Hypso- or bathochromic phosphorescent mechanochromic mononuclear Cu(I) complexes with a bis(2-diphenylphosphinophenyl)ether auxiliary ligand.

Six phosphorescence-emitting metal-organic mononuclear Cu(I) complexes, namely four quinoline-containing three-coordinate Cu(I) complexes and two N-heterocyclic carbene-containing four-coordinate Cu(I) complexes, have been successfully developed and fully characterized. All these Cu(I) complexes include the same bis(2-diphenylphosphinophenyl)ether bidentate auxiliary ligand. Significantly, four-coordinate Cu(I) complexes 1 and 2 display typical aggregation-induced emission phenomena. Their solid samples of luminogenic complexes 1-6 emit a variety of different phosphorescence. Furthermore, solid-state phosphorescence of these Cu(I) complexes can be effectively manipulated by external mechanical force. Remarkably, luminophores 1, 2 and 5 exhibit blue-shifted mechanoluminochromism responses, while luminophores 3, 4 and 6 present red-shifted mechanoluminochromism characteristics. All of the observed mechano-responsive phosphorescence changes of solids 1-6 are reversible by the method of solvent fuming. Powder X-ray diffraction results confirm that the reversible mechanically induced phosphorescence changes of complexes 1-6 are due to the mutual transformation of ordered crystalline and metastable amorphous states.

[Construction of Nursing Quality Index System in Assisted Reproduction Hospitals Based on the Model of "Three-Dimensional Quality Structure"].

Objective To construct a nursing quality index system for the assisted reproduction hospitals integrating outpatient department,wards,and operating rooms and provide a reference for the application of the system in the quality control of clinical reproductive care. Method On the basis of Donabedian's health care quality model of structure-process-outcome,we established a nursing quality index system for assisted reproduction hospitals via literature retrieval,semi-structured interviews,Delphi method,and analytic hierarchy process. Results The two rounds of expert's questionnaire survey demonstrated the response rates of 100% and 92%,the expert authority coefficients of 0.911 and 0.919,and the Kendall coefficients of concordance of 0.228 and 0.253,respectively (all P<0.001).The nursing quality index system for assisted reproduction hospitals was established,which consisted of 3 first-level indicators,13 second-level indicators,and 39 third-level indicators. Conclusion The nursing quality index system of assisted reproduction hospitals is comprehensive,systematic and reasonable,which can be used as quality management standard and provide a reference for clinical application.

CCNB1 promotes the development of hepatocellular carcinoma by mediating DNA replication in the cell cycle.

In our studies, cyclin B1 (CCNB1) mRNA and protein were overexpressed in hepatocellular carcinoma (HCC) tissues compared with non-HCC tissues. Moreover, CCNB1 was overexpressed in the serum of HCC patients. The expression of CCNB1 was associated with several crucial clinicopathologic characteristics, and the HCC patients with overexpressed CCNB1 had worse overall survival outcomes. In the screening of interactional genes, a total of 266 upregulated co-expression genes, which were positively associated with CCNB1, were selected from the datasets, and 67 downregulated co-expression genes, which were negatively associated with CCNB1, were identified. The key genes might be functionally enriched in DNA replication and the cell cycle pathways. CDC20, CCNA2, PLK1, and FTCD were selected for further research because they were highly connected in the protein-protein interaction networks. Upregulated CDC20, CCNA2, and PLK1 and downregulated FTCD might result in undesirable overall survival outcomes for HCC patients. The univariate Cox analysis results showed that CDC20 and PLK1 might be two independent risk factors, while FTCD might be protective in HCC. Therefore, CCNB1 may participate in the cell cycle of HCC by regulating DNA replication, and CCNB1 may provide a direction for the diagnosis of early-stage HCC and targeted HCC therapy.

Untargeted Metabolomic Profiling of Liver in a Chronic Intermittent Hypoxia Mouse Model.

Obstructive sleep apnea (OSA) has been demonstrated to be associated with liver injury. Nevertheless, the mechanisms linking the two disorders remain largely unexplored to date. Based on UHPLC/Q-TOF MS platform, the present study aimed to study the hepatic metabolomic profiling in a chronic intermittent hypoxia (CIH) mouse model to identify altered metabolites and related metabolic pathways. C57BL/6 Mice (n = 12 each group) were exposed to intermittent hypoxia or control conditions (room air) for 12 weeks. At the end of the exposure, liver enzymes and histological changes were assessed. Untargeted metabolomics approach by UHPLC/Q-TOF MS and orthogonal partial least squares-discriminant analysis (OPLS-DA) were applied to screen altered metabolites in mice liver. Bioinformatics analyses were applied to identify the related metabolic pathways. CIH treatment caused a remarkable liver injury in mice. A total of 27 differential metabolites in negative ion mode and 44 in positive ion mode were identified between the two groups. These metabolites were correlated to multiple biological and metabolic processes, including various amino acid metabolism, membrane transport, lipid metabolism, carbohydrate metabolism, nucleotide metabolism, ferroptosis, etc. three differential metabolites including glutathione, glutathione disulfide, arachidonic acid (peroxide free) were identified in the ferroptosis pathway. CIH was associated with a significant metabolic profiling change in mice liver. The metabolites in amino acid metabolism, membrane transport, lipid metabolism, carbohydrate metabolism, nucleotide metabolism, and ferroptosis played an important role in CIH-induced liver injury. These findings contribute to a better understanding of the mechanisms linking OSA and liver injury and help identify potential therapeutic targets.

Comparison of Autocross-Linked Hyaluronic Acid Gel and Intrauterine Device for Preventing Intrauterine Adhesions in Infertile Patients: A Randomized Clinical Trial.

OBJECTIVES: The objective of this study is to evaluate the efficacy of autocross-linked hyaluronic acid (HA) compared with intrauterine device (IUD) for preventing intrauterine adhesions (IUAs) in infertile patients after hysteroscopic adhesiolysis. MATERIALS AND METHODS: A randomized clinical trial (ChiCTR-IOR-16007746). Upon completion of adhesiolysis, 3 ml of HA gel was placed into the uterine cavity in Group A; 3 ml of HA gel and an IUD were placed in Group B; and only an IUD was placed in Group C. A second hysteroscopic examination was performed in all patients at approximately 1 month postoperatively for the evaluation of IUA. The primary outcome measure was the effective rate of IUA prevention based on the American Fertility Society (AFS) scoring system. RESULTS: Eighty-nine women were randomly distributed into two groups for intention to treat with 30 patients in Group A, 24 patients in Group B, and 35 patients in Group C. Patients were scored and stratified into three degrees and were enrolled using the simple random sampling method. The three groups were well balanced. There were no significant differences in age, endometrial thickness, the previous number of pregnancy, and the distribution of adhesion categories across mild, moderate, and severe between the three groups. The effective rate of IUA prevention, the AFS score after therapy, and the percentage improvements of Chinese score and AFS score before and after surgery were statistically significant difference between Groups A and C. The clinical pregnancy rate in Group A was higher than those in Groups B and C, but the difference was not statistically significant. CONCLUSION: HA gel has an advantage over an IUD in reducing IUA recurrence and decreasing adhesions.

Leptin protects brain from ischemia/reperfusion-induced infarction by stabilizing the blood-brain barrier to block brain infiltration by the blood-borne neutrophils.

The cellular and molecular mechanisms underlying leptin-mediated brain protection against cerebral ischemia were investigated at the blood-brain barrier (BBB) and neutrophil level. Through the ischemia/reperfusion (I/R) animal model, we found that leptin expression level was significantly decreased in ischemic hemisphere. Brain injection with leptin (15 µg/kg, intracisternally) could block the I/R-increased BBB permeability, activation of matrix metallopeptidase 9 (MMP-9) and brain infiltration of blood-borne neutrophils to reduce the infarct volume of ischemic brain. The brain expression level of tight junction protein ZO-1 as well as number and motility of neutrophils in blood was all increased by the same injection, indicating BBB stability (rather than reduction in neutrophils) played a major role in the leptin-inhibited brain infiltration of neutrophils. Leptin-mediated protection of BBB was further confirmed in vitro, through a BBB cellular model under the in vitro ischemic condition (G/R: glucose-oxygen-serum deprivation followed by GOS restoration). The results showed that leptin again could block the G/R-increased neutrophil adherence to EC layer as well as BBB permeability, likely by stimulating the endothelial expression of ZO-1 and VE-Cadherin. The study has demonstrated that leptin could protect ischemic brain via multiple ways (other than neuronal protection), by inhibiting the BBB permeability, brain infiltration of the blood-borne neutrophils and neutrophil adherence to vascular ECs. The role of leptin in vascular biology of stroke could further support its therapeutic potential in other neurodegenerative diseases, associated with BBB disorder.

The role of ferroptosis in chronic intermittent hypoxia-induced liver injury in rats.

PURPOSE: Obstructive sleep apnea (OSA) has been related to an increased risk of liver injury. Ferroptosis is a form of programmed cell death implicated in multiple physiological and pathological processes. This study aimed to explore the role of ferroptosis in chronic intermittent hypoxia (CIH)-induced liver injury as well as to uncover the underlying mechanisms using a CIH rat model. METHODS: Fourteen male Sprague-Dawley rats were randomly allocated to either the normal control (NC) (n = 7) or the CIH group (n = 7). Rats were exposed to intermittent hypoxia for 8 weeks in CIH group. Liver function, histological changes, and markers of oxidative stress were evaluated. The protein levels of hypoxia-inducible factor-1α, nuclear factor E2-related factor 2 (Nrf2), Acyl-CoA synthetase long-chain family member 4 (ACSL4), and glutathione peroxidase 4 (GPX4) in liver were examined by Western blot analysis. RESULTS: CIH treatment caused significant increase of serum alanine aminotransferase, aspartate aminotransferase, and malondialdehyde (MDA). Liver MDA was significantly higher in CIH group than that in NC group. Histology showed that CIH treatment induced discernible swelled, disordered hepatocytes, necrosis, and infiltrated inflammatory cells. CIH treatment significantly reduced the expression of GPX4, while markedly up-regulated expression of ACSL4, indicating elevation in hepatic ferroptosis. In addition, the protein expression of Nrf2 in CIH group was significantly lower than that in NC group. CONCLUSIONS: Ferroptosis played a crucial role in CIH-induced liver injury. The hepatic ferroptosis in CIH rat model might be mediated by the dysregulation of Nrf2. This highlights a potential therapeutic target for the treatment of OSA-related liver injury.

Effects of Zuojin pill on depressive behavior and gastrointestinal function in rats with chronic unpredictable mild stress: Role of the brain-gut axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Zoujin pill (ZJP), a medication used to treat gastrointestinal disorders since the 15th Century in China, have been reported to exert anti-depressant effects in various models. STUDY AIM: To assess the effects of ZJP on gastrointestinal function and depressive behavior in rats under chronic unpredictable mild stress (CUMS), and to examine the underlying mechanisms related to brain-gut axis. METHODS: The rats suffered the stressor once daily for 5 weeks. ZJP (0.6 and 1.2 g/kg) and fluoxetine (15 mg/kg) as positive control were administered to the rats through gastric intubation once daily for 5 consecutive weeks. The anti-depression effects were compared by performing sucrose preference tests and open field tests. Gastrointestinal motility was investigated by determining the gastrointestinal transit rate and by electrogastrogram. The serum levels of the gastrointestinal hormone (GAS, MOT, VIP, SP), inflammatory cytokine (IL-1ß, IL-6; , TNFα) and glucagon-like peptide-1 (GLP-1) were assayed by enzyme-linked immunosorbent assay. For monoamine neurotransmitters (NE, 5-HT, DA), the levels were determined by high-performance liquid chromatography and electrochemical detection in conjunction, which was applied on the samples taken from the hypothalamus, hippocampus, and striatum. RESULTS: The depression-like symptoms among rats under CUMS were significantly relieved by ZJP administration (0.6 and 1.2 g/kg). Gastrointestinal motility was also improved by restoring gastric electrical rhythm and promoting gastrointestinal propulsion. The ZJP at 0.6 g/kg dosage obviously up-regulated 5-HT and DA levels in hippocampus. The ZJP at 1.2 g/kg dosage could increase 5-HT and DA levels in hypothalamus, striatum, and hippocampus, while down-regulated the NE level in hypothalamus and hippocampus. ZJP also reversed the alterations in serum gastrointestinal hormones. Furthermore, treatment with ZJP significantly reduced levels of IL-1ß, IL-6 and TNF-α and increased serum GLP-1 compared with the CUMS group. Fluoxetine also exerted similar anti-depressant effects in the absence of effects on gastrointestinal motility and the levels of serum hormone, inflammatory cytokine and GLP-1. CONCLUSION: ZJP imposed anti-depressant and gastrointestinal regulating functions in rats under CUMS, suggesting potential clinical application. .

Effect of chronic intermittent hypoxia on gene expression profiles of rat liver: a better understanding of OSA-related liver disease.

PURPOSE: Obstructive sleep apnea (OSA) and OSA-associated chronic intermittent hypoxia (CIH) have been suggested to be associated with increased risk of liver disease. Little is known about the biological pathophysiology and underlying molecular mechanisms. Here we use whole-genome expression profiling to explore the transcriptomic changes induced by CIH in rat liver. METHODS: Rats (n = 3) were exposed to CIH for 8 weeks and were compared with rats exposed to normoxia (n = 3). Illumina HiSeq 4000 platform was used to examine differentially expressed genes (DEGs) in the liver between control group and CIH rat model. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate DEGs. Biological functions of DEGs were determined by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. RESULTS: Compared with control group, 318 genes were identified to be dysregulated in the liver of CIH rat model, with 211genes upregulated and 107 genes downregulated. Bioinformatics analysis showed that these genes were extensively related to various physiologic processes such as hepatic metabolism, apoptotic process, and oxidative stress. 10 genes with 5 upregulated and 5 downregulated were selected and further verified by qRT-PCR. CONCLUSIONS: CIH resulted in altered gene expression patterns in the liver of rat. The DEGs were related to various physiological and pathological processes in CIH rat liver. These data provide a better understanding of the mechanisms and underlying molecular changes of OSA-related liver disease.