Androgen receptor activity inversely correlates with immune cell infiltration and immunotherapy response across multiple cancer lineages.

There is now increasing recognition of the important role of androgen receptor (AR) in modulating immune function. To gain a comprehensive understanding of the effects of AR activity on cancer immunity, we employed a computational approach to profile AR activity in 33 human tumor types using RNA-Seq datasets from The Cancer Genome Atlas. Our pan-cancer analysis revealed that the genes most negatively correlated with AR activity across cancers are involved in active immune system processes. Importantly, we observed a significant negative correlation between AR activity and IFNγ pathway activity at the pan-cancer level. Indeed, using a matched biopsy dataset from subjects with prostate cancer before and after AR-targeted treatment, we verified that inhibiting AR enriches immune cell abundances and is associated with higher IFNγ pathway activity. Furthermore, by analyzing immunotherapy datasets in multiple cancers, our results demonstrate that low AR activity was significantly associated with a favorable response to immunotherapy. Together, our data provide a comprehensive assessment of the relationship between AR signaling and tumor immunity.

CMTM6 shapes antitumor T cell response through modulating protein expression of CD58 and PD-L1.

The dysregulated expression of immune checkpoint molecules enables cancer cells to evade immune destruction. While blockade of inhibitory immune checkpoints like PD-L1 forms the basis of current cancer immunotherapies, a deficiency in costimulatory signals can render these therapies futile. CD58, a costimulatory ligand, plays a crucial role in antitumor immune responses, but the mechanisms controlling its expression remain unclear. Using two systematic approaches, we reveal that CMTM6 positively regulates CD58 expression. Notably, CMTM6 interacts with both CD58 and PD-L1, maintaining the expression of these two immune checkpoint ligands with opposing functions. Functionally, the presence of CMTM6 and CD58 on tumor cells significantly affects T cell-tumor interactions and response to PD-L1-PD-1 blockade. Collectively, these findings provide fundamental insights into CD58 regulation, uncover a shared regulator of stimulatory and inhibitory immune checkpoints, and highlight the importance of tumor-intrinsic CMTM6 and CD58 expression in antitumor immune responses.

Surface regulation by bifunctional BODIPY to fabricate stable CsPbBr3 for multi-layered optical anti-counterfeiting.

Cesium lead halide perovskite quantum dots (QDs) have attracted immense attention for luminescent materials due to their narrow emission bands and color-tunable emission. However, indispensable surface ligands originating from ligand-assisted synthesis strategies severely deteriorate the stability and luminescence properties of QDs since these ligands have a highly dynamic binding. Herein, we used a green fluorescence BODIPY molecule containing thiol (named SH-BDP) to regulate the CsPbBr3 QDs surface by ligand regulation. Density functional theory calculations proved that the SH-BDP molecule could bind to the exposed Pb of CsPbBr3 QDs stronger than traditional ligands to form stable SH-BDP-QDs. Moreover, the SH-BDP fixed on the CsPbBr3 QDs surface can improve water and light resistance. It also served as a knob to tune their luminescence properties and the reversible thermal-stimuli response. Finally, the multi-response property of SH-BDP-QDs was realized under polar solvent or heat along with UV light. In addition, we used the SH-BDP-QDs to create various anti-counterfeiting labels; several luminous modes were achieved under different external stimuli, which improved the quality of the optical anti-counterfeiting labels and ensured information security. This work indicates the immense potential of surface ligand manipulation in improving the stability and multi-stimuli-responsive optical encoding of perovskite quantum dots.

Stable Core-Shell Structure Nanocrystals of Cs4PbBr6-Zn(moi)2 Achieved by an In Situ Surface Reconstruction Strategy for Optical Anticounterfeiting.

Zero-dimensional Cs4PbBr6 nanocrystals (NCs) possess attractive photoluminescence (PL) properties and feature facile chemical synthesis, making them promising for application in luminescent materials. However, Cs4PbBr6 remains sensitive to polar solvents and thermal stimuli because of soft ionic nature of Cs4PbBr6 and dynamic behavior of surface ligands. Herein, a strategy controlled by an in situ surface coordination reaction is developed to fabricate stable NCs with a Cs4PbBr6-Zn(moi)2 core-shell structure. It was found that the Cs4PbBr6 surface regulated by the use of 2-mercaptoimidazole (called moi) and the coordination between the -NH group of moi and Zn2+ is critical for the formation of Cs4PbBr6-Zn(moi)2 core-shell NCs. Meanwhile, the thickness of the Zn(moi)2 shell can be facilely controlled by the growth time because of the solubility of moi and Zn(OAc)2·2H2O in ethyl acetate. Compared to bare Cs4PbBr6, Cs4PbBr6-Zn(moi)2 NCs exhibited highly improved polar solvent resistance and thermal stability. By combining the sensitivity of Cs4PbBr6 and the stability of Cs4PbBr6-Zn(moi)2, we used two NCs as PL security inks to fabricate optical anticounterfeiting labels. Thus, the disposable or reusable optical anticounterfeiting label is achieved by changing the external dual-stimuli. This work provides a novel strategy to enhance the stability of Cs4PbBr6 and develop its potential interest for application in anticounterfeiting technologies.

Improvement of Biosynthetic Ansamitocin P-3 Production Based on Oxygen-Vector Screening and Metabonomics Analysis.

A novel approach involving exogenous oxygen vectors was developed for improving the production of biosynthetic Ansamitocin P-3 (AP-3). Four types of oxygen vectors including soybean oil, n-dodecane, n-hexadecane, and Tween-80 were applied to explore the effect of exogenous oxygen vectors on AP-3 yield. It was observed that soybean oil exhibited a better ability for promoting AP-3 generation than the other three oxygen vectors. Based on the results of the single-factor experiment, response surface methodology was employed to obtain the optimal soybean oil addition method. The optimum soybean oil concentration was 0.52%, and the addition time was 50 h. Under this condition, the yield of AP-3 reached 106.04 mg/L, which was 49.48% higher than that of the control group without adding oxygen vectors. To further investigate the influence of dissolved oxygen on precious orange tufts actinomycetes variety A. pretiosum strain metabolism and AP-3 yield, metabolomics analysis was carried out by detecting strain intermediate metabolites at various stages under different dissolved oxygen levels. Moreover, differential metabolite screening and metabolic pathway enrichment analysis were combined to exploit the effect mechanism of soybean oil on AP-3 production. Results suggested that primary metabolic levels of the TCA cycle and amino acid metabolism increased with the increase in dissolved oxygen level, which was beneficial to the life activities of bacteria and the synthesis of secondary metabolic precursors, thus increasing the production of AP-3.

Injectable peptide hydrogel as intraperitoneal triptolide depot for the treatment of orthotopic hepatocellular carcinoma.

Chemotherapy is among the limited choices approved for the treatment of hepatocellular carcinoma (HCC) at intermediate and advanced stages. Preferential and prolonged drug exposure in diseased sites is required to maximize the therapeutic index of the drug. Here, we report an injectable supramolecular peptide hydrogel as an intraperitoneal depot for localized and sustained release of triptolide for the treatment of orthotopic HCC. We chose peptide amphiphile C16-GNNQQNYKD-OH-based nanofibers as gelators and carriers for triptolide. Sustained triptolide release from the hydrogel was achieved over 14 days in vitro, with higher accumulation in and cytotoxicity against human HCC Bel-7402 in comparison with L-02 fetal hepatocytes. After intraperitoneal injection, the hydrogel showed prolonged retention over 13 days and preferential accumulation in the liver, realizing HCC growth inhibition by 99.7 ± 0.1% and animal median survival extension from 19 to 43 days, without causing noticeable pathological changes in the major organs. These results demonstrate that injectable peptide hydrogel can be a potential carrier for localized chemotherapy of HCC.

Protective effect of remote ischemic pre-conditioning on patients undergoing cardiac bypass valve replacement surgery: A randomized controlled trial.

Remote ischemic pre-conditioning (RIPC) may have a protective effect on myocardial injury associated with cardiac bypass surgery (CPB). The objective of the present study was to investigate the effect of RIPC on ischemia/reperfusion (I/R) injury and to assess the underlying mechanisms. A total of 241 patients who underwent valve replacement were randomly assigned to receive either RIPC (n=121) or control group (n=120). The primary endpoint was peri-operative myocardial injury (PMI), which was determined by serum Highly sensitive cardiac troponin T (hsTnT). The secondary endpoint was the blood gas indexes, acute lung injury and length of intensive care unit stay, length of hospital stay and major adverse cardiovascular events. The results indicated that in comparison with control group, RIPC treatment reduced the levels of hsTnT at 6 and 24 h post-CPB (P<0.001), as well as the alveolar-arterial oxygen pressure difference and respiratory index after CPB. Furthermore, RIPC reduced the incidence of acute lung injury by 15.3% (54.1% in the control group vs. 41.3% in the RIPC group, P=0.053). It was indicated that RIPC provided myocardial and pulmonary protection during CPB. In addition, the length of the intensive care unit and hospital stay was reduced by RIPC. Mechanistic investigation revealed a reduced content of soluble intercellular adhesion molecule-1, endothelin-1 and malondialdehyde, as well as elevated levels of nitric oxide in the RIPC group compared with those in the control group. This indicated that RIPC protected against I/R injury associated with CPB through reducing the inflammatory response and oxidative damage, as well as improving pulmonary vascular tension. In conclusion, RIPC reduced myocardial and pulmonary injury associated with CPB. This protective effect may be associated with the inhibition of the inflammatory response and oxidative injury. The present study proved the efficiency of this approach in reducing ischemia/reperfusion injury associated with cardiac surgery. Clinical trial registry no. ChiCTR1800015393.

Methylene Blue Attenuates Lung Injury Induced by Hindlimb Ischemia Reperfusion in Rats.

OBJECTIVE: This study was aimed to investigate the protective effect of methylene blue against lung injury induced by reperfusion of ischemic hindlimb in a rat model. METHODS: Twenty-four healthy adult male Sprague-Dawley rats were equally randomized into three groups: sham (SM) group, ischemia reperfusion (IR) group, and methylene blue (MB) group. Rats in both IR and MB groups were subjected to 4 h of ischemia by clamping the left femoral artery and then followed by 4 h of reperfusion. Treatment with 1% methylene blue (50 mg/kg) was administrated intraperitoneally at 10 min prior to reperfusion in the MB group. After 4 h of reperfusion, malondialdehyde (MDA) level, myeloperoxidase (MPO), and superoxide dismutase (SOD) activities in lung tissue were detected; inflammatory cytokines, including IL-1ß and IL-6, were measured in bronchoalveolar lavage fluid (BALF); correspondingly, the morphological changes and water content in both gastrocnemius muscle and lung samples were evaluated. RESULTS: Hindlimb IR caused remarkable morphological abnormalities and edema in both muscle and lung tissues. SOD activity was decreased, both the MPO activity and MDA level in lung tissue, as well as IL-1ß and IL-6 levels in BALF, were increased in the IR group (p < 0.05). Compared with the IR group, SOD activity was increased, whereas MPO activity and MDA level in lung tissue and IL-1ß and IL-6 levels in BALF were decreased in the MB group (p < 0.05). Also, the histological damage and edema in both lung and muscle tissues were significantly attenuated by the treatment of methylene blue. CONCLUSION: Methylene blue attenuates lung injury induced by hindlimb IR in rats, at least in part, by inhibiting oxidative stress.

Eukaryal composition and diversity in anaerobic soils influenced by the novel chiral insecticide Paichongding.

Paichongding (IPP) is a neonicotinoid chiral insecticide with independent intellectual property in China. IPP application can increase crop yield, and also lead to insecticide residue and pollution in soils, which will affect microbial population and community composition in soils. In this study, four different types of soils were employed to inquire into the impact of IPP on eukaryal community and species-group through pyrosequencing of 18S rRNA gene amplicons. Fungal population differed in different soils at different days after IPP treatment (DAT). Eukaryal community species in CK (control check) groups were more rich than that with Paichongding sprayed at 5 DAT, while eukaryal species in CK soils at 60 DAT was relatively slight. Shannon's H' analysis indicated fungal species in CK soils were also higher at 5 DAT and relative lower at 60 DAT, except in soil C. There are also differences in the phyla and genus levels of the eukaryotic communities in the soil. After IPP application, the relative abundance of Nectriaceae increased 3-4 times in soil C. In soil F, Phaeosphaeriaceae increased to 57.3% at 5 DAT. The genus of Guehomyces, Aspergillus and Alternaria increased from 3.1 to 9.7, 1.1 to 4.6, 1.5 to 6.7% in soil H, respectively.

Pyrosequencing Reveals Soil Enzyme Activities and Bacterial Communities Impacted by Graphene and Its Oxides.

Graphene (GN) and graphene oxides (GOs) are novel carbon nanomaterial; they have been attracting much attention because of their excellent properties and are widely applied in many areas, including energy, electronics, biomedicine, environmental science, etc. With industrial production and consumption of GN/GO, they will inevitably enter the soil and water environments. GN/GO may directly cause certain harm to microorganisms and lead to ecological and environmental risks. GOs are GN derivatives with abundant oxygen-containing functional groups in their graphitic backbone. The structure and chemistry of GN show obvious differences compared to those of GO, which lead to the different environmental behaviors. In this study, four different types of soil (S1-S4) were employed to investigate the effect of GN and GO on soil enzymatic activity, microbial population, and bacterial community through pyrosequencing of 16S rRNA gene amplicons. The results showed that soil enzyme activity (invertase, protease, catalase, and urease) and microbial population (bacteria, actinomycetes, and fungi) changed after GN/GO release into soils. Soil microbial community species are more rich, and the diversity also increases after GO/GN application. The phylum of Proteobacteria increased at 90 days after treatment (DAT) after GN/GO application. The phylum of Chloroflexi occurred after GN application at 90 DAT in S1 soil and reached 4.6%. Proteobacteria was the most abundant phylum in S2, S3, and S4 soils; it ranged from 43.6 to 71.4% in S2 soil, from 45.6 to 73.7% in S3 soil, and from 38.1 to 56.7% in S4 soil. The most abundant genera were Bacillus (37.5-47.0%) and Lactococcus (28.0-39.0%) in S1 soil, Lysobacter and Flavobacterium in S2 soil, Pedobacter in S3 soil, and Massilia in S4 soil. The effect of GN and GO on the soil microbial community is time-dependent, and there are no significant differences between the samples at 10 and 90 DAT.

Effect of two administration routes of Shenmai Injection () on pulmonary gas exchange function after tourniquet-induced ischemia-reperfusion.

OBJECTIVE: To compare the effect between nebulized and intravenous administration of Shenmai Injection () on pulmonary gas exchange function of patients following tourniquet-induced lower limb ischemia-reperfusion. METHODS: Thirty-eight patients scheduled for lower extremity surgery were randomized into three groups using the closed envelop method: Shenmai Injection was administered 30 min before tourniquet inflflation by nebulization [0.6 mL/kg in 10 mL normal saline (NS)] in the nebulization group or by intravenous drip (0.6 mL/kg dissolved in 250 mL of 10% glucose) in the intravenous drip group, and equal volume of NS was given intravenously in the NS group; 15 in each group. Arterial blood gases were analyzed, serum levels of malonaldehyde (MDA) and interleukine-6 (IL-6) and interleukine-8 (IL-8) were determined using the method of thiobarbituric acid reaction and enzyme-linked immuno sorbent assay respectively just before tourniquet inflflation (T0), and at 0.5 h (T1), 2 h (T2), 6 h (T3) after tourniquet deflflation. RESULTS: Compared with baselines at T0, MDA levels signifificantly increased at T2, T3 in the NS group and at T3 in the nebulization group, and IL-6 and IL-8 levels were signifificantly increased at T2, T3 in NS, the intravenous drip and the nebulization groups (P <0.05). Arterial pressure of oxygen (PaO2) at T3 was decreased, while alveolararterial oxygen tension showed difference (PA-aDO2) at T3 in the NS group; RI at T3 in both intravenous drip and the nebulization groups were enhanced (P <0.05). Compared with the NS group, MDA and IL-8 levels at T2, T3, IL-6 at T3 in the intravenous drip group, and IL-8 at T3 in the nebulization group were all remarkably increased (P <0.05). Additionally, MDA level at T3 in the nebulization group was higher than that in the intravenous drip group (P <0.05). CONCLUSIONS: Intravenous administration of Shenmai Injection provided a better protective effect than nebulization in mitigating pulmonary gas exchange dysfunction in patients following tourniquet-induced limb ischemia-reperfusion.

COX-2 inhibition attenuates lung injury induced by skeletal muscle ischemia reperfusion in rats.

BACKGROUND: Skeletal muscle ischemia reperfusion accounts for high morbidity and mortality, and cyclooxygenase (COX)-2 is implicated in causing muscle damage. Downregulation of aquaporin-1 (AQP-1) transmembrane protein is implicated in skeletal muscle ischemia reperfusion induced remote lung injury. The expression of COX-2 in lung tissue and the effect of COX-2 inhibition on AQP-1 expression and lung injury during skeletal muscle ischemia reperfusion are not known. We investigated the role of COX-2 in lung injury induced by skeletal muscle ischemia reperfusion in rats and evaluated the effects of NS-398, a specific COX-2 inhibitor. METHODS: Twenty-four Sprague Dawley rats were randomized into 4 groups: sham group (SM group), sham+NS-398 group (SN group), ischemia reperfusion group (IR group) and ischemia reperfusion+NS-398 group (IN group). Rats in the IR and IN groups were subjected to 3h of bilateral ischemia followed by 6h of reperfusion in hindlimbs, and intravenous NS-398 8 mg/kg was administered in the IN group. In the SM and SN groups, rubber bands were in place without inflation. At the end of reperfusion, myeloperoxidase (MPO) activity, COX-2 and AQP-1 protein expression in lung tissue, PGE2 metabolite (PGEM), tumor necrosis factor (TNF)-α and interleukin (IL)-1ß levels in bronchoalveolar lavage (BAL) fluid were assessed. Histological changes in lung and muscle tissues and wet/dry (W/D) ratio were also evaluated. RESULTS: MPO activity, COX-2 expression, W/D ratio in lung tissue, and PGEM, TNF-α and IL-1ß levels in BAL fluid were significantly increased, while AQP-1 protein expression downregulated in the IR group as compared to that in the SM group (P<0.05). These changes were remarkably mitigated in the IN group (P<0.05). NS-398 treatment also alleviated histological signs of lung and skeletal muscle injury. CONCLUSION: COX-2 protein expression was upregulated in lung tissue in response to skeletal muscle ischemia reperfusion. COX-2 inhibition may modulate pulmonary AQP-1 expression and attenuate lung injury.

Effects of the novel cis-nitromethylene neonicotinoid insecticide Paichongding on enzyme activities and microorganisms in yellow loam and Huangshi soils.

Soil enzyme activity and microbial population play important roles in maintaining soil fertility and ensure crop yield. Paichongding (IPP) is a novel cis-nitromethylene neonicotinoid insecticide, which was recently developed in China. In this study, in order to better understand IPP ecological toxicity, the impact of IPP on soil enzyme activity and microbial population in soils was investigated. The results showed that, urease activity was inhibited by IPP before 75 days incubation, after that this inhibiting effect gradually weakened. IPP had different stimulating effects on the activities of dehydrogenase, protease, and catalase. They were consistently stimulated from the initial time in soils. The results of microbial population indicated that the number of bacteria increased after IPP application compared with the control, fungal number increased before 45 days incubation and then decreased. While actinomycete number decreased during degradation period. DT50 (half-life value), k (degradation rate constant) of IPP in S1 (yellow loam soil), and S2 (Huangshi soil) were found 90 days and 173 days, 0.0077 day(-1), and 0.0040 day(-1), respectively.

Impact of the novel neonicotinoid insecticide Paichongding on bacterial communities in yellow loam and Huangshi soils.

Insecticides are widely sprayed in modern agriculture for ensuring the crop yield, which could also lead to contamination and insecticide residue in soils. Paichongding (IPP) is a novel neonicotinoid insecticide and was developed recently in China. Soil bacterial community, diversity, and community composition vary widely depending on environmental factors. As for now, little is known about bacterial species thriving, bacterial community diversity, and structure in IPP-spraying soils. In present study, IPP degradation in yellow loam and Huangshi soils was investigated, and bacterial communities and diversity were examined in soil without IPP spray and with IPP spray through pyrosequencing of 16S ribosomal RNA (rRNA) gene amplicons. The degradation ratio of IPP at 60 days after treatment (DAT) reached 51.22 and 34.01 % in yellow loam and Huangshi soil, respectively. A higher richness of operational taxonomic units (OTUs) was found in yellow loam soil (867 OTUs) and Huangshi soil (762 OTUs) without IPP spray while OUTs were relatively low in IPP-spraying soils. The community composition also differed both in phyla and genus level between these two environmental conditions. Proteobacteria, Firmicutes, Planctomycetes, Chloroflexi, Armatimonadetes, and Chlorobi were stimulated to increase after IPP application, while IPP inhibited the phyla of Bacteroidetes, Actinobacteria, and Acidobacteria.

[Nrf2/ARE pathway mediates the reducing effect of Dexmedeto-midine on ischemia/reperfusion injury in skeletal muscle].

OBJECTIVE: To explore the role of Nrf2/ARE pathway in skeletal muscle ischemia/reperfusion(I/R) injury preconditioning by dexmedetomidine(DEX). METHODS: Twenty-eight SD rats were randomly divided into sham-operated(Sham group)、I/R group、I/R+ DEX(DEX group) and I/R+DEX +Atipamezole (Atip group). In the Atip group, Atip(250 µg/kg) and DEX(25 µg/kg) were injected together after anesthesia; In the Sham and I/R groups, the homologous saline was also injected at the same time; In the DEX group, the homologous DEX and saline were coinjected. After 30 minutes, the hind limb ischemia was induced by clamping the common femoral artery and ligaturing collateral circulation. After 3 h of ischemia, the clamp and tourniquet were removed and the rats underwent 2 h of reperfusion. We measured plasma concentrations of lactate dehydrogenase (LDH) and creatine kinase(CK). The gastrocnemius muscle was harvested and immediately stored at -80℃ for the assessment of malondialdehyde(MDA)、superoxide dismutase(SOD) and Nrf2/HO-1 protein detected by Western blot. The other section muscle was stored in triformol for immunohistochemical and HE staining. The wet/dry was also immediately detecting. RESULTS: The levels of wet/dry、MDA、LDH、CK、Nrf2 and HO-1 were higher(P<0.05) while the level of SOD was lower(P<0.05) in the I/R group than those in sham group. The levels of wet/dry、MDA、LDH、CK were significantly lower(P<0.05) yet the levels of SOD and Nrf2/HO-1 were significantly higher(P<0.05) in DEX group than those in I/R group. However, Atip reversed the effect of DEX in Atip group, each of indicators had significant changes compared with those in the DEX group(P<0.05). CONCLUSIONS: Nrf2 protein was expressed in skeletal muscle of rat and DEX could promote its level in nucleus by α-adrenergic receptor. The down-stream products of Nrf2 have the effect of antioxidant.

Biodegradation of Azo Dye Disperse Orange S-RL by a Newly Isolated Strain Acinetobacter sp. SRL8.

The strain SRL8, which could decolorize the azo dye disperse orange S-RL (S-RL), was first isolated from sludge and identified as Acinetobacter sp. through physiobiochemical identification and 16S rRNA gene sequences. The effects of temperature, pH, dye concentration, O2, and glucose concentration on S-RL decolorization by the strain SRL8 were studied. The optimal conditions were 30 °C, pH 7.0, 4g·L(-1) of inoculation (wet cells), and microaerophilic incubation. The decolorization percentage for S-RL by the strain SRL8 could reach 90.2% under optimal conditions. The strain SRL8 was highly tolerant to the azo dye SRL up to 300 mg·L(-1) and it had a broad decolorizing spectrum. According to the Monod equation, kinetic parameters of decolorization by SRL8 were calculated. The vmax and Km were 5.57×10(-3) h(-1) and 14.53 mg·L(-1), respectively.

Microbial Degradation Mechanism and Pathway of the Novel Insecticide Paichongding by a Newly Isolated Sphingobacterium sp. P1-3 from Soil.

Using 1-((6-chloropydidin-3-yl)methyl)-7-methyl-8-nitro-5propoxy-1,2,3,5,6,7-hexahydroimidazo[1,2-α-]-pyridine (IPP) as the sole carbon source, we isolated a strain with a higher activity of IPP-degrading bacterium Sphingobacterium sp. P1-3 from soil. At 30 °C, pH 7.0 ,and 10 mg L(-1) IPP content, the degradation rate of IPP by Sphingobacterium sp. P1-3 could reach 57.75 and 62.47% in 20 and 30 days, respectively. The value of DT50 of IPP was 27 d at the level of 30 mg L(-1) IPP, while DT50 in the blank test was 151 d. During the IPP biodegradation process, five intermediates (M1-M5) were monitored and identified. On the basis of the identified metabolites and their biodegradation courses, a possible biodegradation pathway was proposed. IPP biodegradation mainly occurred on the tetrahydropyridine ring. IPP was transformed to five different metabolites by strain P1-3 through the oxidation and elimination of methyl, propyl, and nitro groups. Moreover, a new pathway involving M2 (1-((6-chloropydidin-3-yl)methyl)-7-methyl-8-hydroxy-5-propoxy-1,2,3,5,6,7-hexahydroimidazo [1,2-α-]-pyridine), M3 (1-((6-chloropydidin-3-yl)methyl)-7-methyl-5-carbonyl-1,2,3,5,6,7-hexahydroimidazo[1,2-α-]-pyridine), and M5 (8-amino-1,2,3,5,6,7-hexahydroimidazo[1,2-α-]-pyridine) was first monitored and identified.

Pre-emptive peritonsillar infiltration of magnesium sulphate and ropivacaine vs. ropivacaine or magnesium alone for relief of post-adenotonsillectomy pain in children.

OBJECTIVES: The randomized, double-blinded, placebo-controlled study evaluated the administration of local infiltration of magnesium combined with ropivacaine to reduce pain scores after pediatric adenotonsillectomy. METHODS: Sixty one subjects received 5ml solution contained 0.25% ropivacaine plus 5mg/kg magnesium sulphate (Group M+R), 5ml 0.25% ropivacaine (Group R) or 5ml solution contained 5mg/kg magnesium sulphate (Group M). Pain scores in the ward and at home, analgesics received after operation and the adverse effects were recorded. RESULTS: Compared with group M, patients in group M+R and group R had lower pain scores, less emergence agitation and increased time for first analgesic request. Group M+R had no benefit in reducing pain scores after adenotonsillectomy compared with group R. CONCLUSIONS: Pre-emptive peritonsillar infiltration of magnesium sulphate 5mg/kg combined with 0.25% ropivacaine couldn't improve analgesia for pediatric adenotonsillectomy compared with 0.25% ropivacaine alone. However, Group M+R had less incidence of emergence agitation. Compared with group M, both of group M+R and group R had better postoperative analgesia.

Microbial degradation characteristics and kinetics of novel pyrimidynyloxybenzoic herbicide ZJ0273 by a newly isolated Bacillus sp. CY.

ZJ0273 (propyl 4-(2-(4,6-demethoxy pyrimidin-2-yloxy)benzylamino)benzoate) is a novel herbicide developed in China for oilseed crop. Sixteen bacteria capable of utilizing ZJ0273 as the sole carbon source were isolated from soils. One of the isolates was designated as Bacillus sp. CY based on its physiological and biochemical characteristics and phylogenetic analysis of 16S rDNA sequences. The present study aimed to investigate the ZJ0273 degradation characteristics and kinetics by Bacillus sp. CY which has the ability to utilize ZJ0273 as the sole source of carbon and energy under aerobic conditions. The optimum biodegradation temperature, pH, and ZJ0273 initial concentration were 20-40 °C, 5.0-9.0, and 50-400 mg/l, respectively. Strain CY degraded 65 % of ZJ0273 (initial concentration of 50 mg/l) during 30 days of incubation in basal mineral medium at pH 8.0 and 35 °C. DT50 (half-life value), k (degradation rate constant of ZJ0273), and R (2) are 19.20 days, 0.0361 day(-1), and 0.9464, respectively.

Effects of COX-2 inhibitor on ventilator-induced lung injury in rats.

BACKGROUND: Mechanical ventilation especially with large tidal volume has been demonstrated to activate inflammatory response inducing lung injury, which could be attenuated by cyclooxygenase (COX)-2 inhibitors. As the main small integral membrane proteins that selectively conduct water molecules' transportation, aquaporin (AQP)-1 downregulation significantly related to lung edema and inflammation. This study aims to investigate the role of AQP1 in ventilator-induced lung injury in rats and evaluates the effects of COX-2 inhibition. METHODS: Forty rats were allocated into four groups, where rats in Groups LD (low volume+DMSO) and LN (low volume+NS-398) were given intravenously 2ml DMSO and 8mg/kg NS-398 (a specific COX-2 inhibitor, dissolved in 2ml DMSO) before 4-hour lower tidal volume ventilation (8ml/kg), respectively, while DMSO and NS-398 were administrated in the same manner before 4-hour injurious ventilation (40ml/kg) in Groups HD (high volume+DMSO) and HN (high volume+NS-398). The arachidonic acid metabolites (6-keto prostaglandin F1α, thromboxane B2), inflammatory cytokines (tumor necrosis factor-α, interleukin-1ß, 6, 8) and total protein levels in bronchoalveolar lavage (BAL) fluid and COX-2 mRNA and AQP1 protein expression in lung tissue were detected; water content and lung morphology were also evaluated. RESULTS: Compared to Groups LD and LN, the rats in Groups HD and HN suffered obvious lung morphological changes with higher wet-to-dry weight ratio and lung injury score, and the levels of arachidonic acid metabolites, inflammatory cytokines and total protein in BAL fluid were increased, the expression of COX-2 mRNA was significantly upregulated and AQP1 protein was downregulated in lung tissue (p<0.05). The changes in BAL fluid and the severity of lung injury were attenuated, and AQP1 expression was upregulated in Group HN as compared to HD (p<0.05). CONCLUSIONS: Ventilation with large tidal volume causes inflammatory mediator production and AQP1 downregulation, which could be attenuated by COX-2 inhibition.