Evaluation of adverse reactions induced by anti-tuberculosis drugs among hospitalized patients in Wuhan, China: A retrospective study.

The study aims to estimate the incidence and risk factors of adverse drug reactions (ADRs) induced by anti-tuberculosis (TB) drugs. A single center retrospective analysis of patients taking anti-TB therapy from January 2016 to December 2018 in the hospital was conducted. Univariate and multivariate logistic regression analysis were used to identify these risk factors of ADRs induced by anti-TB drugs. Among 1430 patients receiving anti-TB therapy, 440 (30.77%) patients showed at least 1 ADR induced by anti-TB drugs. Hyperuricemia was the most common ADR, followed by hepatic function test abnormality, liver damage and gastrointestinal reactions. Significant differences (P < .05) were also seen in diabetes, age, treatment duration, type of TB (extrapulmonary) and some therapeutic regimens between ADR group and non-ADR group, respectively. Multivariate logistic regression analysis showed that treatment duration (OR = 1.029, 95%CI[1.018-1.040], P = .000), type of TB (extrapulmonary, OR = 1.487, 95%CI[1.134-1.952], P = .004) and some therapeutic regimens (HREZ, OR = 1.425, 95%CI[0.922-2.903], P = .001; HRZS, OR = 2.063, 95% CI[1.234-3.449], P = .006; HRZ, OR = 3.623, 95%CI[2.289-5.736], P = .000) were risk factors for ADRs induced by anti-TB drugs. Anti-TB drugs usually induced the occurrence of severe and frequent adverse effects, such as hyperuricemia. Treatment duration, HREZ, HRZS and HRZ regimens, and type of TB (extrapulmonary) should be considered as high-risk factors. Thus, it should be recommended to consider optimum management during anti-TB therapy, particularly hyperuricemia monitoring and hepatic function test.

Association of T Cell Subsets and Platelet/Lymphocyte Ratio with Long-Term Complications in Kidney Transplant Recipients.

BACKGROUND Infection and chronic rejection remain major issues for kidney transplant recipients (KTRs). The present study aimed to explore the association of CD4+/CD8+ T cell ratio (CD4+/CD8+) and platelet/lymphocyte ratio (PLR) with long-term infection and chronic renal insufficiency in KTRs. MATERIAL AND METHODS KTRs admitted to a single hospital from June 2014 to December 2021 were divided into infected (164) and non-infected (107) groups based on clinical data. The levels of CD4+/CD8+, PLR, neutrophil/lymphocyte ratio (NLR), and C-reactive Protein (CRP) in KTRs with long-term infection, and their correlation with chronic kidney insufficiency, were analyzed. Survival analysis was used to evaluate the risk factors for long-term infection and chronic kidney insufficiency. RESULTS Spearman correlation analysis showed that chronic kidney insufficiency was positively correlated with PLR, and negatively correlated with CRP and CD4+/CD8+ (P<0.05). PLR was positively correlated with CRP, procalcitonin, erythrocyte sedimentation rate, and NLR, but negatively with CD4+/CD8+. CD4+/CD8+ was correlated with CRP, NLR, and PLR (P<0.05). Survival analysis and survival curves showed that PLR and CD4+/CD8+ were risk factors for long-term infection and chronic kidney insufficiency in KTRs (P<0.05). CONCLUSIONS CD4+/CD8+ and PLR were associated with long-term complications, and were risk factors for long-term infection and chronic kidney insufficiency in KTRs.

Analyzing the Activity of Micafungin Combined with Tobramycin Against Pseudomonas Aeruginosa Biofilm.

BACKGROUND: This study assessed the potential effect of combining micafungin and tobramycin in vitro against biofilms of clinical Pseudomonas aeruginosa isolates. METHODS: Nine biofilm-positive clinical isolates of P. aeruginosa were used in this study. The minimum inhibitory concentrations (MICs) of micafungin and tobramycin for planktonic bacteria were determined using the agar dilution method. The planktonic bacterial growth curve was plotted for micafungin treatment. Biofilms of these nine strains were treated with different concentrations of micafungin and combined with tobramycin in microtiter plates. Biofilm biomass was detected by crystal violet staining and spectrophotometry. Phenotypic reduction in biofilm formation and the eradication of mature biofilm were significant based on average optical density (p < 0.05). The kinetics of micafungin combined with tobramycin to eradicate mature biofilms was investigated in vitro using the time-kill method. RESULTS: Micafungin exhibited no antibacterial effect on P. aeruginosa, and tobramycin minimum inhibitory concentrations (MICs) did not change in the presence of micafungin. Micafungin alone inhibited biofilm formation and eradicated established biofilms of all isolates in a dose-dependent manner, but the required minimum concentration varied. An increase in micafungin concentration resulted in an observed inhibition rate of 64.9% - 72.3% and achieved an eradication rate of 59.2% - 64.5%. Its combination with tobramycin exhibited synergistic effects, including inhibiting the biofilm formation of PA02, PA05, PA23, PA24, and PA52 isolates above 1/4 × MIC or 1/2 × MIC and eradicating mature biofilms of PA02, PA04, PA23, PA24, and PA52 above 32 × MIC, 2 × MIC, 16 × MIC, 32 × MIC, and 1 × MIC, respectively. Micafungin addition could eradicate biofilm-embedded bacterial cells more rapidly; at 32 mg/L, the biofilm eradication time lowered from 24 hours to 12 hours for the inoculum groups with 106 CFU/mL, and from 12 hours to 8 hours for 105 CFU/mL. Whereas at 128 mg/L, the time was lowered from 12 hours to 8 hours for the inoculum groups with 106 CFU/mL, and from 8 hours to 4 hours for 105 CFU/mL. CONCLUSIONS: Micafungin showed good anti-biofilm activity at low concentrations. The combination of micafungin with tobramycin displayed a synergistic effect in controlling P. aeruginosa biofilm.

Incidence and non-genetic risk factors of irinotecan-induced severe neutropenia in Chinese adult inpatients.

To analyze the incidence and nongenetic risk factors of irinotecan-induced severe neutropenia in the hospital, and provide additional reference and help for clinical treatment. A retrospective analysis of patients who received irinotecan based chemotherapy from May 2014 to May 2019 in Renmin Hospital of Wuhan University was conducted. Univariate analysis and binary logistic regression analysis with the forward stepwise method were used to assess the risk factors associated with severe neutropenia induced by irinotecan. Of the 1312 patients treated with irinotecan-based regmines, only 612 patients met the inclusion criteria, and 32 patients developed irinotecan-induced severe neutropenia. In the univariate analysis, variables associated with severe neutropenia were tumor type, tumor stage, and therapeutic regimen. In the multivariate analysis, irinotecan plus lobaplatin, lung cancer or ovarian cancer, tumor stage T2, T3, and T4, were identified as risk factors that contributed independently to irinotecan-induced severe neutropenia (P < .05), respectively. The results showed that the incidence of irinotecan-induced severe neutropenia was 5.23% in the hospital. The risk factors included tumor type (lung cancer or ovarian cancer), tumor stage (T2, T3, and T4) and therapeutic regimen (irinotecan plus lobaplatin). Therefore, for patients with these risk factors, it might be advisable to actively consider optimum management to reduce the occurrence of irinotecan-induced severe neutropenia.

High-Frequency 0.36BiScO3-0.64PbTiO3 Ultrasonic Transducer for High-Temperature Imaging Application.

( 1- x )BiScO3- x PbTiO3 (BS-PT) ceramics have excellent piezoelectricity and high Curie temperature at its morphotropic phase boundary (MPB) ( x = 0.64 ), so it is a promising piezoelectric material for fabricating high-temperature ultrasonic transducer (HTUT). Electric properties of 0.36BS-0.64PT ceramics were characterized at different temperatures, and an HTUT with the center frequency of about 15 MHz was designed by PiezoCAD based on the measuring results. The prepared HTUT was tested in a silicone oil bath at different temperatures systematically. The test results show that the HTUT can maintain a stable electrical resonance until 290 °C and get a clear echo response until 250 °C with slight changes of the center frequency. Then, a stepped metal block submerged in silicone oil was imaged by the HTUT until 250 °C. Velocity of silicone oil and axial resolution of the HTUT at different temperatures was calculated. The results verify the capability of 0.36BS-0.64PT-based HTUT for high-temperature ultrasonic imaging applications.

Optimized Backing Layers Design for High Frequency Broad Bandwidth Ultrasonic Transducer.

Ultrasonic transducers with broad bandwidth are considered to have high axial resolution and good ultrasound scanning flexibility for the clinical applications. The limitations of spatial resolution due to bandwidth are of great concern in ultrasound medical imaging. The method of acoustic impedance matching between the piezoelectric element and medium is commonly used to obtain broad bandwidth and high resolution. In this study, an optimized backing layer design was proposed to broaden the bandwidth by adding a tunable acoustic impedance matching layer of backing (AIMLB) between the backing layer and the piezoelectric ceramic element. The Mason equivalent circuit method was used to analyze the effect of the backing material composition and its structure on the bandwidth of the transducer. The optimized transducer was simulated using the finite-element method with the PZFlex software. Based on the PZFlex simulations, a 20-MHz ultrasonic transducer using the AIMLB with a bandwidth of approximately 92.29% was fabricated. The experimental results were in good agreement with the simulations. The ultrasonic imaging indicated that the designed ultrasonic transducer with an additional AIMLB had high performance with good imaging capability.

Root vacuolar sequestration and suberization are prominent responses of Pistacia spp. rootstocks during salinity stress.

Understanding the mechanisms of stress tolerance in diverse species is needed to enhance crop performance under conditions such as high salinity. Plant roots, in particular in grafted agricultural crops, can function as a boundary against external stresses in order to maintain plant fitness. However, limited information exists for salinity stress responses of woody species and their rootstocks. Pistachio (Pistacia spp.) is a tree nut crop with relatively high salinity tolerance as well as high genetic heterogeneity. In this study, we used a microscopy-based approach to investigate the cellular and structural responses to salinity stress in the roots of two pistachio rootstocks, Pistacia integerrima (PGI) and a hybrid, P. atlantica x P. integerrima (UCB1). We analyzed root sections via fluorescence microscopy across a developmental gradient, defined by xylem development, for sodium localization and for cellular barrier differentiation via suberin deposition. Our cumulative data suggest that the salinity response in pistachio rootstock species is associated with both vacuolar sodium ion (Na+) sequestration in the root cortex and increased suberin deposition at apoplastic barriers. Furthermore, both vacuolar sequestration and suberin deposition correlate with the root developmental gradient. We observed a higher rate of Na+ vacuolar sequestration and reduced salt-induced leaf damage in UCB1 when compared to P. integerrima. In addition, UCB1 displayed higher basal levels of suberization, in both the exodermis and endodermis, compared to P. integerrima. This difference was enhanced after salinity stress. These cellular characteristics are phenotypes that can be taken into account during screening for sodium-mediated salinity tolerance in woody plant species.

CD36 deficiency affects depressive-like behaviors possibly by modifying gut microbiota and the inflammasome pathway in mice.

Both inflammatory processes and gut microbiota have been implicated in the pathophysiology of depressive disorders. The class B scavenger receptor CD36 is involved in the cytotoxicity associated with inflammation. However, its role in depression has not yet been examined. In this study, we investigated whether CD36 affects depression by modulating the microbiota-gut-inflammasome-brain axis. We used CD36-/- (knockout) mice subjected to chronic social defeat stress, and measured the expression of CD36 in these depressed mice and in patients with depression. The hippocampus of CD36-/- mice was used to investigate changes in the NLRP3 inflammasome signaling pathway. The 16S rRNA gene sequence-based approach was used to compare the cecal microbial communities in CD36-/- and WT mice. The CD36 deficiency in CD36-/- mice alleviated chronic stress-induced depression-like behaviors. CD36 was upregulated in depressed mice as well as in depressed patients. Furthermore, the NLRP3 inflammasome signaling pathway was downregulated in the hippocampus of CD36-/- mice. The Simpson Diversity Index revealed increased cecal bacterial alpha-diversity in the CD36-/- mice. Among genera, Bacteroides, Rikenella, and Alloprevotella were significantly more abundant in the CD36-/- mice, whereas Allobaculum was less abundant, consistent with the attenuated inflammation in the hippocampus of CD36-/- mice. Our findings suggest that CD36 deficiency changes the gut microbiota composition, which in turn may impact depressive-like behaviors by affecting the inflammasome pathway.

The potential risk factors of nephrotoxicity during vancomycin therapy in Chinese adult patients.

OBJECTIVE: To evaluate potential risk factors that may make patients susceptible to nephrotoxicity in those concomitantly receiving vancomycin in the hospital. METHODS: This was a single-centre retrospective analysis of patients treated with vancomycin for gram-positive or mixed infections in the Renmin Hospital of Wuhan University from January 2017 to May 2018. All of them were treated for ≥48 hours and had no kidney disease. Nephrotoxicity refers to acute kidney diseases and disorders after the use of vancomycin, and includes acute kidney injury. Univariate analysis and binary logistic regression analysis with the forward stepwise method were used to assess the risk factors associated with nephrotoxicity. RESULTS: Of the 790 patients treated with vancomycin, only 257 patients met the inclusion criteria, and 40 (15.6%) subjects developed nephrotoxicity. Significant differences (p<0.05) were seen in the number of combined antimicrobials (p=0.012), dose adjustment (p<0.001), more than three antimicrobials (p=0.015), monitoring trough concentrations (p=0.001), furosemide (p<0.001), torasemide (p<0.001), cefoperazone sodium tazobactam sodium (p=0.039), voriconazole (p=0.012) and ganciclovir (p=0.008). Regression analysis further indicated that furosemide (OR 7.983, p<0.001) and torasemide (OR 3.496, p<0.001) were risk factors for vancomycin nephrotoxicity. Diabetes mellitus (OR 3.062, p=0.035), voriconazole (OR 3.515, p=0.020) and fluconazole (OR 3.326, p=0.018) might be also risk factors. CONCLUSION: Fluconazole and voriconazole might be potential risk factors for vancomycin nephrotoxicity, besides furosemide and torasemide. It is not recommended to use imipenem cilastatin sodium and vancomycin at the same time. If necessary, meropenem may be safer. Appropriate combination drugs, cautious initial dose or timely dose adjustment might reduce the occurrence of nephrotoxicity when using vancomycin.

Investigation of Salt Tolerance Mechanisms Across a Root Developmental Gradient in Almond Rootstocks.

The intensive use of groundwater in agriculture under the current climate conditions leads to acceleration of soil salinization. Given that almond is a salt-sensitive crop, selection of salt-tolerant rootstocks can help maintain productivity under salinity stress. Selection for tolerant rootstocks at an early growth stage can reduce the investment of time and resources. However, salinity-sensitive markers and salinity tolerance mechanisms of almond species to assist this selection process are largely unknown. We established a microscopy-based approach to investigate mechanisms of stress tolerance in and identified cellular, root anatomical, and molecular traits associated with rootstocks exhibiting salt tolerance. We characterized three almond rootstocks: Empyrean-1 (E1), Controller-5 (C5), and Krymsk-86 (K86). Based on cellular and molecular evidence, our results show that E1 has a higher capacity for salt exclusion by a combination of upregulating ion transporter expression and enhanced deposition of suberin and lignin in the root apoplastic barriers, exodermis, and endodermis, in response to salt stress. Expression analyses revealed differential regulation of cation transporters, stress signaling, and biopolymer synthesis genes in the different rootstocks. This foundational study reveals the mechanisms of salinity tolerance in almond rootstocks from cellular and structural perspectives across a root developmental gradient and provides insights for future screens targeting stress response.

Preparation and characterization of dialdehyde ß-cyclodextrin with broad-spectrum antibacterial activity.

Consumers demand more alternatives of riskless antibacterial agents to prevent microbial contamination in food industry. Oxidized carbohydrate may be a potential option as new antibacterial agent. However, the relatively weak antibacterial property of oxidized carbohydrate is not satisfactory. In this paper, dialdehyde ß-cyclodextrins with different oxidation degree were prepared by periodate oxidation and their antibacterial properties were systematically studied. The results showed that multi-aldehyde groups were successfully introduced into ß-cyclodextrin molecules by periodate oxidation. The aqueous solubility and stability of dialdehyde ß-cyclodextrins were improved as expected. It is interesting that dialdehyde ß-cyclodextrins possessed outstanding antibacterial activity against both Gram-positive and Gram-negative bacteria. The minimal inhibitory concentrations against E. coli, S. aureus and B. subtilis reached 0.63, 1.25 and 0.63 mg/mL, respectively. Moreover, dialdehyde ß-cyclodextrins effectively inhibited bacterial growth on the surface of apples. The results demonstrated that oxidized oligosaccharide with multi-aldehyde groups and good dispersibility in aqueous solution possessed satisfactory antibacterial activity, which can be used as new antibacterial agent in food industry.

Placenta growth factor mediated gene regulation in sickle cell disease.

Sickle cell anemia (SCA) is an autosomal recessive disorder caused by mutation in the ß-globin gene. Pulmonary hypertension (PH), a complication of SCA, results in severe morbidity and mortality. PH is a multifactorial disease: systemic vasculopathy, pulmonary vasoconstriction, and endothelial dysfunction and remodeling. Placenta growth factor (PlGF), an angiogenic growth factor, elaborated from erythroid cells, has been shown to contribute to inflammation, pulmonary vasoconstriction and airway hyper-responsiveness (AH) in mouse models of sickle cell disease. In this review, we summarize the cell-signaling mechanism(s) by which PlGF regulates the expression of genes involved in inflammation, PH and AH in cell culture and corroborate these findings in mouse models of SCA and in individuals with SCA. The role of microRNAs (miRNAs) in the post-transcriptional regulation of these genes is presented and how these miRNAs located in their host genes are transcriptionally regulated. An understanding of the transcriptional regulation of these miRNAs provides a new therapeutic approach to ameliorate the clinical manifestations of SCA.

iTRAQ-Based Proteomics Suggests Ephb6 as a Potential Regulator of the ERK Pathway in the Prefrontal Cortex of Chronic Social Defeat Stress Model Mice.

PURPOSE: Major depressive disorder (MDD) is a worldwide concern and devastating psychiatric disease. The World Health Organization claims that MDD leads to at least 11.9% of the global burden of disease. However, the underlying pathophysiology mechanisms of MDD remain largely unknown. EXPERIMENTAL DESIGN: Herein, we proteomic-based strategy is used to compare the prefrontal cortex (PFC) in chronic social defeat stress (CSDS) model mice with a control group. Based on pooled samples, differential proteins are identified in the PFC proteome using iTRAQ coupled with LC-MS/MS. RESULTS: Ingenuity Pathway Analysis (IPA) is then followed to predict relevant pathways, with the ephrin receptor signaling pathway selected for further research. Additionally, as the selected key proteins of the ephrin receptor signaling pathway, ephrin type-B receptor 6 (EphB6) and the ERK pathway are validated by Western blotting. CONCLUSION AND CLINICAL RELEVANT: Altogether, increased understanding of the ephrin receptor signaling pathway in MDD is provided, which implicates further investigation of PFC dysfunction induced by CSDS treatment.

Potential antidepressant and resilience mechanism revealed by metabolomic study on peripheral blood mononuclear cells of stress resilient rats.

Resilience is an active coping response to stress, which plays a very important role in major depressive disorder study. The molecular mechanisms underlying such resilience are poorly understood. Peripheral blood mononuclear cells (PBMCs) were promising objects in unveiling the underlying pathogenesis of resilience. Hereby we carried out successive study on PBMCs metabolomics in resilient rats of chronic unpredictable mild stress (CUMS) model. A gas chromatography-mass spectrometry (GC-MS) metabolomic approach coupled with principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) was used to detect differential metabolites in PBMCs of resilient rats. Ingenuity Pathways Analysis (IPA) was applied for pathway analysis. A set of differential metabolites including Malic acid, Ornithine, l-Lysine, Stigmasterol, Oleic acid, γ-Tocopherol, Adenosine and N-acetyl-d-glucosamine were significantly altered in resilient rats, meanwhile promoting antidepressant research. As revealed by IPA that aberrant energy metabolism, HIFα signaling, neurotransmitter, O-GlcNAcylation and cAMP signaling cascade in peripheral might be evolved in the pathogenesis of coping mechanism. The GC-MS based metabolomics may contribute to better understanding of resilience, as well as shedding light on antidepressant discovery.

Targeted Metabolomic Pathway Analysis and Validation Revealed Glutamatergic Disorder in the Prefrontal Cortex among the Chronic Social Defeat Stress Mice Model of Depression.

Major depressive disorder (MDD) is a severe psychiatric disease that has critically affected life quality for millions of people. Chronic stress is gradually recognized as a primary pathogenesis risk factor of MDD. Despite the remarkable progress in mechanism research, the pathogenesis mechanism of MDD is still not well understood. Therefore, we conducted a liquid chromatography-tandem mass spectrometry (LC-MS/MS) detection of 25 major metabolites of tryptophanic, GABAergic, and catecholaminergic pathways in the prefontal cortex (PFC) of mice in chronic social defeat stress (CSDS). The depressed mice exhibit significant reduction of glutamate in the GABAergic pathway and an increase of L-DOPA and vanillylmandelic acid in catecholaminergic pathways. The data of real-time-quantitative polymerase chain reaction (RT-qPCR) and Western blotting analysis revealed an altered level of glutamatergic circuitry. The metabolomic and molecular data reveal that the glutamatergic disorder in mice shed lights to reveal a mechanism on depression-like and stress resilient phenotype.

GC-MS-based metabolomic study on the antidepressant-like effects of diterpene ginkgolides in mouse hippocampus.

Ginkgo biloba extract (GBE), including EGb-761, have been suggested to have antidepressant activity based on previous behavioral and biochemical analyses. However, because GBE contain many constituents, the mechanisms underlying this suggested antidepressant activity are unclear. Here, we investigated the antidepressant-like effects of diterpene ginkgolides (DG), an important class of constituents in GBE, and studied their effects in the mouse hippocampus using a GC-MS-based metabolomics approach. Mice were randomly divided into five groups and injected daily until testing with 0.9% NaCl solution, one of three doses of DG (4.06, 12.18, and 36.54mg/kg), or venlafaxine. Sucrose preference (SPT) and tail suspension (TST) tests were then performed to evaluate depressive-like behaviors in mice. DG (12.18 and 36.54mg/kg) and venlafaxine (VLX) administration significantly increased hedonic behavior in mice in the SPT. DG (12.18mg/kg) treatment also shortened immobility time in the TST, suggestive of antidepressant-like effects. Significant differences in the metabolic profile in the DG (12.18mg/kg) compared with the control or VLX group indicative of an antidepressant-like effect were observed using multivariate analysis. Eighteen differential hippocampal metabolites were identified that discriminated the DG (12.18mg/kg) and control groups. These biochemical changes involved neurotransmitter metabolism, oxidative stress, glutathione metabolism, lipid metabolism, energy metabolism, and kynurenic acid, providing clues to the therapeutic mechanisms of DG. Thus, this study showed that DG has antidepressant-like activities in mice and shed light on the biological mechanisms underlying the effects of diterpene ginkgolides on behavior, providing an important drug candidate for the treatment of depression.

2D-gel based proteomics unravels neurogenesis and energetic metabolism dysfunction of the olfactory bulb in CUMS rat model.

Major depression is a devastating psychiatric disease worldwide currently. A reduced olfactory sensitivity in MDD patients was well evidenced. We previously interrogated the mechanism of decreasing hippocampus neurogenesis in CUMS rat model of depression. The Olfactory Bulb (OB) is crucial part of the olfactory system which functions in post-developmental neurogenesis. However, the mechanism of the dysfunction of OB induced by CUMS is still largely unknown. Herein, by using the chronic unpredictable mild stress (CUMS) rat model of depression, differential protein expression between the OB proteomes of CUMS and control group was interrogated through two-dimensional electrophoresis coupling with matrix-assisted laser desorption ionization-time of flight tandem mass spectrometry. Twenty nine differential protein expression was analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway over-representation and Ingenuity pathways analysis (IPA). Seven identified differential proteins were selected for Western blotting validation. This study provides insight that neurogenesis and Energy metabolism disorder is involved in OB dysfunction induced by CUMS.

Behavioral characterization of CD36 knockout mice with SHIRPA primary screen.

CD36 is a member of the class B scavenger receptor family of cell surface proteins, which plays a major role in fatty acid, glucose and lipid metabolism. Besides, CD36 functions as a microglial surface receptor for amyloid beta peptide. Regarding this, we suggest CD36 might also contribute to neuropsychiatric disease. The aim of this study was to achieve a behavioral phenotype of CD36 knockout (CD36(-/-)) mice. We characterized the behavior of CD36(-/-) mice and C57BL/6J mice by subjecting them to a series of tests, which include SHIRPA primary behavioral screen test, 1% sucrose preference test, elevated plus-maze test, open-field test and forced swimming test. The results showed that CD36(-/-) mice traversed more squares, emitted more defecation, exhibited higher tail elevation and had more aggressive behaviors than C57BL/6J mice. The CD36(-/-) mice spent more time and traveled longer distance in periphery zone in the open-field test. Meanwhile, the numbers that CD36(-/-) mice entered in the open arms of elevated plus-maze were reduced. These findings suggest that CD36(-/-) mice present an anxious phenotype and might be involved in neuropsychiatric disorders.

Nmf9 Encodes a Highly Conserved Protein Important to Neurological Function in Mice and Flies.

Many protein-coding genes identified by genome sequencing remain without functional annotation or biological context. Here we define a novel protein-coding gene, Nmf9, based on a forward genetic screen for neurological function. ENU-induced and genome-edited null mutations in mice produce deficits in vestibular function, fear learning and circadian behavior, which correlated with Nmf9 expression in inner ear, amygdala, and suprachiasmatic nuclei. Homologous genes from unicellular organisms and invertebrate animals predict interactions with small GTPases, but the corresponding domains are absent in mammalian Nmf9. Intriguingly, homozygotes for null mutations in the Drosophila homolog, CG45058, show profound locomotor defects and premature death, while heterozygotes show striking effects on sleep and activity phenotypes. These results link a novel gene orthology group to discrete neurological functions, and show conserved requirement across wide phylogenetic distance and domain level structural changes.

Molecular characterization of enterohemorrhagic E. coli O157 isolated from animal fecal and food samples in Eastern China.

OBJECTIVE: To elucidate the extent of food contamination by enterohemorrhagic Escherichia coli (EHEC) O157 in Eastern China. METHODS: A total of 1100 food and animal fecal samples were screened for EHEC O157. Then, molecular characterization of each isolate was determined. RESULTS: EHEC O157 was isolated as follows: pig feces, 4% (20/500); cattle feces, 3.3% (2/60); chicken feces, 1.43% (2/140); pork, 2.14% (3/140), milk, 1.67% (1/60); and chicken meat, 1.67% (1/60). The stx1, stx2, eae, and hlyA genes were present in 26.7% (8/30), 40% (12/30), 63.3% (19/30), and 50% (15/30) of the O157 isolates, respectively. Molecular typing showed that strains from fecal and food samples were clustered into the same molecular typing group. Furthermore, the isolates from pork and pig feces possessed the same characterization as the clinical strains ATCC35150 and ATCC43889. Biofilm formation assays showed that 53.3% of the EHEC O157 isolates could produce biofilm. However, composite analyses showed that biofilm formation of EHEC O157 was independent of genetic background. CONCLUSIONS: Animal feces, especially from pigs, serve as reservoirs for food contamination by EHEC O157. Thus, it is important to control contamination by EHEC O157 on farms and in abattoirs to reduce the incidence of foodborne infections in humans.