Visual tracking brain-computer interface.

Brain-computer interfaces (BCIs) offer a way to interact with computers without relying on physical movements. Non-invasive electroencephalography-based visual BCIs, known for efficient speed and calibration ease, face limitations in continuous tasks due to discrete stimulus design and decoding methods. To achieve continuous control, we implemented a novel spatial encoding stimulus paradigm and devised a corresponding projection method to enable continuous modulation of decoded velocity. Subsequently, we conducted experiments involving 17 participants and achieved Fitt's information transfer rate (ITR) of 0.55 bps for the fixed tracking task and 0.37 bps for the random tracking task. The proposed BCI with a high Fitt's ITR was then integrated into two applications, including painting and gaming. In conclusion, this study proposed a visual BCI based-control method to go beyond discrete commands, allowing natural continuous control based on neural activity.

Estimating and approaching the maximum information rate of noninvasive visual brain-computer interface.

An essential priority of visual brain-computer interfaces (BCIs) is to enhance the information transfer rate (ITR) to achieve high-speed communication. Despite notable progress, noninvasive visual BCIs have encountered a plateau in ITRs, leaving it uncertain whether higher ITRs are achievable. In this study, we used information theory to study the characteristics and capacity of the visual-evoked channel, which leads us to investigate whether and how we can decode higher information rates in a visual BCI system. Using information theory, we estimate the upper and lower bounds of the information rate with the white noise (WN) stimulus. Consequently, we found out that the information rate is determined by the signal-to-noise ratio (SNR) in the frequency domain, which reflects the spectrum resources of the channel. Based on this discovery, we propose a broadband WN BCI by implementing stimuli on a broader frequency band than the steady-state visual evoked potentials (SSVEPs)-based BCI. Through validation, the broadband BCI outperforms the SSVEP BCI by an impressive 7 bps, setting a record of 50 bps. The integration of information theory and the decoding analysis presented in this study offers valuable insights applicable to general sensory-evoked BCIs, providing a potential direction of next-generation human-machine interaction systems.

Neutrophils in COVID-19: recent insights and advances.

Coronavirus disease 2019 (COVID-19) is an acute respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can lead to acute respiratory distress syndrome (ARDS), multi-organ failure and death, posing significant threat to human health. Studies have found that pathological mechanisms, such as cytokine storms caused by uncontrolled innate immune system activation, release of damage-associated molecular patterns during tissue injury and a high incidence of thrombotic events, are associated with the function and dysfunction of neutrophils. Specifically, the increased formation of low-density neutrophils (LDNs) and neutrophil extracellular traps (NETs) has been shown to be closely linked with the severity and poor prognosis in patients with COVID-19. Our work focuses on understanding the increased number, abnormal activation, lung tissue infiltration, and elevated neutrophil-to-lymphocyte ratio in the pathogenesis of COVID-19. We also explore the involvement of NETs and LDNs in disease progression and thrombosis formation, along with potential therapeutic strategies targeting neutrophil and NETs formation.

Unveiling the efficient state of Pd catalyst for robust electrocatalytic hydrodechlorination.

The application of electrochemical hydrodechlorination has been impeded due to the low utilization and activity of Pd catalyst. Herein, a series of Pd catalysts were prepared via the controllable evolution of Zn state during the pyrolysis of ZIF-8 nanosheet. Various forms of Pd with different chemical surroundings were generated upon the combined use of galvanic displacement and ion exchange process. Electrocatalytic hydrodechlorination of 4-chlorophenol was performed and the electrocatalytic hydrodechlorination efficiency of Pd/CN reaches 100% within 3 h at extra low Pd concentration. The coexistence of zero-valent Pd (Pd0) and nitrogen coordinated Pd (Pd-N) was verified by XAFS which provide multiple active sites for focusing on adsorbing H* and cracking C-Cl respectively. The synergetic effect between different chemical state of Pd for efficient hydrodechlorination of chloroaromatics and scheme for dexterous preparation of Pd based electrocatalyst are proposed and discussed.

[Research progress on the relationship between low-density neutrophils and infectious diseases].

Neutrophils play an important role in infectious diseases by clearing pathogens in the early stages of the disease and damaging the surrounding tissues along with the disease progress. Low-density neutrophils (LDNs) are a crucial and distinct subpopulation of neutrophils. They are a mixture of activated and degranulated normal mature neutrophils and a considerable number of immature neutrophils prematurely released from the bone marrow. Additionally, they may be involved in the occurrence and development of diseases through the changes in phagocytosis, the generation of reactive oxygen species (ROS), the enhancement of the ability to produce neutrophils extracellular traps and immunosuppression. We summarizes the role of LDNs in the pathogenesis and their correlation with the severity of infectious diseases such as COVID-19, severe fever with thrombocytopenia syndrome (SFTS), AIDS, and tuberculosis.

A human immunodeficiency virus-seronegative acquired immunodeficiency syndrome patient with opportunistic infections: A case report.

BACKGROUND: In rare cases, people living with chronic human immunodeficiency virus (HIV) infection do not develop antibodies despite demonstrable infection. Delayed or missed diagnosis of HIV infection leads to a lack of timely therapy, resulting in rapid disease progression with opportunistic infections or malignancies. CASE REPORT: A 44-year-old Chinese man presented with sore throat, oral leukoplakia, fever, dyspnoea and diffuse ground glass-like lesions in both lungs. Serum cytomegalovirus DNA was detectable, and CD4+ T-cell count was low. The patient was suspected of being a person living with HIV despite of the repeatedly negative HIV antibody tests using enzyme-linked immunsorbent assay and Western blot. Subsequently, high-plasma HIV RNA viral load was found on two repeated tests, while HIV DNA was also positive. Thus, the patient was confirmed as presenting with HIV-seronegative acquired immunodeficiency syndrome (AIDS). The symptoms improved in response to effective anti-fungal and anti-retroviral therapy after diagnosis. CONCLUSION: This is the third reported case of an HIV-seronegative AIDS patient in China, which are also rarely reported globally. HIV nucleic acid testing is important to screen out HIV infection, especially in those who present with severe immunodeficiency but remain HIV serogenative.

[Progress in mechanism of formation of neutrophil extracellular traps: Review].

Neutrophils play their roles via phagocytosis, degranulation and producing reactive oxygen species(ROS). Moreover, a new reaction mechanism of neutrophils producing neutrophil extracellular traps (NETs) has been reported. NETs take part in the innate immune responses. The formation of NETs is called NETosis, which belongs to programmed cell death. NETs could be formed in response to neutrophils activation by a series of processes, including ROS production, neutrophil elastase (NE) and myeloperoxidase (MPO) transportation to nucleus, histones modification, chromatin decoagulation, and membrane breakage. This process is called NADPH-dependent NETosis. In addition, peptidyl arginine deiminase 4 (PAD4) is needed for NADPH-independent NETosis. Furthermore, NETs can also be rapidly formed. Herein, we mainly reviewed the mechanism of NETosis.

Small cell carcinoma of the bladder: the characteristics of molecular alterations, treatment, and follow-up.

Small cell carcinoma of the bladder (SCCB) is a rare disease associated with high invasiveness and mortality. Histologically, SCCB is difficult to distinguish from small cell lung cancer (SCLC); however, it shares more similar molecular alterations with urothelial carcinoma (UC). As a result, now, the widely accepted theory about the cells of origin is that SCCB and UC probably have a common clone origin. Even the former probably comes from a preexisting UC. At present, given its rarity, early diagnoses, treatments, and follow-ups are not well established, which are vital to patients with SCCB. Inspirationally, in recent years, with the development of molecular diagnostic methods, molecular alterations of SCCB have been understood partially, which are propitious to excavate new potential therapeutic strategies and establish sound follow-ups. Therefore, the future will be light for patients with SCCB.

Fraction spatial distributions and ecological risk assessment of heavy metals in the sediments of Baiyangdian Lake.

Baiyangdian Lake has been the ecological foundation of the Xiongan New Area, a newly developing economic zone in northern China since 2017, meaning that it is increasingly significant to recognize the contamination of the lake. In this work, the spatial distribution and ecological risk of heavy metals in the lake sediments were examined based on field investigation, multivariate statistical analyses and X-ray diffraction techniques (XRD). The results showed that the heavy metals in sediments pose moderate to high risks in most of the sample sites. The heavily contaminated sites presented more unstable chemical (exchangeable and reducible) fractions, and the ecological risk is highly sensitive to the exchangeable fraction in highly contaminative sites. The results of statistical analyses demonstrated that metal fractions were significantly correlated with physicochemical properties, and TP, TN and TOC exhibited a strong correlation with the exchangeable fraction of As, Cd, Pb and Zn. In contrast, Fe and Mn were weakly correlated with the fractions, which due to the high proportion of the nutrient elements in the sediment. Furthermore, the results from the XRD patterns demonstrated that the mineralogy phases of the various heavy metals contributed to the different chemical fractions. Those results demonstrated that further research on metal fraction distribution and influencing factors in the sediment should be implemented to ascertain the degree of toxicity to carry out effective strategies to remediate the lake sediment.

Modulation of Tim-3 Expression by Antigen-Dependent and -Independent Factors on T Cells from Patients with Chronic Hepatitis B Virus Infection.

T-cell immunoglobulin domain and mucin domain-containing molecule-3 (Tim-3) was up-regulated on viral specific T cells and contributed to T cells exhaustion during chronic hepatitis B virus (HBV) infection. However, modulation of Tim-3 expression was still not fully elucidated. To evaluate the potential viral and inflammatory factors involved in the inductor of Tim-3 expression on T cells, 76 patients with chronic HBV infection (including 40 chronic hepatitis B [CHB] and 36 asymptomatic HBV carriers [AsC]) and 40 of normal controls (NCs) were enrolled in this study. Tim-3 expressions on CD4+ and CD8+ T cells were assessed in response to HBV-encoding antigens, HBV peptide pools, and common γ-chain (γc) cytokines stimulation by flow cytometry. HBV peptides and anti-CD3/CD28 directly induced Tim-3 expression on T cells. γc cytokines also drive Tim-3 up-regulations on both CD4+ and CD8+ T cells in patients with chronic HBV infection. However, γc cytokines did not enhance the Tim-3 inductions by either anti-CD3/CD28 or HBV peptides stimulation. Furthermore, γc cytokines-mediated Tim-3 induction could not be abrogated by γc cytokine receptor-neutralizing antibodies. The current results suggested that elevation of Tim-3 expression on T cells could be regulated by both antigen-dependent and -independent manner in patients with chronic HBV infection. The role of γc cytokines in modulation of inhibitory pathway might be evaluated as immunotherapies in humans.

Effect of 48-week pegylated interferon α-2a or nucleos(t)ide analogue therapy on renal function in Chinese patients with chronic hepatitis B.

BACKGROUND: Controversy remains as to whether antiviral agents contribute to renal dysfunction in patients with chronic hepatitis B virus (HBV) infection. Thus, the aim of study was to analyze the changes in renal function of chronic hepatitis B (CHB) patients in response to anti-HBV therapy and the association with treatments. METHOD: We performed a retrospective observational cohort study to investigate factors associated with renal function in 249 Chinese CHB patients who were treated with pegylated interferon α-2a (PEG-IFN-α-2a) or nucleos(t)ide analogues for 48 weeks. Changes of estimated glomerular filtration rate (eGFR), which was computed with both the Chronic Kidney Disease Epidemiology Collaboration and the Modification of Diet in Renal Disease formulas, were tested by repeated measures One-way analysis of variance within groups. A linear mixed effects model for repeated measures was also used to evaluate the association between baseline information and eGFR changes over time in all enrolled patients. The model considered the baseline age, sex, HBV DNA, aminotransferase, blood urea nitrogen, treatment group, time, and group-by-time interaction as fixed effects and incorporated random effects for individual subjects. RESULTS: The eGFR increased in patients given PEG-IFN-α-2a, decreased in patients given adefovir, but remained stable in patients given entecavir. Age and blood urea nitrogen were significant negative predictive factors for eGFR changes. CONCLUSION: In real-life study, PEG-IFN-α-2a therapy in CHB patients increased eGFR, thus may associate with renoprotective effects when compared with adefovir or entecavir therapies.

Measuring Interobserver Disagreement in Rating Diagnostic Characteristics of Pulmonary Nodule Using the Lung Imaging Database Consortium and Image Database Resource Initiative.

RATIONALE AND OBJECTIVES: The purpose of this study was to measure and analyze interobserver disagreement in rating diagnostic characteristics of pulmonary nodules on computed tomography scans using the Lung Imaging Database Consortium and Image Database Resource Initiative (LIDC/IDRI) database, and then to provide investigators with understanding the variability in rating diagnostic characteristics among radiologists. MATERIALS AND METHODS: A histogram-based accumulated nodule-level approach is proposed to measure interobserver disagreement in rating diagnostic characteristics of pulmonary nodules among radiologists. The mean rating differences of radiologists on nodule level are calculated; next, a histogram of the accumulated nodule-level disagreements is constructed; and finally, mean, variance, skewness, and kurtosis statistics based on the histogram are extracted to analyze and summary interobserver disagreement in terms of the assessment of diagnostic characteristics of radiologists. Using the developed computer scheme, the disagreement of radiologists in rating all of 1880 distinct nodules from 1018 computed tomography scans are analyzed using original ratings as well as combined ratings according to the LIDC/IDRI instruction. RESULTS: The interobserver disagreement in rating diagnostic characteristics according to the defined categories of the LIDC/IDRI is substantial. The mean values of disagreement range from 0.0052 to 0.2341. The highest disagreement lies in rating subtlety characteristics, whereas internal structure receives the lowest disagreement of 0.0052. The calcification, texture, spiculation, lobulation, malignancy, sphericity, and margin receive disagreements of 0.0393, 0.1351, 0.1616, 0.1943, 0.2144, 0.2174, and 0.2228, respectively. CONCLUSIONS: Disagreements exist across radiologists in rating diagnostic characteristics of pulmonary nodules, and the disagreement levels vary from each other. Agreement among radiologists is improved by combining ratings according to the LIDC/IDRI instruction. For investigators, understanding and appreciating the disagreement level of each diagnostic characteristic is required when using them in related researches.

Notch Signaling Contributes to Liver Inflammation by Regulation of Interleukin-22-Producing Cells in Hepatitis B Virus Infection.

The mechanism of hepatitis B virus (HBV) induced liver inflammation is not fully elucidated. Notch signaling augmented interleukin (IL)-22 secretion in CD4+ T cells, and Notch-IL-22 axis fine-tuned inflammatory response. We previously demonstrated a proinflammatory role of IL-22 in HBV infection. Thus, in this study, we analyzed the role of Notch in development of IL-22-producing cells in HBV infection by inhibition of Notch signaling using γ-secretase inhibitor DAPT in both hydrodynamic induced HBV-infected mouse model and in peripheral blood cells isolated from patients with HBV infection. mRNA expressions of Notch1 and Notch2 were significantly increased in livers and CD4+ T cells upon HBV infection. Inhibition of Notch signaling in vivo leaded to the reduction in NKp46+ innate lymphoid cells 22 (ILC22) and lymphoid tissue inducer 4 (LTi4) cells in the liver. This process was accompanied by downregulating the expressions of IL-22 and related proinflammatory cytokines and chemokines in the liver, as well as blocking the recruitment of antigen-non-specific inflammatory cells into the liver and subsequent liver injury, but did not affect HBV antigens production and IL-22 secretion in the serum. Furthermore, IL-22 production in HBV non-specific cultured CD4+ T cells, but not HBV-specific CD4+ T cells, was reduced in response to in vitro inhibition of Notch signaling. In conclusion, Notch siganling appears to be an important mediator of the liver inflammation by modulating hepatic ILC22. The potential proinflammatory effect of Notch-mediated ILC22 may be significant for the development of new therapeutic approaches for treatment of hepatitis B.

Toll-like receptor 2 promotes T helper 17 cells response in hepatitis B virus infection.

PURPOSE: Innate and adaptive immune responses play vital roles in initiating and maintaining the immunological homeostasis in both physiological and pathological processes. However, the expression and function of the important cells and molecules as well as their interaction in hepatitis B virus (HBV) infection has not been well elucidated. The aim of the current study was to determine the pattern of Toll-like receptor 2 (TLR2) in T cells in HBV infection and the function of TLR2 in regulation of T helper 17 (Th17) cells response. METHODS: Thirty-four patients with HBV infection (ten acute and twenty-four chronic) were enrolled. HBV-specific and -nonspecific Th17 cells and TLR2 expression in T cells were analyzed by flow cytometry. The function of TLR2 agonist for induction of IL-17 production was also determined. RESULTS: HBV-specific and -nonspecific IL-17 secretion in CD4(+) (Th17 cells) and CD8(+) T cells was significantly elevated in chronic HBV infection. Viral-specific TLR2 expression in CD4(+), CD8(+), and Th17 cells was also remarkably increased in patients with chronic hepatitis B. Moreover, TLR2 agonist Pam3Csk4 directly activated Th17 cells response without antigen stimulation in HBV infection. CONCLUSION: TLR2, which traditionally associated with innate immunity, might also promote Th17 cells response in HBV infection. The function of TLRs in regulation of adaptive immune response in HBV infection, which might play an important role in persistent HBV infection.

A fusion DNA vaccine encoding middle version of HBV envelope protein fused to interleukin-21 did not enhance HBV-specific immune response in mice.

DNA vaccination can generate both humoral and cellular immunity, resulting in potential prophylactic and therapeutic vaccines in variety of conditions, including hepatitis B virus (HBV) infection. Fusion of cytokine gene is one of the ways to increase the immunogenicity of DNA vaccine. Interleukin (IL)-21 has been demonstrated to play an immunomodulatory role in HBV infection. Thus, we aimed to investigate the ability of IL-21 in the regulation of middle version of HBV envelop protein (MS) DNA vaccine. Fusion plasmid encoding IL-21 linked with MS was constructed. Normal and HBV transgenic mice were immunized by plasmid. pcDNA-IL-21/S2S induced a comparable level of anti-HBs antibody and HBsAg-specific CD8+ T-cell response with pcDNA-S2S. Furthermore, the level of circulating HBsAg was decreased by induction of anti-HBs antibody and HBsAg-specific CD8+ T-cell response to both pcDNA-IL-21/S2S and pcDNA-S2S vaccination in HBV transgenic mice. Thus, immunization with DNA vaccine encoding HBV MS protein induced both T- and B-cell response by targeting the specific antigen. Furthermore, it was also revealed that MS DNA vaccination could break immune tolerance in HBV transgenic mice. But IL-21 did not strengthen immune response induced by HBV DNA immunization. Our study suggested that MS-expressing plasmid may be useful for both preventive and therapeutic methods in HBV infection. However, IL-21 does not improve the immunogenicity and efficacy of MS DNA vaccination, and thus may not be used as a therapeutic marker for chronic hepatitis B.

Expression profiles of circulating cytokines, chemokines and immune cells in patients with hepatitis B virus infection.

BACKGROUND: Immune cells and molecules play a vital role in initiating, maintaining, regulating immunological homeostasis and inflammation in many pathological and physiological processes; however, the changes on expressions and functions of these cells and molecules in hepatitis B virus (HBV) infection have not been elucidated well. OBJECTIVES: The current study aimed to determine the expression pattern of different cytokines, chemokines, immune cells in HBV infection and their association with disease progression. PATIENTS AND METHODS: Sixty-nine patients with chronic HBV infection were enrolled. Five immune cell subsets and 46 cytokines and chemokines were analyzed by flow cytometry and Luminex 200. RESULTS: In comparison to healthy individuals and asymptomatic HBV carriers, expression of CXCL9, CXCL10, CXCL11, and IL-10 were elevated in patients with chronic active HBV and had positive correlation with ALT levels. In contrast, G-CSF, MCP-3, and IFN-γ levels were significantly decreased in patients with chronic active HBV infection in contrast to carriers and healthy individuals; however, these down regulations did not show any correlation with either virological findings or liver inflammation. Although the proportion of CD4(+) CD25 (high) regulatory T cells (Tregs) was higher in patients with HBV infection than in healthy controls, no correlations were found between Tregs and other cytokines or chemokines. CONCLUSIONS: CXCR3-associated chemokines might contribute to liver inflammation in chronic hepatitis B, while MCP-3 and G-CSF were inhibited by HBV infection. Host immune response was suppressed as manifested by an increase in CD4(+) CD25(high) Tregs and IL-10 as well as a decrease in IFN-γ. Exploiting the expression pattern of cytokine and chemokine may help to develop a better understanding of chronic HBV infection pathogenesis.

Telbivudine plus adefovir therapy for chronic hepatitis B patients with virological breakthrough or genotypic resistance to telbivudine.

BACKGROUND/AIM: There is very limited experience in the management of telbivudine (LdT)-associated virological breakthrough (VBT) and resistance in the treatment of chronic hepatitis B (CHB) patients, and the guideline recommendations are primitively based on the general principles of rescue therapy to nucleos(t)ide analog resistance. The aim of this study is to determine the effect of the addition of adefovir (ADV) in hepatitis B e antigen (HBeAg)-positive CHB patients with VBT or resistance to LdT. METHODS: Thirty-seven CHB patients with confirmed VBT and 31 patients with genotypic resistance to LdT were enrolled and thereafter treated with a combination of LdT and ADV for 12 months. RESULTS: Combination therapy was safe and the majority of patients tolerated the therapy. LdT+ADV led to rapid decreases in viral loads, and viral replications were persistently suppressed, with 2.17 (VBT) and 2.31 (resistance) log(10) copies/ml reductions 12 months after rescue therapy, respectively. The rates corresponding to virological and biochemical responses were similar between the two groups at the end of observations (70.3 vs. 74.2% for virological response, P=0.720; 64.0 vs. 65.5% for biochemical response, P=0.907). The cumulative rates of serological responses were higher in patients with VBT than in those with resistance (35.1 vs. 9.67% for HBeAg loss, P=0.014; 10.8 vs. 3.23% for HBeAg/anti-HBe seroconversion, P=0.233). CONCLUSION: LdT and ADV combination therapy led to significant decreases in serum hepatitis B virus DNA levels and normalization of alanine aminotransferase levels in patients with VBT or genotypic resistance to LdT. This rescue strategy was also associated with a higher rate of HBeAg serological outcomes in patients with confirmed LdT-related VBT.

Dysregulation of the ß3 integrin-VEGFR2 complex in Hantaan virus-directed hyperpermeability upon treatment with VEGF.

Hantaviruses infect human endothelial cells (ECs) and are known to cause vascular-permeability-based diseases, including hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). The αvß3 integrins, which are highly expressed on the surface of ECs, serve as hantavirus receptors. Specifically, the ß3 integrin and vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) form a functional complex and interact with each other. Signaling through this complex causes cytoskeletal reorganization, which is one of the most important mechanisms underlying hyperpermeability. In this study, we show that VEGF dramatically enhances Hantaan virus (HTNV)-directed permeability and increases the reorganization of the cytoskeleton and the disruption of junctional organizations in an EC monolayer at 3 days postinfection. HTNV infection reduced the effect of VEGF on adhesion, migration, and the upregulation of ß3 expression, but the infection alone upregulated the expression of ß3 and VEGFR2. These results indicate that in addition to its role in blocking ß3 integrin activation as reported previously, HTNV blocks the function of the complex of VEGFR2 and ß3 integrin, and the dysfunction of the complex may contribute to cytoskeletal reorganization in an HTNV-directed hyperpermeability response to VEGF.

[Immune response to HBsAg can not be enhanced with B7-H1 protein vaccine].

AIM: To observe the immunization effect to HBsAg by B7-H1 protein vaccine in transgenic mice, and to explore new methods for the treatment of chronic hepatitis B. METHODS: After the joint immunization in HBV transgenic mice with different doses of hepatitis B virus (HBV) vaccine and B7-H1 protein, the anti-B7-H1 antibody titors, Th1 type of cytokines (IFN-γ and IL-2) from the spleen cells of mice, the number of the T cells secreting IFN-γ and the number of the mice lymphocyte proliferation were measrued by ELISA, ELISPOT and MTT technique respectively, to compare the immune effect of different immune methods and regimen. RESULTS: The immune plans were completed successfully. The anti-B7-H1 antibody was detected in the fifth week after immunization with B7-H1 vaccine, at the same time no obvious difference of antibodies titors between groups were found. IL-2 and the number of T cells secreting IFN-γ were significantly reduced(P<0.05)in joint immunization group with B7-H1 protein and HBsAg, but no difference in other immune tests, such as IFN-γ, lymphocyte proliferation. CONCLUSION: A lower doses of HBsAg can cause the secretion of Th1 type of cytokines and lymphocyte proliferation. B7-H1 protein vaccines have a better immunogetic effect for HBV transgenic mice, but can notupregulate the immune response to HBsAg.