenol (4-NP) into non-toxic 4-aminophenol (4-AP) with a reduction rate constant as high as 0.422 min−1. This work paves the way towards the green and low-cost industrial production of AuNPs/rGO nanocomposites which have great potentials in a variety of application fields.

Surface-enhanced Raman scattering (SERS)-based capillary system is a promising route toward fast, real-time, and in-situ detection using a facile sampling process. Here, we demonstrate for the firs...

Radiation-induced bystander effect (RIBE), e.g. the biological response occurring in unirradiated cells when their neighboring cells are irradiated, is the consequence of intercellular communication between irradiated and unirradiated cells and intracellular signal transduction of these two cell populations. Although several miRNAs have been found to play an important role in RIBEs, the evidence for the regulatory effects of miRNAs on RIBEs is still limited. In this study, by using a two cell-line co-culture system, we first found that the migration of unirradiated bystander WS1 skin fibroblasts was inhibited after co-culture with irradiated HaCaT skin keratinocytes. Further study revealed that HaCaT cells exposed to α-particles and X-rays quickly showed an elevated miR-27a expression, which was essential for the induction of the bystander effect, resulting in the secretion of miR-27a-containing exosomes as a major RIBE signaling factor. Upon uptake of these exosomes, the recipient unirradiated WS1 cells displayed oxidative stress and increased miR-27a levels. Elevated levels of miR-27a that targets MMP2 in the recipient WS1 cells then led to slowed cell migration, which was dependent upon the redox status of WS1 cells. To summarize, the present study has revealed a critical role of miR-27a in every step of the induction of bystander migration inhibition of unirradiated WS1 fibroblasts co-cultured with irradiated HaCaT keratinocytes, confirming the important regulatory effects of miRNAs in RIBEs. Additionally, we provided direct evidence that RIBEs could affect wound healing.

Background: DDIT4 is a tumor metabolism-related protein which is involved in the proliferation and survival of various tumors. However, the function of DDIT4 in the pancreatic cancer is still unknown.Methods: We collected clinical samples of pancreatic cancer and established animal models of pancreatic cancer and DDIT4-HET animal models. We examined the expression of DDIT4 in pancreatic cancer tissues by IHC and WB and the degree of fat infiltration in the pancreas by HE staining and oil-red O staining. What’s more, the Western blot and immunohistochemical methods were applied to test the expression levels of PPAR-γ and CD36. Meanwhile, the apoptosis and proliferation levels were also examined in DDIT4-HET pancreatic cancer model.Results:The expression of DDIT4 is decreased in pancreatic cancer and DDIT4 regulates the development of pancreatic cancer by participating in fat infiltration. The degree of fat infiltration in DDIT4-HET pancreatic cancer tumors is higher than that in wild-type pancreatic cancer tumors. Through transgenic animal models, we found that DDIT4 regulates lipid metabolism in pancreatic cancer by regulating PPAR-γ and its downstream proteins CD36 and ATGL, and DDIT4-mediated lipid metabolism abnormality is involved in the proliferation and apoptosis of pancreatic cancer.Conclusion: The low expression of DDIT4 promotes the proliferation and survival by regulating lipid metabolism in pancreatic cancer cells.

The lack of highly efficient blue‐emitting perovskite nanocrystals limits their development for optoelectronic applications. In article number 2001698, Bartomeu Monserrat, Shuyu Zhang, and co‐workers develop blue‐emitting neodymium‐doped CsPbBr3 nanocrystals with high photoluminescence quantum yield (PLQY) and narrow spectral width. First principles calculations reveal the microscopic mechanisms for the blueshift of photoluminescence and the enhancement of PLQY upon doping. [Image: see text]

A novel ynamide-mediated synthesis of thionoesters and dithioesters is described. The selective addition reactions of various monothiocarboxylic acids with ynamide furnish α-thioacyloxyenamides, which undergo transesterification with nucleophilic -OH or -SH species to afford thionoesters and dithioesters, respectively. The broad substrate scope, mild reaction conditions, and excellent yields make this method an attractive synthetic approach to thionoesters and dithioesters.

This study explored the triggering mechanism of interstitial lung disease (ILD). We established the effects of immunogenic and neurogenic calcitonin gene-related peptide (CGRP) imbalance on the regulation of aquaporin 5 (AQP5) expression and the repair responses that promote the transition from alveolar epithelial cell (AEC) apoptosis to pulmonary fibrosis. Newly diagnosed ILD patients (

Background Radiation-induced skin injury is one of the main adverse effects and a dose-limiting factor of radiotherapy without feasible treatment. The underlying mechanism of this disease is still limited. Objective To investigate the potential molecular pathways and mechanisms of radiation-induced skin injury. Methods mRNA expression profiles were determined by Affymetrix Human HTA2.0 microarray.IFI6 overexpression and knockdown were mediated by lentivirus. The functional changes of skin cells were measured by flow cytometry, ROS probe and Edu probe. Protein distribution was detected by immunofluorescence experiment, and IFI6-interacting proteins were detected by immunoprecipitation (IP) combined with mass spectrometry. The global gene changes in IFI6-overexpressed skin cells after irradiation were detected by RNA-seq. Results mRNA expression profiling showed 50 upregulated and 13 down regulated genes and interferon alpha inducible protein 6 (IFI6) was top upregulated. Overexpression of IFI6 promoted cell proliferation and reduced cell apoptosis as well as ROS production following radiation, and conversely, increased the radiosensitivity of HaCaT and human skin fibroblast (WS1). IFI6 was translocated into nucleus in irradiated skin cells and the interacting relationship with mitochondrial single-stranded DNA-binding protein 1 (SSBP1), which could enhance the transcriptional activity of heat shock transcription factor 1 (HSF1).IFI6 augmented HSF1 activity following radiation in HaCaT and WS1 cells. RNA-seq analysis showed IFI6 modulated virus infection and cellular response to stress pathways, which may help to further explore how IFI6 regulate the transcriptional activity of HSF1. Conclusion This study reveals that IFI6 is induced by ionizing radiation and confers radioprotection in skin cells.

BACKGROUND Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in China, constitutes a Public Health Emergency of International Concern. It is well known that COVID-19 patients may have increased serum lactate dehydrogenase (LDH) levels in the early stage. The clinical changes in LDH may have predictive value in disease evolution and prognosis in critically ill COVID-19 patients. AIM To examine serum LDH and clinical characteristics in patients with COVID-19 and their predictive value for prognosis. METHODS This retrospective study analyzed the clinical data of forty-seven critical COVID-19 patients in the intensive care unit of the Third People's Hospital of Yichang City from January 27 to March 25, 2020 and divided them into survivors and non-survivors. The patients were diagnosed according to the World Health Organization interim guidance and critical cases met any one of the following criteria: Respiratory failure and required mechanical ventilation, the occurrence of shock, and the combined failure of other organs that required intensive care unit monitoring and treatments, according to the diagnostic criteria of critical COVID-19. Clinical data including symptoms, detection of SARS-CoV-2, chest computed tomography (CT) images, changes in serum LDH in different clinical phases, and prognosis were collected. Statistical analysis of the data was performed. Continuous variables were expressed as median (interquartile range) and compared with the Mann-Whitney U test. Categorical variables were compared with the Chi-square test. Survival data were analyzed using Kaplan-Meier survival curves and log-rank tests. RESULTS According to chest CT images, we observed the alveolitis and fibrosis stages in all critical patients in this study. Most non-survivors died in the fibrosis stage. Non-survivors had fewer days of hospitalization, shorter disease duration, shorter duration of alveolitis and fibrosis, and had dyspnea symptoms at disease onset (P = 0.05). Both first and lowest LDH values in the alveolitis stage were more pronounced in non-survivors than in survivors (449.0 U/L vs 288.0 U/L, P = 0.0243; 445.0 U/L vs 288.0 U/L, P = 0.0199, respectively), while the first, lowest and highest values of serum LDH in non-survivors were all significantly increased compared to survivors in the fibrosis phase (449.0 U/L vs 225.5 U/L, P = 0.0028; 432.0 U/L vs 191.0 U/L, P = 0.0007; 1303.0 U/L vs 263.5 U/L, P = 0.0001, respectively). The cut-off points of first LDH values in the alveolitis and fibrosis phase for distinction of non-survivors from survivors were 397.0 U/L and 263.0 U/L, respectively. In the fibrosis stage, non-survivors had more days with high LDH than survivors (7.0 d vs 0.0 d, P = 0.0002). Importantly, patients with high LDH had a significantly shorter median survival time than patients with low LDH in the alveolitis phase (22.0 d vs 36.5 d, P = 0.0002), while patients with high LDH also had a significantly shorter median survival time than patients with low LDH in the fibrosis phase (27.5 d vs 40.0 d, P = 0.0008). The proportion of non-survivors with detectable SARS-CoV-2 until death in the alveolitis stage was significantly increased compared with that in the fibrosis stage (100% vs 35.7%, P = 0.0220). CONCLUSION High LDH and dyspnea symptoms were positive predictors of an adverse outcome in critical COVID-19. The rapid progressive fibrosis stage was more perilous than the alveolitis stage, even if SARS-CoV-2 is undetectable.

To enhance the therapeutic efficiency and reduce side effects from drug delivery and chemotherapy, image-guided nanoscale systems have attracted tremendous attention in recent decades. In this study, we developed a novel method to fabricate a colchicine/gadolinium-loaded tubulin self-assembly nanocarrier (Col-Gd@Tub NC) for the image-guided chemotherapy of glioma. The Col-Gd@Tub NCs were spontaneously formed via tubulin self-assembly and were subsequently functionalized by colchicine and gadolinium elements. These resultant Col-Gd@Tub NCs with a diameter of 45 nm exhibited uniform particle size distribution and favorable stability without any leakage of gadolinium in water. Meanwhile, the introduction of gadolinium endowed Col-Gd@Tub NCs with high T 1-weighted MRI performance in vitro. After tail vein injection, Col-Gd@Tub NCs exhibited excellent MRI contrast capability and relatively long circulation time (∼12 h) and were finally cleared out from the bladder. More significantly, the binding colchicine still exerted an anti-tumor effect after the Col-Gd@Tub NCs were taken up by the tumor cells. These results show that the Col-Gd@Tub NCs may be served as a versatile nanoscale platform for the integration of biomedical imaging probes and therapeutic molecules for tumor therapy.

To investigate immune activity of pine nut peptides treated by PEF technology and mechanism of targeting immunoactive sitesits, immune regulatory active was evaluated by RAW 264.7 cells model and the structures of pine nut peptides were researched by fluorescence, CD, and 1D/2D NMR spectrum. These consequences showed the ability of macrophages to phagocytosis neutral red and the production of nitric oxide (NO) were improved after PEF treatment. KWFCT treated by PEF treatment with 40 kV/cm obtained the best immunocompetence. The CD spectroscopy showed that PEF could transform the secondary structures of pine nut peptides. The short-range correlation between Cγ H (1.65 ppm) and Cα H (3.35 ppm), and long-range correlation between Cα H (3.37 ppm) and Nα H (8.07 ppm) were enhanced by PEF treatment. PEF treatment of tryptophan in the pine nut peptides enhanced the immunological activity of the pine nut peptides. PRACTICAL APPLICATIONS: Bioactive peptides derived from food proteins have been extensively studied in recent years. However, little research has been done on the immunoactive peptide of pine nut source. PEF treatment is promising for improving certain properties of foods while maintaining the flavor, color, taste, and nutritional value of the food. This research demonstrated that PEF treatment increased the immunological activity of KWFCT and KWFM. The primary structure of KWFCT and KWFM did not change after PEF treatment, but the secondary structure was transformed into each other. A new perspective on the PEF action site is proposed, which is beneficial to the application of PEF technology.

Ionizing radiation causes damage to a variety of tissues, especially radiation-sensitive tissues, such as the small intestine. Radiation-induced damage is caused primarily by increased oxidative stress in the body. Studies have shown that trace metal elements play an irreplaceable role in oxidative stress in humans, which may be associated with radiation-induced tissue damage. However, the alteration and functional significance of trace metal elements in radiation-induced injury is not clear. In this study, we explored the association between radiation-induced damage and 7 trace metal elements in mouse models. We found that the concentration of zinc and copper in mice serum was decreased significantly after irradiation, whereas that of nickel, manganese, vanadium, cobalt, and stannum was not changed by inductively coupled plasma mass spectrometry. The role of copper in radiation-induced intestines was characterized in detail. The concentration of copper was increased in irradiated intestine but reduced in irradiated heart. Immunohistochemistry staining showed that copper transporter protein copper transport 1 expression was upregulated in irradiated mouse intestine, suggesting its potential involvement in radiation-induced copper accumulation. At the cellular level, the addition of CuCl2potentiated radiation-induced reactive oxygen species in intestine-derived human intestinal epithelial cell and IEC-6 cells. Moreover, the level of copper in damaged cells may be related to the severity of radiation-induced damage as evidenced by a cell viability assay. These results indicate that copper may be involved in the progression of radiation-induced tissue damage and may be a potential therapeutic target.

Integrating information on physical function and pain intensity into a composite measure may provide a useful method for assessing treatment efficacy in clinical trials of chronic pain. Accordingly, we evaluated composite outcomes in trials of duloxetine, gabapentin, and pregabalin. Data on 2287 patients in 9 trials for painful diabetic peripheral neuropathy (DPN) and 1513 patients in 6 trials for postherpetic neuralgia (PHN) were analyzed. All trials assessed pain intensity on a 0 to 10 numeric rating scale and physical function with the 10-item subscale of the Short Form-36, ranging 0 to 100 with higher scores indicating better function. Correlation between change in pain intensity from baseline to posttreatment and change in physical function was small in DPN (ρ = -0.22; P < 0.001) and nonsignificant in PHN (ρ = -0.05; P = 0.08). Assay sensitivities of 10 composite outcomes were examined in a random subsample of patients enrolled in pregabalin trials for DPN and PHN. Of these, a responder outcome of ≥50% improvement in pain intensity, or a ≥20% improvement in pain intensity and ≥30% improvement in physical function was not only significantly associated with pregabalin vs placebo in the development cohorts for both pain conditions but also in the validation cohorts. Furthermore, this composite outcome was cross-validated in trials of gabapentin for PHN and duloxetine for DPN, and had slightly lower number needed to treat than a standard responder outcome of ≥50% reduction in pain intensity. In summary, this study identified a composite outcome of pain intensity and physical function that may improve the assay sensitivity of future neuropathic pain trials.

The combination of dexmedetomidine (DEX) and propofol (PPF) is extensively used in the field of anaesthesiology. This study aimed to develop and validate a rapid, simple and sensitive ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC–MS/MS) method for the determination of DEX in human plasma. The method was applied to evaluate the effect of DEX concentration on the target-controlled infusion (TCI) concentration of PPF. Analytes were separated on a Waters XTERRA ® MS C18 column with a mobile phase of acetonitrile-methanol-water containing 0.1% formic acid and 5 mM ammonium acetate (70:10:20, v/v/v ) at a flow-rate of 0.3 mL/min. Mass spectrometry was performed in the positive selection reaction monitoring mode. The 201.12 → 95.12 and 515.29 → 275.68 mass transitions of DEX and IS (telmisartan), respectively, were monitored. The calibration curve of DEX was linear over the concentrations of 0.1–10 ng/mL. The intra-batch and inter-batch precisions of quality control samples were less than 10.05% and had accuracies of less than 6.25%. The newly developed method was successfully applied to quantify the DEX concentrations of plasma samples from 34 patients who were co-medicated with DEX prior to receiving anaesthesia by PPF. Results showed that comedication with DEX could reduce the requirements of PPF. Specifically, it was firstly found that the concentration of DEX is negatively correlated with the TCI concentration of PPF at the time of loss of consciousness.

A fluorescent assay for Hg 2+ was developed based on magnetic separation and the formation of T-Hg 2+ -T base pairs. The aptamers were immobilized on the surfaces of magnetic beads to form aptamers-functionalized magnetic beads (AMB). In the absence of Hg 2+ , the signal transduction probe (STP) can combine with AMB through complementary base pairing. There is almost no STP in the detection solution after magnetic separation, which results in the fluorescence signal quite weak. The presence of Hg 2+ leads to the formation of T-Hg 2+ -T base pairs between aptamers and help DNA. After magnetic separation, Hg 2+ is separated from the system and STP is left in the solution, so the fluorescence signal was significantly enhanced. The fluorescence intensity linearly increased with the increasing of Hg 2+ concentration from 2 to 160 nM with the detection limit of 0.2 nM. This method has been successfully applied to test and quantify Hg 2+ in river water and ribbon fish with satisfactory recoveries, and the results were in full agreement with those from the atomic fluorescence spectroscopy (AFS). As-built method could avoid the direct binding of Hg 2+ with the fluorescent signal probe. Therefore, combining with magnetic separation, the heavy metal-fluorescence quenching effects could be effectively eliminated.

Qinhuangdao is a provincial municipality under the jurisdiction of Hebei Province and a coastal city in China. Beidaihe is a district under the jurisdiction of Qinhuangdao and is a famous seaside scenic area. Alliance Peak, located in Beidaihe seashore scenic West. Jinshan mouth is the peak of the Union Peak, located in the easternmost Beidaihe waterfront. In this paper, we use the observed data of air negative ions in the Beidaihe, Qinhuangdao, Jinshanzui and Lianfeng Mountains for seven years to study the distribution characteristics of negative air ions in different ecological environments through meteorological observation. Research shows that the annual mean of air anion concentration fluctuates less. The annual mean is 1730 ind·cm-3, and the difference between the highest and lowest concentrations is 535 ind·cm-3. The average air anion concentration was the highest in August at 7785 ind·cm-3 and the lowest in January at 365 ind·cm-3. Negative air ions have obvious spatial characteristics, and negative ion concentrations of the sea and forest air are significantly high. The average annual mean of the sea is 3902 ind·cm-3, and that of the forest is 5403 ind·cm-3. The concentration of air anion changes daily, and daytime concentration is significantly lower than nighttime concentration. The highest peak appears at night or in the morning, while the lowest value appears between noon and afternoon. Inter-annual features and concentration of negative air ions, as well as annual rain days, total rainfall, thunderstorm days, and average relative humidity, are negatively related to the annual average temperature and sunshine hours. However, in the average concentration of negative air ions, the average correlation test of meteorological elements was insignificant. The air anion concentration is negatively correlated with the PM2.5 concentration of fine particulate matter. The concentrations of nitrogen dioxide, sulfur dioxide, and carbon monoxide in the fine particulate matter are negatively correlated with the ozone concentration, which is positively correlated with ozone concentration and is tested by significance. Atmospheric discharge (thunderstorm) can produce a considerable amount of air anion. Air negative ions are an important indicator of air quality, which is of great significance to the living environment. The distribution of negative ions in the study space and its influencing factors in order to provide a basis for air quality assessment in the region and provide references for the long-term research on air anion in different urban areas.

The methane production potential of kitchen waste (KW) obtained from different sources was compared through mesophilic and thermophilic anaerobic digestion. The methane yields (MYs) obtained with the same KW sample under different temperatures were similar, whereas the MYs obtained with different samples differed significantly. The highest MY obtained in S7 was 54%–60% higher than the lowest MY in S3. The modified Gompertz model was utilized to simulate the methane production process. The maximum production rate of methane under thermophilic conditions was 2%–86% higher than that under mesophilic conditions. The characteristics of different KW samples were studied. In the distribution of total chemical oxygen demand, the diversity of organic compounds of KW was the most dominant factor that affected the potential MYs of KW. The effect of the C/N and C/P ratios or the concentration of metal ions was insignificant. Two typical methods to calculate the theoretical MY (TMY) were compared, the organic composition method can simulate methane production more precisely than the elemental analysis method. Significant linear correlations were found between TMYorg and MYs under mesophilic and thermophilic conditions. The organic composition method can thus be utilized as a fast technique to predict the methane production potential of KW.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. (-)-Epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, is widely studied as a cancer chemopreventive agent with potential anti-cancer effects. The NF-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway is considered to mediate cellular resistance to EGCG. Metformin, a classical antidiabetic drug, has been shown to prevent cancer progression. Researchers have not reported whether metformin potentiates the anti-cancer efficacy of EGCG. In this study, metformin inhibited HO-1 expression and augmented the anti-tumor effect of EGCG. Metformin also enhanced ROS (reactive oxygen species) generation induced by EGCG (100 μM), subsequently resulting in apoptosis. Based on the results of the in vivo study, size of xenografts treated with the combination of metformin and EGCG was smaller than other groups. Mechanistically, metformin modulated the EGCG-activated Nrf2/HO-1 pathway through Sirtuin 1 (SIRT1)-dependent deacetylation of Nrf2. Moreover, metformin upregulated SIRT1 expression partially through the NF-kB pathway. Comparatively, the combination of EGCG and metformin showed little impact on normal lung epithelial BEAS-2B cells. Based on our findings, metformin sensitized NSCLC cells to the EGCG treatment by suppressing the Nrf2/HO-1 signaling pathway.

This study was aimed to explore the mechanism of peptides antioxidant activity improvement treated by pulsed electric field (PEF). The pine nut (Pinus koraiensis Sieb. et Zucc) peptides were used as the experimental materials. DPPH radical inhibition and cellular antioxidant activity (CAA) were applied to evaluate the peptides antioxidant activity. Structures of PEF-treated peptides were analyzed by mid-infrared (MIR) and circular dichroism (CD) spectroscopy. Peptides were indentified including Gln-Cys-His-Lys-Pro, Gln-Cys-His-Gln-Pro, Lys-Cys-His-Gln-Pro(KCHQP), and Lys-Cys-His-Lys-Pro. KCHQP was with the strongest DPPH radical scavenging of 89.10% ± 0.20%, and CAA units of 78.40 ± 1.71. Moreover, the DPPH radical scavenging of KCHQP was significantly increased from 89.10% ± 0.20% to 93.22% ± 0.09% under the PEF treatment conditions (pulse frequency 1800 Hz, and electric field intensity 15 kV/cm). The MIR and CD spectroscopy indicated that the structure of KCHQP was not changed by PEF. However, the zeta potential was reduced from 11.6 ± 0.28 mV to 0.4 ± 0.06 mV. This study enriched the resource of antioxidant peptides with indentified amino acid sequence. It provided a way to investigate mechanism of peptides antioxidant activity improvement treated by PEF.

A novel peptide from egg white, Asp-His-Thr-Lys-Glu (DHTKE), contains specific amino acids associated with iron binding. The present study aims to better understand the molecular basis of interactions between the DHTKE peptide and iron ions. The ultraviolet-visible and fluorescence spectra indicate an interaction between the DHTKE peptide and iron ions, which leads to the formation of a DHTKE-iron complex. Notably, Asp, Glu, His, and Lys in the DHTKE peptide play crucial roles in the formation of the DHTKE-iron complex, and the iron-binding site of the DHTKE peptide corresponds primarily to the amide and carboxyl groups. The DHTKE peptide can bind iron ions in a 1 : 2 ratio with a binding constant of 1.312 × 105 M-1. Moreover, the DHTKE-iron complex belongs to thermodynamically stable nanoparticles that are present in the crystalline structure, which might be attributed to peptide folding induced by iron binding. Meanwhile, the DHTKE-iron complex exhibits a relatively high iron-releasing percentage and exerts excellent solubility in the human gastrointestinal tract in vitro. This suggests a potential application of peptides containing Asp, Glu, His, or Lys residues as potential iron supplements.

A number of studies have shown that aldosterone serves an important role in promoting renal interstitial fibrosis, although the specific mechanism remains to be elucidated. A previous study revealed that the fibrotic effect of aldosterone was associated with the expression of allograft inflammatory factor 1 (AIF‑1) in RAW264.7 macrophage cells, in a time‑ and concentration‑dependent manner. However, the exact mechanism through which aldosterone promotes renal interstitial fibrosis remains unknown. In the present study, the effects of aldosterone on renal inflammatory cell infiltration, collagen deposition and the expression levels of AIF‑1, phosphatidylinositol 3‑kinase (PI3K), AKT serine/threonine kinase (AKT), mammalian target of rapamycin (mTOR), the oxidative stress factor NADPH oxidase 2 (NOX2) and nuclear transcription factor erythroid‑related factor 2 (Nrf2) were assessed in normal rats, rats treated with aldosterone, rats treated with aldosterone and spironolactone and those treated with spironolactone only (used as the control). The effect of aldosterone on these factors was also investigated in the renal interstitium of unilateral ureteral obstruction (UUO) rats. Additionally, the AIF‑1 gene was overexpressed and knocked down in macrophage RAW264.7 cells, and the effects of aldosterone on PI3K, AKT, mTOR, NOX2 and Nrf2 were subsequently investigated. The results showed that aldosterone promoted inflammatory cell infiltration, collagen deposition and the expression of AIF‑1, PI3K, AKT, mTOR and NOX2, but inhibited the expression of Nrf2. In the UUO rats, aldosterone also promoted renal interstitial inflammatory cell infiltration, collagen deposition and the expression of AIF‑1, NOX2, PI3K, AKT and mTOR, whereas the expression of Nrf2 was downregulated by aldosterone compared with that in the UUO‑only group; the influence of aldosterone was counteracted by spironolactone in the normal and UUO rats. In vitro, aldosterone upregulated the expression levels of AKT, mTOR, NOX2 and Nrf2 in RAW264.7 cells compared with those in untreated cells. Suppressing the expression of AIF‑1 inhibited the effects of aldosterone, whereas the overexpression of AIF‑1 enhanced these effects in RAW264.7 cells. These findings indicated that aldosterone promoted renal interstitial fibrosis by upregulating the expression of AIF‑1 and that the specific mechanism may involve AKT/mTOR and oxidative stress signaling.

Radiation-induced lung injury is a major dose-limiting toxicity that occurs due to thoracic radiotherapy. Metabolomics is a powerful quantitative measurement of low-molecular-weight metabolites in response to environmental disturbances. However, the metabolomic profiles of radiation-induced lung injury have not been reported yet. In this study, male Sprague-Dawley rats were subjected to a single dose of 10 or 20 Gy irradiation to the right lung. One week after radiation, the obvious morphological alteration of lung tissues after radiation was observed by hematoxylin and eosin staining through a transmission electron microscope. We then analyzed the metabolites and related pathways of radiation-induced lung injury by gas chromatography–mass spectrometry, and a total of 453 metabolites were identified. Compared to the nonirradiated left lung, 19 metabolites (8 upregulated and 11 downregulated) showed a significant difference in 10 Gy irradiated lung tissues, including mucic acid, methyl-β-d-galactopyranoside, quinoline-4-carboxylic acid, and pyridoxine. There were 31 differential metabolites (16 upregulated and 15 downregulated) between 20 Gy irradiated and nonirradiated lung tissues, including taurine, piperine, 1,2,4-benzenetriol, and lactamide. The Kyoto Encyclopedia of Genes and Genomes–based pathway analysis enriched 32 metabolic pathways between the irradiated and nonirradiated lung tissues, including pyrimidine metabolism, ATP-binding cassette transporters, aminoacyl-tRNA biosynthesis, and β-alanine metabolism. Among the dysregulated metabolites, we found that taurine promoted clonogenic survival and reduced radiation-induced necrosis in human embryonic lung fibroblast (HELF) cells. This study provides evidence indicating that radiation induces metabolic alterations of the lung. These findings significantly advance our understanding of the pathophysiology of radiation-induced lung injury from the perspective of metabolism.

Background Radiation-induced skin injury is a serious concern during radiotherapy and radiation accidents. Skin fat represents the dominant architectural component of the human skin. However, the interplay between skin fat and the progression of radiation-induced skin injury remains largely unexplored. Objective This study aims to elucidate the interplay between skin fat and the progression of radiation-induced skin injury. Methods SD rats were irradiated with an electron beam. mRNA profiles were determined by RNA-Seq. The skin lipid mass was monitored by magnetic resonance imaging (MRI) and lipid profiles were measured by liquid chromatography-mass spectrometry (LC–MS). Human mature adipocytes isolated from dermal and subcutaneous white adipose tissues (WATs) were co-cultured with human keratinocytes (HaCaT) and skin fibroblasts (WS1) in the transwell culture system. Cell migration ability was measured by migration assay. Results Radiation modulated cutaneous lipid metabolism by downregulating multiple pathways. Moreover, radiation decreased skin fat mass with altered lipid metabolite profiles. The rats fed with a high-fat diet showed resistance to radiogenic skin injury compared with that with a control diet, indicating that skin lipid plays a radioprotective role. Mature adipocytes promoted the migration but not the proliferation of co-cultured skin keratinocytes and fibroblasts. Palmitic acid, the most abundant fatty acid in skin tissues, facilitated the migration of WS1 cells. Moreover, fatty acid-binding protein 4 (FABP4) could be incorporated into skin cells and promote DNA damage repair in irradiated skin fibroblasts. Conclusion Radiation induces cutaneous lipid remolding, and skin adipocytes confer a protective role against radiation-induced skin injury.

Radiation-induced liver damage (RILD) has become a limitation in radiotherapy for hepatocellular carcinoma. We established a rabbit model of RILD by CyberKnife. Electron microscopy analysis revealed obvious nuclear atrophy and disposition of fat in the nucleus after irradiation. We then utilized a mass spectrometry-based label-free relative quantitative proteomics approach to compare global proteomic changes of rabbit liver in response to radiation. In total, 2365 proteins were identified, including 338 proteins that were significantly dysregulated between irradiated and nonirradiated liver tissues. These differentially expressed proteins included USP47, POLR2A, CSTB, MCFD2, and CSNK2A1. Real-time polymerase chain reaction confirmed that USP47 and CABLES1 transcripts were significantly higher in irradiated liver tissues, whereas MCFD2 and CSNK2A1 expressions were significantly reduced. In Clusters of Orthologous Groups of proteins analysis, differentially expressed proteins were annotated and divided into 24 categories, including posttranslational modification, protein turnover, and chaperones. Kyoto Encyclopedia of Genes and Genomes analysis revealed that the enriched pathways in dysregulated proteins included the vascular endothelial growth factors (VEGF) signaling pathway, the mitogen-activated protein kinase (MAPK) signaling pathway, and the adipocytokine signaling pathway. The identification of proteins and pathways is crucial toward elucidating the radiation response process of the liver, which may facilitate the discovery of novel therapeutic targets.

In this study, Alg-Gly-Ala-Val-Leu-His (RGAVLH) obtained from pine nut ( Pinus koraiensis Sieb. et Zucc.) protein was chosen to investigate the phenomenon of immunomodulatory activity improvement upon pulsed electric field (PEF) processing. The influence of electric field intensity on immunomodulatory activity of RGAVLH was evaluated using RAW 264.7 cells. It was found that RGAVLH can not only significantly ( p < 0.05) improve the capability of macrophage phagocytosis but also promote the production of nitric oxide. RGAVLH treated under an electric field intensity of 40 kV/cm exhibited the best immunomodulatory activity. The primary and secondary structures of PEF-treated peptides were analyzed by mid-infrared (MIR) spectroscopy, Raman spectroscopy, circular dichroism spectroscopy, and one-dimensional/two-dimensional nuclear magnetic resonance spectroscopy. After PEF treatment, the primary structure of RGAVLH was not influenced, as evaluated by MIR and Raman spectra. In addition, the content of β-sheet was decreased and active hydrogen was changed in PEF-treated RGAVLH solution. Moreover, the long-range connectivity between CαH (3.39 ppm) and NαH (8.24 ppm) was enhanced by PEF. Therefore, the improvement of the immunomodulatory activity of RGAVLH might result from the changes of the spatial state and spatial force in the peptide solution system.

Ovomucin (OVM) is one of the most main allergens in egg white, which limits the application of egg in the field of food processing. In this study, the effect of pulsed electric fields (PEF) on the IgG1 and IgE binding capability and the composition changes of OVM was studied by indirect competitive ELISA, SDS-PAGE, Fourier transform infrared spectroscopy (FTIR), circular dichroism (CD) spectroscopy, contact angle meter, fluorescence spectrophotometer and scanning electron microscopes (SEM). The results suggested that PEF treatment couldsignificantly reduce the IgG1 and IgE binding capacity of OVM, especially under the condition of 30 kV/cm. PEF treatment could cause partial unfolding of the protein, which was attributed to the destruction of the epitope structure that binds to IgG1 and IgE in OVM. Results indicated that PEF treatment significantly changed the primary structure, secondary structure and tertiary structure of the protein. Specifically, the secondary structure of the protein was partially unwound, and hydrophobic amino acids were exposed after PEF treatment. In addition, we observed that the microstructure of the OVM also changed significantly after PEF treatment.

The possible mechanism was investigated for the antioxidant activity improvement on a novel peptide QMDDQ obtained from shrimp protein by PEF in this study. It was found that QMDDQ that treated under 40 kV/cm exhibited the best antioxidant activity. After PEF treatment, the primary structure of QMDDQ was not influenced, while the β-sheet content was decreased and the random coil content was correspondingly increased in PEF-treated QMDDQ solution. The cross peak between CαH (4.53 ppm) on 4-Asp and CγH (1.78 ppm) on 5-Gln residue disappeared in PEF-treated peptide. After applying PEF treatment, the side chain of C-terminus residue Glutamine at was stretched to expose more active sites to combine with free radicals, thus enhancing the scavenging effect of radical. Hence, the antioxidant activity improvement of QMDDQ might be attributed to the targeted regulation of PEF treatment at C-terminal.

In this study, the targeted regulatory mechanism of pulsed electric field (PEF) was explored for antioxidant activity improvement in four peptides, RGAVIH, RGAVLH, VNAVIH, and VNAVLH, of the pine nut (Pinus koraiensis Sieb. et Zucc). The VNAVLH peptide exhibited the best antioxidant activity and the β-sheet content decreased to a minimum value at 40 kV/cm. Moreover, the chemical shifts of hydrogen atoms of 2-H Asn and 6-H His shifted to a higher magnetic field. The connectivity between NαH (3.62 ppm) and CαH (8.10 ppm) of 6-His residue disappeared in PEF-treated peptide. Molecule dynamics (MD) simulation verified that the distances of Nα(H78)-Cα(H80) and H82-O94 increased, whereas –OH and –Cβ(H83) got closer in histidine residue after applying the electric field force. Therefore, the antioxidant activity enhancement of VNAVLH might due to the targeted regulation of PEF treatment on NαH-CαH and imidazole group in histidine.

AIMS To compare effects of basal insulin peglispro (BIL), a hepatopreferential insulin, to insulin glargine (glargine) on aminotransferases and liver fat content (LFC) in patients with type 1 and type 2 diabetes (T1D, T2D). MATERIALS AND METHODS Data from two Phase 2 and five Phase 3 randomized trials comparing BIL and glargine in 1709 T1D and 3662 T2D patients were integrated for analysis of liver laboratory tests. LFC, measured by magnetic resonance imaging (MRI) at baseline, 26 and 52 weeks, was analyzed in 182 T1D patients, 176 insulin-naive T2D patients and 163 T2D patients previously treated with basal insulin. RESULTS Alanine aminotransferase (ALT) increased in patients treated with BIL, was higher than in glargine-treated patients at 4-78 weeks (difference at 52 weeks in both T1D and T2D: 7 international units/litre (IU/L), P

We acknowledge financial support from FP7 project “Laser Induced Synthesis of Polymeric Nanocomposite Materials and Development of Micro-Patterned Hybrid Light Emitting Diodes (LED) and Transistors (LET)”-LAMP (Project G.A.247928). A.K.B. and I.D.W.S. also acknowledge financial support from EPSRC Programme “Challenging the Limits of Photonics: Structured Light” Grant EP/J01771X/1. Quantum dots are of growing interest as emissive materials in light emitting devices. Here first we report the formation of highly luminescent organic capped colloidal cadmium sulfide (CdS) nanoparticles having the highest photoluminescence quantum yield of 69% in solutions and 34% in neat thin films in the near-infrared range. Second, we also show efficient electroluminescence in the near-infrared from solution processed hybrid light emitting diodes (LEDs) based on such colloidal CdS quantum dots embedded in an organic semiconductor matrix forming a nanocomposite active layer. We also discuss the device structure and role of the doped active layer in efficiency improvement. With optimized active layer thickness and concentration of QDs, the device exhibits an external electroluminescence quantum efficiency of 0.62% at a peak emission wavelength of 760 nm, providing a route to solution processable flexible light sources for biosensors and medicine. Publisher PDF

Colloidal CsPbX3 (X = Br, Cl, and I) perovskite nanocrystals exhibit tunable bandgaps over the entire visible spectrum and high photoluminescence quantum yields in the green and red regions. However, the lack of highly efficient blue‐emitting perovskite nanocrystals limits their development for optoelectronic applications. Herein, neodymium (III) (Nd3+) doped CsPbBr3 nanocrystals are prepared through the ligand‐assisted reprecipitation method at room temperature with tunable photoemission from green to deep blue. A blue‐emitting nanocrystal with a central wavelength at 459 nm, an exceptionally high photoluminescence quantum yield of 90%, and a spectral width of 19 nm is achieved. First principles calculations reveal that the increase in photoluminescence quantum yield upon doping is driven by an enhancement of the exciton binding energy due to increased electron and hole effective masses and an increase in oscillator strength due to shortening of the PbBr bond. Putting these results together, an all‐perovskite white light‐emitting diode is successfully fabricated, demonstrating that B‐site composition engineering is a reliable strategy to further exploit the perovskite family for wider optoelectronic applications.