Loss of ADAR1 induces ferroptosis of breast cancer cells.

Adenosine deaminases acting on RNA 1(ADAR1), an RNA editing enzyme that converts adenosine to inosine by deamination in double-stranded RNAs, plays an important role in occurrence and progression of various types of cancer. Ferroptosis has emerged as a hot topic of cancer research in recent years. We have previously reported that ADAR1 promotes breast cancer progression by regulating miR-335-5p and METTL3. However, whether ADAR1 has effects on ferroptosis in breast cancer cells is largely unknown. In this study, we knocked down ADAR1 using CRISPR-Cas9 technology or over-expressed ADAR1 protein using plasmid expressing ADAR1 in MCF-7 and MDA-MB-231 breast cancer cell lines, then detected cell viability, and levels of ROS, MDA, GSH, Fe2+, GPX4 protein and miR-335-5p. We showed that the cell proliferation was inhibited, levels of ROS, MDA, Fe2+, and miR-335-5p were increased, while GSH and GPX4 levels were decreased after loss of ADAR1, compared to the control group. The opposite effects were observed after ADAR1 overexpression in the cells. Further, we demonstrated that ADAR1-controlled miR-335-5p targeted Sp1 transcription factor of GPX4, a known ferroptosis molecular marker, leading to inhibition of ferroptosis by ADAR1 in breast cancer cells. Moreover, RNA editing activity of ADAR1 is not essential for inducing ferroptosis. Collectively, loss of ADAR1 induces ferroptosis in breast cancer cells by regulating miR-335-5p/Sp1/GPX4 pathway. The findings may provide insights into the mechanism by which ADAR1 promotes breast cancer progression via inhibiting ferroptosis.

Negative associations between folate and bacterial vaginosis in the NHANES 2001 to 2004.

BACKGROUND: Bacterial vaginosis (BV) is one of the most common infections among women of reproductive age and accounts for 15-50% of infections globally. The role played by folate in the pathogenesis and progression of BV is poorly understood. The aim of this study was to investigate the association between serum folate, red blood cell (RBC) folate, and BV in American women. METHODS: 1,954 participants from the 2001-2004 National Health and Nutrition Examination Survey (NHANES) program were included in this study. Multiple logistic regression was used to analyze the association between serum folate, RBC folate, and BV, and covariates including race, age, education level, and body mass index were used to construct adjusted models. Stratified analysis was used to explore the stability of the above associations in different populations. RESULTS: In the present cross-sectional study, we found that serum folate and RBC folate were inversely associated with the risk of BV. In the fully adjusted model, the risk of BV was reduced by 35% (OR=0.65, 95% CI: 0.51~0.83, p=0.0007) in the highest serum folate group and 32% (OR=0.68, 95% CI: 0.53~0.87, p=0.0023) in the highest RBC folate group compared to the lowest group. CONCLUSIONS: The results of this study indicated that serum folate and RBC folate were inversely associated with the risk of BV folate supplementation may play an important role in the prevention and management of BV.

Exploring the correlation between serum fibroblast growth factor-21 levels and Sarcopenia: a systematic review and meta-analysis.

BACKGROUND: Fibroblast growth factor 21 (FGF-21) plays an important role in the growth and metabolism of skeletal muscle cells. This study aims to systemically review the evidence regarding the relationship between FGF-21 levels and Sarcopenia, as well as the related influential factors. METHODS: This review was conducted according to the PRISMA guidelines. We comprehensively searched PubMed, EMBASE, the Web of Science, Scopus, and Chinese Databases (CNKI, Wan Fang, VIP, and CBM) up to 1 May 2023. 3 investigators performed independent literature screening and data extraction of the included literature, and two investigators performed an independent quality assessment of case-control studies using the Joanna Briggs Institute (JBI) tool. Data analysis was performed using Review Manager 5.4 software. For continuous various outcomes, mean difference (MD) or standard mean difference (SMD) with 95% confidence intervals (CIs) was applied for assessment by fixed-effect or random-effect model analysis. The heterogeneity test was performed by the Q-statistic and quantified using I2, and publication bias was evaluated using a funnel plot. RESULTS: Five studies with a total of 625 cases were included in the review. Meta-analysis showed lower BMI in the sarcopenia group [MD= -2.88 (95% CI, -3. 49, -2.27); P < 0.00001; I2 = 0%], significantly reduced grip strength in the sarcopenia group compared to the non-sarcopenia group [MD = -7.32(95% CI, -10.42,-4.23); P < 0.00001; I2 = 93%]. No statistically significant differences in serum FGF21 levels were found when comparing the two groups of subjects [SMD = 0.31(95% CI, -0.42, 1.04); P = 0.41; I2 = 94%], and no strong correlation was found between the onset of sarcopenia and serum FGF21 levels. CONCLUSION: The diagnosis of sarcopenia is followed by a more significant decrease in muscle mass and strength, but there is a lack of strong evidence to support a direct relationship between elevated organismal FGF21 and sarcopenia, and it is not convincing to use FGF21 as a biological or diagnostic marker for sarcopenia. The currently used diagnostic criteria for sarcopenia and setting of cut-off values for each evaluation parameter no longer seem to match clinical practice.

One-pot hydrothermal synthesis of Si-doped carbon quantum dots with up-conversion fluorescence as fluorescent probes for dual-readout detection of berberine hydrochloride.

Here, the high fluorescent silicon-doped carbon quantum dots (Si-CQDs) were prepared by a facile and one-pot hydrothermal assay using 3-aminopropyltrimethoxysilane as the carbon and silicon source. The prepared Si-CQDs exhibit favorable water-soluble, high-temperature resistance, acid resistance, alkali resistance, high ionic strength resistance, high photostability, film-forming ability and solid-state fluorescence. Compared to other Si-CQDs that have been reported, the prepared Si-CQDs show unique up-conversion fluorescence. Furthermore, it is found that berberine hydrochloride (BH) can effectively quench the down- and up-conversion fluorescence of the Si-CQDs, making it can be used as a highly sensitive and specific probe for BH dual-mode sensing. Meanwhile, the linear range of down-conversion fluorescence detection for BH is 0.5-30.0 µmol/L with a limit of detection (LOD) of 50 nmol/L, and the linear range of up-conversion fluorescence assay for BH is 0-25.0 µmol/L. The mechanism of down-conversion fluorescence quenching by BH was investigated through a series of studies. The results show the quenching mechanism is the inner filter effect (IFE). Moreover, this proposed strategy has been well used to analyze BH in urine samples with satisfactory results.

Complete Genome Sequencing and Comparative Analysis of the Clinically-Derived Apiotrichum mycotoxinivorans Strain GMU1709.

Over the past decade, Apiotrichum mycotoxinivorans has been recognized globally as a source of opportunistic infections. It is a yeast-like fungus, and its association as an uncommon pulmonary pathogen with cystic fibrosis patients has been previously reported. Immunocompromised patients are at the highest risk of A. mycotoxinivorans infections. Therefore, to investigate the genetic basis for the pathogenicity of A. mycotoxinivorans, we performed whole-genome sequencing and comparative genomic analysis of A. mycotoxinivorans GMU1709 that was isolated from sputum specimens of a pneumonia patient receiving cardiac repair surgery. The assembly of Oxford Nanopore reads from the GMU1709 strain and its subsequent correction using Illumina paired-end reads yielded a high-quality complete genome with a genome size of 30.5 Mb in length, which comprised six chromosomes and one mitochondrion. Subsequently, 8,066 protein-coding genes were predicted based on multiple pieces of evidence, including transcriptomes. Phylogenomic analysis indicated that A. mycotoxinivorans exhibited the closest evolutionary affinity to A. veenhuisii, and both the A. mycotoxinivorans strains and the formerly Trichosporon cutaneum ACCC 20271 strain occupied the same phylogenetic position. Further comparative analysis supported that the ACCC 20271 strain belonged to A. mycotoxinivorans. Comparisons of three A. mycotoxinivorans strains indicated that the differences between clinical and non-clinical strains in pathogenicity and drug resistance may be little or none. Based on the comparisons with strains of other species in the Trichosporonaceae family, we identified potential key genetic factors associated with A. mycotoxinivorans infection or pathogenicity. In addition, we also deduced that A. mycotoxinivorans had great potential to inactivate some antibiotics (e.g., tetracycline), which may affect the efficacy of these drugs in co-infection. In general, our analyses provide a better understanding of the classification and phylogeny of the Trichosporonaceae family, uncover the underlying genetic basis of A. mycotoxinivorans infections and associated drug resistance, and provide clues into potential targets for further research and the therapeutic intervention of infections.

Memantine Promotes Bactericidal Effect of Neutrophils Against Infection with Pseudomonas aeruginosa and Its Drug-Resistant Strain, by Improving Reactive Oxygen Species Generation.

Pseudomonas aeruginosa is an opportunistic pathogen, which usually presents multiple antibiotic resistance. Host-directed therapy involves modulating the host defense system and the interplay between innate and adaptive immunity is a new strategy for designing anti-infection drugs. Memantine (MEM), a drug used to treat Alzheimer's disease, has a good inhibitory effect on neonatal mice with Escherichia coli-associated bacteremia and meningitis; however, the inhibitory effect and mechanisms of MEM against P. aeruginosa infection remain unclear. Here, we investigated whether MEM could inhibit P. aeruginosa infection and explored the potential mechanisms. MEM significantly promoted the bactericidal effect of neutrophils against P. aeruginosa and its drug-resistant strain. The combination index of MEM and amikacin (AMK) was <1. In vivo experiments showed that the bacteremia and inflammation severities in the MEM-treated group were less than those in the untreated group, and the bacterial load in the organs was significantly less than that in the control group. Combining MEM with the reactive oxygen species (ROS) inhibitor, N-acetyl-l-cysteine, weakened the anti-infective effect of MEM. MEM increased the expression of NADPH p67phox and promoted neutrophilic ROS production. Deleting the p67phox gene significantly weakened the effects of MEM on ROS generation and improving bactericidal effect of neutrophils. In conclusion, MEM promoted the bactericidal effect of neutrophils against P. aeruginosa and its drug-resistant strain, and had a synergistic antibacterial effect when combined with AMK. MEM may exert its anti-infective effects by promoting neutrophilic bactericidal activity via increasing the expression level of p67phox and further stimulating ROS generation.

[Pharmacodynamics and intestinal flora research on different processed products of Puerariae Lobatae Radix and Puerariae Thomsonii Radix].

This study aims to explore the pharmacodynamic differences of Puerariae Lobatae Radix(PLR), Puerariae Thomsonii Radix(PTR) and their different processed products and the influences of these medical materials on the diversity of intestinal flora. The Sennae Folium-induced diarrhea model, streptozotocin(STZ)-induced diabetes model and L-nitro-arginine methyl ester(L-NAME)-induced hypertension model were used to compare the pharmacodynamic differences in anti-diarrhea, blood glucose reduction and blood pressure lowering among raw, roasted and vinegar-processed PLR and PTR. The effects of raw and processed PLR and PTR on intestinal flora diversity of rats were evaluated by 16 S rDNA high-throughput sequencing. The roasted PLR and PTR performed better in anti-diarrhea, especially the former. PLR and its processed products all presented the efficacy of reducing blood glucose, and the vinegar-processed PLR was the most outstanding. The raw PTR was not that effective in reducing blood glucose, whereas its efficacy was improved after roasting and vinegar processing. Both PLR and PTR were capable of lowering blood pressure to a certain extent, and PLR is superior to PTR in this aspect. Further, the vinegar-processed PLR showed the best effect. The diversity of intestinal flora was different among rats to which different products of PLR and PTR were administered. The roasted PLR led to the highest abundance of Lactobacillus, which was closely related to its best antidiarrheal effect. The highest abilities of vinegar-processed PLR to lower blood glucose and blood pressure were associated with the high abundance of Blautia and Prevotella_9. This study lays a foundation for elucidating the processing mechanisms of PLR and PTR and provides a basis for their further development and application.

Utility of process capability indices in assessment of quality control processes at a clinical laboratory chain.

BACKGROUND: To evaluate the utility of the process capability indices Cp and Cpk for assessing the quality control processes at chain laboratory facilities. METHODS: In April 2020, the minimum Cp and Cpk values for 33 assays of a laboratory chain with 19 facilities were collected for further analysis and a total of 627 datasets (Cp and Cpk ) were compared. In addition, standard values for Cp and Cpk , defined as the lowest of the top 20%, were obtained for comparison and the indices were used to determine whether precision or trueness improvements were required for the corresponding assay. RESULTS: A total of 627 datasets of 33 assays from 19 laboratory facilities were collected for further analysis. Based on the Cp results, 329 (52.5%), 211 (33.7%), 65 (10.3%), and 22 (3.5%) were rated as excellent, good, marginal, and poor, respectively. While the corresponding results for Cpk were 300 (47.8%), 216 (34.4%), 79 (12.6%), and 32 (5.1%). In addition, it was noteworthy that eight (Cp criteria) and six assays (Cpk criteria) were rated as excellent or good at all 19 facilities. Comparison of the process capability indices at the Jinan KingMed Center with the standard values revealed that total protein, albumin, and urea showed trueness individual improvement, precision individual improvement, and precision common improvement, respectively, while the results of other assays were stable. CONCLUSION: Process capability indices are useful for evaluating the quality control procedures in laboratory facilities and can help improve the precision and trueness of laboratory tests.

Engineering a novel antibacterial agent with multifunction: Protocatechuic acid-grafted-quaternized chitosan.

As a mild cationic antibacterial agent, hydroxypropyltrimethyl ammonium chloride chitosan (HACC) could kill gram-positive bacteria and gram-positive drug-resistant bacteria without cytotoxicity. Nevertheless, it was not effective against gram-negative bacteria. Herein, protocatechuic acid (PA) with broad-spectrum antibacterial properties and pharmacological activities was grafted on HACC. PA-g-HACC showed favourable antioxidant capacity and anti-inflammatory properties. Most importantly, the results of antibacterial assay indicated that the antibacterial rates of all PA-g-HACC groups against Staphylococcus aureus (S. aureus) and methicillin-resistant Staphylococcus aureus (MRSA) were above 92 %, and the antibacterial rate of PA-g-HACC against E. coli was increased with the amount of grafted PA. Furthermore, the cytocompatibility of PA-g-HACC was improved by appropriate grafting ratio of PA, while excessive grafted PA can lead to toxicity. We believe that PA-g-HACC in optimum grafting ratio of PA with favorable antibacterial properties, pharmacological activities and cytocompatibility will be potential antibacterial agent for treating infections.

Altered anxiety and social behaviors in a mouse model of Fragile X syndrome treated with hyperbaric oxygen therapy.

Fragile X syndrome (FXS) is a common mental retardation syndrome. Anxiety and abnormal social behaviors are prominent features of FXS in humans. To better understand the effects of hyperbaric oxygen therapy (HBOT) on these behaviors, we analyzed anxiety-related and social behaviors in Fmr1 knockout mice treated by HBOT. In the open field test, HBOT group mice preferred the periphery to central areas and tended to run or walk along the wall. The results suggested that thigmotaxis was significantly increased in the HBOT group compared with the control group. In the elevated plus maze test, the percentage of distance traveled was significantly increased in the open arm and significantly decreased in the closed arm for HBOT group mice compared with control group mice. These results suggested that HBOT group mice displayed enhanced motor activity in the open arm and exhibited fewer anxiety-related behaviors. In the three-chambered social approach test, the HBOT group mice made more approaches to the wire cup containing an acquaintance mouse than control group mice in the sociability test and made more approaches to the wire cup containing a stranger mouse than control group mice in the social novelty preference test. The results suggested that HBOT group mice showed increased levels of social interaction and decreased "social anxiety" than the control group to partner mice in this test. Our findings indicated that HBOT resulted in altered anxiety and social behavior in Fmr1 knockout mice and could possibly be used as a treatment for FXS.

A meta-analysis of diffusion tensor imaging of substantia nigra in patients with Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disease characterized by severe, selective loss of pigmented neurons in the substantial nigra (SN). Previous studies have indicated that such loss could be detected by diffusion tensor imaging (DTI). Here, we try to consolidate current DTI data to both quantitatively determine the imaging changes in SN, as well as explore the potential use of DTI for PD diagnosis. Fourteen research articles are included in this meta-analysis, each obtained by searching PubMed, EMBASE, or Cochrane library database dated until July 2017. The articles contain 14 trials with 298 total PD patients and 283 healthy controls (HCs). The results show not only significantly lower FA values of SN in PD compared to that of HCs (WMD = -0.02, 95% CI = [-0.03, -0.02], p < 0.00001), but also a significantly higher MD in PD compared to HCs (WMD = 0.05, 95% CI = [0.03, 0.07], P < 0.0001). This indicates that the sharp difference detected between PD patients and HCs can be detected by DTI. By further analyzing the heterogeneity, we found that FA measurement of SN could be potentially used as a surrogate, noninvasive diagnostic marker toward PD diagnosis.

Deceleration capacity-a novel measure for autonomic nervous system in patients with vasovagal syncope on tilt-table testing.

This study was to investigate the changes of autonomic nerve function and hemodynamics in patients with vasovagal syncope (VVS) during head-up tilt-table testing (HUT). HUT was performed in 68 patients with unexplained syncope and 18 healthy subjects served as control group. According to whether bradycardia, hypotension or both took place during the onset of syncope, the patients were divided during the test into three subgroups: vasodepressor syncope (VD), cardioinhibitory syncope (CI) and mixed syncope (MX) subgroups. Heart rate, blood pressure, heart rate variability (HRV), and deceleration capacity (DC) were continuously analyzed during HUT. For all the subjects with positive responses, the normalized low frequency (LFn) and the LF/HF ratio markedly decreased whereas normalized high frequency (HFn) increased when syncope occurred. Syncopal period also caused more significant increase in the power of the DC in positive groups. These changes were more exaggerated compared to controls. All the patients were indicative of a sympathetic surge in the presence of withdrawal vagal activity before syncope and a sympathetic inhibition with a vagal predominance at the syncopal stage by the frequency-domain analysis of HRV. With the measurements of DC, a decreased vagal tone before syncope stage and a vagal activation at the syncopal stage were observed. The vagal tone was higher in subjects showing cardioinhibitory responses at the syncopal stage. DC may provide an alternative method to understand the autonomic profile of VVS patients.

HLA-A*24:02 as a common risk factor for antiepileptic drug-induced cutaneous adverse reactions.

OBJECTIVE: To investigate the involvement of human leukocyte antigen (HLA) loci in aromatic antiepileptic drug-induced cutaneous adverse reactions. METHODS: A case-control study was performed to detect HLA loci involved in aromatic antiepileptic drug-induced Stevens-Johnson syndrome in a southern Han Chinese population. Between January 1, 2006, and December 31, 2015, 91 cases of Stevens-Johnson syndrome induced by aromatic antiepileptic drugs and 322 matched drug-tolerant controls were enrolled from 8 centers. Important genotypes were replicated in cases with maculopapular eruption and in the meta-analyses of data from other populations. Sequence-based typing determined the HLA-A, HLA-B, HLA-C, and HLA-DRB1 genotypes. RESULTS: HLA-B*15:02 was confirmed as strongly associated with carbamazepine-induced Stevens-Johnson syndrome (p = 5.63 × 10-15). In addition, HLA-A*24:02 was associated significantly with Stevens-Johnson syndrome induced by the aromatic antiepileptic drugs as a group (p = 1.02 × 10-5) and by individual drugs (carbamazepine p = 0.015, lamotrigine p = 0.005, phenytoin p = 0.027). Logistic regression analysis revealed a multiplicative interaction between HLA-B*15:02 and HLA-A*24:02. Positivity for HLA-A*24:02 and/or HLA-B*15:02 showed a sensitivity of 72.5% and a specificity of 69.0%. The presence of HLA-A*24:02 in cases with maculopapular exanthema was also significantly higher than in controls (p = 0.023). Meta-analysis of data from Japan, Korea, Malaysia, Mexico, Norway, and China revealed a similar association. CONCLUSIONS: HLA-A*24:02 is a common genetic risk factor for cutaneous adverse reactions induced by aromatic antiepileptic drugs in the southern Han Chinese and possibly other ethnic populations. Pretreatment screening is recommended for people in southern China.

One-Pot Hydrothermal Synthesis of Carbon Dots with Efficient Up- and Down-Converted Photoluminescence for the Sensitive Detection of Morin in a Dual-Readout Assay.

Blue luminescent carbon dots (CDs) with a high photoluminescence (PL) quantum yield (48.3 ± 5.3%) were prepared by the one-pot hydrothermal reaction of citric acid with poly(ethylenimine) (PEI). The CDs display bright PL, narrow emission spectra, pH-dependent PL intensity, high photostability, and up-converted luminescence. The CDs exhibit a quenching of both down- and up-conversion PL in the presence of morin and thus serve as useful probes for morin detection. Both down- and up-conversion measurements allow the quantification of concentrations from 0 to 300 µmol/L with a detection limit of 0.6 µmol/L, and this dual-mode detection increases the reliability of the measurement. The proposed method of determination is simple, sensitive, and cost-effective, with potential applications in clinical and biochemical assays.

Deceleration Capacity—A Novel Measure for Autonomic Nervous System in Patients with Vasovagal Syncope on Tilt-table Testing / 华中科技大学学报（医学）（英德文版）

This study was to investigate the changes of autonomic nerve function and hemodynamics in patients with vasovagal syncope (VVS) during head-up tilt-table testing (HUT).HUT was performed in 68 patients with unexplained syncope and 18 healthy subjects served as control group.According to whether bradycardia,hypotension or both took place during the onset of syncope,the patients were divided during the test into three subgroups:vasodepressor syncope (VD),cardioinhibitory syncope (CI) and mixed syncope (MX) subgroups.Heart rate,blood pressure,heart rate variability (HRV),and deceleration capacity (DC) were continuously analyzed during HUT.For all the subjects with positive responses,the normalized low frequency (LFn) and the LF/HF ratio markedly decreased whereas normalized high frequency (HFn) increased when syncope occurred.Syncopal period also caused more significant increase in the power of the DC in positive groups.These changes were more exaggerated compared to controls.All the patients were indicative of a sympathetic surge in the presence of withdrawal vagal activity before syncope and a sympathetic inhibition with a vagal predominance at the syncopal stage by the frequency-domain analysis of HRV.With the measurements ofDC,a decreased vagal tone before syncope stage and a vagal activation at the syncopal stage were observed.The vagal tone was higher in subjects showing cardioinhibitory responses at the syncopal stage.DC may provide an alternative method to understand the autonomic profile of VVS patients.

Clinical significance of dynamic detection for serum levels of MCP-1, TNF-α and IL-8 in patients with acute pancreatitis.

OBJECTIVE: To observe dynamic changes of levels of monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α) and interleukin-8 (IL-8) in patients with acute pancreatitis and to investigate its evaluation value on the severity of acute pancreatitis. METHODS: A total of 109 patients with acute pancreatitis admitted were divided into mild acute pancreatitis group (MAP group, 42 cases), moderately severe acute pancreatitis (MSAP group, 35 cases) and severe acute pancreatitis (SAP group, 32 cases). ELISA was used to detect the serum levels of MCP-1, TNF-α and IL-8 of patients at day 1, day 4 and day 7 of admission to hospital. RESULTS: The serum levels of MCP-1, TNF-α and IL-8 from MAP group, MSAP group and SAP group at day 1 of admission to hospital all significantly increased. There was a significant difference between MAP group and control group, MSAP group and MAP group, SAP group and MSAP group (P < 0.05). The serum concentrations of IL-8 from MASP group and SAP group obviously increased at day 1, and there was significant difference between MASP group and MAP group, SAP group and MSAP group (P < 0.05), while the difference between MAP group and control group was not obvious (P > 0.05); The serum concentrations of MCP-1, TNF-α and IL-8 from MAP group all reached the highest level at day 4, which were significantly higher than the detection levels at day 1. In MSAP group and SAP group, the serum concentrations of MCP-1, TNF-α and IL-8 were the highest at day 1, which were significantly higher than the detection levels at day 4 and 7. At each detecting timing, the serum concentrations of MCP-1, TNF-α and IL-8 from MSAP group and SAP group were all higher than those of MAP group and MSAP group, respectively. CONCLUSIONS: The dynamic changes of serum levels of MCP-1, TNF-α and IL-8 in patients with acute pancreatitis have their rules, and the change rule of MAP group was different with that of MSAP and SAP group, which showed the reference value for the diagnosis and illness severity evaluation of acute pancreatitis.

Involvement of polyphosphate kinase in virulence and stress tolerance of uropathogenic Proteus mirabilis.

Proteus mirabilis (P. mirabilis), a gram-negative enteric bacterium, frequently causes urinary tract infections. Many virulence factors of uropathogenic P. mirabilis have been identified, including urease, flagella, hemolysin and fimbriae. However, the functions of polyphosphate kinase (PPK), which are related to the pathogenicity of many bacteria, remain entirely unknown in P. mirabilis. In this study, a ppk gene encoding the PPK insertional mutant in P. mirabilis strain HI4320 was constructed, and its biological functions were examined. The results of survival studies demonstrated that the ppk mutant was deficient in resistance to oxidative, hyperosmotic and heat stress. The swarming and biofilm formation abilities of P. mirabilis were also attenuated after the ppk interruption. In vitro and in vivo experiments suggested that ppk was required for P. mirabilis to invade the bladder. The negative phenotypes of the ppk mutant could be restored by ppk gene complementation. Furthermore, two-dimensional gel electrophoresis and liquid chromatography-mass spectrometry were used to analyze the proteomes of the wild-type strain and the ppk mutant. Compared with the wild-type strain, seven proteins including TonB-dependent receptor, universal stress protein G, major mannose-resistant/Proteus-like fimbrial protein (MR/P fimbriae), heat shock protein, flagellar capping protein, putative membrane protein and multidrug efflux protein were down-regulated, and four proteins including exported peptidase, repressor protein for FtsI, FKBP-type peptidyl-prolyl cis-trans isomerase and phosphotransferase were up-regulated in the ppk mutant. As a whole, these results indicate that PPK is an important regulator and plays a crucial role in stress tolerance and virulence in uropathogenic P. mirabilis.

[Effects of nitrogen management on maize nitrogen utilization and residual nitrate nitrogen in soil under maize/soybean and maize/sweet potato relay strip intercropping systems].

A large amount of nitrogen (N) fertilizers poured into the fields severely pollute the environment. Reasonable application of N fertilizer has always been the research hotpot. The effects of N management on maize N utilization and residual nitrate N in soil under maize/soybean and maize/ sweet potato relay strip intercropping systems were reported in a field experiment in southwest China. It was found that maize N accumulation, N harvest index, N absorption efficiency, N contribution proportion after the anthesis stage in maize/soybean relay strip intercropping were increased by 6.1%, 5.4%, 4.3%, and 15.1% than under maize/sweet potato with an increase of 22.6% for maize yield after sustainable growing of maize/soybean intercropping system. Nitrate N accumulation in the 0-60 cm soil layer was 12.9% higher under maize/soybean intercropping than under maize/sweet potato intercropping. However, nitrate N concentration in the 60-120 cm soil layer when intercropped with soybean decreased by 10.3% than when intercropped with sweet potato, indicating a decrease of N leaching loss. Increasing of N application rate enhanced N accumulation of maize and decreased N use efficiency and significantly increased nitrate concentration in the soil profile except in the 60-100 cm soil layer, where no significant difference was observed with nitrogen application rate at 0 to 270 kg · hm(-2). Further application of N fertilizer significantly enhanced nitrate leaching loss. Postponing N application increased nitrate accumulation in the 60-100 cm soil layer. The results suggested that N application rates and ratio of base to top dressing had different influences on maize N concentration and nitrate N between maize/soybean and maize/sweet potato intercropping. Maize N concentration in the late growing stage, N harvest index and N use efficiency under maize/soybean intercropping increased (with N application rate at 180-270 kg · hm(-2) and ratio of base to top dressing = 3:2:5) and decreased nitrate leaching loss with yield reaching 7757 kg · hm(-2) on average. However, for maize/sweet potato, N concentration and use efficiency and maize yield increased significantly with N application rate at 180 kg · hm(-2) and ratio of base to top dressing = 5:5 than that under other treatments with yield reaching 6572 kg · hm(-2). Under these circumstances, it would be possible to realize maize high yield, high efficiency and safety of N man- agement under maize/soybean and maize/sweet potato relay strip intercropping systems.

Synthesis and cytotoxic activities of novel hybrid 2-phenyl-3-alkylbenzofuran and imidazole/triazole compounds.

A series of novel hybrid compounds of 2-phenyl-3-alkylbenzofuran and imidazole or triazole were prepared and evaluated in vitro against a panel of human tumor cell lines. The results suggest that the 2-ethyl-imidazole ring, and substitution of the imidazolyl-3-position with a 2-bromobenzyl or naphthylacyl group, were vital for modulating inhibitory activity. In particular, hybrid compound 31 was found to be the most potent derivative with IC50 values of 0.08-0.55 µM against five strains human tumor cell lines and was found to be more selective against breast carcinoma (MCF-7) and colon carcinoma (SW480) (IC50 values 40.8-fold and 40.1-fold lower than cisplatin (DDP)).

Design, synthesis and cytotoxic activities of novel hybrid compounds between 2-phenylbenzofuran and imidazole.

A series of novel hybrid compounds between 2-phenylbenzofuran and imidazole have been prepared and evaluated in vitro against a panel of human tumor cell lines. The results suggest that substitution of the imidazolyl-3-position with a naphthylacyl or bromophenacyl group, were vital for modulating cytotoxic activity. In particular, hybrid compound 15 was found to be the most potent compound against 4 strains human tumor cell lines and more active than cisplatin (DDP), and exhibited cytotoxic activity selectively against liver carcinoma (SMMC-7721).