Isorhamnetin Suppresses Human Gastric Cancer Cell Proliferation through Mitochondria-Dependent Apoptosis.

Derivates of natural products have been wildly utilized in the treatment of malignant tumors. Isorhamnetin (ISO), a most important active ingredient derived from flavonoids, shows great potential in tumor therapy. However, the therapeutic effects of ISO on gastric cancer (GC) remain unclear. Here, we demonstrate that ISO treatment dramatically inhibited the proliferation of two types of GC cells (AGS-1 and HGC-27) both in vitro and in vivo in time- and dose-dependent manners. These results are consistent with the transcriptomic analysis of ISO-treated GC cells, which yielded hundreds of differentially expressed genes that were enriched with cell growth and apoptosis. Mechanically, ISO treatment initiated the activation of caspase-3 cascade and elevated the expression of mitochondria-associated Bax/Bcl-2, cytosolic cytochrome c, followed by the activation of the cleavage of caspase-3 as well as poly ADP-ribose polymerase (PARP), resulting in the severe reduction of the mitochondrial potential and the accumulation of reactive oxygen species (ROS), while pre-treatment of the caspase-3 inhibitor could block the anti-tumor effect. Therefore, these results indicate that ISO treatment induces the apoptosis of GC cells through the mitochondria-dependent apoptotic pathway, providing a potential strategy for clinical GC therapy.

Construct and clinical verification of a nurse-led rapid response systems and activation criteria.

BACKGROUND: Effective team leadership and good activation criteria can effectively initiate rapid response system (RRS) to reduce hospital mortality and improve quality of life. The first reaction time of nurses plays an important role in the rescue process. To construct a nurse-led (nurse-led RRS) and activation criteria and then to conduct a pragmatic evaluation of the nurse-led RRS. METHODS: We used literature review and the Delphi method to construct a nurse-led RRS and activation criteria based on the theory of "rapid response system planning." Then, we conducted a quasi-experimental study to verify the nurse-led RRS. The control group patients were admitted from August to October 2020 and performed traditional rescue procedures. The intervention group patients were admitted from August to October 2021 and implemented nurse-led RRS. The primary outcome was success rate of rescue. SETTING: Emergency department, Gansu Province, China. RESULTS: The nurse-led RRS and activation criteria include 4 level 1 indicators, 14 level 2 indicators, and 88 level 3 indicators. There were 203 patients who met the inclusion criteria to verify the nurse-led RRS. The results showed that success rate of rescue in intervention group (86.55%) was significantly higher than that in control group (66.5%), the rate of cardiac arrest in intervention group (33.61%) was significantly lower than that in control group (72.62%), the effective rescue time of intervention group (46.98 ± 12.01 min) was shorter than that of control group (58.67 ± 13.73 min), and the difference was statistically significant (P < 0.05). The rate of unplanned ICU admissions in intervention group (42.85%) was lower than that in control group (44.04%), but the difference was not statistically significant (P > 0.05). CONCLUSIONS: The nurse-led RRS and activation criteria can improve the success rate of rescue, reduce the rate of cardiac arrest, shorten the effective time of rescue, effectively improve the rescue efficiency of patients.

miR-96-5p attenuates malathion-induced apoptosis of human kidney cells by targeting the ER stress marker DDIT3.

Micro RNAs (miRNAs) are major players in cellular responses to xenobiotic compounds and toxins. However, their functions in organophosphate-induced cytotoxicity remain unclear. This study investigated the involvement of miR-96-5p in the non-cholinergic toxicity of malathion in normal human kidney cells (HK-2 cells). Malathion decreased HK-2 cell viability and the expression of miR-96-5p in a dose- and time-dependent manner. In addition, transfection with miR-96-5p mimics attenuated malathion-induced HK-2 cell apoptosis, whereas transfection with a miR-96-5p inhibitor increased HK-2 cell apoptosis. Luciferase assays indicated that miR-96-5p could bind directly to the 3'-untranslated region of DDIT3, a well-known marker of endoplasmic reticulum stress. Further analyses of the expression of apoptosis-related genes and proteins indicated that miR-96-5p may function to reduce malathion-induced HK-2 cell apoptosis via regulation of the DDIT3/B-cell lymphoma (BCL)-2/caspase-3 signaling pathway. In summary, the results of the present study indicate that miR-96-5p protects HK-2 cells from malathion-induced ER stress-dependent apoptosis by targeting DDIT3.

The c-MYC-BMI1 axis is essential for SETDB1-mediated breast tumourigenesis.

Characterising the activated oncogenic signalling that leads to advanced breast cancer is of clinical importance. Here, we showed that SET domain, bifurcated 1 (SETDB1), a histone H3 lysine 9 methyltransferase, is aberrantly expressed and behaves as an oncogenic driver in breast cancer. SETDB1 enhances c-MYC and cyclin D1 expression by promoting the internal ribosome entry site (IRES)-mediated translation of MYC/CCND1 mRNA, resulting in prominent signalling of c-MYC to promote cell cycle progression, and provides a growth/self-renewal advantage to breast cancer cells. The activated c-MYC-BMI1 axis is essential for SETDB1-mediated breast tumourigenesis, because silencing of either c-MYC or BMI1 profoundly impairs the enhanced growth/colony formation conferred by SETDB1. Furthermore, c-MYC directly binds to the SETDB1 promoter region and enhances its transcription, suggesting a positive regulatory interplay between SETDB1 and c-MYC. In this study, we identified SETDB1 as a prominent oncogene and characterised the underlying mechanism whereby SETDB1 drives breast cancer, providing a therapeutic rationale for targeting SETDB1-BMI1 signalling in breast cancer. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Copy number variations of MTHFSD gene across pig breeds and its association with litter size traits in Chinese indigenous Xiang pig.

Copy number variation (CNV) is a major proportion of genetic variation, which changes the gene structure and dosage and affects gene expression and function. To validate the presence and the function of CNV in pig, we used real-time quantitative polymerase chain reaction (qPCR) method to validate a 496 kb CNV region comprising MTHFSD gene on chromosome 6 of Xiang pig detected by single nucleotide polymorphism (SNP) array. Then we investigated the distribution of the MTHFSD CNV in a total of 545 pigs in four breeds. About 46.2% and 32.7% individuals in the four pig breeds were detected to be types of loss and gain of MTHFSD locus. The relative copy numbers of MTHFSD gene showed the largest variation range (0-55 copies) in the Xiang pig population. The copy numbers of MTHFSD gene presented the positive correlations with the transcript level of MTHFSD gene in adult ovaries. Statistical analysis indicated that CNVs of MTHFSD gene was significantly changed the litter size traits of Xiang pigs, and the individuals with CNV gain showed more litter size than the CNV loss pigs. We have reasons to believe that the MTHFSD as RNA-binding protein play an important role in pig reproduction as a result of regulating MTHFS mRNA metabolism.

The spectral-structural relationship of a series of oxyluciferin derivatives.

The absorption and emission spectra of a series of oxyluciferin derivatives with different substituents, as well as 6'-amino oxyluciferins in different enol and keto forms, with or without an active-site model of luciferase, were systematically investigated using density functional theory. The effects of substituents, microenvironment, and the luciferase on the structures, absorption spectra, and fluorescent emission were all taken into account. It was found that a wide range of emission colors can be obtained from various oxyluciferin derivatives with the inclusion of active site residues modeling the luciferase active site. Enol and keto forms are responsible for the emissions observed in experiments. It was suggested that the active site of luciferase must be included in the calculation in order to determine the form of the emitters.

Use of ultrasonic and pepsin treatment in tandem for collagen extraction from meat industry by-products.

BACKGROUND: Relatively little attention is paid to collagen-rich cattle short tendons (musculus extensor communis, musculus flexor digitorum, musculus digitorum profundis) as a source of high content and relatively pure collagen, a meat-processing by-product that is used to a minimal extent. Thus, suitable extraction processes from a meat production by-product to gain intact collagen is promising, which thus become interesting from an economic and environmental point of view. RESULTS: Two extraction methods were compared: a 48 h pepsin treatment using 0.5 mol L⁻¹ acetic acid and an extraction using pepsin treatment after ultrasonic treatment in a 0.5 mol L⁻¹ acetic acid solution (the total ultrasonic and pepsin treatment time was 48 h). The results indicated that the optimal conditions for the extraction of collagen from cattle tendon with the ultrasonic-pepsin tandem method is: 4°C, tendon pre-swollen for 12 h in 0.5 mol L⁻¹ acetic acid, pepsin amount: 50 U mg⁻¹ of sample, ultrasonic-pepsin tandem treatment time for 18 h and 30 h, respectively. Extracted cattle tendon collagen using ultrasonic and pepsin treatment in tandem was characterised by amino acid analysis, SDS-PAGE, FT-IR, solubility and thermal denaturation temperature. The results show that the ultrasonic-pepsin tandem method can effectively improve the efficiency of pepsin extraction of natural collagen without any compromise of the resultant collagen quality. CONCLUSION: This study provides a favourable process to deal with poorly extractable residue by use of ultrasonic and pepsin treatment in tandem. Extracted collagen possesses an intact molecular structure, which is useful and particularly important for its biomedical applications, such as drug delivery systems, wound dressings, and scaffolds.

[Determination of sucralose in foods and beverages by ultraviolet derivatization-high performance liquid chromatography].

OBJECTIVE: To establish a method for determination of sucralose in foods and beverages using high performance liquid chromatography. METHODS: Sucralose was extracted with water and centrifuged, and then derivatized with benzoyl chloride in alkaline medium. The ultraviolet absorbing derivatives were separated on a Hydro-RP 80 angstroms C18 column (250 mm x 4.6 mm, 4 microm, Synergi) using methanol-water (95:5,V/V) as mobile phase with UV detection at 232 nm. RESULTS: A good correlation (correlation coefficient=0. 999 8) between detected and actual sucralose was achieved in the range of 0.05 to 1.00 microg. The detection limit of sucralose was 0.00125 microg. The recoveries were in the range from 97.4% to 102.0% with relative standard deviations of less than 5.0%. The intraday and interday relative standard deviations of the method were 1.52% and 4.04%, respectively. CONCLUSION: This method is simple, rapid, and accurate without the need of special detectors, and it can be used for rapid determination of sucralose in foods and beverages.

[Simultaneous determination of sugar alcohols and sugars in functional foods by precolumn ultraviolet derivatization--high performance liquid chromatography].

OBJECTIVE: To establish a method using precolumn ultraviolet derivatization coupled with high performance liquid chromatography (HPLC) for simultaneous determination of erythritol, xylitol, galactitol, sorbitol, mannitol, maltitol, glucose and sucrose in functional foods. METHODS: Target sugar alcohols and sugars in food samples were extracted in water by ultrasonic method and then reacted with benzoyl chloride to form violet-absorbing products, which were separated on a C18 column with gradient elution using methanol and water as mobile phase. The experiment was performed using a flow rate of 1.00 mL/min, column temperature at 30 degrees C and detected wavelength at 232 nm. RESULTS: The linear correlation coefficients of all the derivatives were more than 0. 999. The detection limits of the method were as low as 2. 2 microg/mL. The average recoveries were 89.6%-117.0%, with intraday relative standard derivations lower than 5%. CONCLUSION: This method is simple, inexpensive and easy to operate and it is suitable for the determination of sugar alcohols and glucose and sucrose in functional foods.

How the secrets behind photocurrents are revealed in Ag-TiO2 heterostructures-based plasmonic photoelectrochemical systems: A collaborative approach of EC-SERS and photoelectrochemical methods.

Plasmon-mediated chemical reactions (PMCR) have garnered growing interest as a promising concept for photocatalysis. However, in electrochemical systems at solid-liquid interfaces, the photo-induced charge transfer on the surface of metal-semiconductor heterostructures involves complex processes and mechanisms, which are still poorly understood. We explore the plasmon-mediated carrier transfer mechanism and the synergistic effect of light and electric fields on Ag-TiO2 heterostructures, through a combination of electrochemical surface-enhanced Raman spectroscopy and photoelectrochemical methods, with para-aminothiophenol (PATP) serving as a probe molecule. The results show that photocurrent responses are dependent on not only excitation wavelengths and applied potentials, but also the irreversibility of redox. The relationship between photocurrent responses and the chemical transformation between PATP and 4,4'-dimercaptoazobenzene is established, reflecting the photo-induced charge transfer of the heterostructures. The collaboration of spectroscopic and photoelectrochemical methods provide valuable insights into the chemical transformation and kinetic information of adsorbed molecules on the heterostructure during PMCR, offering opportunities for modulating of photocatalytic activities of hot carriers.

[Multicenter Prospective Study of Different Induction Regimens of Azacytidine in Treatment of Elderly Patients with Acute Myeloid Leukemia].

OBJECTIVE: To observe the efficacy and safety of different induction regimens of same total dosage of azacitidine (Aza), including standard dose (standard dose group) and low-dose long-term (adjusted dose group), in the treatment of elderly acute myeloid leukemia (AML). METHODS: A total of 103 elderly patients with AML (non-acute promyelocytic leukemia) from January 2020 to June 2021 were enrolled. Aza was administered at the standard dose of 75 mg/(m2·d) for 7 days in the standard dose group (50 cases), while at 100 mg/d for 7-12 days in the adjusted dose group (53 cases). The administration days in adjusted dose group was calculated based on the total standard dose of the patient's single course of treatment. The efficacy and safety between standard dose group and adjusted dose group were compared. Subgroup analysis were performed in the two groups for Aza alone, Aza combined with BCL-2 inhibitor, and Aza combined with low-dose chemotherapy for efficacy and safety. RESULTS: There were no significant differences in overall response rate (ORR), incidence of adverse reaction, and 1-year overall survival (OS) rate between standard dose group and adjusted dose group (P >0.05). The ORR of combination was higher than that of Aza alone (P < 0.05), while there was no significant difference in ORR between Aza combined with BCL-2 inhibitor and Aza combined with low-dose chemotherapy (P >0.05). The combination of BCL-2 inhibitor did not increase the incidence of adverse reactions compared wtih Aza alone. There was a higher risk of myelosuppression and pulmonary infection with a combination of low-dose chemotherapy than with a combination of BCL-2 inhibitor and Aza alone (P <0.05). No significant difference was observed in 1-year OS between Aza alone, Aza combined with BCL-2 inhibitor, and Aza combined with low-dose chemotherapy (P >0.05). CONCLUSIONS: Both two induction regimens can be used in elderly AML patients who cannot tolerate intensive chemotherapy with similar overall effectiveness and safety. Aza combined with low-dose chemotherapy may result in increased ORR and an increased incidence of serious adverse reactions, and may not result in longer survival compared with Aza alone. Aza combined with BCL-2 inhibitor not only has similar effect in complete remission, objective response rate, and OS compared with Aza combined with low-dose chemotherapy, but also has higher safety.

Targeting RNA Exonuclease XRN1 Potentiates Efficacy of Cancer Immunotherapy.

Despite the remarkable clinical responses achieved with immune checkpoint blockade therapy, the response rate is relatively low and only a subset of patients can benefit from the treatment. Aberrant RNA accumulation can mediate IFN signaling and stimulate an immune response, suggesting that targeting RNA decay machinery might sensitize tumor cells to immunotherapy. With this in mind, we identified an RNA exoribonuclease, XRN1, as a potential therapeutic target to suppress RNA decay and stimulate antitumor immunity. Silencing of XRN1 suppressed tumor growth in syngeneic immunocompetent mice and potentiated immunotherapy efficacy, while silencing of XRN1 alone did not affect tumor growth in immunodeficient mice. Mechanistically, XRN1 depletion activated IFN signaling and the viral defense pathway; both pathways play determinant roles in regulating immune evasion. Aberrant RNA-sensing signaling proteins (RIG-I/MAVS) mediated the expression of IFN genes, as depletion of each of them blunted the elevation of antiviral/IFN signaling in XRN1-silenced cells. Analysis of pan-cancer CRISPR-screening data indicated that IFN signaling triggered by XRN1 silencing is a common phenomenon, suggesting that the effect of XRN1 silencing may be extended to multiple types of cancers. Overall, XRN1 depletion triggers aberrant RNA-mediated IFN signaling, highlighting the importance of the aberrant RNA-sensing pathway in regulating immune responses. These findings provide the molecular rationale for developing XRN1 inhibitors and exploring their potential clinical application in combination with cancer immunotherapy. SIGNIFICANCE: Targeting XRN1 activates an intracellular innate immune response mediated by RNA-sensing signaling and potentiates cancer immunotherapy efficacy, suggesting inhibition of RNA decay machinery as a novel strategy for cancer treatment.

The Effect of Health Literacy Intervention on Patients with Diabetes: A Systematic Review and Meta-Analysis.

Relevant studies published between January 2010 and June 2021 were identified through relevant databases, including the Science Citation Index Expanded (SCIE) database of Web of Science, PubMed, and Embase, in order to assess the effect of health literacy (HL) intervention on patients with diabetes. A total of 21 articles were eligible. The results showed that: (1) this review involved different HL assessment tools, most of which were self-designed scales and assessment tools focused on measuring functional HL. (2) The differences in glycosylated hemoglobin (HbA1c) (weighted mean difference [WMD] = -0.78, 95% confidence interval [CI]: -0.94, -0.62) and medication adherence (standardized mean difference [SMD] = 1.85, 95% CI: 0.19, 3.52) between the HL intervention group and the usual care group were statistically significant. There was no significant improvement in systolic blood pressure (SMD = -0.05, 95% CI: -0.34, 0.25). Furthermore, this review reported that self-efficacy (SMD = 0.85, 95% CI: 0.65, 1.04) was increased, and the level of HL was improved. In the assessments of risk of bias, 90% of the studies were classified as medium. The quality of the evidence of medication adherence was very low, and the reliability of the conclusions was not enough to confirm the effect of HL.

Multimodal neuroimage data fusion based on multikernel learning in personalized medicine.

Neuroimaging has been widely used as a diagnostic technique for brain diseases. With the development of artificial intelligence, neuroimaging analysis using intelligent algorithms can capture more image feature patterns than artificial experience-based diagnosis. However, using only single neuroimaging techniques, e.g., magnetic resonance imaging, may omit some significant patterns that may have high relevance to the clinical target. Therefore, so far, combining different types of neuroimaging techniques that provide multimodal data for joint diagnosis has received extensive attention and research in the area of personalized medicine. In this study, based on the regularized label relaxation linear regression model, we propose a multikernel version for multimodal data fusion. The proposed method inherits the merits of the regularized label relaxation linear regression model and also has its own superiority. It can explore complementary patterns across different modal data and pay more attention to the modal data that have more significant patterns. In the experimental study, the proposed method is evaluated in the scenario of Alzheimer's disease diagnosis. The promising performance indicates that the performance of multimodality fusion via multikernel learning is better than that of single modality. Moreover, the decreased square difference between training and testing performance indicates that overfitting is reduced and hence the generalization ability is improved.

Effects of Health Literacy Intervention on Health Literacy Level and Glucolipid Metabolism of Diabetic Patients in Mainland China: A Systematic Review and Meta-Analysis.

OBJECTIVE: To systematically evaluate the effects of health literacy intervention on health literacy level and glycolipid metabolism of people with diabetes in mainland China. METHODS: A systematic review of journal articles discussing diabetes and health literacy was performed by searching PubMed, Embase, the Science Citation Index Expanded (SCIE) database of Web of Science, the China National Knowledge Infrastructure (CNKI) database, the Chinese Scientific and Technical Journals database (CQVIP), and the Wanfang database. Cochrane Effective Practice and Organization of Care Review Group (EPOC) standards were applied for quality assessment. A meta-analysis was performed using Stata 12.0 software. RESULTS: A total of 44 articles, including seven controlled before-and-after trials (CBAs), 27 randomized controlled trials (RCTs), and 10 nonrandomized controlled trials (non-RCTs), were included. The results showed that (1) health literacy level in the intervention group was improved compared with the preintervention and the control group; (2) fasting plasma glucose (FPG) (standardized mean difference (SMD) = -1.85, 95% CI: -2.28, -1.42), 2-hour plasma glucose (2hPG) (SMD = -2.18, 95% CI: -2.68, -1.68), and HbA1c (weighted mean difference (WMD) = -1.21, 95% CI: -1.48, -0.94) were significantly reduced in the intervention group; (3) total cholesterol (TC) (WMD = -0.43, 95% CI: -0.64, -0.23) was significantly reduced in the intervention group, although there were no statistically significant differences for triglycerides (TG) (WMD = -0.34, 95% CI: -0.73, 0.05), low-density lipoprotein cholesterol (LDL-C) (WMD = -0.20, 95% CI: -0.46, 0.07), or high-density lipoprotein cholesterol (HDL-C) (WMD = -0.06, 95% CI: -0.29, 0.17). CONCLUSION: Intervention based on health literacy can effectively improve health literacy levels and reduce glucose metabolism and TC level among people with diabetes mellitus, although it has no significant effect on TG, LDL-C, or HDL-C.

[Clinical Comparation of Two Kinds of Chemotherapy Regimens in the Treatment of Patients with MDS-RAEB/AML-MRC].

OBJECTIVE: To investigate the influence of conventional CAG regimen and decitabine + decreased dose CAG (D+dCAG) regimen on the clinical efficacy and safety of patients with MDS-RAEB/AML-MRC. METHODS: The clinical data of 67 patients with MDS-RAEB/AML-MRC hospitalized in our hospital from March 2012 to July 2017 were analyzed retrospectively. According to chemotherapecctic regimens, 76 patients were divided into 2 groups: 37 patients treated with conventional CAG regimen were enrolled in control group, 30 patients treated with decitabine + decreased dose CAG regimen were enrolled in D+dCAG group. The complete remission (CR) rate, overall remission rate (ORR), OS and PFS time and incidence of adverse reactions in 2 groups were compared. RESULTS: The CR in D+dCAG group was significantly higher than that in control group (P＜0.05). ORR was not significanly different between 2 groups (P＞0.05). There was no significant difference in the cumulative OS rate between 2 groups (P＞0.05). There was no significant difference in the cumulative OS rate and PFS rate in nonimplantation between 2 groups (P＞0.05). The incidence of adverse reactions of hematological system, pulmonary infection, skin and soft tissue infection, agranulocytosic fever and mycotic infection was not significanly different between 2 groups (P＞0.05). The duration of granulocyte deficiency and platelet count less than 20×109/L were not significanly different between 2 groups (P＞0.05). CONCLUSION: Compared with conventional CAG regimen, decitabine + decreased dose CAG regimen in the treatment of patients with MDS-RAEB/AML-MRC can efficiently improve the remission effects and showed the well overall safety, but can not increase the survival rate.

RNA-Binding Protein ZFP36L1 Suppresses Hypoxia and Cell-Cycle Signaling.

ZFP36L1 is a tandem zinc-finger RNA-binding protein that recognizes conserved adenylate-uridylate-rich elements (ARE) located in 3'untranslated regions (UTR) to mediate mRNA decay. We hypothesized that ZFP36L1 is a negative regulator of a posttranscriptional hub involved in mRNA half-life regulation of cancer-related transcripts. Analysis of in silico data revealed that ZFP36L1 was significantly mutated, epigenetically silenced, and downregulated in a variety of cancers. Forced expression of ZFP36L1 in cancer cells markedly reduced cell proliferation in vitro and in vivo, whereas silencing of ZFP36L1 enhanced tumor cell growth. To identify direct downstream targets of ZFP36L1, systematic screening using RNA pull-down of wild-type and mutant ZFP36L1 as well as whole transcriptome sequencing of bladder cancer cells {plus minus} tet-on ZFP36L1 was performed. A network of 1,410 genes was identified as potential direct targets of ZFP36L1. These targets included a number of key oncogenic transcripts such as HIF1A, CCND1, and E2F1. ZFP36L1 specifically bound to the 3'UTRs of these targets for mRNA degradation, thus suppressing their expression. Dual luciferase reporter assays and RNA electrophoretic mobility shift assays showed that wild-type, but not zinc-finger mutant ZFP36L1, bound to HIF1A 3'UTR and mediated HIF1A mRNA degradation, leading to reduced expression of HIF1A and its downstream targets. Collectively, our findings reveal an indispensable role of ZFP36L1 as a posttranscriptional safeguard against aberrant hypoxic signaling and abnormal cell-cycle progression. SIGNIFICANCE: RNA-binding protein ZFP36L1 functions as a tumor suppressor by regulating the mRNA stability of a number of mRNAs involved in hypoxia and cell-cycle signaling.

Theoretical study on photophysical properties of ambipolar spirobifluorene derivatives as efficient blue-light-emitting materials.

The aim of this work is to provide an in-depth interpretation of the optical and electronic properties of a series of spirobifluorene derivatives. These materials show great potential for application in organic light-emitting diodes as efficient blue-light-emitting materials due to the tuning of the optical and electronic properties by the use of different electron donors (D) and electron acceptors (A). The geometric and electronic structures of the molecules in the ground state are studied with density functional theory (DFT) and ab initio HF, whereas the lowest singlet excited states are optimized by ab initio CIS. The energies of the lowest singlet excited states are calculated by employing time-dependent density functional theory (TD-DFT). The results show that the HOMOs, LUMOs, energy gaps, ionization potentials, electron affinities, reorganization energies, and exciton binding energies for these complexes are affected by different D and A moieties. Also, it has obtained that these blue-light-emitting materials have improved charge transport rate and charge transfer balance performance and can be used as efficient ambipolar-transporting materials in organic light-emitting diodes.

Downregulated Dopamine Receptor 2 and Upregulated Corticotrophin Releasing Hormone in the Paraventricular Nucleus Are Correlated With Decreased Glucose Tolerance in Rats With Bilateral Substantia Nigra Lesions.

Patients with Parkinson's disease (PD) have a high prevalence of glucose metabolism abnormalities. However, the mechanism underlying these symptoms remains unclear. The hypothalamic-pituitary-adrenal (HPA) axis is the major neuroendocrine axis that regulates homeostasis in mammals, including glucose metabolism. Corticotrophin releasing hormone (CRH), which is synthesized in the paraventricular nucleus (PVN) of the hypothalamus, plays an important role in the regulation of blood glucose levels via the HPA axis. Our previous studies have reported that PVN neurons express numerous dopamine receptors (DRs) and accept direct projections from the substantia nigra (SN). We hypothesize that damage to dopaminergic neurons in the SN might influence the blood glucose level through the HPA system. Rats with bilateral SN lesions induced by 6-hydroxydopamine (6-OHDA) (referred to as 6-OHDA rats) were used to investigate alterations in the levels of blood glucose, CRH, and factors related to the HPA axis and to explore possible mechanisms. Blood glucose levels were detected at different time points after the glucose solution was intraperitoneally administered. CRH and DRs in the PVN were evaluated by immunofluorescence and western blot analysis. Adrenocorticotropic hormone (ACTH) in the pituitary and plasma corticosterone (CORT) was evaluated by radioimmunoassay (RIA). The results showed that 6-OHDA rats exhibited significantly decreased tyrosine hydroxylase (TH) in the SN and decreased glucose tolerance at 6 weeks, but not at 4 weeks. In the PVN, dopamine receptor 2 (D2) was expressed on CRH-positive neurons, and D2-positive neurons were surrounded by TH-positive fibers. Additionally, the expression of CRH was upregulated, whereas the expression of D2 and TH were downregulated in 6-OHDA rats compared with control rats. In D2 knock-out mice, the significantly enhanced expression of CRH and reduced expression of D2 were detected in the PVN. Furthermore, RIA revealed increased ACTH in the pituitary and elevated CORT in the blood. In summary, the present study suggests that the dopaminergic neurons in the SN are involved in the regulation of body glucose metabolism through CRH neurons that express D2 in the hypothalamic PVN. SN lesions decrease glucose tolerance mainly by downregulating D2 and upregulating CRH in the PVN through the HPA neuroendocrine system.

Expression of Dopamine Receptors in the Lateral Hypothalamic Nucleus and Their Potential Regulation of Gastric Motility in Rats With Lesions of Bilateral Substantia Nigra.

Most Parkinson's Disease (PD) patients experience gastrointestinal (GI) dysfunction especially the gastroparesis, but its underlying mechanism is not clear. We have previously demonstrated that the neurons in the substantia nigra (SN) project to the lateral hypothalamic nucleus (LH) and the dorsal motor nucleus of vagus (DMV) receives the neural projection from LH by the means of anterograde and retrograde neural tracing technology. Orexin A (OXA) is predominately expressed in the LH. It has been reported that OXA can alter the gastric motility through the orexin receptor 1 (OX1R) in DMV. We speculated that this SN-LH-DMV pathway could modulate the motility of stomach because of the important role of LH and DMV in the regulation of gastric motility. However, the distribution and expression of dopamine receptors (DR) in the LH is unknown. In the present study, using a double-labeling immunofluorescence technique combined with confocal microscopy, we significantly extend our understanding of the SN-LH-DMV pathway by showing that (1) a considerable quantity of dopamine receptor 1 and 2 (D1 and D2) was expressed in the LH as well as the OX1R was expressed in the DMV; (2) Nearly all of the D1-immuoreactve (IR) neurons were also OXA-positive while only a few neurons express both D2 and OXA in the LH, and the DR-positive neurons were surrounded by the dopaminergic neural fibers; In the DMV, OX1R were colocalized with choline acetyltransferase (ChAT)-labeled motor neurons; (3) When the gastroparesis was induced by the destruction of dopaminergic neurons in the SN, the decreased expression of D1 and OXA was observed in the LH as well as the reduced OX1R and ChAT expression in the DMV. These findings suggest that SN might regulate the function of OXA-positive neurons via D1 receptor, which then affect the motor neurons in the DMV through OX1R. If the SN is damaged the vagal pathway would be affected, which may lead to gastric dysfunction. The present study raises the possibility that the SN-LH-DMV pathway can regulate the movement of stomach.