A dynamic prediction model of landslide displacement based on VMD-SSO-LSTM approach.

Addressing the limitations of existing landslide displacement prediction models in capturing the dynamic characteristics of data changes, this study introduces a novel dynamic displacement prediction model for landslides. The proposed method combines Variational Mode Decomposition (VMD) with Sparrow Search Optimization (SSO) and Long Short-Term Memory (LSTM) techniques to formulate a comprehensive VMD-SSO-LSTM model. Through the application of VMD, the method dissects cumulative displacement and rainfall data, thereby extracting distinct components such as trend, periodicity, and fluctuation components for displacement, as well as low-frequency and high-frequency components for rainfall. Furthermore, leveraging Gray Correlational Analysis, the interrelationships between the periodic component of displacement and the low-frequency component of rainfall, as well as the fluctuation component of displacement and the high-frequency component of rainfall, are established. Building upon this foundation, the SSO-LSTM model dynamically predicts the interrelated displacement components, synthesizing the predicted values of each component to generate real-time dynamic forecasts. Simulation results underscore the effectiveness of the proposed VMD-SSO-LSTM model, indicating root-mean-square error (RMSE) and mean absolute percentage error (MAPE) values of 1.2329 mm and 0.1624%, respectively, along with a goodness of fit (R2) of 0.9969. In comparison to both back propagation (BP) prediction model and LSTM prediction model, the VMD-SSO-LSTM model exhibits heightened predictive accuracy.

Construction safety influencing factor analysis of bridge-erecting machines based on structural equation modeling.

To reduce the frequency of bridge-erecting machine accidents and ensure construction safety, it is necessary to correctly understand the factors affecting the construction safety of bridge-erecting machines and their relative importance. Through a literature review and a field investigation, 15 factors were identified affecting the construction safety of bridge-erecting machines. Then, questionnaire survey items are established. Structural equation modeling (SEM) was used to build the relationship model among the factors. The model included four aspects-human, mechanical equipment, and environmental safety and management-to discuss the influence of each factor on the safety of bridge-erecting machine construction. Additionally, the relationships between the influencing factors is studied and analyzed. The results show that human, mechanical equipment, and environmental safety and management capacity have significant normal influences on the construction safety of bridge-erecting machines. Human safety has the greatest influence on the construction safety of bridge-erecting machines, followed by management capacity, mechanical equipment safety, and environmental safety. In addition, the four influencing factors have a certain degree of mutual influence.

Comparison of NAFLD, MAFLD and MASLD characteristics and mortality outcomes in United States adults.

BACKGROUND & AIMS: Following the classification of metabolic dysfunction-associated fatty liver disease (MAFLD), non-alcoholic fatty liver disease (NAFLD) has recently been redefined again as metabolic dysfunction-associated steatotic liver disease (MASLD). However, the distinctions in characteristics and mortality outcomes between NAFLD, MAFLD and MASLD remain unclear. METHODS: We analysed data from 7519 participants in the third National Health and Nutrition Examination Surveys of United States (US) and their linked mortality until 2019. Survey weight-adjusted multivariable Cox proportional model was used to study the mortality over three terms. RESULTS: The prevalence of NAFLD, MAFLD and MASLD was 18.5%, 19.3% and 20.8%, respectively. Most individuals with NAFLD (94.5%) or MAFLD (100%) can be classified as MASLD, while a relatively low percentage of those with MASLD were also diagnosed with either NAFLD (84.1%) or MAFLD (92.7%). During a median follow-up of 26.9 years, both MAFLD and MASLD were associated with increased risk of all-cause mortality (adjusted hazard ratio [aHR] 1.18, 95% CI 1.04-1.33 and 1.19, 1.06-1.34, respectively), this association was mainly observed in NAFLD-/MASLD+ subgroups. NAFLD was not associated with all-cause mortality. However, all three terms were associated with an increased risk of all-cause mortality in individuals with advanced fibrosis (aHR: 1.71-1.81). Subgroup analyses showed that higher risk of all-cause mortality for both MAFLD and MASLD were observed among older adults (≥65 year), non-Hispanic whites and those without diabetes. CONCLUSIONS: Both MASLD and MALFD were linked to higher all-cause mortality risk, but MASLD identified a greater number of individuals compared to MAFLD.

Avian ANP32A incorporated in avian influenza A virions promotes interspecies transmission by priming early viral replication in mammals.

Species-specific differences in acidic nuclear phosphoprotein 32 family member A (ANP32A) determine the restriction of avian-signature polymerase in mammalian cells. Mutations that evade this restriction, such as PB2-E627K, are frequently acquired when avian influenza A viruses jump from avian hosts to mammalian hosts. However, the mechanism underlying this adaptation process is still unclear. Here, we report that host factor ANP32 proteins can be incorporated into influenza viral particles through combination with the viral RNA polymerase (vPol) and then transferred into targeted cells where they support virus replication. The packaging of the ANP32 proteins into influenza viruses is dependent on their affinity with the vPol. Avian ANP32A (avANP32A) delivered by avian influenza A virions primes early viral replication in mammalian cells, thereby favoring the downstream interspecies transmission event by increasing the total amount of virus carrying adaptive mutations. Our study clarifies one role of avANP32A where it is used by avian influenza virus to help counteract the restriction barrier in mammals.

Prognostic evaluation of the novel blueprint of DNA methylation sites by integrating bulk RNA-sequencing and methylation modification data in endometrial cancer.

INTRODUCTION: Endometrial cancer (EC) is a prevalent malignancy affecting the female population, with an increasing incidence among younger age groups. DNA methylation, a common epigenetic modification, is well-established to play a key role in cancer progression. We suspected whether DNA methylation could be used as biomarkers for EC prognosis. METHODS: In the present study, we analyzed bulk RNA-sequencing data from 544 EC patients and DNA methylation data from 430 EC patients in the TCGA-UCEC cohort. We applied weighted correlation network analysis to select a key gene set associated with panoptosis. We conducted correlation analysis between transcriptomic data of the selected key genes and DNA methylation data to identify valuable DNA methylation sites. These sites were further screened by Cox regression and least absolute shrinkage and selection operator analysis. Immune microenvironment differences between high-risk and low-risk groups were assessed using single-sample gene set enrichment analysi, xCell and MCPcounter algorithms. RESULTS: Our results identified five DNA methylation sites (cg03906681, cg04549977, cg06029846, cg10043253 and cg15658376) with significant prognostic value in EC. We constructed a prognostic model using these sites, demonstrating satisfactory predictive performance. The low-risk group showed higher immune cell infiltration. Notably, methylation of site cg03906681 was negatively related to CD8 T cell infiltration, whereas cg04549977 exhibited positive correlations with immune infiltration, particularly in macrophages, activated B cells, dendritic cells and myeloid-derived suppressor cells. PD0325901_1060 was strongly correlated with risk scores, indicating a potential therapeutic response for high-risk EC patients. CONCLUSION: We have developed a robust DNA methylation-based prognostic model for EC, which holds promise for improving prognosis prediction and personalized treatment approaches. These findings may contribute to better management of EC patients, particularly in identifying those at higher risk who may benefit from tailored interventions.

Assessment of identification performance for high emission heavy-duty diesel vehicles by means of remote sensing.

To improve the accuracy of detecting high NO (nitric oxide) emissions from heavy-duty diesel vehicles (HDDV) by remote sensing (RS), the emissions of one HDDV complied with China V regulation and one HDDV complied with China VI regulation at constant speeds, with and without after-treatment devices, are tested by a portable emission measurement system (PEMS) and RS. The optimized measurement procedures for detecting high NO emissions from China V and China VI HDDVs by RS are summarized. The correlation of RS and PEMS data shows that the ratio of NO to CO2 (carbon dioxide) is a more appropriate RS measurement than NO concentration alone for identifying high emitters, although NO concentrations of 600 ppm and 100 ppm can be used as a basis for distinguishing between China V and China VI HDDVs, respectively. When the NO/CO2 ratio is >200 × 10-4 and 25 × 10-4, identifying China V and China VI HDDV high emitters, respectively, is possible. Additionally considering the vehicle speed can reduce the high emitter identification error rate, and excluding data where vehicle acceleration is less than -0.1 m/s2 can further improve identification accuracy. Four new high-emitter identification methods based on different combinations of measurements are shown to improve identification efficiency with only small increases in identification error. This study provides evidence to support the future development of high-precision RS methodologies for identifying high-emission vehicles.

Identification of new reference genes for colony counting by reverse-transcription quantitative PCR in Bifidobacterium animalis.

Bifidobacterium animalis, one of the predominant bacteria in the intestines of humans and other mammals, is widely added to dairy products. We employed RNA sequencing to analyze gene expression variance on a genome-wide scale and found stable reference genes (RG) in B. animalis. A total of 1,665 genes were identified by analyzing the data from the transcriptome under 4 different conditions, and 13 probable candidate RG with variation coefficient values <0.1 were validated using reverse-transcription quantitative PCR (RT-qPCR). The amplification efficiency of candidate RG were ranging from 94.16% to 126.25%. We integrated the analysis results of BestKeeper, geNorm, NormFinder, and RefFinder algorithms and revealed that rplD and atpA comprehensive ranked 1.68 and 2.82, respectively, which were more stable than traditional RG. Compared with plate count (1.58 × 106 cfu/mL), the concentrations of B. animalis AR668 by RT-qPCR using rplD, atpA, and 16S rRNA as RG were 2.27 × 106, 2.24 × 106, and 6.66 × 106 cfu/mL, respectively, after 10 h of fermentation in fermented skim milk. It suggested that rplD and atpA as RG can be accurate for colony counting of B. animalis. Our study provides the foundation for more accurate analysis of colony counting by RT-qPCR of B. animalis in dairy foods.

Fault Root Cause Tracking of the Mechanical Components of CNC Lathes Based on Information Transmission.

This study proposes a new method for the immediate fault warning and fault root tracing of CNC lathes. Here, the information acquisition scheme was formulated based on the analysis of the coupling relationship between the mechanical parts of CNC lathes. Once the collected status signals were de-noised and coarse-grained, transfer entropy theory was introduced to calculate the net entropy of information transfer between the mechanical parts, after which the information transfer model was constructed. The sliding window method was used to determine the probability threshold interval of the net information transfer entropy between the lathe mechanical parts under different processing modes. Therefore, the transition critical point was determined according to the information entropy, and the fault development process was clarified. By analyzing the information transfer changes between the parts, fault early warning and fault root tracking on the CNC lathe were realized. The proposed method realizes the digitalization and intelligentization of fault diagnosis and has the advantages of timely and efficient diagnosis. Finally, the effectiveness of the proposed method is verified by a numerical control lathe tool processing experiment.

Research on an evaluation index system and evaluation method of green and low-carbon expressway construction.

To promote the development of green and low-carbon expressway construction, an evaluation index system and associated evaluation method for the construction of green and low-carbon expressways suitable for multiple bridges and tunnels is proposed. The evaluation index system was created from three layers: the goal layer, the criterion layer, and the indicator layer. The criterion layer includes 4 first-level indices and the indicator layer includes 18 second-level indices. The weight of each index in the criterion layer and indicator layer is determined using the improved analytic hierarchy process (AHP) method, and green and low-carbon expressway construction is then graded using the gray fuzzy comprehensive evaluation method combined quantitative indices with qualitative indices. The method with the selected indices is then verified in a case study on the Huangling-Yan'an Expressway, with the evaluation grade being "Excellent" and the evaluation value being 9.1255. The proposed evaluation method can provide theoretical and practical guidance for effective evaluation for green and low-carbon expressway construction.

Humoral responses after primary and booster SARS-CoV-2 inactivated vaccination in patients with chronic hepatitis B virus infection: A longitudinal observational study.

Given the pandemic of severe acute respiratory syndrome coronavirus 2 Omicron variants, booster vaccination (BV) using inactivated virus vaccines (the third dose) has been implemented in China. However, the immune responses after BV, especially those against Omicron, in patients with chronic hepatitis B virus (HBV) infection (CHB) are unclear. In this prospective longitudinal study, 114 patients with CHB and 68 healthy controls (HCs) were recruited after receiving inactivated vaccination. The anti-receptor-binding domain (RBD) immunoglobulin G (IgG), neutralizing antibodies (NAbs), neutralization against Omicron (BA2.12.1, BA.4/5), and specific B/T cells were evaluated. In patients, anti-RBD IgG was elevated significantly after BV; the titers were as high as those in HCs. Similar results were obtained for the NAbs. However, compared with that against wild type (WT), the neutralization against Omicron was compromised after BV. The frequency of RBD+ atypical memory B cells increased, but spike-specific cluster of differentiation 4+ /8+ T cells remained unchanged after BV. Moreover, no serious adverse events or HBV reactivation were observed after BV. These results suggest that BV significantly enhanced antibody responses against WT; however, it resulted in compromised antibody responses against Omicron in patients with CHB. Hence, new all-in-one vaccines and optimal vaccination strategies should be studied promptly.

Dual-Aptamer-Assisted Ratiometric SERS Biosensor for Ultrasensitive and Precise Identification of Breast Cancer Exosomes.

Due to the heterogeneity of breast cancer, its early accurate diagnosis remains a challenge. Exosomes carry abundant genetic materials and proteins and are ideal biomarkers for early cancer detection. Herein, a ratiometric surface-enhanced Raman scattering (SERS) biosensor for exosome detection was constructed using a regularly arranged Au@Ag nanoparticles/graphene oxide (Au@Ag NPs/GO) substrate with 4-nitrothiophenol (4-NTP) molecules as an internal standard. Aptamers of two overexpressed proteins (epithelial cell adhesion molecule and human epidermal growth factor receptor 2) were linked by a short complementary DNA with rhodamine X modified at the 3'-terminal to form V-shaped double-stranded DNA, which attached to the surface of Au@Ag NPs/GO substrate for the selective recognition of breast cancer cell-derived exosomes. In the presence of exosomes, a competitive reaction occurred, resulting in the formation of the V-shaped double-stranded DNA/exosomes complex, and the V-shaped double-stranded DNA separated from the SERS substrate. The SERS signal of rhodamine X on the V-shaped double-stranded DNA decreased with the concentration of exosomes increasing, whereas the SERS signal of 4-NTP on the substrate remained stable. The ratiometric SERS strategy provides huge electromagnetic enhancement and abundant DNA adsorbing sites on the GO layer, achieving a wide detection range of 2.7 × 102 to 2.7 × 108 particles/mL and an ultralow limit of detection down to 1.5 × 102 particles/mL, without the requirement of any nucleic acid amplification. Particularly, the proposed method has significant applications in early cancer diagnosis as it can accurately identify breast cancer cell-derived exosomes in clinical serum samples and can differentiate pancreatic cancer patients and healthy individuals.

UHPLC Q-Orbitrap Mass Spectrometry-Based Molecular Networking for Identification of Chemical Constituents in the Multi-Herb Formula Runyan Mixture.

Traditional Chinese medicine (TCM) in-hospital preparations are approved for use only in the hospital where they are prepared. They are widely used in China because of their efficacy and affordable price. However, few researchers focused on their quality controls and treatment mechanisms, for which a key consideration is the elucidation of their chemical composition. Runyan mixture (RY) is a typical in-hospital TCM preparation comprising a formula of eight herbal drugs used for adjuvant therapy of upper respiratory tract infections. The chemical constituents of formulated RY have not yet been elucidated. In the present work, RY was analyzed by a ultrahigh-performance liquid chromatography system equipped with high-resolution orbitrap mass spectrometry (MS). The acquired MS data were processed by MZmine and a feature-based molecular networking was constructed to identify the metabolites of RY. 165 compounds including 41 flavonoid O-glycosides, 11 flavonoid C-glycosides, 18 quinic acids, 54 coumaric acids, 11 iridoids, and 30 others were identified. This study demonstrates an efficient method to identify compounds in complex herbal drug mixtures using high-resolution MS and molecular networking tools which will support future research into quality controls and treatment mechanisms of in-hospital TCM preparations.

Weakened humoral and cellular immune response to the inactivated COVID-19 vaccines in Chinese individuals with obesity/overweight.

Inactivated COVID-19 vaccines have been widely used to vaccinate the Chinese population. However, limited literature exists to explore the effect of obesity on the humoral and cellular immune response to these vaccines. In this study, 132 high BMI (Body mass index) (obesity and overweight, BMI ≥ 24 kg/m2) and 82 normal BMI (BMI < 24 kg/m2) participants were enrolled. Adverse events (AEs), Spike receptor-binding domain IgG antibody (anti-RBD-IgG), neutralizing antibodies (NAbs), and specific B-cell and T-cell responses were evaluated 21-105 days after full-course inactivated COVID-19 vaccination. The overall incidence of AEs was similar in individuals with and without obesity/overweight. No serious vaccine-related AEs occurred. Individuals with obesity/overweight had a reduced seropositivity rate of NAbs compared to those with normal BMI. Anti-RBD-IgG and NAbs titers in the high BMI group were significantly lower than those in the normal BMI group. The frequencies of RBD-specific memory B cells (MBCs) and the numbers of spike-specific TNF-α+ spot-forming cells (SFCs) in individuals with obesity/overweight were reduced compared with those noted in individuals without obesity/overweight. A similar trend of weakened humoral responses was also observed in individuals with central obesity. Our study results suggested that inactivated COVID-19 vaccines were safe and well tolerated but induced poor humoral and cellular immune responses in Chinese individuals with obesity/overweight.

Design, synthesis, and evaluation of JTE-013 derivatives as novel potent S1PR2 antagonists for recovering the sensitivity of colorectal cancer to 5-fluorouracil.

Targeting sphingosine-1-phosphate receptor 2 (S1PR2) has been proved as a promising strategy to reverse 5-fluorouracil (5-FU) resistance. Here, we report the discovery of the novel JTE-013 derivative compound 37 h as a more effective S1PR2 antagonist to reverse 5-FU resistance in SW620/5-FU and HCT116DPD cells than JTE-013 and previously reported compound 5. Compound 37 h could effectively bind S1PR2 and reduce its expression, thus leading to decreased expression of JMJD3 and dihydropyrimidine dehydrogenase (DPD), while also increasing the level of H3K27me3 to decrease the degradation of 5-FU and thereby increase its intracellular concentration in SW620/5-FU, HCT116DPD, and L02 cells. Furthermore, compound 37 h showed good selectivity to other S1PRs and normal colon cell line NCM460. Western blot analysis demonstrated that compound 37 h could abrogate the FBAL-stimulated upregulation of DPD expression by S1PR2. Importantly, compound 37 h also showed favorable metabolic stability with a long half-life (t1/2) of 7.9 h. Moreover, compound 37 h significantly enhanced the antitumor efficacy of 5-FU in the SW620/5-FU animal model. Thus, the JTE-013-based derivative compound 37 h represents a promising lead compound for the development of novel 5-FU sensitizers for colorectal cancer (CRC) therapy.

Dynamic Humoral Immune Response to Primary and Booster Inactivated SARS-CoV-2 Vaccination in Patients with Cirrhosis.

Background and Aims: Our aim was to determine the immune efficacy of a severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) booster vaccination in cirrhotic patients who had received the primary series. Methods: We performed a longitudinal assessment in 48 patients with cirrhosis, 57 patients with chronic hepatitis B (CHB) and 68 healthy controls (HCs) to continuously track the dynamics of SARS-CoV-2 specific antibodies and memory B cells after receiving the primary series and booster dose at different times. A pseudovirus neutralization assay was used to determine neutralization against Omicron subvariants BA.2.12.1, BA.4 and BA.5 from serum samples collected from three cohorts. Results: Serum anti-receptor-binding domain (RBD) immunoglobulin (Ig)G and neutralizing antibody (NAb) levels in cirrhotic patients were elevated within 15-45 days after completing the primary series before rapidly declining and reaching a valley at around 165-195 days. After receiving the booster dose, both antibody levels were significantly increased to levels comparable to patients with CHB and HCs. Subgroup analysis showed that booster vaccination induced weaker antibody responses in patients with decompensated cirrhosis than in those with compensated cirrhosis. The SARS-CoV-2 memory B-cell response in cirrhotic patients was durable during follow-up regardless of the hepatic fibro-cirrhosis grade. However, compared with the primary series, the booster dose did not result in an evident improvement of neutralization activity against the Omicron subvariants BA.2.12.1 and BA.4, and was followed by a significant decrease in the titer against BA.5. Conclusions: A booster dose elicited a robust and durable humoral response to the wild-type strain in cirrhotic patients but not the Omicron subvariants. Repeated vaccination of inactivated SARS-CoV-2 vaccine may not benefit cirrhotic patients in neutralization against newly circulating strains.

A biochip based on shell-isolated Au@MnO2 nanoparticle array-enhanced fluorescence effect for simple and sensitive exosome assay.

Exosomes, carrying specific molecular information of their parent cells, have been regarded as a kind of promising noninvasive biomarker for liquid biopsy. Plentiful fluorescence methods have been proposed for exosome assay. However, most of them are dependent on nucleic acid signal amplification strategies, which require complicated sequence design and experimental operation. Herein, a metal-enhanced fluorescence (MEF) biochip based on shell-isolated Au@MnO2 nanoparticle array was designed for simple and sensitive assay of exosomes. The designed method consists of only two parts: signal conversion and MEF amplification. The conversion of exosome signals to DNA signals was realized by means of chain displacement reaction. The subtle conversion effectively averts the effect of steric hindrance on MEF while amplifying the signal easily for the first time. The MEF biochip based on shell-isolated Au@MnO2 nanoparticle array achieves a second signal amplification in a simple way. Profiting from the two signal amplifications, this strategy displays high sensitivity toward exosomes with a detection limit of 4.5 × 103 particles µL-1. Compared with the result without MEF, the sensitivity is enhanced about thirty times. As far as we know, this is the first attempt for exosome assay by using MEF strategy. In addition to the favorable fluorescence enhancement, both shell-isolated Au@MnO2 nanoparticles and Au@MnO2 nanoparticle array show excellent stability in buffer solutions, which is conducive to practical application. Moreover, the proposed method is able to distinguish breast cancer patients from healthy people, showing its potential for exosome-based liquid biopsy.

Comparative analysis of expression profiles of metacaspase (MC) genes between two apple (Malus domestica) cultivars with distinct ripening behavior.

The purpose of this research was to determine expression profiles of metacaspase (MC) genes during ripening and senescence of two apple cultivars with distinct ripening behavior. "Golden Delicious" and "Fuji" harvested at commercial maturity were used as materials. Our data revealed that flesh firmness, respiration rate, ethylene production, metacaspase (MC) activity, superoxide anion (O2 •- ) production rate, relative electrical conductivity (REC), hydrogen peroxide (H2 O2 ), and malondialdehyde (MDA) contents in "Golden Delicious" were higher than in "Fuji" during ripening. At 35 days, no DNA ladder was observed in both cultivars, and tonoplast disintegration was only observed in "Golden Delicious" by transmission electron microscope (TEM), indicating that programmed cell death (PCD) was initiated earlier in "Golden Delicious" than in "Fuji." A total of 18 MC genes were detected to be expressed in both cultivars. For those genes expressed only in "Golden Delicious," MdMC06, MdMC10, MdMC12, and MdMC21 might play a role in the early stage of ripening, whereas MdMC19 might be associated with the late stage of ripening. MdMC15 was expressed only in "Fuji." The remaining MC genes were differentially expressed in both cultivars during ripening. These results would provide useful information to further underlie the relationships among MC genes, PCD and storability of different apple cultivars. PRACTICAL APPLICATIONS: Apple is one of the most popular fruits in the world. Different apple cultivars vary in their ripening behavior and storability, but the molecular mechanism has not yet been fully elucidated. "Golden Delicious" and "Fuji" are two important apple cultivars worldwide. Our data indicated that PCD was initiated earlier in "Golden delicious" than in "Fuji" during postharvest ripening and senescence. MdMCs showed variable expression patterns in both cultivars during ripening. MdMC15 and MdMC19 might be closely associated with the early stage of PCD. These results would provide useful information to further decode the molecular mechanisms responsible for different storage storability of apple cultivars.

Increased ILT2 expression contributes to dysfunction of CD56dimCD16+NK cells in chronic hepatitis B virus infection.

Natural killer (NK) cells play a crucial role in the control of human viral infections but their activity is significantly impaired in patients infected with chronic hepatitis B (CHB). The mechanism that contributes to NK cell dysfunction in CHB needs further elucidation. In this study, we analyzed the expression and function of the novel inhibitory receptor immunoglobulin-like transcript-2 (ILT2) on NK cells from 131 CHB patients and 36 healthy controls. We observed that ILT2 expression on circulating CD56dimCD16+NK cells was increased in immune-tolerant, immune-active and HBeAg-negative hepatitis patients compared with inactive carriers and controls. The frequency of ILT2+CD56dimNK cells was positively correlated with serum viral load in immune-tolerant patients. The percentage of ILT2+CD56dimNK cells decreased along with HBV load in CHB patients who received antiviral therapy. Functional analysis showed that ILT2+CD56dimNK cells in CHB patients had significantly reduced degranulation and IFN-γ production. Upregulation of ILT2 was associated with high levels of apoptosis in CD56dimCD16+NK cells from CHB patients. ILT2 blockade was shown to increase the cytotoxicity and IFN-γ production of CD56dimNK cells in some CHB patients. Finally, ILT2 was found to be moderately upregulated by TGF-ß1, which was increased in immune-tolerant, immune-active and HBeAg-negative hepatitis patients. Our results show that chronic HBV infection increases the levels of the inhibitory receptor ILT2 on CD56dimNK cells and inhibits their functions, providing a new mechanism of NK-cell disability in CHB patients.