Risk factors of low-level viremia in chronic hepatitis B patients receiving Entecavir monotherapy: a retrospective cohort study.

BACKGROUND AND AIM: Low-level viremia (LLV), a special case of poor response to antiviral therapy, has become a focus of liver disease research; however, most studies have focused on poor response to antiviral therapy, and little attention has been paid to LLV. Therefore, this study aimed to investigate the factors influencing LLV in patients with chronic hepatitis B (CHB) receiving entecavir (ETV) monotherapy. METHODS: Clinical data of CHB patients receiving ETV treatment for at least 1 year at the outpatient department of the Affiliated Hospital of Xuzhou Medical University from November 2018 to June 2020 were collected. Patients were divided into LLV (180 cases) and sustained virological response (SVR) groups (337 cases) according to the hepatitis B virus (HBV) DNA load at the end of the observation period. Demographic features and laboratory markers were also examined. Univariate and multivariate logistic regression analyses were performed to examine factors influencing LLV in patients receiving long-term ETV monotherapy. RESULTS: Significant differences were noted between the LLV and SVR groups in terms of age, sex, presence or absence of cirrhosis, HBeAg positivity rate, baseline HBV DNA load, and baseline HBsAg level before treatment. Multivariate logistic regression analysis showed that baseline HBeAg status, HBV DNA load, and HBsAg quantification were pretreatment risk factors for LLV in long-term ETV antiviral therapy. CONCLUSIONS: CHB patients with a high HBV DNA load, high HBsAg quantification, and positive HBeAg results tend to have a high risk of LLV despite long-term ETV antiviral treatment and should be dynamically monitored.

Colorimetric and ratiometric supramolecular AIE fluorescent probe for the on-site monitoring of fipronil.

The overuse of fipronil (FPN, a broad-spectrum insecticide) in agriculture has brought great concerns for environmental pollution and food safety. The development of a rapid, reliable, and portable analytical method for the on-site monitoring of FPN is therefore of great significance but is full of challenge. Herein, a novel supramolecular probe using human serum albumin (HSA) as the host and an aggregation-induced emission-active fluorescence probe LIQ-TPA-TZ as the guest was developed for the colorimetric and ratiometric detection of FPN, displaying fast response (30 s), high sensitivity (LOD ∼ 0.05 µM), and good selectivity and anti-interference performance. Moreover, portable paper-based test strips could be facilely obtained and utilized for the determination of FPN, showing colorimetric changes from yellow to orange. This supramolecular probe also demonstrated great potential in real applications for choosing the best cleaning method to reduce the residue rate of FPN on apples. This study provides a versatile tool for the fast and real-time analysis of FPN, which greatly benefits the on-site determination of pesticides with the use of simple testing apparatus.

Theoretical insights into the gaseous and heterogeneous reactions of halogenated phenols with ˙OH radicals: mechanism, kinetics and role of (TiO2)n clusters in degradation processes.

Halogenated phenols are highly toxic chemicals with serious health risks, and the removal of these persistent environmental pollutants remains a challenge. Based on quantum chemistry calculations, the homogeneous/heterogeneous degradation mechanism and kinetics of C6X5OH (X = F, Cl, and Br) initiated by ˙OH radicals in the gas phase and TiO2 cluster surfaces are investigated in this work. Four ˙OH-addition and one proton-coupled electron-transfer (PCET) reaction channels for each halogenated phenol were found and the ˙OH-addition channels were more favorable than the PCET pathway without TiO2 clusters. At 296 K, the calculated total rate constant for ˙OH with C6F5OH in the atmosphere well agreed with the limited experimental data of (6.88 ± 1.37) × 10-12 cm3 molecule-1 s-1. The lifetimes of C6F5OH, C6Cl5OH, and C6Br5OH were about 12.04-12.86 h at 296 K, which favored their medium-range transport in the atmosphere. In the presence of (TiO2)n clusters (n = 4, 6, 8, 12, and 16), the PCET mechanism for hydrogen transfer reaction of C6F5OH with ˙OH radicals was changed from the previous four-electron/three-center into four-electron/two-center, which results in the PCET pathway becoming more favorable than the ˙OH-addition channels. Meanwhile, the heterogeneous degradation rate constants of C6F5OH were accelerated by more than 10 orders of magnitude within 200-430 K compared with those of the naked reaction. The effects of (TiO2)n cluster (n = 4, 6, 8, 12, and 16) size on the degradation rates were analyzed at 200-430 K, and the reaction on the (TiO2)8 cluster had a faster rate. The subsequent reactions including the bond cleavage of the benzene ring and O2 addition or abstraction were studied. This work provides new insights into halogenated aromatic atmospheric chemistry and nanoscale TiO2 photocatalysis in air or wastewater management.

Aliovalent-Ion-Induced Lattice Regulation Based on Charge Balance Theory: Advanced Fluorophosphate Cathode for Sodium-Ion Full Batteries.

There are still many problems that hinder the development of sodium-ion batteries (SIBs), including poor rate performance, short-term cycle lifespan, and inferior low-temperature property. Herein, excellent Na-storage performance in fluorophosphate (Na3 V2 (PO4 )2 F3 ) cathode is achieved by lattice regulation based on charge balance theory. Lattice regulation of aliovalent Mn2+ for V3+ increases both electronic conductivity and Na+ -migration kinetics. Because of the maintaining of electrical neutrality in the material, aliovalent Mn2+ -introduced leads to the coexistence of V3+ and V4+ from charge balance theory. It decreases the particle size and improves the structural stability, suppressing the large lattice distortion during cathode reaction processes. These multiple effects enhance the specific capacity (123.8 mAh g-1 ), outstanding high-rate (68% capacity retention at 20 C), ultralong cycle (only 0.018% capacity attenuation per cycle over 1000 cycles at 1 C) and low-temperature (96.5% capacity retention after 400 cycles at -25 °C) performances of Mn2+ -induced Na3 V1.98 Mn0.02 (PO4 )2 F3 when used as cathode in SIBs. Importantly, a feasible sodium-ion full battery is assembled, achieving outstanding rate capability and cycle stability. The strategy of aliovalent ion-induced lattice regulation constructs cathode materials with superior performances, which is available to improve other electrode materials for energy storage systems.

USP39 promotes malignant proliferation and angiogenesis of renal cell carcinoma by inhibiting VEGF-A165b alternative splicing via regulating SRSF1 and SRPK1.

BACKGROUND: The benefit of targeted therapy for renal cell carcinoma (RCC) is largely crippled by drug resistance. Rapid disease progression and poor prognosis occur in patients with drug resistance. New treatments demand prompt exploration for clinical therapies. Ubiquitin-specific peptidase 39 (USP39) serves as the pro-tumor factor in several previous studies of other malignant tumors. To investigate the function and mechanism of USP39 in promoting malignant proliferation and angiogenesis of RCC. METHODS: We applied ONCOMINE database to analyze the correlation between USP39 expression level and the clinical characteristics of RCC. USP39 knockdown or overexpression plasmids were transfected into 786-O and ACHN cells. The HUVEC received cell supernatants of 786-O and ACHN cells with knockdown or overexpression USP39.The effect of USP39 on RCC was evaluated by MTT assay, cell cycle analysis, colony formation assay and tubule formation assay. The interaction between USP39 and VEGF-A alternative splicing was assessed by affinity purification and mass spectrometry, co-immunoprecipitation and Western blot assays. RESULTS: The mRNA expression level of USP39 in RCC was significantly higher than that in normal renal tissue (P < 0.001), and negatively correlated with the survival rate of RCC patients (P < 0.01). Silencing of USP39 in 786-O and ACHN cells inhibited cell proliferation and colony formation, and induced S phase arrest. USP39 overexpression significantly increased the number of tubules (P < 0.05) and branches (P < 0.01) formed by HUVEC cells, and USP39 knockdown produced an opposite effect (P < 0.05). The USP39 (101-565) fragment directly mediated its binding to SRSF1 and SRPK1, and promoted the phosphorylation of SRSF1 to regulate VEGF-A alternative splicing. USP39 knockdown upregulated the expression of VEGF-A165b, and USP39 overexpression downregulated the expression of VEGF-A165b significantly (both P < 0.05). CONCLUSION: USP39 acted as a pro-tumor factor by motivating the malignant biological processes of RCC, probably through inhibiting VEGF-A165b alternative splicing and regulating SRSF1 and SRPK1. USP39 may prove to be a potential therapeutic target for RCC.

TRIM47 promotes malignant progression of renal cell carcinoma by degrading P53 through ubiquitination.

BACKGROUND: Renal cell carcinoma (RCC) is one of the most common malignant tumors originating from the renal parenchymal urinary epithelial system. Tripartite motif 47 (TRIM47) is a member of the TRIM family proteins, which has E3 ligase activity and has been demonstrated to be involved in the occurrence and prognosis of many tumors. The main purpose of this study is to explore the role and potential mechanism of TRIM47 in promoting malignant biological behavior of RCC. MATERIALS AND METHODS: TRIM47 mRNA and protein levels in human renal cancer and paired normal adjacent tissues were detected by qRT-PCR and Western blot. The effects of TRIM47 knockdown and overexpression in renal cell carcinoma cells on cell proliferation, invasion and xenograft tumor growth in nude mice were analyzed. The molecular mechanism was explored by mass spectrometric exploration,Western blot and immunoprecipitation assays. RESULTS: TRIM47 promoted RCC cell proliferation in vitro and in vivo as an oncogene. Mechanistically, TRIM47 exerted an E3 ligase activity by interacting with P53 protein to increase its ubiquitination and degradation, which further promoted the malignant biological behavior of RCC. CONCLUSIONS: Our study demonstrated that the TRIM47-P53 axis played a functional role in RCC progression and suggested a potential therapeutic target for RCC.

Atmospheric oxidation of fluoroalcohols initiated by ˙OH radicals in the presence of water and mineral dusts: mechanism, kinetics, and risk assessment.

The transport and formation of fluorinated compounds are greatly significant due to their possible environmental risks. In this work, the ˙OH-mediated degradation of CF3CF2CF2CH2OH and CF3CHFCF2CH2OH in the presence of O2/NO/NO2 was studied by using density functional theory and the direct kinetic method. The formation mechanisms of perfluorocarboxylic/hydroperfluorocarboxylic acids (PFCAs/H-PFCAs), which were produced from the reactions of α-hydroxyperoxy radicals with NO/NO2 and the ensuing oxidation of α-hydroxyalkoxy radicals, were clarified and discussed. The roles of water and silica particles in the rate constants and ˙OH reaction mechanism with fluoroalcohols were investigated theoretically. The results showed that water and silica particles do not alter the reaction mechanism but obviously change the kinetic properties. Water could retard fluoroalcohol degradation by decreasing the rate constants by 3-5 orders of magnitude. However, the heterogeneous ˙OH-rate coefficients on the silica particle surfaces, including H4SiO4, H6Si2O7, and H12Si6O18, are larger than that of the naked reaction by 1.20-24.50 times. This finding suggested that these heterogeneous reactions may be responsible for the atmospheric loss of fluoroalcohols and the burden of PFCAs. In addition, fluoroalcohols could be exothermically trapped by H12Si6O18, H6Si2O7, and H4SiO4, in which the chemisorption on H12Si6O18 is stronger than that on H6Si2O7 or H4SiO4. The global warming potentials and radiative forcing of CF3CF2CF2CH2OH/CF3CHFCF2CH2OH were calculated to assess their contributions to the greenhouse effect. The toxicities of individual species were also estimated via the ECOSAR program and experimental measurements. This work enhances the understanding of the environmental formation of PFCAs and the transformation of fluoroalcohols.

Atmospheric chemistry of thiourea: nucleation with urea and roles in NO2 hydrolysis.

Nitrogenous particle participation in the formation of clusters has attracted considerable attention from numerous researchers in recent years. Urea and thiourea (TU), as the common fertilizers in agriculture, have a significant impact on the atmospheric environment, whereas their implications have not been comprehended widely. Herein, we have used quantum calculations and ABCluster to explore the potential roles of thiourea and urea in particle formation events. A vital implication of these results is that they may contribute toward particle formation in marine environments and Asia region where the concentration of thiourea and urea has been increasing for a few years. Furthermore, the mechanisms of NO2 hydrolysis in the presence of thiourea and subsequent reactions were studied deeply. The results indicate that, although these reactions are not thermodynamically favorable at 298.15 K under homogeneous gas-phase conditions, thiourea may promote the hydrolysis of NO2 in heterogeneous environments containing very high concentrations of these molecules. The kinetics analysis shows that the rate constants of the hydrolysis reaction catalyzed by thiourea with N2O4-W and TU-W are about 2-5 and 1-2 orders of magnitude faster than those of the naked reaction. Thiourea nitrate and its aquo-complex were also studied, and the results suggest that the reaction produced an acid-base complex in which the trans- configuration is the final form for nitrous acid. We hope that these findings would inspire field measurements for detecting urea and thiourea in the troposphere.

A simple, quick, and efficient CRISPR/Cas9 genome editing method for human induced pluripotent stem cells.

Induced pluripotent stem cells (iPSCs) have become an essential research platform to study different human diseases once being discovered by Dr. Shinya Yamanaka in 2006. Another breakthrough in biomedical research is the application of CRISPR/Cas9 system for genome editing in mammalian cells. Although numerous studies have been done to develop methods for gene editing in iPSCs, the current approaches suffer from several limitations, including time and labor consuming, low editing efficiency, and potential off-target effects. In the current study, we report an electroporation-mediated plasmid CRISPR/Cas9 delivery approach for genome editing in iPSCs. With this approach, an edited iPSC cell line could be obtained within 2 weeks. In addition, the transit introducing of CRISPR/Cas9 machinery could minimize genomic integration of Cas9 gene, which avoided potential long-term side effects of Cas9 enzyme. We showed that CRISPR/Cas9-mediated genomic editing did not affect pluripotency and differentiation ability of iPSCs. With the quickly evolving of both iPSC and CRISPR/Cas9-mediated genome editing research fields, we believe that our method can significantly facilitate the application of genome editing in iPSCs research.

VDR rs7975232/ApaI genetic variation predicts sustained HBsAg loss in HBeAg-positive chronic hepatitis B patients treated with pegylated interferon.

AIM: To evaluate the predictive value of vitamin D and its metabolic pathway gene polymorphisms in response to pegylated interferon (Peg-IFN) in hepatitis B early antigen (HBeAg)-positive chronic hepatitis B (CHB) patients. METHODS: One hundred and nineteen HBeAg-positive CHB patients who received Peg-IFN monotherapy for 48 weeks and then were followed-up for another 48 weeks were prospectively enrolled; baseline 25-hydroxy vitamin D (25-(OH)D) and hepatitis B virus serologic marker levels were detected, nine critical single nucleotide polymorphisms within vitamin D metabolism were genotyped. RESULTS: Forty-five (37.8%), 44 (37.0%), 35 (29.4%), and 11 (9.2%) of the patients achieved virological response (VR), HBeAg loss, combined response (CR), and hepatitis B surface antigen (HBsAg) level < 200 IU/mL at the end of treatment (EOT; week 48), respectively; 42 (35.3%) and six (5.0%) people achieved HBeAg and HBsAg loss at the end of follow-up (EOF; week 96). Baseline HBeAg level was independent predictor of VR (odds ratio [OR], 0.470; 95% confidence interval [CI], 0.294-0.751; P = 0.002), HBeAg loss (OR, 0.395; 95% CI, 0.243-0.643; P < 0.001), CR (OR, 0.392; 95% CI, 0.215-0.714; P = 0.002) at EOT and HBeAg loss at EOF (OR, 0.334; 95% CI, 0.203-0.559; P < 0.001); baseline HBsAg level itself was independent predictor of both HBsAg < 200 IU/mL at EOT (OR, 0.257; 95% CI, 0.103-0.642; P = 0.004) and HBsAg loss at EOF (OR, 0.232; 95% CI, 0.077-0.702; P = 0.010). Age was also independent predictors of HBsAg loss at EOF (OR, 0.775; 95% CI, 0.634-0.948; P = 0.013). Concerning genetic variation of VDR rs7975232/ ApaI, A allele was the genetic independent predictor of VR at EOT (OR, 1.824; 95% CI, 1.024-3.248; P = 0.041) and HBsAg loss at EOF (OR, 3.566; 95% CI, 1.057-12.029; P = 0.040). CONCLUSIONS: Genetic variation of VDR rs7975232/ ApaI is a pretreatment predictor of sustained HBsAg loss in HBeAg-positive CHB patients with Peg-IFN monotherapy.

New insights into 3M3M1B: the role of water in ˙OH-initiated degradation and aerosol formation in the presence of NOX (X = 1, 2) and an alkali.

The oxidation mechanisms and dynamics of 3-methoxy-3-methyl-1-butanol (3M3M1B) initiated by ˙OH radicals were assessed by the density functional theory and canonical variational transition state theory. The effects of ubiquitous water on the title reactions were analyzed by utilizing an implicit solvation model in the present system. The results suggested that aqueous water played a negative role in the ˙OH-initiated degradation of 3M3M1B with an increase in the Gibbs free barriers. Meanwhile, the barriers were almost independent when explicit water molecules were involved in the gaseous phase, which could reduce the rate constant by approximately 3 orders of magnitude. The kinetic calculations showed that the rate constants were smaller by about 15, 9, 8, and 8 orders of magnitude for hydroxyl-, ammonia-, formic acid-, and sulfur acid-participating reactions, respectively, than that from an unassisted reaction. The results indicated that water, hydroxyl, ammonia, formic acid, or sulfur acid could not facilitate the title reaction when performed in the atmosphere. The investigations of the subsequent oxidation processes of the alkyl radical CH3OC(CH3)2CH2C·HOH indicated that CH3OC(CH3)2CH2CHO was the most favorable product by eliminating an HO2˙ radical. Additionally, the HO2˙ radical could serve as a self-catalyst to affect the above reaction through a double proton transfer process. With the introduction of NO, CH3OC(CH3)2CH2COOH and HNO2 were found to be the main products, which may be regarded as the new source of atmospheric nitrous acid. In the NO2-rich environment, the peroxynitrate of CH3OC(CH3)2CH2CH(OONO2)OH could be formed via the reaction of the CH3OC(CH3)2CH2CH(OO˙)OH radical with NO2. The degradation mechanism of CH3OC(CH3)2CH2CH(OONO2)OH in the presence of water, ammonia, and methylamine was demonstrated, and it was shown that water, ammonia, and methylamine could promote the formation of nitric hydrate and nitrate aerosol. The main species detected in the experiment were confirmed by a theoretical study. The atmospheric lifetimes of 3M3M1B in the temperature range of 217-298 K and altitude of 0-12 km were within the range of 6.83-8.64 h. This study provides insights into the transformation of 3M3M1B in a complex environment.

[Preliminary application of Early Start Denver Model in children with autism spectrum disorder].

OBJECTIVE: To investigate the clinical effect of the Early Start Denver Model (ESDM) in children with autism spectrum disorder (ASD). METHODS: Forty children aged 2-5 years who were diagnosed with ASD from September 2017 to January 2018 were enrolled in the study and were randomly divided into conventional intervention group and ESDM intervention group (n=20 each). Both groups were assessed by the Aberrant Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), and Clinical Global Impression-Severity (CGI-S) scale before intervention and by the ABC, CARS, CGI-S scale, and Clinical Global Impression-Improvement (CGI-I) scale after 3 months of intervention. RESULTS: After 3 months of intervention, the total scores of ABC and CARS were both significantly decreased in the two groups (P<0.01); the scores on the social withdrawal and hyperactivity subscales of ABC were significantly decreased in the conventional intervention group (P<0.01), and the scores on the mood swings, social withdrawal, hyperactivity, and stereotyped behavior subscales of ABC were significantly decreased in the ESDM intervention group (P<0.01). Compared with the conventional intervention group, the ESDM intervention group had significantly greater changes in total score of ABC, scores on three subscales of ABC (mood swings, social withdrawal, and hyperactivity), and total score of CARS after intervention (P<0.05). After 3 months of intervention, the CGI-I scoring system showed that the disease improvement was significantly better in the ESDM intervention group than in the conventional intervention group (P<0.05). CONCLUSIONS: Both conventional intervention and ESDM intervention can improve the social withdrawal and hyperactivity in children with ASD aged 2 to 5 years, but ESDM is more effective in improving the aberrant behavior of children with ASD.

Grape seed-derived procyanidins alleviate gout pain via NLRP3 inflammasome suppression.

BACKGROUND: Gout is one of the common inflammatory arthritis which affects many people for inflicting unbearable pain. Macrophage-mediated inflammation plays an important role in gout. The uptake of monosodium urate (MSU) crystals by macrophages can lead to activation of NOD-like receptors containing a PYD 3 (NLRP3) inflammasome, thus accelerating interleukin (IL)-1ß production. Reactive oxygen species (ROS) promoted development of the inflammatory process through NLRP3 inflammasome. Our study aimed to find a food-derived compound to attenuate gout pain via the specific inhibition of the NLRP3 inflammasome in macrophages. METHODS: CD-1 mice were used to evaluate the degree of pain and the swelling dimension of joints after an intra-articular (IA) MSU injection in the ankle. The murine macrophage cell line Raw 264.7 was used to investigate the effects of procyanidins and the mechanism underlying such effects. Histological analysis was used to measure the infiltration of inflammatory cells. ROS produced from Raw 264.7 cells were evaluated by flow cytometry. Cell signaling was measured by Western blot assay and immunofluorescence. RESULTS: Procyanidins significantly attenuated gout pain and suppressed ankle swelling. Procyanidins also inhibited MSU-induced activation of the NLRP3 inflammasome and increase of IL-1ß. Furthermore, procyanidins decreased ROS levels in Raw 264.7 cells. CONCLUSIONS: Suppression of the NLRP3 inflammasome in macrophages contributes to the amelioration of gout pain by procyanidins.

Theoretical Study of the Gaseous Hydrolysis of NO2 in the Presence of Amines.

The effects on the hydrolysis of NO2 in the presence of methylamine and dimethylamine molecules were investigated by theoretical calculations of a series of the molecular clusters 2NO2-mH2O-CH3NH2 (m = 1-3) and 2NO2-mH2O-(CH3)2NH (m = 1, 2). With methylamine included in the clusters, the energy barrier is reduced by 3.2 kcal/mol from that with ammonia, and the corresponding products may form without an energy barrier. The results show that amines have larger effects than ammonia in promoting the hydrolysis of NO2 on thermodynamics. The additional water molecules can stabilize the transition states and the product complexes, and we infer that adding more water molecules in the reactions mainly act as solvent and promoting to form the methylamine nitrate (CH3NH3+NO3-). In addition, the interactions of CH3NH2 and (CH3)2NH on the hydration of HNO3 are also more effective than NH3, and the NH4NO3, CH3NH3NO3, and (CH3)2NH2NO3 complexes tend to form the larger aerosols with the increasing of water molecules. The equilibrium geometries, harmonic vibrational frequencies, and intensities of both HONO-CH3NH2 and HONO-NH3 complexes were investigated. Calculations predict that the binding energies of both HONO-CH3NH2 complexes are larger than HONO-NH3 complexes, and the OH stretching vibrational frequencies and intensities are most affected. The natural bond orbital analysis was performed to describe the donor-acceptor interactions on a series of complexes in the reactions 2NO2 + H2O + CH3NH2 and 2NO2 + H2O + (CH3)2NH, as well as the complexes of HONO-NH3 and HONO-CH3NH2. The results show that the interactions with amines are relatively larger, and the higher stabilization energies between CH3NH2 and HONO are found.

Effects of neuro-immuno-modulation on healing of wound combined with local radiation injury in rats.

PURPOSE: To investigate effects of neuro-immuno-modulation on wound healing by observing changes of cytokines and hypothalamic-pituitary-adrenal (HPA) axis hormones in acute stress reaction in rats with wound and combined local radiation injury. METHODS: Sixty female Wistar rats (weighting 200 ± 20 g) were randomly divided into normal control group, wound group and combined wound-local radiation (CWR) group (25 Gy local radiation post wound), 20 rats in each group. Contents of IL-1ß, IL-6 and IFN-γ and IL-4 in serum were measured and changes of adrenocorticotropic hormone (ACTH) and glucocorticoid (GC) in serum were analyzed by using enzyme-linked immunosorbent assay and radioimmunologic assay, respectively at different time points post wound and radiation. RESULTS: (1) The level of IFN-γ, one of the Th1 cell cytokines increased significantly at 14 d post CWR, which was markedly higher than that in control group and wound group. However, the level of IL-4, IL-1ß and IL-6, one of the Th2 cell cytokines, did not show obvious change. (2) Ratio of Th1/Th2 (IFN-γ/IL-4) in wound group and CWR group increased significantly at 7 d after wound and radiation, which suggested that Th1/Th2 balance drifted to Th1 immune response. The ratio of Th1/Th2 in wound group returned to the normal level up to 14 d after the wound and radiation, while the Th1/Th2 ratio in CWR group increased persistently and was much higher than that in control and wound groups. (3) Level of serous ACTH and GC in CWR group increased at 3 d post wound and radiation, and among them, level of GC showed statistically significant increase, which was much higher than that in control and wound groups. CONCLUSION: Level of serous neurohormone GC in rats increased significantly immediately after wound and radiation; while the level of IFN-γ showed significant increase only up to 14 d after wound and radiation, and the Th1/Th2 imbalance sustained till 28 d post wound and radiation. In order to reduce acute damage caused by CWR, organic immune system and nerve system showed up a marked regulate effects simultaneously and mutually. Nonetheless, the excessive stress induced by CWR causes disturbance of immunoregulation, which is one of the key reasons for delayed wound healing in CWR.

[Prognostic Significance of ERG Gene Rearrangement and Protein Expression in Prostate Cancer].

OBJECTIVES: To investigate gene rearrangement and protein expression of ETS related gene (ERG ) in prostate cancer of Chinese patients and its correlation with clinicopathological characteristics and prognosis. METHODS: This study collected 482 cases of prostatic adenocarcinomas diagnosed by prostate biopsy in West China Hospital of Sichuan University from 2009 to 2014. Fluorescencein situ hybridization (FISH) and immuno-histochemical staining (IHC) were performed to access the ERG rearrangement and protein expression respectively. Relationship between ERG rearrangement and protein expression was assessed by Spearman rank order correlation. The correlations of ERG rearrangement and protein expression with clinicopathological variables and prognosis were further analyzed. RESULTS: ERG rearrangement was detected in 87 (18.0 %) cases, of which 45 (51.7%) was translocation and 42 (48.3%) was deletion. ERG protein expression was detected in 74 (15.4%) cases. Follow-up data was obtained in 368 cases. ERG rearrangement and protein expression had no correlations to age, Gleason score and pre-operation PSA level ( P>0.05), but ERG protein level was decreased in metastatic cases or castration resistant prostate cancer (CRPC) cases ( P<0.05) . Kaplan-Meier curve showed both gene rearrangement and protein expression of ERG had no prognostic significance. CONCLUSIONS: ERG rearrangement, as well as ERG protein expression, could not serve as an independent prognostic biomarker.

Procyanidins alleviates morphine tolerance by inhibiting activation of NLRP3 inflammasome in microglia.

BACKGROUND: The development of antinociceptive tolerance following repetitive administration of opioid analgesics significantly hinders their clinical use. Evidence has accumulated indicating that microglia within the spinal cord plays a critical role in morphine tolerance. The inhibitor of microglia is effective to attenuate the tolerance; however, the mechanism is not fully understood. Our present study investigated the effects and possible mechanism of a natural product procyanidins in improving morphine tolerance via its specific inhibition on NOD-like receptor protein3 (NLRP3) inflammasome in microglia. METHODS: CD-1 mice were used for tail-flick test to evaluate the degree of pain. The microglial cell line BV-2 was used to investigate the effects and the mechanism of procyanidins. Reactive oxygen species (ROS) produced from BV-2 cells was evaluated by flow cytometry. Cell signaling was measured by western blot assay and immunofluorescence assay. RESULTS: Co-administration of procyanidins with morphine potentiated its antinociception effect and attenuated the development of acute and chronic morphine tolerance. Procyanidins also inhibited morphine-induced increase of interleukin-1ß and activation of NOD-like receptor protein3 (NLRP3) inflammasome. Furthermore, procyanidins decreased the phosphorylation of p38 mitogen-activated protein kinase, inhibited the translocation of nuclear factor-κB (NF-κB), and suppressed the level of reactive oxygen species in microglia. CONCLUSIONS: Procyanidins suppresses morphine-induced activation of NLRP3 inflammasome and inflammatory responses in microglia, and thus resulting in significant attenuation of morphine antinociceptive tolerance.

Theoretical Studies of the Reactions CFx H3-x COOR+Cl and CF3 COOCH3 +OH.

The mechanism and kinetics of the reactions of CF(3)COOCH(2)CH(3), CF(2)HCOOCH(3), and CF(3)COOCH(3) with Cl and OH radicals are studied using the B3LYP, MP2, BHandHLYP, and M06-2X methods with the 6-311G(d,p) basis set. The study is further refined by using the CCSD(T) and QCISD(T)/6-311++G(d,p) methods. Seven hydrogen-abstraction channels are found. All the rate constants, computed by a dual-level direct method with a small-curvature tunneling correction, are in good agreement with the experimental data. The tunneling effect is found to be important for the calculated rate constants in the low-temperature range. For the reaction of CF(3)COOCH(2)CH(3) +Cl, H-abstraction from the CH(2) group is found to be the dominant reaction channel. The standard enthalpies of formation for the species are also calculated. The Arrhenius expressions are fitted within 200-1000 K as kT(1) =8.4×10(-20) T (2.63) exp(381.28/T), kT(2) =2.95×10(-21) T (3.13) exp(-103.21/T), kT(3) =1.25×10(-23) T (3.37) exp(791.98/T), and kT(4) =4.53×10(-22) T (3.07) exp(465.00/T).

Theoretical study on the reactions of (CF3)2CFOCH3 + OH/Cl and reaction of (CF3)2CFOCHO with Cl atom.

Reactions of (CF3)2CFOCH3 and (CF3)2CFOCHO with hydroxyl radical and chlorine atom are studied at the B3LYP and BHandHLYP/6-311+G(d,p) levels along with the geometries and frequencies of all stationary points. This study is further refined by CCSD(T) and QCISD(T)/6-311+G(d,p) methods in the minimum energy paths. For the reaction (CF3)2CFOCH3 + OH, two hydrogen abstraction channels are found. The total rate constants for the reactions (CF3)2CFOCH3 + OH/Cl and (CF3)2CFOCHO + Cl are followed by means of the canonical variational transition state with the small-curvature tunneling correction. The comparison between the hydrogen abstraction rate constants by hydroxyl and chlorine atom is discussed. Calculated rate constants are in reasonable agreement with the available experiment data. The standard enthalpies of formation for the reactants, (CF3)2CFOCH3 and (CF3)2CFOCHO, and two products, (CF3)2CFOCH2 and (CF3)2CFOCO, are evaluated by a series of isodesmic reactions. The Arrhenius expressions for the title reactions are given as follows: k1= 1.08 × 10(-22) T(3.38) exp(-213.31/T), k2= 3.55 × 10(-22) T(3.61) exp(-240.26/T), and k3= 3.00 × 10 (-19) T(2.58) exp(-1294.34/T) cm(3) molecule(-1) s(-1).