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Abstract This research explores the causal link between dietary habits and hypertension through Mendelian randomization, providing distinct perspectives on the role of diet in addressing this worldwide health issue. Utilizing instrumental variables, we applied advanced statistical methods, including the weighted median, inverse variance weighted, and MR‐Egger, to evaluate the impact of 17 dietary elements on hypertension. These elements ranged across various food groups, such as fruits, meats, vegetables, and beverages, both alcoholic and nonalcoholic. Our results identified a significant positive association of hypertension with weekly alcohol consumption (OR 1.340 [95%CI 1.0001 to 1.794], p = .0499) and poultry intake (OR 2.569 [95%CI 1.305 to 5.057], p = .00631). Conversely, a negative association was observed with lamb/mutton (OR 0.550 [95%CI 0.343 to 0.881], p = .0129), cheese (OR 0.650 [95%CI 0.519 to 0.813], p = .000159), tea (OR 0.797 [95%CI 0.640 to 0.993], p = .0433), cereal (OR 0.684 [95%CI 0.494 to 0.948], p = .0227), and dried fruit consumption (OR 0.492 [95%CI 0.343 to 0.707], p = .000127). These findings suggest that dietary modifications, such as increasing consumption of specific foods like cheese, lamb/mutton, tea, cereals, and dried fruits, could potentially reduce hypertension risk while reducing intake of alcoholic beverages and poultry might mitigate its increase. No direct causal relationships were established between other dietary factors and hypertension. The study highlights the importance of specific dietary modifications for the prevention and control of hypertension, making a substantial contribution to public health tactics and recommendations.

Abstract As a signaling molecule, nitric oxide (NO) regulates the development and stress response in different organisms. The major biological activity of NO is protein S‐nitrosylation, whose function in fungi remains largely unclear. Here, it is found in the rice blast fungus Magnaporthe oryzae, de‐nitrosylation process is essential for functional appressorium formation during infection. Nitrosative stress caused by excessive accumulation of NO is harmful for fungal infection. While the S‐nitrosoglutathione reductase GSNOR‐mediated de‐nitrosylation removes excess NO toxicity during appressorium formation to promote infection. Through an indoTMT switch labeling proteomics technique, 741 S‐nitrosylation sites in 483 proteins are identified. Key appressorial proteins, such as Mgb1, MagB, Sps1, Cdc42, and septins, are activated by GSNOR through de‐nitrosylation. Removing S‐nitrosylation sites of above proteins is essential for proper protein structure and appressorial function. Therefore, GSNOR‐mediated de‐nitrosylation is an essential regulator for appressorium formation. It is also shown that breaking NO homeostasis by NO donors, NO scavengers, as well as chemical inhibitor of GSNOR, shall be effective methods for fungal disease control.

Abstract During the COVID-19 pandemic, Pfizer-BioNTech and Moderna successfully developed nucleoside-modified mRNA lipid nanoparticle (LNP) vaccines. SARS-CoV-2 spike protein expressed by those vaccines are identical in amino acid sequence, but several key components are distinct. Here, we compared the effect of ionizable lipids, untranslated regions (UTRs), and nucleotide composition of the two vaccines, focusing on mRNA delivery, antibody generation, and long-term stability. We found that the ionizable lipid, SM-102, in Moderna’s vaccine performs better than ALC-0315 in Pfizer-BioNTech’s vaccine for intramuscular delivery of mRNA and antibody production in mice and long-term stability at 4 °C. Moreover, Pfizer-BioNTech’s 5′ UTR and Moderna’s 3′ UTR outperform their counterparts in their contribution to transgene expression in mice. We further found that varying N1-methylpseudouridine content at the wobble position of mRNA has little effect on vaccine efficacy. These findings may contribute to the further improvement of nucleoside-modified mRNA-LNP vaccines and therapeutics.

BackgroundEvidence indicates that chronic non-alcoholic fatty liver disease (NAFLD) can increase the risk of atherosclerosis (AS), but the underlying mechanism remains unclear.ObjectiveThis study is intended for confirming key genes shared between NAFLD and AS, and their clinical diagnostic value to establish a foundation for searching novel therapeutic targets.MethodsWe downloaded the Gene Expression Omnibus (GEO) datasets, GSE48452 and GSE89632 for NAFLD and GSE100927, GSE40231 and GSE28829 for AS. The progression of NAFLD co-expression gene modules were recognized via weighted gene co-expression network analysis (WGCNA). We screened for differentially expressed genes (DEGs) associated with AS and identified common genes associated with NAFLD and AS using Venn diagrams. We investigated the most significant core genes between NAFLD and AS using machine learning algorithms. We then constructed a diagnostic model by creating a nomogram and evaluating its performance using ROC curves. Furthermore, the CIBERSORT algorithm was utilized to explore the immune cell infiltration between the two diseases, and evaluate the relationship between diagnostic genes and immune cells.ResultsThe WGCNA findings associated 1,129 key genes with NAFLD, and the difference analysis results identified 625 DEGs in AS, and 47 genes that were common to both diseases. We screened the core RPS6KA1 and SERPINA3 genes associated with NAFLD and AS using three machine learning algorithms. A nomogram and ROC curves demonstrated that these genes had great clinical meaning. We found differential expression of RPS6KA1 in patients with steatosis and NASH, and of SERPINA3 only in those with NASH compared with normal individuals. Immune infiltration findings revealed that macrophage and mast cell infiltration play important roles in the development of NAFLD and AS. Notably, SERPINA3 correlated negatively, whereas RPS6KA1 correlated positively with macrophages and mast cells.ConclusionWe identified RPS6KA1 and SERPINA3 as potential diagnostic markers for NAFLD and AS. The most promising marker for a diagnosis of NAFLD and AS might be RPS6KA1, whereas SERPINA3 is the most closely related gene for NASH and AS. We believe that further exploration of these core genes will reveal the etiology and a pathological relationship between NAFLD and AS.

ObjectiveThis study aimed to assess the association between Red Cell Distribution Width-to-Albumin Ratio (RAR) and the clinical outcomes in Pediatric Intensive Care Unit (PICU) patients.DesignThis is a retrospective cohort study.MethodsWe conducted a retrospective cohort study based on the Pediatric Intensive Care database. The primary outcome was the 28-day mortality rate. Secondary outcomes included the 90-day mortality rate, in-hospital mortality rate, and length of hospital stay. We explored the relationship between RAR and the prognosis of patients in the PICU using multivariate regression and subgroup analysis.ResultsA total of 7,075 participants were included in this study. The mean age of the participants was 3.4 ± 3.8 years. Kaplan–Meier survival curves demonstrated that patients with a higher RAR had a higher mortality rate. After adjusting for potential confounding factors, we found that for each unit increase in RAR, the 28-day mortality rate increased by 6% (HR = 1.06, 95% CI: 1.01–1.11, P = 0.015). The high-RAR group (RAR ≥ 4.0) had a significantly increased 28-day mortality rate compared to the low-RAR group (RAR ≤ 3.36) (HR = 1.7, 95% CI: 1.23–2.37, P

This study aims to assess the ecological restoration effects of Vallisneria natans in a multitrophic level ecosystem. The water-purification effects of two hierarchical configuration modes of V. natans-Bellamya aeruginosa and V. natans-B. aeruginosa-Hyriopsis cumingii were studied. Results show that a V. natans and B. aeruginosa configuration ratio of 15:2 stabilizes water quality at Grade IV (TN ≤ 1.5 mg/L, TP ≤ 0.3 mg/L), and increasing B. aeruginosa density significantly reduces total phosphorus. The V. natans, B. aeruginosa, and H. cumingii configuration at 15:2:10 stabilizes water at Grade III (TN ≤ 1.0 mg/L, TP ≤ 0.2 mg/L), with a positive correlation between H. cumingii density and chlorophyll-a removal. Furthermore, the filtration and biocycling actions of B. aeruginosa (snails) and H. cumingii (mussels) significantly reduce levels of Total Nitrogen (TN), Total Phosphorus (TP), and Ammonium (NH4+-N) in water, thus enhancing the self-purification capacity of the water bodies. However, the bioturbation effect of H. cumingii can temporarily increase phosphorus release from sediments, leading to a short-term rise in TP concentration in the water. Overall, the study concludes that multitrophic level ecosystems are effective in purifying water quality and offer significant ecological restoration benefits. This research provides crucial data support for future construction and ecological restoration projects involving multitrophic level approaches in China’s rivers and lakes.

Natural killer (NK) cells are derived from hematopoietic stem cells. They belong to the innate lymphoid cell family, which is an important part of innate immunity. This family plays a role in the body mainly through the release of perforin, granzyme, and various cytokines and is involved in cytotoxicity and cytokine-mediated immune regulation. NK cells involved in normal immune regulation and the tumor microenvironment (TME) can exhibit completely different states. Here, we discuss the growth, development, and function of NK cells in regard to intrinsic and extrinsic factors. Intrinsic factors are those that influence NK cells to promote cell maturation and exert their effector functions under the control of internal metabolism and self-related genes. Extrinsic factors include the metabolism of the TME and the influence of related proteins on the ''fate'' of NK cells. This review targets the potential of NK cell metabolism, cellular molecules, regulatory genes, and other mechanisms involved in immune regulation. We further discuss immune-mediated tumor therapy, which is the trend of current research.

Aortic dissection (AD) is a cardiovascular disease that seriously endangers the lives of patients. The mortality rate of this disease is high, and the incidence is increasing annually, but the pathogenesis of AD is complicated. In recent years, an increasing number of studies have shown that immune cell infiltration in the media and adventitia of the aorta is a novel hallmark of AD. These cells contribute to changes in the immune microenvironment, which can affect their own metabolism and that of parenchymal cells in the aortic wall, which are essential factors that induce degeneration and remodeling of the vascular wall and play important roles in the formation and development of AD. Accordingly, this review focuses on the independent and interactive roles of immunity and metabolism in AD to provide further insights into the pathogenesis, novel ideas for diagnosis and new strategies for treatment or early prevention of AD.

Electrocatalytic recycling of waste nitrate to NH3 under ambient conditions maybe an appealing alternative to the Haber−Bosch process. Here the authors report a tandem catalyst system involving cooperative adsorption of reaction intermediate on different transition metal active sites for nitrate electroreduction with high efficiency.

The nickel (Ni) was coated onto carbon fibers (CFs) through an electroplating process to enhance the infiltration of aluminum (Al) matrix to fiber. Moreover, these continuous CFs reinforced Al matrix (CF/Al) composites were fabricated via a twin-roll casting method. Here, the effects of rolling speed, pouring temperature and solidification times on the morphologies of CF/Al composites were discussed. The results show that the rolling speed of 4 rad/min provided excellent integrity between reinforcement and matrix. Moreover, solidification times of 60 s offered an effective balance between the heat transfer and infiltration. Furthermore, pouring temperature of 700 °C was advantageous to infiltrate Al matrix into fibers. In addition, the influence of heat-treatment time on coating evolution and property of the materials were discussed through microstructure evolution, phases composition and mechanical property tests. The results confirmed that composites with outstanding mechanical properties were acquired at the temperature of 600 °C for 160 min in a tube furnace. Hence, it is concluded that the twin-roll casting approach has great application prospects in the fabrication of CF/Al composites with high tensile properties.

The landing gear structure suffers from large loads during aircraft takeoff and landing, and an accurate prediction of landing gear performance is beneficial to ensure flight safety. Nevertheless, the landing gear performance prediction method based on machine learning has a strong reliance on the dataset, in which the feature dimension and data distribution will have a great impact on the prediction accuracy. To address these issues, a novel MCA-MLPSA is developed. First, an MCA (multiple correlation analysis) method is proposed to select key features. Second, a heterogeneous multilearner integration framework is proposed, which makes use of different base learners. Third, an MLPSA (multilayer perceptron with self-attention) model is proposed to adaptively capture the data distribution and adjust the weights of each base learner. Finally, the excellent prediction performance of the proposed MCA-MLPSA is validated by a series of experiments on the landing gear data.

CRISPR effector proteins introduce double-stranded breaks into the mammalian genome, facilitating gene editing by non-homologous end-joining or homology-directed repair. Unlike the more commonly studied Cas9, the CRISPR effector protein Cas12a/Cpf1 recognizes a T-rich protospacer adjacent motif (PAM) and can process its own CRISPR RNA (crRNA) array, simplifying the use of multiple guide RNAs. We observed that the Cas12a ortholog of Lachnospiraceae bacterium MA2020 (Lb2Cas12a) edited mammalian genes with efficiencies comparable to those of AsCas12a and LbCas12a. Compared to these well-characterized Cas12a orthologs, Lb2Cas12a is smaller and recognizes a narrow set of PAM TTTV. We introduced two mutations into Lb2Cas12a, Q571K and C1003Y, that increased its cleavage efficiency for a range of target sequences beyond those of the commonly used Cas12a orthologs AsCas12a and LbCas12a. In addition to the canonical TTTV PAM, this variant, Lb2-KY, also efficiently cleaved target regions with CTTN PAMs. Finally, we demonstrated that Lb2-KY ribonucleoprotein (RNP) complexes edited two hemoglobin target regions useful for correcting common forms of sickle-cell anemia more efficiently than commercial AsCas12a RNP complexes. Thus, Lb2-KY has distinctive properties useful for modifying a range of clinically relevant targets in the human genome.

How to control the frequent occurrence of cyanobacteria, especially the outbreak of toxin-producing Microcystis aeruginosa, has been a subject of constant research. This investigation focused on the effect of Moina mongolica on restricting M. aeruginosa blooms under different variables (temperature, light intensity, and salinity) and its growth at the molecular level. The results of batch experiments showed that the range of M. mongolica feeding rates was from 4.02 ± 0.81 × 103~182.23 ± 5.37 × 103 cells/ind·h in the whole experiment, where the highest feeding rates of larva M. mongolica and adult M. mongolica were 133.21 ± 5.24 × 103 vs. 182.23 ± 5.37 × 103 cells/ind·h at 30 °C, 85.88 ± 0.44 × 103 vs. 143.15 ± 14.07 × 103 cells/ind·h at 3000 lx and 88.18 ± 0.32 × 103 vs. 84.49 ± 4.95 × 103 cells/ind·h at 0‰ salinity, respectively. The results of transcriptomics further demonstrated that the response of M. mongolica to M. aeruginosa toxicity was caused by the downregulation of relevant functional genes (cell components, cell processes, metabolic processes, and protein complexes) and related signaling pathways (apoptosis, phagosome, lysosome, ribosome, oxidative phosphorylation, amino and nucleoside sugar metabolism, and PPAR signaling pathways). The findings show that M. mongolica can be released to low-salinity lakes and coastal areas (the subtropic and temperate zones) to prevent and inhibit M. aeruginosa blooms in the early summer phase. Additionally, the results achieved by the investigation will provide the relevant technology for inhibiting cyanobacteria blooms because M. mongolica even resists the produced toxin by M. aeruginosa.

The growing world population has produced an increasing demand for seafood, and the aquaculture industry is under corresponding pressure to fill this demand. The offshore ecology and environment are under significant threat with the continuous expansion of the scale and intensity of aquaculture. Integrated multi-tropic aquaculture (IMTA) is a healthy and sustainable mariculture model based on ecosystem-level management, and has become popular in recent years. It is an effective way to cope with the significant changes in offshore ecosystems under multiple stressors. Phytoplankton bacteria are essential to maintaining the marine ecosystem’s balance and stability. Investigating the changes in the community structure of marine planktonic bacteria can elucidate the impact of mariculture on the marine ecological environment. This study took the fish-shell IMTA system with natural macroalgae nearby as the object, and monitored the plankton community’s structure in the system’s surface seawater for four quarters from July 2020 to April 2021. The space–time distribution characteristics and influencing factors of the plankton community in the surface water were examined. The results showed no significant difference between the planktonic bacterial communities at different sampling sites. There was also no significant difference in the α-diversity index. However, the dominant species and abundance of planktonic bacteria at the sampling sites differed significantly. Proteobacteria and Bacteroides were the dominant groups of planktonic bacteria. The results of the distance-based redundancy analysis demonstrated that chemical oxygen demand, chlorophyll a, and dissolved oxygen constituted the primary environmental factors affecting the planktonic bacterial community structures. The heatmap also showed that NH4+- N, temperature, and salinity levels were also related to certain planktonic bacteria. This study preliminarily identified the distribution of the surface bacterial plankton community and its response to changes in environmental factors in the sea area near Xiasanhengshan Island. The results provide a preliminary basis for assessing the health and stability of the IMTA system in open sea areas.

With the rapid development of technologies in the field of service computing, and increasing of complex business requirements, more and more large-scale service ecosystem emerges. Thus, many researches of service ecosystem focus on issues related to optimization such as service recommendation and load balancing, so the API popularity prediction problem studied in this paper, which is basis for this service ecosystem optimization, becomes a research hotspot in this field. However, many existing researches are predicting the popularity of APIs based on API functions, QoS, history usage patterns and social relationships, which are difficult to obtain and cannot reflect the overall structure of the underlying service ecosystem. Therefore, we propose an innovative API popularity prediction method in service ecosystem based on Graph Neural Network (GNN). Concretely, a Global-Service Ecosystem Network (GSEN) model is proposed firstly, for modeling a given service ecosystem to a network that can depict the complex structure of service ecosystem and the functions, QoS, history usage patterns and social relationships of APIs. Then, a Graph Heterogeneous Spatiotemporal Convolutional Network (GHSCN) model is proposed to predict the popularity of APIs based on GSEN, and for getting better prediction accuracy, four different Heterogeneous Spatiotemporal Convolutional Kernels are proposed to extract the features of different elements which have different mechanisms to affect the popularity of target API. Finally, extensive experiments based on the data crawled from ProgrammableWeb.com show that our method achieves a superior performance in API popularity prediction, and the importance of the introduction of our model to service ecosystems.

All available vaccines for coronavirus disease 2019 (COVID-19) express or deliver the full-length SARS-CoV-2 spike (S) protein. We show that this antigen is not optimal, consistent with observations that the vast majority of the neutralizing response to the virus is focused on the S-protein receptor-binding domain (RBD).

One of the highest treelines in the world is at 4810 m above sea level on the Sajama Volcano in the central Andes. The climatological cause of that exceptionally high treeline position is still unclear. Although it has been suggested that the mass elevation effect (MEE) explains the upward shift of treelines in the Altiplano region, the magnitude of MEE has not yet been quantified for that region. This paper defines MEE as the air temperature difference in summer at the same elevation between the inner mountains/plateaus (Altiplano) and the free atmosphere above the adjacent lowlands of the Andean Cordillera. The Altiplano air temperature was obtained from the Global Historical Climatology Network-Monthly temperature database, and the air temperature above the adjacent lowlands was interpolated based on the National Center for Environmental Prediction/National Center for Atmospheric Research Reanalysis 1 data set. We analyzed the mean air temperature differences for January, July, and the warm months from October to April. The air temperature was mostly higher on the Altiplano than over the neighboring lowlands at the same altitude. The air temperature difference increased from the outer Andean east-facing slope to the interior of the Altiplano in summer, and it increased from high latitudes to low latitudes in winter. The mean air temperature in the Altiplano in summer is approximately 5 K higher than it is above the adjacent lowlands at the same mean elevation, averaging about 3700 m above sea level. This upward shift of isotherms in the inner part of the Cordillera enables the treeline to climb to 4810 m, with shrub-size trees reaching even higher. Therefore, the MEE explains the occurrence of one of the world’s highest treelines in the central Andes.

Hepatitis B virus (HBV) infection is a major global health problem. Currently-available therapies are ineffective in curing chronic HBV infection. HBV and its satellite hepatitis D virus (HDV) infect hepatocytes via binding of the preS1 domain of its large envelope protein to sodium taurocholate cotransporting polypeptide (NTCP). Here, we developed novel human monoclonal antibodies that block the engagement of preS1 with NTCP and neutralize HBV and HDV with high potency. One antibody, 2H5-A14, functions at picomolar level and exhibited neutralization-activity-mediated prophylactic effects. It also acts therapeutically by eliciting antibody-Fc-dependent immunological effector functions that impose durable suppression of viral infection in HBV-infected mice, resulting in reductions in the levels of the small envelope antigen and viral DNA, with no emergence of escape mutants. Our results illustrate a novel antibody-Fc-dependent approach for HBV treatment and suggest 2H5-A14 as a novel clinical candidate for HBV prevention and treatment of chronic HBV infection.

As an inhibitor of microtubule assembly, combretastatin A-4 (CA-4)-induced biological responses in tumor cells have been well known, but the corresponding changes in nano-biophysical properties were not investigated given the lack of an ideal tool. Using AFM technique, we investigated the alteration of nano-biophysical properties when CA-4-treated tumor cells underwent the different biological processes, including cell cycle arrest, apoptosis and autophagy. We found that CA-4-resistant cells were rougher with the presence of characteristic "ridges", indicating that the development of "ridge" structure may be a determinant of the sensitivity of cells to CA-4 compounds. CA-4 induced G2/M arrest and apoptosis in sensitive cells but triggered anti-apoptotic autophagy in resistant cells. CA-4 treatment caused an increase in stiffness in both sensitive and resistant cells. However, these cells exhibited different changes in cell surface roughness. CA-4 decreased Ra and Rq values in sensitive cells but increased these values in resistant cells. The reorganization of F-actin might contribute to the different changes of nano-biophysical properties in CA-4-sensitive and-resistant cells. Our results suggest that cellular nano-biophysical properties, such as "ridges", roughness and stiffness, could be applied as potential biomarkers for evaluating CA-4 compounds, and knowledge regarding how biological alterations cause changes in cellular nano-biophysical properties is helpful to develop a new high-resolution screening tool for anti-tumor agents.

Hepatitis B virus (HBV) infection of hepatocytes begins by binding to its cellular receptor sodium taurocholate cotransporting polypeptide (NTCP), followed by the internalization of viral nucleocapsid into the cytoplasm. The viral relaxed circular (rc) DNA genome in nucleocapsid is transported into the nucleus and converted into covalently closed circular (ccc) DNA to serve as a viral persistence reservoir that is refractory to current antiviral therapies. Host DNA repair enzymes have been speculated to catalyze the conversion of rcDNA to cccDNA, however, the DNA polymerase(s) that fills the gap in the plus strand of rcDNA remains to be determined. Here we conducted targeted genetic screening in combination with chemical inhibition to identify the cellular DNA polymerase(s) responsible for cccDNA formation, and exploited recombinant HBV with capsid coding deficiency which infects HepG2-NTCP cells with similar efficiency of wild-type HBV to assure cccDNA synthesis is exclusively from de novo HBV infection. We found that DNA polymerase κ (POLK), a Y-family DNA polymerase with maximum activity in non-dividing cells, substantially contributes to cccDNA formation during de novo HBV infection. Depleting gene expression of POLK in HepG2-NTCP cells by either siRNA knockdown or CRISPR/Cas9 knockout inhibited the conversion of rcDNA into cccDNA, while the diminished cccDNA formation in, and hence the viral infection of, the knockout cells could be effectively rescued by ectopic expression of POLK. These studies revealed that POLK is a crucial host factor required for cccDNA formation during a de novo HBV infection and suggest that POLK may be a potential target for developing antivirals against HBV.

Atom-resolved microstructure variations and deactivation effects on the commercial NiMo/γ-Al2O3 catalysts were revealed by aberration-corrected scanning transmission electron microscope (Cs-STEM) equipped with enhanced energy dispersive X-ray spectroscopy (EDS). Structural information parallel to and vertical to the electron beam provides definitive insight toward an understanding of structure−activity relations. Under the mild to harsher reaction conditions, “fragment” structures (like metal single atoms, metal clusters, and nanoparticles) of commercial NiMo/γ-Al2O3 catalysts, gradually reduces, while MoS2 nanoslabs get longer and thinner. Such a result about active slabs leads to the reduction in the number of active sites, resulting in a significant decrease in activity. Likewise, the average atomic ratio of promoter Ni and Ni/(Mo + S) ratio of slabs decrease from 2.53% to 0.45% and from 0.0788 to 0.0326, respectively, by means of EDS under the same conditions stated above, reflecting the weakening of the promotional effect. XPS result confirms the existence of NixSy species in deactivated catalysts. This could be ascribed to the Ni segregation from active phase. Furthermore, statistical data give realistic coke behaviors associated with the active metals. With catalytic activity decreasing, the coke on the active metals regions tends to increase faster than that on the support regions. This highlights that the commercial NiMo/γ-Al2O3 catalyst during catalysis is prone to produce more coke on the active metal areas.

Hepatitis D virus (HDV) is the smallest virus known to infect human. About 15 million people worldwide are infected by HDV among those 240 million infected by its helper hepatitis B virus (HBV). Viral hepatitis D is considered as one of the most severe forms of human viral hepatitis. No specific antivirals are currently available to treat HDV infection and antivirals against HBV do not ameliorate hepatitis D. Liver sodium taurocholate co-transporting polypeptide (NTCP) was recently identified as a common entry receptor for HDV and HBV in cell cultures. Here we show HDV can infect mice expressing human NTCP (hNTCP-Tg). Antibodies against critical regions of HBV envelope proteins blocked HDV infection in the hNTCP-Tg mice. The infection was acute yet HDV genome replication occurred efficiently, evident by the presence of antigenome RNA and edited RNA species specifying large delta antigen in the livers of infected mice. The resolution of HDV infection appears not dependent on adaptive immune response, but might be facilitated by innate immunity. Liver RNA-seq analyses of HDV infected hNTCP-Tg and type I interferon receptor 1 (IFNα/βR1) null hNTCP-Tg mice indicated that in addition to induction of type I IFN response, HDV infection was also associated with up-regulation of novel cellular genes that may modulate HDV infection. Our work has thus proved the concept that NTCP is a functional receptor for HDV infection in vivo and established a convenient small animal model for investigation of HDV pathogenesis and evaluation of antiviral therapeutics against the early steps of infection for this important human pathogen.