Local feature acquisition and global context understanding network for very high-resolution land cover classification.

Very high-resolution remote sensing images hold promising applications in ground observation tasks, paving the way for highly competitive solutions using image processing techniques for land cover classification. To address the challenges faced by convolutional neural network (CNNs) in exploring contextual information in remote sensing image land cover classification and the limitations of vision transformer (ViT) series in effectively capturing local details and spatial information, we propose a local feature acquisition and global context understanding network (LFAGCU). Specifically, we design a multidimensional and multichannel convolutional module to construct a local feature extractor aimed at capturing local information and spatial relationships within images. Simultaneously, we introduce a global feature learning module that utilizes multiple sets of multi-head attention mechanisms for modeling global semantic information, abstracting the overall feature representation of remote sensing images. Validation, comparative analyses, and ablation experiments conducted on three different scales of publicly available datasets demonstrate the effectiveness and generalization capability of the LFAGCU method. Results show its effectiveness in locating category attribute information related to remote sensing areas and its exceptional generalization capability. Code is available at https://github.com/lzp-lkd/LFAGCU .

Genomic and spatial analysis reveal the transmission dynamics of tuberculosis in areas with high incidence of Zhejiang, China: A prospective cohort study.

In the mountainous, rural regions of eastern China, tuberculosis (TB) remains a formidable challenge; however, the long-term molecular epidemiological surveillance in these regions is limited. This study aimed to investigate molecular and spatial epidemiology of TB in two mountainous, rural counties of Zhejiang Province, China, from 2015 to 2021, to elucidate the recent transmission and drug-resistance profiles. The predominant Lineage 2 (L2) Beijing family accounted for 80.1% of total 532 sequenced Mycobacterium tuberculosis (Mtb) strains, showing consistent prevalence over seven years. Gene mutations associated with drug resistance were identified in 19.4% (103/532) of strains, including 47 rifampicin or isoniazid-resistant strains, eight multi-drug-resistant (MDR) strains, and five pre-extensively drug-resistant (pre-XDR) strains. Genomic clustering revealed 53 distinct clusters with an overall transmission clustering rate of 23.9% (127/532). Patients with a history of retreatment and those infected with L2 strains had a higher risk of recent transmission. Spatial and epidemiological analysis unveiled significant transmission hotspots, especially in densely populated urban areas, involving various public places such as medical institutions, farmlands, markets, and cardrooms. The study emphasizes the pivotal role of Beijing strains and urban-based TB transmission in the western mountainous regions in Zhejiang, highlighting the urgent requirement for specific interventions to mitigate the impact of TB in these unique communities.

Evaluation of nucleotide MALDI-TOF-MS for the identification of Mycobacterium species.

Background: The accurate identification of the Mycobacterium tuberculosis complex (MTBC) and different nontuberculous mycobacteria (NTM) species is crucial for the timely diagnosis of NTM infections and for reducing poor prognoses. Nucleotide matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) has been extensively used for microbial identification with high accuracy and throughput. However, its efficacy for Mycobacterium species identification has been less studied. The objective of this study was to evaluate the performance of nucleotide MALDI-TOF-MS for Mycobacterium species identification. Methods: A total of 933 clinical Mycobacterium isolates were preliminarily identified as NTM by the MPB64 test. These isolates were identified by nucleotide MALDI-TOF-MS and Sanger sequencing. The performance of nucleotide MALDI-TOF MS for identifying various Mycobacterium species was analyzed based on Sanger sequencing as the gold standard. Results: The total correct detection rate of all 933 clinical Mycobacterium isolates using nucleotide MALDI-TOF-MS was 91.64% (855/933), and mixed infections were detected in 18.65% (174/933) of the samples. The correct detection rates for Mycobacterium intracellulare, Mycobacterium abscessus, Mycobacterium kansasii, Mycobacterium avium, MTBC, Mycobacterium gordonae, and Mycobacterium massiliense were 99.32% (585/589), 100% (86/86), 98.46% (64/65), 94.59% (35/37), 100.00% (34/34), 95.65% (22/23), and 100% (19/19), respectively. For the identification of the MTBC, M. intracellulare, M. abscessus, M. kansasii, M. avium, M. gordonae, and M. massiliense, nucleotide MALDI-TOF-MS and Sanger sequencing results were in good agreement (k > 0.7). Conclusion: In conclusion, nucleotide MALDI-TOF-MS is a promising approach for identifying MTBC and the most common clinical NTM species.

Associations of genetic variants within TYK2 with pulmonary tuberculosis among Chinese population.

BACKGROUND: Pulmonary tuberculosis (PTB) is a common infectious disease caused by mycobacterium tuberculosis (MTB) and the present study aims to explore the associations of genetic variants within tyrosine kinases 2 (TYK2) with PTB incidence. METHODS: A population-based case control study including 168 smear-positive PTB cases and 251 controls was conducted. Five single nucleotide polymorphisms (SNPs) including rs280520, rs91755, rs2304256, rs12720270, rs280519 located within TYK2 gene were selected and MassARRAY® MALDI-TOF system was employed for genotyping. SPSS 19.0 was adopted for statistical analysis, non-conditional logistic regression was conducted. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were computed to estimate their contributions to PTB incidence. RESULTS: In the overall study population, rs91755 TT and rs280519 AA genotypes were found to be associated with reduced PTB risk (OR = 0.34, 95% CI: 0.16-0.72; OR = 0.38, 95% CI: 0.18-0.79, respectively). After stratification for sex, we found that among the male population, rs91755TG/TT, rs12720270AG/GG and rs280519AG/AA genotypes were associated with reduced PTB risk (OR = 0.41, 95% CI: 0.21-0.80; OR = 0.44, 95% CI: 0.21-0.94; OR = 0.42, 95% CI: 0.21-0.82, respectively). After stratification for age, we found that among those aged <60 years, rs91755TT and rs280519AA genotype were associated with reduced PTB risk (OR = 0.29, 95% CI: 0.09-0.90; OR = 0.34, 95% CI: 0.11-1.08, respectively); while rs2304256AC/AA genotype was associated with increased PTB risk (OR = 2.68, 95% CI: 1.05-6.85). Haplotype analysis revealed that AGAAG and ATCGA (Combined with rs280520, rs91755, rs2304256, rs12720270 and rs280519) were associated with increased (OR = 1.54, 95% CI: 1.01-2.37) and decreased PTB risk (OR = 0.70, 95% CI: 0.52-0.94), respectively. CONCLUSIONS: The genetic variants located within TYK2 including rs91755, rs12720270 and rs280519 were found to be associated with modified PTB risk and the SNPs had potential to be the biomarkers to predict PTB incidence risk.

Bedaquiline Resistance and Molecular Characterization of Rifampicin-Resistant Mycobacterium Tuberculosis Isolates in Zhejiang, China.

Purpose: This study aimed to determine the prevalence and molecular characterization of bedaquiline (BDQ) resistance among rifampicin-resistant tuberculosis (RR-TB) isolates collected from Zhejiang, China. Patients and Methods: A total of 245 RR-TB isolates were collected from 19 municipal TB hospitals in Zhejiang province, China between January and December 2021. Microplate assays were used to determine the minimum inhibitory concentrations (MIC) of BDQ. Whole-genome sequencing (WGS) was performed on isolates with MIC values for BDQ ≥ 0.25 µg/mL. Results: Five (2.04%) BDQ-resistant strains were isolated from 245 tuberculosis patients. The resistance rate of BDQ was not correlated to the sex, age, treatment history, or occupation of patients. Four BDQ-resistant isolates and three BDQ-sensitive isolates were found to carry Rv0678 mutations, and one BDQ-resistant strain carried both Rv0678 and pepQ mutations. No mutations within the atpE and Rv1979c genes were observed. Conclusion: BDQ demonstrated strong in vitro antibacterial activity against RR-TB isolates, and the Rv0678 gene was identified as the primary mechanism contributing to BDQ resistance among RR-TB isolates from Zhejiang, China. Furthermore, in addition to the four currently known resistance-associated genes (atpE, Rv0678, Rv1979c, and pepQ), other mechanisms of resistance to BDQ may exist that need further study.

Corrigendum: Analysis of a super-transmission of SARS-CoV-2 omicron variant BA.5.2 in the outdoor night market.

[This corrects the article DOI: 10.3389/fpubh.2023.1153303.].

The Efficacy and Safety of Bedaquiline in the Treatment of Pulmonary Tuberculosis Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Bedaquiline (BDQ) has been designated as a Group A drug by the World Health Organization (WHO) for the management of multi-drug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). This systematic review and meta-analysis aim to evaluate the efficacy and safety of BDQ-containing regimens for the treatment of patients with pulmonary TB. METHODS: PubMed (MEDLINE), Elton B. Stephens Company (EBSCO) database, the Cochrane Register of Controlled Trials, and the China National Knowledge Infrastructure (CNKI) database were initially searched on 15 June 2022 and again on 20 March 2023. We included randomized controlled trials (RCTs) and non-randomized studies (NRSs) that administered BDQ to TB patients. The outcomes of interest were as follows: (1) efficacy, including the rate of sputum culture conversion at 8 weeks, 24 weeks, and during follow-up, as well as the rates of completion cure, death, treatment failure, and loss at follow-up and at the end of the treatment; and (2) safety, which encompassed the incidences of cardiotoxicity, hepatotoxicity, and grade 3-5 adverse events during the treatment period. RESULTS: A total of 29 articles were included in this meta-analysis, representing 23,358 individuals. Patients who were treated with BDQ were compared with patients who were not exposed to BDQ. The use of BDQ-containing regimens demonstrated improved rates of sputum conversion in RCTs at 24 weeks (RR = 1.27, 95% CI: 1.10 to 1.46) and during follow-up (RR = 1.33, 95% CI: 1.06 to 1.66). Additionally, BDQ-containing regimens showed increased cure rates (RR = 1.60, 95% CI: 1.13 to 2.26) and decreased failure rates (RR = 0.56, 95% CI: 0.56 to 0.88). In NRSs, BDQ-containing regimens improved the sputum culture conversion rate during follow-up (RR = 1.53, 95% CI: 1.07 to 2.20), increased the rate of cure (RR = 1.86, 95% CI: 1.23 to 2.83), reduced deaths from all causes (RR = 0.68, 95% CI: 0.48 to 0.97), and reduced failure rates (RR = 0.57, 95% CI: 0.46 to 0.71). However, the use of BDQ-containing regimens was associated with increased incidences of cardiotoxicity (RR = 4.54, 95% CI: 1.74 to 11.87) and grade 3-5 adverse events (RR = 1.42, 95% CI: 1.17 to 1.73) in RCTs. NRSs also showed an association between BDQ-containing regimens and cardiotoxicity (RR = 6.00, 95% CI: 1.32 to 27.19). No significant differences were observed between intervention groups and control groups with respect to other outcomes. CONCLUSIONS: Data from both RCTs and NRSs support the efficacy of BDQ for the treatment of pulmonary tuberculosis. However, the use of BDQ is associated with a higher incidence of cardiotoxicity and serious adverse events. Comparative data on efficacy and safety are limited, and further confirmation is required, due to potential bias and discrepancies in the available studies.

Whole-Genome Sequencing to Predict Mycobacterium tuberculosis Drug Resistance: A Retrospective Observational Study in Eastern China.

Pulmonary tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (MTB). Whole-genome sequencing (WGS) holds great promise as an advanced technology for accurately predicting anti-TB drug resistance. The development of a reliable method for detecting drug resistance is crucial in order to standardize anti-TB treatments, enhance patient prognosis, and effectively reduce the risk of transmission. In this study, our primary objective was to explore and determine the potential of WGS for assessing drug resistance based on genetic variants recommended by the World Health Organization (WHO). A total of 1105 MTB strains were selected from samples collected from 2014-2018 in Zhejiang Province, China. Phenotypic drug sensitivity tests (DST) of the anti-TB drugs were conducted for isoniazid (INH), rifampicin (RFP), streptomycin, ethambutol, fluoroquinolones (levofloxacin and moxifloxacin), amikacin, kanamycin, and capreomycin, and the drug-resistance rates were calculated. The clean WGS data of the 1105 strains were acquired and analyzed. The predictive performance of WGS was evaluated by the comparison between genotypic and phenotypic DST results. For all anti-TB drugs, WGS achieved good specificity values (>90%). The sensitivity values for INH and RFP were 91.78% and 82.26%, respectively; however, they were ≤60% for other drugs. The positive predictive values for anti-TB drugs were >80%, except for ethambutol and moxifloxacin, and the negative predictive values were >90% for all drugs. In light of the findings from our study, we draw the conclusion that WGS is a valuable tool for identifying genome-wide variants. Leveraging the genetic variants recommended by the WHO, WGS proves to be effective in detecting resistance to RFP and INH, enabling the identification of multi-drug resistant TB patients. However, it is evident that the genetic variants recommended for predicting resistance to other anti-TB drugs require further optimization and improvement.

Analysis of a super-transmission of SARS-CoV-2 omicron variant BA.5.2 in the outdoor night market.

Introduction: The COVID-19 pandemic continues to ravage the world, and mutations of the SARS-CoV-2 continues. The new strain has become more transmissible. The role of aerosol transmission in the pandemic deserves great attention. Methods: In this observational study, we collected data from market customers and stallholders who had been exposed to the virus in the Qingkou night market on July 31 and were subsequently infected. We analyzed the possible infection zones of secondary cases and aerosol suspension time in ambient air. We described and analyzed the characteristics of the secondary cases and the transmission routes for customers. Results: The point source outbreak of COVID-19 in Qingkou night market contained a cluster of 131 secondary cases. In a less-enclosed place like the Qingkou night market, aerosols with BA.5.2 strain released by patients could suspend in ambient air up to 1 h 39 min and still be contagious. Conclusion: Aerosols with viruses can spread over a relatively long distance and stay in ambient air for a long time in a less enclosed space, but shorter than that under experimental conditions. Therefore, the aerosol suspension time must be considered when identifying and tracing close contact in outbreak investigations.

CNTNAP2 intracellular domain (CICD) generated by γ-secretase cleavage improves autism-related behaviors.

As the most prevalent neurodevelopmental disorders in children, autism spectrum disorders (ASD) are characterized by deficits in language development, social interaction, and repetitive behaviors or inflexible interests. Contactin associated protein like 2 (CNTNAP2), encoding a single transmembrane protein (CNTNAP2) with 1331 amino acid residues, is a widely validated ASD-susceptible gene. Cntnap2-deficient mice also show core autism-relevant behaviors, including the social deficits and repetitive behavior. However, the cellular mechanisms underlying dysfunction CNTNAP2 and ASD remain elusive. In this study, we found a motif within the transmembrane domain of CNTNAP2 was highly homologous to the γ-secretase cleavage site of amyloid-ß precursor protein (APP), suggesting that CNTNAP2 may undergo proteolytic cleavage. Further biochemical analysis indicated that CNTNAP2 is cleaved by γ-secretase to produce the CNTNAP2 intracellular domain (CICD). Virally delivery of CICD to the medial prefrontal cortex (mPFC) in Cntnap2-deficient (Cntnap2-/-) mice normalized the deficit in the ASD-related behaviors, including social deficit and repetitive behaviors. Furthermore, CICD promoted the nuclear translocation of calcium/calmodulin-dependent serine protein kinase (CASK) to regulate the transcription of genes, such as Prader Willi syndrome gene Necdin. Whereas Necdin deficiency led to reduced social interaction in mice, virally expression of Necdin in the mPFC normalized the deficit in social preference of Cntnap2-/- mice. Our results thus reveal a critical function of CICD and highlight a role of the CNTNAP2-CASK-Necdin signaling pathway in ASD.

TransFlow: a Snakemake workflow for transmission analysis of Mycobacterium tuberculosis whole-genome sequencing data.

MOTIVATION: Whole-genome sequencing (WGS) is increasingly used to aid the understanding of Mycobacterium tuberculosis (MTB) transmission. The epidemiological analysis of tuberculosis based on the WGS technique requires a diverse collection of bioinformatics tools. Effectively using these analysis tools in a scalable and reproducible way can be challenging, especially for non-experts. RESULTS: Here, we present TransFlow (Transmission Workflow), a user-friendly, fast, efficient and comprehensive WGS-based transmission analysis pipeline. TransFlow combines some state-of-the-art tools to take transmission analysis from raw sequencing data, through quality control, sequence alignment and variant calling, into downstream transmission clustering, transmission network reconstruction and transmission risk factor inference, together with summary statistics and data visualization in a summary report. TransFlow relies on Snakemake and Conda to resolve dependencies among consecutive processing steps and can be easily adapted to any computation environment. AVAILABILITY AND IMPLEMENTATION: TransFlow is free available at https://github.com/cvn001/transflow. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The role of Xpert MTB/RIF using bronchoalveolar lavage fluid in active screening: insights from a tuberculosis outbreak in a junior school in eastern China.

Background: Tuberculosis (TB) outbreaks in schools present a public health challenge. In order to effectively control the spread of transmission, timely screening, accurate diagnosis and comprehensive epidemiological investigations are essential. Methods: In July 2021, a TB outbreak occurred in a junior high school in Y City, Zhejiang Province. Students and faculty were screened for TB by symptom screening, chest radiography, and tuberculin skin test during four rounds of contact screenings. For sputum smear-negative and sputum-scarce patients, bronchoscopy was used to collect BAL samples for Xpert Mycobacterium tuberculosis/rifampin (MTB/RIF). Whole-genome sequencing and bioinformatics analysis were performed on isolates to identify the strains of MTB isolates and predict drug resistance. Results: Between July 2021 and November 2021, a total of 1,257 students and faculty were screened for TB during screenings. A total of 15 students (1.2% of persons screened) aged 15 years were diagnosed with TB. Eighty percent (12/15) of the cases were laboratory-confirmed (10/12 [83%] Xpert MTB/RIF-positive, 2/12 [17%] culture-positive). Most cases (12/15 [80%]) were in students from Class 2. All cases were asymptomatic except for the index case who had symptoms for more than two months. Seven MTB isolates were collected and belonged to lineage 2. Conclusion: Our findings demonstrated the potential of Xpert MTB/RIF using BAL as a screening tool in school TB outbreaks for sputum smear-negative and sputum-sparse suspects, which may not only rapidly improves diagnostic accuracy, but also facilitates epidemiological investigations and homology analysis.

Investigating a pulmonary Mycobacterium abscessus infection outbreak among elderly inpatients in the intensive care ward.

INTRODUCTION: Mycobacterium abscessus is an opportunistic nontuberculous mycobacteria pathogen; however, the prevalence of nosocomial and community infections is increasing. In January 2016, several bedridden inpatients in the intensive care unit of a hospital had positive sputum smears for acid-fast bacilli, suggesting a mycobacteria outbreak. METHODOLOGY: Acid-fast bacilli smear microscopy, isolation, and culturing were performed twice using sputa from each suspected intensive care unit inpatient (n = 13); in addition, medical history was obtained for each inpatient with suspected infection. Furthermore, environmental specimens were surveyed, collected, and cultured. We used DNA microarray chip analysis to identify positive mycobacterial isolates at the species level and performed whole-genome sequencing and phylogenetic tree construction. RESULTS: Seven inpatients had M. abscessus pulmonary infection, confirmed by 2 positive cultures; five of the inpatients had only one positive culture, while one had two negative cultures. Six of 13 ventilator condensate samples were mycobacterial culture-positive, identified as M. abscessus; the other environmental samples were negative. The M. abscessus isolates (15 sputa and 4 environmental samples) clustered together in the phylogenic analysis with only one single-nucleotide polymorphism difference. All patients were symptom-free after 8 months of multi-drug treatment. CONCLUSIONS: We confirmed a pulmonary M. abscessus outbreak among 12 bedridden patients in the intensive care unit through microbiological, molecular epidemiological, and environmental investigations. The possible infection source was contaminated ventilator condensate. This outbreak reemphasizes the importance of standardized ventilator maintenance and disinfection for preventing ventilator-associated pneumonia and is a reminder that nontuberculous mycobacteria-related ventilator-associated pneumonia is possible.

Resveratrol rescued the pain related hypersensitivity for Cntnap2-deficient mice.

Contactin-associated protein-like 2 (CNTNAP2 or CASPR2) is a neuronal transmembrane protein of the neurexin superfamily which is correlated with pain related hypersensitivity. Recent results indicated that the hyperactive phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway may be a promising therapeutic target for pain-related hypersensitivity in patients with dysfunction of CNTNAP2. Resveratrol is one of the most widely studied polyphenols with several beneficial properties. In the present study, we investigated the effects of resveratrol on the pain related hypersensitivity. And we found that the up-regulated phosphorylation of S6 could be suppressed by resveratrol. The nocifensive behavior duration time to heat and chemical algogens stimulation in Cntnap2-deficiency (Cntnap2-/-) mice could be attenuated by resveratrol. Our results indicated that resveratrol could rescue the pain related hypersensitivity for Cntnap2-/- mice may be via mTOR signaling pathway.

Hyperactive Akt-mTOR pathway as a therapeutic target for pain hypersensitivity in Cntnap2-deficient mice.

Contactin-associated protein-like 2 (CNTNAP2 or CASPR2) is a neuronal transmembrane protein of the neurexin superfamily that is involved in many neurological diseases, such as autism and pain hypersensitivity. We recently found that Cntnap2-/- mice showed elevated Akt-mTOR activity in the brain, and suppression of the Akt-mTOR pathway rescued the social deficit in Cntnap2-/- mice. In this study, we found that the dorsal root ganglion (DRG) from Cntnap2-/- mice also showed hyperactive Akt-mTOR signaling. Treatment with the Akt inhibitor LY94002 or the mTOR inhibitor rapamycin attenuated pain-related hypersensitivity to noxious mechanical stimuli, heat, and inflammatory substances. Further, suppression of mTOR signaling by rapamycin decreased DRG neuronal hyperexcitability. We further indicated that treatment with the FDA-approved drug metformin normalized the hyperactive Akt-mTOR signaling, and attenuated pain-related hypersensitivity in Cntnap2-/- mice. Our results thus identified hyperactive Akt-mTOR signaling pathway as a promising therapeutic target for pain-related hypersensitivity in patients with dysfunction of CNTNAP2.

Suppression of Akt-mTOR pathway rescued the social behavior in Cntnap2-deficient mice.

Autism spectrum disorders (ASD) form a heterogeneous, neurodevelopmental syndrome characterized by deficits in social interactions and repetitive behavior/restricted interests. Dysregulation of mTOR signaling has been implicated in the pathogenesis of certain types of ASD, and inhibition of mTOR by rapamycin has been demonstrated to be an effective therapeutics for impaired social interaction in Tsc1+/-, Tsc2+/-, Pten-/- mice and valproic acid-induced ASD animal models. However, it is still unknown if dysregulation of mTOR signaling is responsible for the ASD-related deficit caused by other genes mutations. Contactin associated protein-like 2 (CNTNAP2) is the first widely replicated autism-predisposition gene. Mice deficient in Cntnap2 (Cntnap2-/- mice) show core ASD-like phenotypes, and have been demonstrated as a validated model for ASD-relevant drug discovery. In this study, we found hyperactive Akt-mTOR signaling in the hippocampus of Cntnap2-/- mice with RNA sequencing followed with biochemical analysis. Treatment with Akt inhibitor LY294002 or mTOR inhibitor rapamycin rescued the social deficit, but had no effect on hyperactivity and repetitive behavior/restricted behavior in Cntnap2-/- mice. We further showed that the effect of LY294002 and rapamycin on social behaviors is reversible. Our results thus identified hyperactive Akt-mTOR signaling pathway as a therapeutic target for abnormal social behavior in patients with dysfunction of CNTNAP2.

Effect of cisplatin on the clock genes expression in the liver, heart and kidney.

Cisplatin is a platinum-based chemotherapy drug that is widely used to treat various types of malignancies. Although the involvement of circadian clock in cisplatin metabolism and excretion has been reported, the effect of cisplatin on circadian rhythm remains unclear. In the present study, we investigated the effects of cisplatin on clock genes expression in mouse peripheral tissues. Cisplatin induced severe nephrotoxicity, as revealed by the significant increase of blood urea nitrogen and serum creatinine levels. Moreover, cisplatin circadian time-dependently induced p21 expression in the liver, heart and kidney, with the highest increase during the dark phase. In addition, cisplatin altered the clock genes expression in the liver, heart and kidney in a tissue- and gene-specific manner. Interesting, the expression of D site of the albumin promoter binding protein (Dbp), a gene involved in detoxification and drug metabolism, was consistently suppressed in the liver, heart and kidney after cisplatin treatment, implying a role of DBP in the toxicity of cisplatin.

Approaching charge balance in organic light-emitting diodes by tuning charge injection barriers with mixed monolayers.

Self-assembled monolayers (SAMs) of binary mixtures of 1-butylphosphonic acid and the trifluoromethyl-terminated analogue (4,4,4-trifluoro-1-butylphosphonic acid) were formed on ITO surfaces to tune the work function of ITO over a range of 5.0 to 5.75 eV by varying the mixing ratio of the two adsorbents. The mixed SAM-modified ITO surfaces were used as the anode in the fabrication of OLED devices with a configuration of ITO/SAM/HTL/Alq3/MX/Al, where HTL was the NPB or BPAPF hole-transporting layer and MX was the LiF or Cs(2)CO(3) injection layer. It was shown that, depending on the HTL or MX used, the maximum device current and the maximum luminance efficiency occurred with anodes of different modifications because of a shift in the point of hole/electron carrier balance. This provides information on the charge balance in the device and points to the direction to improve the performance.

Continuous modulation of electrode work function with mixed self-assembled monolayers and its effect in charge injection.

Self-assembled monolayers (SAMs) of binary mixtures of n-decanethiol and the fluorinated analogue (3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoro-1-decanethiol) were formed on silver surface. The film structure was characterized by reflection absorption IR and XPS to be a homogeneous mixture of the two components. The mixed monolayers serve to tune the work function of silver over a wide range by varying the surface composition of the mixed monolayer from 4.1 to 5.8 eV. The mixed SAM-modified Ag surfaces were used as the anode in the fabrication of hole-only devices with the device structure Ag/SAM/HTL/Ag, where HTL represents a hole-transporting layer. It is shown that depending on the HTL used and thus the HOMO level involved, the maximum current injection into the device occurred with differently modified Ag. Top-emitting organic light-emitting diodes fabricated with differently modified silver electrodes showed that the maximum current and maximum luminance efficiency occur at anodes of different modifications due to a change in the hole-electron charge balance.