[Mechanism of Wuling Capsules against hepatic fibrosis based on network pharmacology and animal experiments].

The present study aimed to explore the underlying mechanism of Wuling Capsules in the treatment of hepatic fibrosis(HF) through network pharmacology, molecular docking, and animal experiments. Firstly, the chemical components and targets of Wuling Capsules against HF were searched from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), Traditional Chinese Medicines Integrated Database(TCMID), GeneCards, and literature retrieval. The protein-protein interaction(PPI) network analysis was carried out on the common targets by STRING database and Cytoscape 3.9.1 software, and the core targets were screened, followed by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. Enrichment analysis was conducted on the core targets and the "drug-core component-target-pathway-disease" network was further constructed. Subsequently, molecular docking between core components and core targets was conducted using AutoDock Vina software to predict the underlying mechanism of action against HF. Finally, an HF model induced by CCl_4 was constructed in rats, and the general signs and liver tissue morphology were observed. HE and Masson staining were used to analyze the liver tissue sections. The effects of Wuling Capsules on the levels of inflammatory factors, hydroxyproline(HYP) levels, and core targets were analyzed by ELISA, RT-PCR, etc. A total of 445 chemical components of Wuling Capsules were screened, corresponding to 3 882 potential targets, intersecting with 1 240 targets of HF, and 47 core targets such as TNF, IL6, INS, and PIK3CA were screened. GO and KEGG enrichment analysis showed that the core targets mainly affected the process of cell stimulation response and metabolic regulation, involving cancer, PI3K-Akt, MAPK, and other signaling pathways. Molecular docking showed that the core components of Wuling Capsules, such as lucidenic acid K, ganoderic acid B, lucidenic acid N, saikosaponin Q2, and neocryptotanshinone, had high affinities with the core targets, such as TNF, IL6 and PIK3CA. Animal experiments showed that Wuling Capsules could reduce fat vacuole, inflammatory infiltration, and collagen deposition in rat liver, decrease the levels of inflammatory cytokines TNF-α, IL-6, and HYP, and downregulated the expressions of PI3K and Akt mRNA. This study suggests that the anti-HF effect of Wuling Capsules may be achieved by regulating the PI3K-Akt signaling pathway, reducing the levels of TNF-α and IL-6 inflammatory factors, and inhibiting the excessive deposition of collagen.

Thermally Hypsochromic or Bathochromic Emissions? The Silver Nuclei Does Matter.

Structural modulation of core-shell silver nanoclusters from the inside is a huge challenge but of great importance in their syntheses. Herein, two silver nanoclusters [Ag3 S9 @Ag42 ] (SD/Ag45b) and [Ag9 S9 @Ag42 ] (SD/Ag51a) are isolated in the presence of different kinds of sulfonic acids. Uniquely, SD/Ag45b and SD/Ag51a show typical core-shell structures with the similar Ag42 shell but different cores. The outer shell of 42 silver atoms comprises two Ag3 trigons at two poles encircled by three equatorial distorted square cupolas (J4 , Ag12 ). The core in SD/Ag45b is a silver trigon ligated by nine S2- ions (Ag3 S9 ), while a tricapped triangular prismatic Ag9 also ligated by the same amount of S2- ions (Ag9 S9 ) is observed in the inner core of SD/Ag51a. The electrospray ionization mass spectrometry (ESI-MS) indicates that the introduction of p-toluenesulfonic acid can realize the transformation from SD/Ag45b to Ag51 . SD/Ag45b and SD/Ag51a show inverse luminescence thermochromic behaviors in the near-infrared (NIR) region, mainly dictated by the inner silver cores. This work not only realizes the synthesis of new silver nanoclusters by core modulation but also provides a prototype to get molecular-level insight into the correlation between structure and luminescence thermochromism.

[Identification of Q-markers for Cistanches Herba based on HPLC-Q-TOF-MS/MS and network pharmacology].

This study aims to establish a method for analyzing the chemical constituents in Cistanches Herba by high performance liquid chromatography(HPLC) and quadrupole-time-of-flight tandem mass spectrometry(HPLC-Q-TOF-MS/MS), and to reveal the pharmacological mechanism based on network pharmacology for mining the quality markers(Q-markers) of Cistanches Herba. The chemical constituents of Cistanche deserticola and C. tubulosa were analyzed via HPLC-Q-TOF-MS/MS. The potential targets and pathways of Cistanches Herba were predicted via SwissTargetPrediction and DAVID. The compound-target-pathway-pharmacological action-efficacy network was constructed via Cytoscape. A total of 47 chemical constituents were identified, involving 95 targets and 56 signaling pathways. We preliminarily elucidated the pharmacological mechanisms of echinacoside, acteoside, isoacteoside, cistanoside F, 2'-acetylacteoside, cistanoside A, campneoside Ⅱ, salidroside, tubuloside B, 6-deoxycatalpol, 8-epi-loganic acid, ajugol, bartsioside, geniposidic acid, and pinoresinol 4-O-ß-D-glucopyranoside, and predicted them to be the Q-markers of Cistanches Herba. This study identified the chemical constituents of Cistanches Herba, explained the pharmacological mechanism of the traditional efficacy of Cistanches Herba based on network pharmacology, and introduced the core concept of Q-markers to improve the quality evaluation of Cistanches Herba.

[Comparison of therapeutic efficacy of Wuling Capsules prepared with different methods for rats with syndrome of liver Qi stagnation, spleen deficiency, and blood stasis].

Wuling Capsules is one of the commonly used drugs for the clinical treatment of chronic hepatitis B with the syndrome of liver Qi stagnation, spleen deficiency, and blood stasis. However, the present preparation method of Wuling Capsules ignores some macromolecules like polysaccharides. In this study, the influences of different ethanol concentrations in the preparation process on the extraction rates of macro-and micro-molecules were investigated. Further, the therapeutic efficacy of Wuling Capsules was evaluated with the reserpine-induced rat model of liver Qi stagnation, spleen deficiency, and blood stasis. When 50% ethanol was used for the last time of extraction, the concentrations of polysaccharides, salvianolic acid B, and schisandrin in the extract, as well as the dry extract yield, increased significantly compared with those of the original preparation method. However, the fingerprints of micro-molecules showed little difference between the two methods, with a similarity of 0.862. The study then set the 50% ethanol extraction as the new preparation method. The pharmacodynamics evaluation showed that the Wuling Capsules prepared with the original and new methods both significantly alleviated the emotional depression and metabolic disturbance in model rats, demonstrating good performance in protecting the rats against gastric mucosal injuries, modulating intestinal function, and activating blood circulation. The mechanism of action may be related to the regulation of gastrointestinal hormone secretion, reduction of inflammation, and promotion of dopamine synthesis in cortex and hippocampus. At the same dose, the Wuling Capsules prepared with the original and new methods showed roughly the same overall therapeutic efficacy. However, the Wuling Capsules prepared with the new method had stronger effect in activating blood circulation and modulating inflammation, but weaker effects in regulating gastrin and dopamine. The present study provides basis data for optimizing the preparation process of Wuling Capsules and deciphering the mechanism of its therapeutic effect on liver Qi stagnation, spleen deficiency, and blood stasis.

[Pulmonary hemorrhage in very low birth weight infants: risk factors and clinical outcome]. / æžä½Žå‡ºç”Ÿä½“é‡å„¿å‘ç”Ÿè‚ºå‡ºè¡€çš„å±é™©å› ç´ åŠå ¶ä¸´åºŠè½¬å½’.

OBJECTIVES: To investigate the risk factors for pulmonary hemorrhage and its clinical outcome in very low birth weight infants (VLBWIs). METHODS: The medical data were collected from all live VLBWIs (gestational age <35 weeks) who were admitted to Jiangsu Women and Children Health Hospital and Children's Hospital of Nanjing Medical University between January 1, 2020 and December 31, 2021. Based on inclusion and exclusion criteria, 574 VLBWIs were included in the study, with 44 VLBWIs in the pulmonary hemorrhage group and 530 VLBWIs in the non-pulmonary hemorrhage group. The clinical data were compared between the two groups. A multivariate logistic regression analysis was used to identify the risk factors for pulmonary hemorrhage. RESULTS: There were significant differences between the two groups in maternal age, rate of positive-pressure ventilation for resuscitation, rate of tracheal intubation for resuscitation, and minimum body temperature within 1 hour after birth (P<0.05). The pulmonary hemorrhage group had a higher proportion of VLBWIs with grade Ⅲ-Ⅳ respiratory distress syndrome or early-onset sepsis than the non-pulmonary hemorrhage group (P<0.05). The pulmonary hemorrhage group also had a higher proportion of VLBWIs with a capillary refilling time of >3 seconds within 1 hour after birth and with the maximum positive end-expiratory pressure (PEEP) of <5 cmH2O within 24 hours after birth (P<0.05). The multivariate regression analysis showed that maternal age of 30-<35 years (OR=0.115, P<0.05) was a protective factor against pulmonary hemorrhage, while a lower temperature (<34°C) within 1 hour after birth, the maximum PEEP of <5 cm H2O within 24 hours after birth, and early-onset sepsis were risk factors for pulmonary hemorrhage (OR=11.609, 11.118, and 20.661, respectively; P<0.05). For all VLBWIs, the pulmonary hemorrhage group had a longer duration of invasive ventilation and a higher mortality rate than the non-pulmonary hemorrhage group (P<0.05); for the survival VLBWIs, the pulmonary hemorrhage group had a higher incidence rate of bronchopulmonary dysplasia than the non-pulmonary hemorrhage group (P<0.05). CONCLUSIONS: Maintaining the stability of temperature, giving appropriate PEEP, and identifying sepsis as early as possible can reduce the incidence rate of pulmonary hemorrhage, thereby helping to reduce the incidence of bronchopulmonary dysplasia and mortality in VLBWIs.

Chemistry-specific responses due to rice-microbe interactions in the rhizosphere to counteract mefenacet stress.

The widespread use of herbicides has raised considerable concern with regard to their harmful consequences on plant growth, crop yield and the soil ecological environment. It has been well documented that colonization of rhizobacteria in the plant root system has a positive effect on activation of plant defenses to protect the plant from damage. Using the platform of high-throughput analysis with tandem mass spectrometry and Illumina sequencing, we identified the specific activated rhizobacteria, the key growth stimulating substances and the metabolic pathways involved in seedling stage tolerance to mefenacet stress in rice. The relative abundance of beneficial rhizospheremicrobes such as Acidobacteria and Firmicutes increased with mefenacet treatment, indicating that the rhizosphere recruited some beneficial microbes to resist mefenacet stress. Mefenacet treatment induced alterations in several interlinked metabolic pathways, many of which were related to activation of defense response signaling, especially the indole-3-pyruvate pathway. Indole-3-acetaldehyde and indole-3-ethanol from this pathway may act as flexible storage pools for indole-3-acetic acid (IAA). Our findings also suggest that a significant increase of IAA produced by the enrichment of beneficial rhizospheremicrobes, for example genus Bacillus, alleviated the dwarfing phenomenon observed in hydroponic medium following mefenacet exposure, which may be a key signaling molecule primarily for phytostimulation and phytotolerance in microbe-plant interactions.

Factors Associated With Long-Term Risk of Recurrence After Percutaneous Radiofrequency Thermocoagulation of the Gasserian Ganglion for Patients With Trigeminal Neuralgia Involving the Ophthalmic Division: A Retrospective Study.

OBJECTIVE: To evaluate risk factors associated with recurrence after radiofrequency thermocoagulation (RFT) of the gasserian ganglion among patients with ophthalmic trigeminal neuralgia (TN) and prognostic factors in terms of recurrence-free survival (RFS) during a long-term follow-up. METHODS: From January 2005 to December 2017, 300 patients with ophthalmic TN underwent RFT. A retrospective analysis of 14-year outcomes was performed. Kaplan-Meier analysis was used for RFS after the procedure. Univariate and multivariate Cox regression analyses were performed to identify risk factors for pain recurrence. RESULTS: The initial effective rate of RFT for ophthalmic TN was 92%. The mean follow-up time was 77.38 ± 43.24 months. The cumulative probability of RFS was 86.94% at 1 year, 80.03% at 2 years, 77.27% at 3 years, 74.01% at 5 years, and 59.92% at 10 years after RFT. The mean duration of RFS was 114.67 months (95% confidence interval [CI] 106.27 to 123.06 months). In multivariate analysis, atypical pain (hazard ratio [HR] = 2.831, 95% CI 1.759 to 4.554, P < 0.001) and mild facial hypesthesia (HR = 2.540, 95% CI 1.309 to 4.931, P = 0.006) before RFT were independently associated with pain recurrence. Patients with a prognostic index (PI) > 1.27 were at high risk for pain recurrence. Major complications included troublesome dysesthesia (0.7%), keratitis (10.9%), diplopia (0.4%), facial paresthesia (6.2%), and masseter weakness (12.7%). Masseter weakness was more common in patients with V3 branch involvement. Three patients lost their sight due to keratitis. CONCLUSION: Our study investigated long-term outcomes and complications of RFT for ophthalmic TN. Patients at high risk for pain recurrence were identified, which might provide a basis for clinical decision making before RFT.

Solvothermal Synthesis of Novel Magnetic Nickel Based Iron Oxide Nanocomposites for Selective Capture of Global- and Mono-Phosphopeptides.

A facile solvothermal method was developed for synthesis of magnetic nickel-based iron oxide nanocomposites (MNFOs) with different ratios of Ni2+ to Fe3+ for different reaction time. Two factors including dosage of Ni source and length of reaction were investigated for influence on the morphology and composition of MNFOs, as well as their distinct selectivity for different phosphopeptides. After thorough characterization, the possible formation mechanism of MNFOs was proposed. Very interestingly, MNFOs with Ni2+/Fe3+ ratios of 4:5 prepared for 8 h (MNFO-S) and for 24 h (MNFO-L) can selectively capture global- and monophosphopeptides at the fmol level with excellent enrichment performance. These two affinity probes have been exploited to isolate and enrich the phosphopeptides from human normal hepatic cells HL 7702 after exposure to atmospheric fine particulates (PM2.1), which revealed that the protein phosphorylation level was increased significantly in cells after stimulation by fine particulate matters. The findings could provide a new insight for the nickel-based affinity protocol to analyze the mutation of phosphopeptides during cellular signaling pathways in response to exogenous environment stimulation. Consequently, this present work proposed a promising strategy to isolate monophosphopeptides from global phosphopeptides for phosphoproteome research.

Diagnostic value of platelet-lymphocyte ratio and hemoglobin-platelet ratio in patients with rectal cancer.

BACKGROUND: This study aimed to investigate the diagnostic value of platelet-lymphocyte ratio (PLR) and hemoglobin-platelet ratio (HPR) combined or not with carcinoembryonic antigen (CEA) in rectal cancer. METHODS: We recruited 235 patients pathologically diagnosed with rectal cancer, 113 patients with benign rectal diseases, and 229 healthy control patients in this retrospective analysis. Then, the correlation between PLR, HPR, and clinicopathological findings was analyzed. Receiver operating characteristic (ROC) curve was used to assess the diagnostic value of PLR and HPR combined or not with CEA in rectal cancer patients. RESULTS: The levels of PLR, HPR, and CEA were higher in rectal cancer patients than those in the subjects with benign rectal diseases (P < .001) and the healthy controls (P < .001). Platelet-lymphocyte ratio and HPR were associated with lymph node metastasis and tumor stage, rather than serosa invasion, distant metastasis, or tumor size. PLR or HPR combined with CEA produced larger area under curve (AUC) (AUCPLR+CEA  = 0.75, 95% CI = 0.70-0.79, AUCHPR+CEA  = 0.76, 95% CI = 0.71-0.80) than PLR (P < .0001), HPR (P < .0001), or CEA (P = .024) alone. CONCLUSION: Our results suggest that PLR or HPR combined with CEA can increase diagnostic efficacy and may be a useful diagnostic marker for patients with rectal cancer.

Cytotoxicity and toxicoproteomic analyses of human lung epithelial cells exposed to extracts of atmospheric particulate matters on PTFE filters using acetone and water.

Differences of cytotoxicity associated with exposure to different extracts of atmospheric particulate matters (PMs) are still not well characterized by in vitro toxicoproteomics. In this study, in vitro cytotoxicity assays and toxicoproteomic analyses were carried out to investigate toxic effects of PM collected using polytetrafluoroethylene (PTFE) filters extracted with acetone for PM2.1 and water for PM2.1 and PM10 on A549 human lung epithelial cells. The cytotoxicity assays based on cell viability, cell apoptosis and reactive oxygen species generation indicated that PM2.1 extracted with acetone had the highest toxicity. iTRAQ labeling and LC-MS/MS analyses indicated that the number of differentially expressed proteins in A549 cells affected by PM2.1 extracted with acetone was noticeably higher than that of the other two groups. Hierarchical cluster analyses showed that the influences of the extracts of PM2.1 and PM10 using water on the proteome of A549 cells were similar, whereas significantly different from the effect of PM2.1 extracted with acetone. Pathways analyses indicated that PM2.1 extracted with acetone influenced the expression of proteins involved in 14 pathways including glycolysis/gluconeogenesis, pentose phosphate pathway, proteasome, etc. PM2.1 extracted with water affected the expression of proteins involved in 3 pathways including non-homologous end-joining, ribosome and endocytosis. However, PM10 extracted with water affected the expression of proteins involved in only spliceosome pathway. The extracts of PM using different extractants to detach PM from PTFE filters influenced the cytotoxic effects of PM and the proteome of A549 cells. Therefore, extractants should be assessed carefully before the investigations on cytotoxicity to improve the compatibility of experimental results among research teams.

Factors Predicting Successful Outcomes for Percutaneous Radiofrequency Thermocoagulation in Patients With Idiopathic Trigeminal Neuralgia: Implications for Surgical Decision Making.

OBJECTIVES: In this study we aimed to identify specific factors predicting successful outcomes after percutaneous radiofrequency thermocoagulation (RFT) for idiopathic trigeminal neuralgia (ITN) and risk factors that were associated with inferior outcomes. METHODS: We retrospectively reviewed our cohort of 1,624 patients who underwent RFT for trigeminal neuralgia between January 2000 and December 2017. Demographic and clinical data including age, gender, disease duration, affected side, baseline pain score, pain distribution, history of previous surgical intervention, and pain characteristics were collected and evaluated for their association with outcome using univariate and multivariate logistic regression analysis. RESULTS: 78.1% of patients experienced a successful outcome of RFT for ITN as predefined criteria. Pain characteristics and history of surgical treatment were significant predictors associated with successful outcomes in regression analysis. Multivariate analysis identified provoked episodic pain at diagnosis (odds ratio [OR] = 23.629, 95% confidence interval [CI]: 16.316 to 34.219, P = 0.010), mixed pain (OR = 8.394, 95% CI: 5.951 to 11.840, P = 0.011), and no history of surgical treatment (OR = 2.189, 95% CI: 1.411 to 3.396, P = 0.019) as independent predictors for successful RFT outcome. CONCLUSION: Presence of provoked episodic pain and mixed pain were significantly associated with successful outcome of RFT for ITN. Moreover, patients with ITN who underwent RFT for the first time were more likely to benefit from successful outcome. These findings should be considered when managing ITN with RFT to improve the likelihood of a successful outcome.

Effect of topography-dependent light coupling through a near-field aperture on the local photocurrent of a solar cell.

An aperture-type scanning near-field optical microscope (a-SNOM) is readily used for the optical and optoelectronic characterizations of a wide variety of chemical, biological and optoelectronic samples with sub-wavelength optical resolution. These samples mostly exhibit nanoscale topographic variations, which are related to local material inhomogeneity probed either by an optical contrast or by secondary effects such as photoconductivity or photoluminescence. To date, in the interpretation and evaluation of the measurement results from a-SNOM or derived methods, often only the local material inhomogeneity is taken into account. A possible influence of the optical interaction between the scanning probe and the surface topography is rarely discussed. In this paper, we present experimental and theoretical investigation of the effects of nanoscale topographic features on a-SNOM measurement results. We conduct local photocurrent measurements on a thin-film solar cell with an a-SNOM as the illumination source. A clear correlation between the photocurrent response and local topography is observed in all measurements with a signal contrast of up to ∼30%, although the sample features homogeneous permittivity and electrical properties. With the help of finite-difference time-domain (FDTD) simulations, this correlation is reproduced and local light coupling is identified as the mechanism which determines the local photocurrent response. Our results suggest that a-SNOM-based measurements of any sample with material inhomogeneity will be superimposed by the local light-coupling effect if surface topography variation exists. This effect should always be taken into consideration for an accurate interpretation of the measurement results.

Separation of selenium species and their sensitive determination in rice samples by ion-pairing reversed-phase liquid chromatography with inductively coupled plasma tandem mass spectrometry.

A highly sensitive method was developed for the simultaneous separation and determination of organic and inorganic selenium species in rice by ion-pairing reversed-phase chromatography combined with inductively coupled plasma tandem mass spectrometry. To achieve a good separation of these species, a comparison between anion-exchange chromatography and ion-pairing reversed-phase chromatography was performed. The results indicated that ion-pairing reversed-phase chromatography was more suitable due to better separation and higher sensitivity for all analytes. In this case, a StableBond C18 column proved to be more robust or to have a better resolution than other C18 columns, when 0.5 mM tetrabutylammonium hydroxide and 10 mM ammonium acetate at pH 5.5 were used as the mobile phase. Moreover, an excellent sensitivity was obtained in terms of interferences by means of tandem mass spectrometry in the hydrogen mode. The detection limits were 0.02-0.12 µg/L, and recoveries of five selenium species were 75-114%, with relative standard deviations ≤ 9.4%. This method was successfully applied to the analysis of rice samples. Compared with previous studies, the proposed method not only gave comparable results when used for measuring selenium-enriched rice, but it can provide greater sensitivity for the detection of low concentrations of selenium species in rice.

Novel primary amine diazeniumdiolates-Chemical and biological characterization.

Hit, Lead & Candidate Discovery Diazeniumdiolates, also known as NONOates, are extensively used in biochemical, physiological, and pharmacological studies due to their ability to release nitric oxide (NO. ) and/or their congeneric nitroxyl (HNO). The purpose of this work was to synthesize a series of primary amine-based diazeniumdiolates as HNO/NO donors and to determine their efficacy as anticancer and antifungal agents in vivo. The seven compounds (3a-3g) were successfully synthesized and characterized, one of which had been previously reported in the literature (3g). Two compounds showed anti-proliferative effects against ovarian (ES2 and SKOV3) and AML monocyte-derived cancer cells (THP-1) when tested with standard MTT assays. Compounds 3a and 3g demonstrated reduced ovarian cancer cell proliferation when treated at doses from 0.033 to 1.0 mg/mL at the 24 hr time point. These compounds also exhibited moderate and selective antifungal activity against Fusarium oxysporum f.sp. lycopersici, one cause of opportunistic infections of immunocompromised patients, inhibiting the growth of the fungi at LD50 at 10 mg/mL. A third compound (3e) did not exhibit similar activities, possibly due to the alkyl chain. Our results suggest that the primary amine diazeniumdiolates may offer a versatile platform for the development of HNO/NO donors for biomedical applications.

A new anthraquinone and a new naphthoquinone from the whole plant of Spermacoce latifolia.

A phytochemical study on the whole plant of Spermacoce latifolia led to the isolation of a new anthraquinone, 1,2,6-trihydroxy-5-methoxy-9,10-anthraquinone (1), and a new naphthoquinone, (2R)-6-hydroxy-7-methoxy-dehydroiso-α-lapachone (2), together with three known anthraquinones (3-5). Their structures were established on the basis of detailed spectroscopic analysis, including one- and two-dimensional NMR, ESI-MS, and HR-ESI-MS techniques. All the compounds were isolated from S. latifolia for the first time. Compounds 1, 2, 4, and 5 showed significant antibacterial activity toward Bacillus subtilis with MIC values ranging from 0.9 to 31.2 µg/ml, and compound 4 aslo exhibited antibacterial activity against Bacillus cereus with a MIC value 62.5 µg/ml. Compound 1 was further revealed to show significant in vitro α-glucosidase inhibitory activity with IC50 value of 0.653 mM.

[Diagnostic values of prealbumin and retinol-binding protein for liver damage caused by different degrees of neonatal asphyxia].

OBJECTIVE: To investigate the diagnostic values of prealbumin (PAB) and retinol-binding protein (RBP) for liver damage caused by mild or severe asphyxia. METHODS: A retrospective analysis was performed on 185 neonates (including 84 premature infants and 101 full-term infants) with asphyxia. Based on the Apgar score, they were divided into two groups: mild asphyxia group (n=150) and severe asphyxia group (n=35). The levels of PAB, RBP, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were measured and compared. Their diagnostic values for liver damage were evaluated by ROC curve analysis. RESULTS: The premature infants in the severe asphyxia group had significantly higher AST level and significantly lower levels of PAB and RBP than those in the mild asphyxia group (P<0.05). The full-term infants in the severe asphyxia group had a significantly lower PAB level than those in the mild asphyxia group (P<0.05). After treatment, the PAB level was significantly improved in the premature infants in the severe asphyxia group and in the full-term infants in both mild and severe asphyxia group (P<0.05). The full-term infants in the mild asphyxia groups also showed a significant improvement in AST level (P<0.05). The ROC curve analysis showed that PAB had a good sensitivity and specificity for identifying liver damage caused by mild or severe asphyxia in full-term and preterm infants. CONCLUSIONS: PAB can be used as an indicator of liver damage caused by asphyxia in neonates, and can be used to assess the degree of asphyxia.

LIGHT/IFN-γ triggers ß cells apoptosis via NF-κB/Bcl2-dependent mitochondrial pathway.

LIGHT recruits and activates naive T cells in the islets at the onset of diabetes. IFN-γ secreted by activated T lymphocytes is involved in beta cell apoptosis. However, whether LIGHT sensitizes IFNγ-induced beta cells destruction remains unclear. In this study, we used the murine beta cell line MIN6 and primary islet cells as models for investigating the underlying cellular mechanisms involved in LIGHT/IFNγ - induced pancreatic beta cell destruction. LIGHT and IFN-γ synergistically reduced MIN6 and primary islet cells viability; decreased cell viability was due to apoptosis, as demonstrated by a significant increase in Annexin V(+) cell percentage, detected by flow cytometry. In addition to marked increases in cytochrome c release and NF-κB activation, the combination of LIGHT and IFN-γ caused an obvious decrease in expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL, but an increase in expression of the pro-apoptotic proteins Bak and Bax in MIN6 cells. Accordingly, LIGHT deficiency led to a decrease in NF-κB activation and Bak expression, and peri-insulitis in non-obese diabetes mice. Inhibition of NF-κB activation with the specific NF-κB inhibitor, PDTC (pyrrolidine dithiocarbamate), reversed Bcl-xL down-regulation and Bax up-regulation, and led to a significant increase in LIGHT- and IFN-γ-treated cell viability. Moreover, cleaved caspase-9, -3, and PARP (poly (ADP-ribose) polymerase) were observed after LIGHT and IFN-γ treatment. Pretreatment with caspase inhibitors remarkably attenuated LIGHT- and IFNγ-induced cell apoptosis. Taken together, our results indicate that LIGHT signalling pathway combined with IFN-γ induces beta cells apoptosis via an NF-κB/Bcl2-dependent mitochondrial pathway.

High-Nuclear Organometallic Copper(I)-Alkynide Clusters: Thermochromic Near-Infrared Luminescence and Solution Stability.

Cu(CF3 COO)2 reacts with tert-butylacetylene (tBuC≡CH) in methanol in the presence of metallic copper powder to give two air-stable clusters, [CuI15 (tBuC≡C)10 (CF3 COO)5 ]⋅tBuC≡CH (1) and [CuI16 (tBuC≡C)12 (CF3 COO)4 (CH3 OH)2 ] (2). The assembly process involves in situ comproportionation reaction between Cu2+ and Cu0 and the formation of two different clusters is controlled by reactants concentration. The clusters consist of Cu15 and Cu16 cores co-stabilized by strong by σ- and π-bonded tert-butylethynide and CF3 COO- (together with methanol molecule in 2). Their stabilities in solution were confirmed using electrospray ionization mass spectrometry in which the cluster core remains intact for 1 in chloroform and acetone, and for 2 in acetonitrile. Strong thermochromic luminescence in the near infrared (NIR) region was observed in the solid-state. Of particular interest, the emission maximum of 1 is red-shifted from 710 nm at 298 K to 793 nm at 93 K, along with a 17-fold fluorescence enhancement. In contrast, 2 exhibits red shift from 298 to 123 K followed by blue shift from 123 to 93 K. The emission wavelength was correlated with the structural parameters using variable-temperature X-ray single-crystal analyses. The rich cuprophilic interaction plays a significant role in the formation of 3 LMCT (tBuC≡C→Cux ) excited state mixed with cluster-centered (3 CC) characters, which can be considerably influenced by temperature, leading to thermochromic luminescence. The present work provides 1) a new synthetic protocol for the high-nuclear CuI -alkynyl clusters; 2) a comprehensive insight into the mechanism of thermochromic luminescence; 3) unusual emissive materials with the characters of NIR and thermochromic luminescence simultaneously.

Characterization of the phytochelatins and their derivatives in rice exposed to cadmium based on high-performance liquid chromatography coupled with data-dependent hybrid linear ion trap orbitrap mass spectrometry.

RATIONALE: The identification and quantification of phytochelatins (PCs) and their derivatives are important to understand their roles in plant growth and development. A method couplling high-performance liquid chromatography with hybrid linear ion trap Orbitrap mass spectrometry (HPLC-LTQ/Orbitrap) was developed to screen PCs that have the same characteristic product ions. This approach was used for the fragmentation pattern analysis of glutathione (GSH) and PC standards, which allowed identification of the fragmentation pathways of their derivatives isolated from rice roots, stems and leaves. METHODS: In this study, we developed a method to detect and identify PCs and their derivatives in rice based on HPLC/LTQ-Orbitrap. Spectrum interpretation and MS/MS fragmentation patterns of PCs provide sufficient information to discover the novel PC derivatives. This approach includes precursor ion scan and product ion scan to detect and character the novel PC derivatives. RESULTS: Based on HCD-MS/MS fragmentation patterns, four PCs and 18 PC derivatives were identified. Among them, seven PC derivatives, i.e., iso-PC2 (Asn), iso-PC3 (Asn), iso-PC2 (Cys), des-γGlu-iso-PC3 (Ser), des-Cys-iso-PC2 (Glu), des-Cys-iso-PC3 (Glu) and des-Cys-iso-PC4 (Glu), have not been previously reported. This method was validated by profiling GSH, PCs and PC derivatives in rice. Preliminary results revealed that PCs and their derivatives, except GSH, are markedly induced by Cd treatment. CONCLUSIONS: The HPLC/LTQ-Orbitrap method was successfully developed for the identification of PCs and their derivatives. The C-terminal linked to Gly is replaced with Glu, Ser, Asn, Gln or Cys, thereby creating a family of chemicals that share several structural properties. This technique could be particularly useful for investigators studying plant metabolomics. Copyright © 2016 John Wiley & Sons, Ltd.

Near-Infrared Emitters: Stepwise Assembly of Two Heteropolynuclear Clusters with Tunable Ag(I):Zn(II) Ratio.

Two 3d-4d heteropolynuclear clusters with Ag-Zn ratios of 9:2 and 9:4 were stepwise constructed from a robust nonanuclear silver cluster. Their crystal structures consist of a common bucket-shaped [Ag9(mba)9](9-) (H2mba = 2-mercaptobenzoic acid) core with different numbers of Zn(II) connected by different exo-oriented carboxylates. Most fascinating is the observation of emission (∼703 nm) in the near-infrared (NIR) region at 300 K that may be compared to the related Ag9Zn3 cluster with aliphatic polyamine as auxiliary ligand that emits from the visible (∼580 nm). The shift is associated with the change of ligand field of the 2,2'-bipyridine. The emission intensity and lifetime were dramatically enhanced along with the slight bathochromic shift upon cooling from 300 K to 80 K. The results raise two significant issues: (a) the structural and electronic effects of the secondary metal binding to the metalloligand and the factors influencing the heteropolynuclear cluster assembly and (b) the use of NIR fluorescence, introduced by integrating two luminophores into one heteropolynuclear entity, in detecting free-moving zinc in biological systems both in vivo and in vitro.