Antimicrobial and antibiofilm effects of essential fatty acids against clinically isolated vancomycin-resistant Enterococcus faecium.

Introduction: Enterococcus faecium is a leading cause of hospital-acquired infections, which has become a serious public health concern. The increasing incidence of vancomycin-resistant E. faecium (VRE-fm) raises an urgent need to find new antimicrobial agents as a complement to traditional antibiotics. The study aimed to evaluate the antimicrobial and antibiofilm activity of essential fatty acids (EFAs) against VRE-fm, and further explore the molecular mechanism of the antibiofilm activity of EFAs. Method: The microdilution broth method was used for antimicrobial susceptibility testing with traditional antibiotics and EFAs, including α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid (LOA), γ-linolenic acid (GLA), and arachidonic acid (AA). The effect of EFAs on cell morphology of VRE-fm was investigated by scanning electron microscopy. The crystal violet method was used to evaluate the antibiofilm activities of EFAs against VRE-fm. Furthermore, the expression of biofilm-related genes (acm, atlA, esp, and sagA) of VRE-fm isolates under the action of GLA was analyzed using quantitative reverse transcription PCR (qRT-PCR) assay. Results: VRE-fm isolates were highly resistant to most traditional antibiotics, only highly susceptible to quinupristin-dalfopristin (90.0%), tigecycline (100%), and linezolid (100%). EPA, DHA, and GLA exhibited excellent antimicrobial activity. The MIC50/90 of EPA, DHA, and GLA were 0.5/1, 0.25/0.5, and 0.5/1 mM, respectively. SEM imaging showed that strain V27 adsorbed a large number of DHA molecules. Furthermore, all EFAs exhibited excellent inhibition and eradication activities against VRE-fm biofilms. The biofilm inhibition rates of EFAs ranged from 45.3% to 58.0%, and eradication rates ranged from 54.1% to 63.4%, against 6 VRE-fm isolates with moderate biofilm formation ability. GLA exhibited remarkable antibiofilm activity against VRE-fm isolates. The qRT-PCR analysis showed that GLA could significantly down-regulate the expression of the atlA gene (P < 0.01) of VRE-fm. Conclusion: DHA showed the strongest antibacterial activity, while GLA showed the strongest antibiofilm effect among the EFAs with antibacterial activity. Our novel findings indicate that the antibiofilm activity of GLA may be through down-regulating the atlA gene expression in VRE-fm. Therefore, DHA and GLA had the potential to be developed as therapeutic agents to treat infections related to multiple antimicrobial-resistant E. faecium.

Antibiofilm Activity of Essential Fatty Acids Against Candida albicans from Vulvovaginal Candidiasis and Bloodstream Infections.

Purpose: The biofilm formation of Candida albicans is an important virulence factor as it can increase tolerance to conventional antifungal drugs and the host immune system. The study aimed to assess the effect of essential fatty acids (EFAs) against biofilm formation and mature biofilms of C. albicans strains, which were isolated from vulvovaginal candidiasis and candidemia. Methods: The biofilm formation ability of C. albicans and antifungal activities of fluconazole were determined. Additionally, the effects of six EFAs [α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid (LOA), γ-linolenic acid (GLA), and arachidonic acid (AA)] against C. albicans under planktonic and biofilm conditions were evaluated. Results: 94.1% of C. albicans exhibited biofilm formation capacity, and 98.5% of C. albicans were susceptible to fluconazole. The biofilms of C. albicans were highly resistant to fluconazole with minimum biofilm eradication concentration values ≥ 64 µg/mL. The EFAs attenuated biofilm formation in a dose-dependent manner, and GLA displayed a remarkable inhibitory activity against biofilm formation of C. albicans. In addition, EPA, DHA, and GLA at 0.1 mM could inhibit the biofilm formation of C. albicans without affecting the planktonic growth rate. Notably, EPA and AA at 1 mM had both inhibitory and eradication activities on C. albicans biofilms. Conclusion: This is the first study to directly compare different EFAs for their capacity to affect C. albicans biofilm formation as well as biofilm eradication. These results suggest EPA and AA could serve as potential new antifungal agents for the treatment of clinical infections caused by C. albicans biofilms.

The modulation of HBsAg level by sI126T is affected by additional amino acid substitutions in the S region of HBV.

The hepatitis B surface antigen (HBsAg) is a vital serum marker for hepatitis B virus (HBV) infection. Amino acid (AA) substitutions in small hepatitis B surface protein (SHBs) are known to affect HBsAg level. However, how the genetic backbones of SHBs sequences would affect the roles of a specific AA substitution on HBsAg level remains unclear. In this study, we found that sI126 had a very high substitution detection rate of 17.54% (40/228) in untreated chronic hepatitis B cohort with subgenotype C2 HBV infection. Among different substitution types at sI126, the sI126T (N = 28) was found to be associated with significantly lower serum HBsAg level. Clone sequencing revealed that sI126T-harboring SHBs sequences had varied genetic backbones with zero to nine additional AA substitutions. Thus, we constructed 24 HBsAg expression plasmids harboring sI126T without (plasmid 1, P1) or with (P2-P24) additional AA substitution(s) and studied them in the HepG2 cells. The HBsAg levels were determined by both ELISA and Western blot. In vitro experiments showed that P1 significantly reduced HBsAg level and its secretion (p < .05), however, P2-P24 showed various extracellular and intracellular HBsAg levels. No significant differences were detected among the HBsAg mRNA levels of nine representative mutant plasmids. Our findings suggest that the modulation of HBsAg level by sI126T is affected by additional AA substitution(s) in the S region of HBV. The effects of AA combination substitutions in SHBs sequences on HBsAg levels are worthwhile for more attentions in terms of HBV biology and its clinical application.

Characteristics of HBV infection in 705 HIV-infected patients under lamivudine-based antiretroviral treatment from three regions in China.

PURPOSE: This study aimed to investigate the HIV and hepatitis B virus (HBV) co-infection in three HIV high endemic areas with different modes of HIV transmission and explore the HBV nucleos(t)ide analogue resistance (NUCr) substitutions in this cohort receiving antiretroviral therapy (ART). PATIENTS AND METHODS: The enrolled 705 HIV-infected patients were from three different regions in China and received lamivudine-based ART for at least 1 year. After screening for hepatitis B surface antigen (HBsAg), the hepatitis B e antigen (HBeAg), and antibody against hepatitis B core antigen (anti-HBc and anti-HBc IgM), HBV DNA in plasma of patients positive for HBsAg was tested. The reverse transcriptase (RT) sequences of HBV were analyzed by direct sequencing. RESULTS: The overall HBsAg-positive rate was 7.1% (50/705) (Guangxi [25/170, 14.7%], Xinjiang [13/257, 5.1%], and Henan [12/278, 4.3%]). The age, transmission route, and ethnic status were found to be associated with HIV/HBV co-infection. We obtained 23 HBV RT sequences belonging to genotypes B (9/23, 39.1%), C (13/23, 56.5%), and D (1/23, 4.4%). About 65.2% (15/23) of RT sequences harbored NUCr substitutions, all of which had combination substitution patterns. Patients with HBV NUCr had significantly higher HBV DNA level and ratio of HBeAg-positive than those without NUCr. None of the patients was found to have both lamivudine-resistant HBV and HIV. CONCLUSION: Our results suggested that HBsAg-positive rate in the studied patients was similar to that of the general population in each of the studied regions, where the age, transmission route, and ethnic status might also play roles in HIV/HBV co-infection. The HBV combination NUCr substitutions were common in co-infected patients under ART. Monitoring of HBV infection and NUCr substitutions in HIV-infected patients would help in providing better clinical decisions and management, thus lowering patients' risks to develop end-stage liver diseases.

Impacts of HBV rtH55R polymerase substitution on viral replication and rtM204I/V resistance to nucleoside/nucleotide antiviral drugs.

BACKGROUND: High genetic variability at the reverse transcriptase (RT) region of HBV could confer resistance to nucleoside/nucleotide analogues (NUCs). The aim of this study was to identify new RT amino acid (AA) substitutions related to NUC resistance. METHODS: HBV RT sequences of genotype C from 501 chronic hepatitis B (CHB) patients were analysed to identify potential RT substitutions related to NUC resistance. In vitro studies without and with NUCs were performed in a HepG2 cell line transfected by clones with RT harbouring wild-type or substituted AA(s) of interest. RESULTS: Among 261 NUC-treated CHB patients, we found a high detection rate of rtM204I/V substitution (30.7% [80/261]). We identified a new substitution of rtH55R, and its detection rate had a significantly increasing trend from 3.8% (9/240) in the untreated group to 7.2% (13/181) or 33.8% (27/80) in the treated group with rtM204 or with rtM204I/V substitutions (P<0.0001). In vitro studies showed that rtH55R had a similar HBV DNA level compared to wild type. The rtH55R+rtM204I clone had a significantly better replication capacity than the rtM204I clone without NUCs (P<0.05). The replication capacity of the rtM204I clone was found to significantly decrease under lamivudine treatment, but this was not found in the rtH55R+rtM204I clone. CONCLUSIONS: We identified a new HBV RT substitution of rtH55R in genotype-C-infected CHB patients. It is frequently found in combination with rtM204I/V substitution under NUC treatment. In vitro studies suggest that it might play some replication compensatory role in rtM204I mutants under lamivudine treatment.

Serum Hepatitis B Virus DNA, RNA, and HBsAg: Which Correlated Better with Intrahepatic Covalently Closed Circular DNA before and after Nucleos(t)ide Analogue Treatment?

The study was designed to investigate whether serum hepatitis B virus (HBV) RNA is a strong surrogate marker for intrahepatic HBV covalently closed circular DNA (cccDNA) compared with serum HBV DNA, hepatitis B surface antigen (HBsAg), and hepatitis B e antigen (HBeAg) in HBeAg-positive chronic hepatitis B (CHB) patients. Serum HBV RNA, HBV DNA, HBsAg, HBeAg, and intrahepatic cccDNA were quantitatively detected at baseline (n = 82) and 96 weeks (n = 62) after treatment with nucleos(t)ide analogue (NUC) in HBeAg-positive CHB patients. The correlations among serum HBV RNA, HBV DNA, HBsAg, HBeAg, and intrahepatic cccDNA levels were then statistically analyzed. The results showed that pretreatment intrahepatic cccDNA levels correlated better with serum HBV DNA levels (r = 0.36, P < 0.01) than with serum HBV RNA levels (r = 0.25, P = 0.02), whereas no correlations were found between pretreatment intrahepatic cccDNA levels and HBsAg (r = 0.15, P = 0.17) or HBeAg (r = 0.07, P = 0.56) levels. At 96 weeks after NUC treatment, intrahepatic cccDNA levels correlated well with HBsAg levels (r = 0.39, P < 0.01) but not with serum HBV RNA, HBV DNA, and HBeAg levels (all P > 0.05). Besides, the decline in the intrahepatic cccDNA level from baseline to week 96 correlated better with the reduction in the serum HBsAg levels than with the decreases in the levels of the other markers (for the HBsAg decline, r = 0.38, P < 0.01; for the HBV DNA decline, r = 0.35, P = 0.01; for the HBV RNA decline, r = 0.28, P < 0.05; for the HBeAg decline, r = 0.18, P = 0.19). In conclusion, the baseline serum HBV RNA level or its decline after 96 weeks of NUC therapy correlated with the corresponding intrahepatic cccDNA level, while it was less than that seen with serum HBV DNA at baseline and HBsAg (or its decline) at 96 weeks after treatment, respectively.

HBV Drug Resistance Substitutions Existed before the Clinical Approval of Nucleos(t)ide Analogues: A Bioinformatic Analysis by GenBank Data Mining.

Naturally occurring nucleos(t)ide analogue resistance (NUCr) substitution frequencies in the reverse transcriptase (RT) of the hepatitis B virus (HBV) were studied extensively after the clinical approval of nucleos(t)ide analogues (NUCs; year of approval 1998). We aimed to study NUCr substitutions in HBV RT sequences obtained before 1998 and better understand the evolution of RT sequences without NUC pressures. Our strategy was to retrieve HBV sequences from GenBank deposited before 1998. The initial search used the keywords "hepatitis B virus" or "HBV" and 1139 sequences were found. Data analyses included information extraction: sequence quality control and amino acid substitution analysis on 8 primary NUCr and 3 secondary substitution codons. Three hundred and ninety-four RT-containing sequences of 8 genotypes from 25 countries in 4 continents were selected. Twenty-seven (6.9%) sequences were found to harbor substitutions at NUCr-related codons. Secondary substitutions (rtL80V and rtV173G/A/L) occurred more frequently than primary NUCr substitutions (rtI169L; rtA181G; T184A/S; rtS202T/R; rtM204L and rtM250K). Typical amino acid substitutions associated with NUCr were of rtL80V, rtV173L and rtT184A/S. We confirm the presence of naturally occurring typical HBV NUCr substitutions with very low frequencies, and secondary substitutions are more likely to occur than primary NUCr substitutions without the selective pressure of NUCs.

Growth of Large-Scale, Large-Size, Few-Layered α-MoO3 on SiO2 and Its Photoresponse Mechanism.

Layered α-MoO3 is a multifunctional material that has significant application in optoelectronic devices. In this study, we show the growth of large-scale, large-size, few-layered (FL) α-MoO3 nanosheet directly on technical substrates (SiO2 and Si) by physical vapor deposition. We suggest that the growth is self-limiting in the [010] direction because of the re-evaporation and high diffusion capacity of MoOx species at high temperature. As-prepared FL α-MoO3 is nonconductive and shows poor response to photoillumination with wavelength of 405 and 630 nm. Its work function is strongly altered by the substrate. Improvement of conductivity and photoresponse is observed after the FL device is annealed in vacuum. Line defects along the [001], [100], and [101] directions belonging to the generation of Os and Oa vacancy states appear, and the interfacial effect is suppressed. Scanning near-field optical microscope shows that the defects are absorption sites. Kelvin probe force microscope reveals decrease of apparent work function under illumination, which confirms that electrons are excited from defects states. Our findings show that intense studies on defect engineering are required to push forward the application of two-dimensional metal oxides.

The nucleotide changes within HBV core promoter/precore during the first 12weeks of nucleos(t)ide treatment might be associated with a better virological response.

OBJECTIVES: We aimed to study the dynamic changes of hepatitis B virus (HBV) core promoter/precore (CP/preC) sequences during antiviral treatment and their associations with virological responses. MATERIALS AND METHODS: The baseline and 12-week CP/preC sequences (nts 1655-2014) were obtained from 52 chronic hepatitis B patients with positive hepatitis B e antigen (HBeAg), who received a 104-week lamivudine and adefovir dipivoxil combination therapy. The mutations within the CP/preC were analyzed against genotype specific reference sequences. The nucleotide change rates in individuals during therapy were analyzed in a pairwise comparison manner. RESULTS: There was no significant difference of the mutation rate at each nucleotide site between baseline and week 12 of treatment (P>0.05). The mutation rates of A1762T/G1764A and G1896A were found to decrease from 46.2% (24/52) at baseline to 36.5% (19/52) at week 12 (P=0.426) and from 28.8% (15/52) to 21.2% (11/52) (P=0.497), respectively. The nucleotide change rates varied from 0.0% - 7.8% in individuals [0.0% in Group 1 (N=26); 0.3% - 7.8% in Group 2 (N=26)] during the first 12-week treatment. HBV DNA levels in Group 2 were significantly lower than those in Group 1 throughout therapy (P<0.01) (e.g., 1.5±1.3log10 IU/ml vs. 2.6±1.0log10 IU/ml at week 104, P=0.001). At week 104 the rates of HBV DNA undetectable and HBeAg loss in Group 2 were significantly higher than those in Group 1 (P<0.05). Along with the increased nucleotide change rates, the rate of HBV DNA undetectable at week 104 tended to increase (odds ratio=0.323, 95% confidence interval=0.138-0.758, P<0.001). CONCLUSION: Our findings suggested that the nucleotide changes within HBV CP/preC region during the first 12-week treatment might be associated with a better virological response.

Effects of amino acid substitutions in hepatitis B virus surface protein on virion secretion, antigenicity, HBsAg and viral DNA.

BACKGROUND & AIMS: As important virological markers, serum hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA levels show large fluctuations among chronic hepatitis B patients. The aim of this study was to reveal the potential impact and mechanisms of amino acid substitutions in small hepatitis B surface proteins (SHBs) on serum HBsAg and HBV DNA levels. METHODS: Serum samples from 230 untreated chronic hepatitis B patients with genotype C HBV were analyzed in terms of HBV DNA levels, serological markers of HBV infection and SHBs sequences. In vitro functional analysis of the identified SHBs mutants was performed. RESULTS: Among 230 SHBs sequences, there were 39 (16.96%) sequences with no mutation detected (wild-type) and 191 (83.04%) with single or multiple mutations. SHBs consist of 226 amino acids, of which 104 (46.02%) had mutations in our study. Some mutations (e.g., sE2G, sL21S, sR24K, sT47A/K, sC69stop (sC69∗), sL95W, sL98V, and sG145R) negatively correlated with serum HBsAg levels. HBsAg and HBV DNA levels from this group of patients had a positive correlation (r=0.61, p<0.001). In vitro analysis showed that these mutations reduced extracellular HBsAg and HBV DNA levels by restricting virion secretion and antibody binding capacity. Virion secretion could be rescued for sE2G, sC69∗, and sG145R by co-expression of wild-type HBsAg. CONCLUSION: The serum HBsAg levels were lower in untreated CHB patients with novel SHBs mutations outside the major antigenic region than those without mutations. Underlying mechanisms include impairment of virion secretion and lower binding affinity to antibodies used for HBsAg measurements. LAY SUMMARY: The hepatitis B surface antigen (HBsAg) is a major viral protein of the hepatitis B virus (HBV) secreted into patient blood serum and its quantification value serves as an important marker for the evaluation of chronic HBV infection and antiviral response. We found a few new amino acid substitutions in HBsAg associated with lower serum HBsAg and HBV DNA levels. These different substitutions might impair virion secretion, change the ability of HBsAg to bind to antibodies, or impact HBV replication. These could all result in decreased detectable levels of serum HBsAg. The factors affecting circulating HBsAg level and HBsAg detection are varied and caution is needed when interpreting clinical significance of serum HBsAg levels. Clinical trial number: NCT01088009.

Higher detection rates of amino acid substitutions in HBV reverse transcriptase/surface protein overlapping sequence is correlated with lower serum HBV DNA and HBsAg levels in HBeAg-positive chronic hepatitis B patients with subgenotype B2.

OBJECTIVES: Hepatitis B virus (HBV) subgenotype B2 is prevalent in China and some other parts of Asia. This study aimed to carry out a subgenotype B2 specific mutation analysis on important amino acid (AA) sites in overlapping reverse transcriptase (RT) and surface (S) protein coding regions of HBV. MATERIALS AND METHODS: A total of 143 hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients with HBV subgenotype B2 infection were enrolled. HBV RT/S regions were sequenced focusing on 43 RT resistance AA sites and 31 S AA sites with functional/structural/conformational importance. RESULTS: According to the consensus AA sequence for subgenotype B2, 49.7% (71/143) of RT and 33.6% (48/143) of S protein sequences contained detectable substitutions at 58.1% (25/43) of studied AA sites in RT and 51.6% (16/31) of AA sites in S proteins, respectively. The most frequently detected substitutions were rtN134D/S (44/143, 30.8%) and sT126A/S (22/143, 15.4%), which were located in the RT A-B interdomain region and the corresponding antigenicity determinant region of S protein, respectively. In addition, two patients harboring drug resistance mutations rtL80V+rtM204I and rtL180M+rtM204V were found. Interestingly, the patients with detectable AA substitutions at any of the 74 sites in either/both of RT/S sequences had significantly lower serum HBV DNA and HBsAg levels than that in patients without detectable RT/S AA substitutions (P<0.05). A trend Chi-squared test indicated that a negative association of serum HBsAg level with S protein sequence substitution rate was statistically significant (P=0.047). CONCLUSION: This subgenotype B2 specific mutation analysis revealed some naturally occurring hot spot substitutions at important AA sites of HBV RT/S proteins, which together might influence the serum HBV DNA and HBsAg levels in HBeAg-positive CHB patients.

Nanoscale Insights into the Hydrogenation Process of Layered α-MoO3.

The hydrogenation process of the layered α-MoO3 crystal was investigated on a nanoscale. At low hydrogen concentration, the hydrogenation can lead to formation of HxMoO3 without breaking the MoO3 atomic flat surface. For hydrogenation with high hydrogen concentration, hydrogen atoms accumulated along the <101> direction on the MoO3, which induced the formation of oxygen vacancy line defects. The injected hydrogen atoms acted as electron donors to increase electrical conductivity of the MoO3. Near-field optical measurements indicated that both of the HxMoO3 and oxygen vacancies were responsible for the coloration of the hydrogenated MoO3, with the latter contributing dominantly. On the other hand, diffusion of hydrogen atoms from the surface into the body of the MoO3 will encounter a surface diffusion energy barrier, which was for the first time measured to be around 80 meV. The energy barrier also sets an upper limit for the amount of hydrogen atoms that can be bound locally inside the MoO3 via hydrogenation. We believe that our findings has provided a clear picture of the hydrogenation mechanisms in layered transition-metal oxides, which will be helpful for control of their optoelectronic properties via hydrogenation.

Self-Powered, High-Speed and Visible-Near Infrared Response of MoO(3-x)/n-Si Heterojunction Photodetector with Enhanced Performance by Interfacial Engineering.

Photodetectors with a wide spectrum response are important components for sensing, imaging, and other optoelectronic applications. A molybdenum oxide (MoO(3-x))/Si heterojunction has been applied as solar cells with great success, but its potential in photodetectors has not been explored yet. Herein, a self-powered, high-speed heterojunction photodetector fabricated by coating an n-type Si hierarchical structure with an ultrathin hole-selective layer of molybdenum oxide (MoO(3-x)) is first investigated. Excellent and stable photoresponse performance is obtained by using a methyl group passivated interface. The heterojunction photodetector demonstrated high sensitivity to a wide spectrum from 300 to 1100 nm. The self-powered photodetector shows a high detectivity of (∼6.29 × 10(12) cmHz(1/2) W(-1)) and fast response time (1.0 µs). The excellent photodetecting performance is attributed to the enhanced interfacial barrier height and three-dimensional geometry of Si nanostructures, which is beneficial for efficient photocarrier collection and transportation. Finally, our devices show excellent long-term stability in air for 6 months with negligible performance degradation. The thermal evaporation method for large-scale fabrication of MoO(3-x)/n-Si photodetectors makes it suitable for self-powered, multispectral, and high-speed response photodetecting applications.

Interaction at the silicon/transition metal oxide heterojunction interface and its effect on the photovoltaic performance.

The interfacial reaction and energy level alignment at the Si/transition metal oxide (TMO, including MoO3-x, V2O5-x, WO3-x) heterojunction are systematically investigated. We confirm that the interfacial reaction appears during the thermal deposition of TMO, with the reaction extent increasing from MoO3-x, to V2O5-x, and to WO3-x. The reaction causes the surface oxidation of silicon for faster electron/hole recombination, and the reduction of TMO for effective hole collection. The photovoltaic performance of the Si/TMO heterojunction devices is affected by the interface reaction. MoO3-x are the best hole selecting materials that induce least surface oxidation but strongest reduction. Compared with H-passivation, methyl group passivation is an effective way to reduce the interface reaction and improve the interfacial energy level alignment for better electron and hole collection.

Naturally occurring deletion/insertion mutations within HBV whole genome sequences in HBeAg-positive chronic hepatitis B patients are correlated with baseline serum HBsAg and HBeAg levels and might predict a shorter interval to HBeAg loss and seroconversion during antiviral treatment.

OBJECTIVES: Deletion/insertion (Del/Ins) throughout hepatitis B virus (HBV) genome has not been well studied for HBeA-positive chronic hepatitis B (CHB) patients. This study aimed to characterize the HBV Del/Ins mutations in full-length genome quasispecies sequences in such patients at antiviral baseline and to reveal their potential impacts on HBV serological markers and responses to nucleos(t)ide analogue (NUC) treatment. MATERIALS AND METHODS: A total of 30 HBeAg-positive CHB patients with genotype C infection receiving a 104-week lamivudine (LMV) and adefovir dipivoxil (ADV) combination therapy were enrolled. HBV whole genome sequences in serum samples at baseline were clone sequenced and analyzed using bioinformatics tools. RESULTS: Among 306 unspliced clone sequences, 61.8% (189/306) had Del/Ins mutations, 38.2% (117/306) were full-length genomes without any Del/Ins. Due to different combinations of 125 deletion types and 45 insertion types, we identified 55 Del/Ins-harboring HBV genome patterns, which affected a single or several functional genomic regions. Importantly, the proportion of Del/Ins-harboring clones was found to be significantly negatively correlated with HBsAg (r = -0.3985, P = 0.0292) and HBeAg (r = -0.3878, P = 0.0342) at baseline. Higher percentage of Del/Ins-harboring clones at baseline was found to predict a shorter interval to HBeAg loss and seroconversion. CONCLUSION: Del/Ins mutations within HBV whole genome were prevalent in HBeAg-positive CHB patients prior to antiviral treatment. A higher detection rate of these mutations at baseline might correlate with a better response to LMV and ADV combination therapy.

Characteristics of a silicon nanowires/PEDOT:PSS heterojunction and its effect on the solar cell performance.

The interfacial energy-level alignment of a silicon nanowires (SiNWs)/PEDOT:PSS heterojunction is investigated using Kelvin probe force microscopy. The potential difference and electrical distribution in the junction are systematically revealed. When the PEDOT:PSS layer is covered at the bottom of the SiNW array, an abrupt junction is formed at the interface whose characteristics are mainly determined by the uniformly doped Si bulk. When the PEDOT:PSS layer is covered on the top, a hyperabrupt junction localized at the top of the SiNWs forms, and this characteristic depends on the surface properties of the SiNWs. Because the calculation shows that the absorption of light from the SiNWs and the Si bulk are equally important, the bottom-coverage structure leads to better position matching between the depletion and absorption area and therefore shows better photovoltaic performance. The dependence of JSC and VOC on the junction characteristic is discussed.