The complete chloroplast genome of Urtica angustifolia Fisch. ex Hornem. (Urticaceae), an important kind of traditional Chinese medicine in China.

Urtica angustifolia Fisch. ex Hornem. is an important Chinese medicine. Here, the complete chloroplast genome of U. angustifolia was assembled and characterized. The length of the chloroplast genome was 146,679 bp with the typical quadripartite structure, containing two inverted repeats (IRs) of 24,595 bp separated by a large single-copy (LSC) region of 79,820 bp and a small single-copy (SSC) region of 17,669 bp. The whole chloroplast genome of U. angustifolia contains 111 genes, including 77 protein-coding genes, 30 tRNA genes, and 4 rRNA genes. Nucleotide variability analysis identified three hotspot regions (trnK-rps16, ndhF-rps32, and ycf1b) for genomic divergence and 52 simple sequence repeats. Phylogenetic analysis based on the complete chloroplast genomes exhibited that U. angustifolia formed a clade with Urtica lobatifolia and Hesperocnide tenella.

Identification and Validation of the Prognostic Panel in Clear Cell Renal Cell Carcinoma Based on Resting Mast Cells for Prediction of Distant Metastasis and Immunotherapy Response.

Clear cell renal cell carcinoma (ccRCC) has a high metastatic rate, and its incidence and mortality are still rising. The aim of this study was to identify the key tumor-infiltrating immune cells (TIICs) affecting the distant metastasis and prognosis of patients with ccRCC and to construct a relevant prognostic panel to predict immunotherapy response. Based on ccRCC bulk RNA sequencing data, resting mast cells (RMCs) were screened and verified using the CIBERSORT algorithm, survival analysis, and expression analysis. Distant metastasis-associated genes were identified using single-cell RNA sequencing data. Subsequently, a three-gene (CFB, PPP1R18, and TOM1L1) panel with superior distant metastatic and prognostic performance was established and validated, which stratified patients into high- and low-risk groups. The high-risk group exhibited lower infiltration of RMCs, higher tumor mutation burden (TMB), and worse prognosis. Therapeutically, the high-risk group was more sensitive to anti-PD-1 and anti-CTLA-4 immunotherapy, whereas the low-risk group displayed a better response to anti-PD-L1 immunotherapy. Furthermore, two immune clusters revealing distinct immune, clinical, and prognosis heterogeneity were distinguished. Immunohistochemistry of ccRCC samples verified the expression patterns of the three key genes. Collectively, the prognostic panel based on RMCs is able to predict distant metastasis and immunotherapy response in patients with ccRCC, providing new insight for the treatment of advanced ccRCC.

Chloroplast genome characteristics of Corylopsis microcarpa H.T. Chang (Hamamelidaceae).

Corylopsis microcarpa H.T. Chang 1960 is a relict species from China. The chloroplast genome of C. microcarpa is 159,438 bp in size and shows typical quadripartite structure, which includes a pair of inverted repeat regions (26,280 bp), a large single-copy region (88,185 bp), and a small single-copy region (18,693 bp). The whole chloroplast genome encodes 114 unique genes, including 80 protein-code genes, 30 transfer RNA (tRNA) genes, and four ribosomal RNA (rRNA) genes. Ninety-one SSRs were identified. The phylogenetic analysis revealed C. microcarpa diverged early in Corylopsis.

A novel nomogram and risk classification system predicting the Ewing sarcoma: a population-based study.

Ewing sarcoma (ES) is a rare disease that lacks a prognostic prediction model. This study aims to develop a nomogram and risk classification system for estimating the probability of overall survival (OS) of patients with ES. The clinicopathological data of ES were collected from the Surveillance, Epidemiology and Final Results (SEER) database from 2010 to 2018. The primary cohort was randomly assigned to the training set and the validation set. Univariate and multiple Cox proportional hazard analyses based on the training set were performed to identify independent prognostic factors. A nomogram was established to generate individualized predictions of 3- and 5-year OS and evaluated by the concordance index (C-index), the receiver operating characteristic curve (ROC), the calibration curve, the integrated discrimination improvement (IDI) and the net reclassification improvement (NRI). Based on the scores calculated with the nomogram, ES patients were divided into three risk groups to predict their survival. A total of 935 patients were identified, and a nomogram consisting of 6 variables was established. The model provided better C-indices of OS (0.788). The validity of the Cox model assumptions was evaluated through the Schönfeld test and deviance residual. The ROC, calibration curve, IDI and NRI indicated that the nomogram exhibited good performance. A risk classification system was built to classify the risk group of ES patients. The nomogram compares favourably and accurately to the traditional SEER tumour staging systems, and risk stratification provides a more convenient and effective tool for clinicians to optimize treatment options.

Association between socioeconomic status and survival in patients with hepatocellular carcinoma.

BACKGROUND: The effect of socioeconomic status (SES) on hepatocellular carcinoma (HCC) is still unclear, and there is no nomogram integrated SES and clinicopathological factors to predict the prognosis of HCC. This research aims to confirm the effects of SES on predicting patients' survival and to establish a nomogram to predict the prognosis of HCC. METHODS: The data of HCC patients were collected from the Surveillance, Epidemiology, and Final Results (SEER) database from 2011 to 2015. SES (age at diagnosis, race and sex, median family income, education level, insurance status, marital status, residence, cost of living index, poverty rate) and clinicopathological factors were included in univariate and multivariate Cox regression analysis. Nomograms for predicting 1-, 3-, and 5-year cancer-specific survival (CSS) and overall survival (OS) were established and evaluated by the concordance index (C-index), the receiver operating characteristic curve (ROC), the calibration plot, the integrated discrimination improvement (IDI), and the net reclassification improvement (NRI). RESULTS: A total of 33,670 diagnosed HCC patients were involved, and nomograms consisting of 19 variables were established. The C-indexes of the nomograms are higher than TNM staging system, which predicts the CSS (0.789 vs. 0.692, p < 0.01) and OS (0.777 vs. 0.675, p < 0.01). The ROC curve, calibration diagram, IDI, and NRI showed the improved prognostic value in 1-, 3-, and 5-year survival rates. CONCLUSION: SES plays an important role in the prognosis of HCC patients. Therefore, policymakers can make more precise and socially approved policies to improve HCC patients' CSS and OS.

Robot-assisted vs freehand cannulated screw placement in femoral neck fractures surgery: A systematic review and meta-analysis.

BACKGROUND: Several studies have reported that medical robot-assisted method (RA) might be superior to conventional freehand method (FH) in orthopedic surgery. Yet the results are still controversial, especially in terms of femoral neck fractures surgery. Here, 2 methods were assessed based on current evidence. METHODS: Electronic databases including Cochrane Library, PubMed, Web of Science. and EMBASE were selected to retrieved to identify eligible studies between freehand and RAs in femoral neck fractures, with 2 reviewers independently reviewing included studies as well as collecting data. RESULTS: A total of 5 studies with 331 patients were included. Results indicated that 2 surgical methods were equivalent in terms of surgical duration, Harris score, fracture healing time, fracture healing proportion and complications, while RA showed clinical benefits in radiation exposure, intraoperative bleeding, total drilling times, and screw parallelism. CONCLUSIONS: Current literature revealed significantly difference between 2 techniques and suggested that RA might be beneficial for patients than freehand method.

Complete chloroplast genome of Engelhardtia fenzlii (Juglandaceae).

In this study, we successfully assembled and analyzed the chloroplast genome of Engelhardtia fenzlii. The chloroplast genome of E. fenzlii was very similar to those of other Juglandaceae species. The E. fenzlii chloroplast genome is 161,713 bp in length and displays the typical quadripartite structure, which consists of a pair of IR regions (26,016 bp) separated by an LSC region (90,478 bp) and an SSC region (19,203 bp). The chloroplast genome of E. fenzlii contained a total of 112 unique genes, including 78 protein-coding genes, 30 tRNAs, and 4 rRNAs. Phylogenetic analysis based on the complete chloroplast genomes showed that Engelhardtia formed a monophyletic clade and E. fenzlii was sister to E. roxburghiana.

TRPV4 Complexes With the Na+/Ca2+ Exchanger and IP3 Receptor 1 to Regulate Local Intracellular Calcium and Tracheal Tension in Mice.

Intracellular Ca2+ is critical for regulating airway smooth muscle (ASM) tension. A rapid rise in the intracellular Ca2+ concentration ([Ca2+]i) of ASM cells is crucial for modulating the intensity and length of the ASM contraction. Because this rapid increase in [Ca2+]i largely depends on the balance between Ca2+ released from intracellular Ca2+ stores and extracellular Ca2+ entry, exploring the mechanisms mediating Ca2+ transport is critical for understanding ASM contractility and the pathogenesis of bronchial contraction disorders. Transient receptor potential vanilloid 4 (TRPV4) is a highly Ca2+-permeable non-selective cation channel that mediates Ca2+ influx to increase [Ca2+]i, which then directly or indirectly regulates the contraction and relaxation of ASM. The [Ca2+]i returns to basal levels through several uptake and extrusion pumps, such as the sarco(endo)plasmic reticulum Ca2+ ATPase and inositol 1,4,5-trisphosphate receptors (IP3Rs), the plasmalemmal Ca2+ ATPase, and the plasma membrane Na+/Ca2+ exchanger (NCX). Thus, to further understand ASM tension regulation in normal and diseased tissue, the present study examined whether an interaction exists among TRPV4, IP3Rs, and NCX. The TRPV4-specific and potent agonist GSK1016790A increased [Ca2+]i in mouse ASM cells, an effect that was completely blocked by the TRPV4-specific antagonist HC067047. However, GSK1016790A induced relaxation in mouse tracheal rings precontracted with carbachol in vitro. To determine the mechanism underlying this TRPV4-induced relaxation of ASM, we blocked specific downstream molecules. We found that the GSK1016790A-induced relaxation was abolished by the NCX inhibitors KB-R7943 and LiCl but not by specific inhibitors of the Ca2+-activated large-, intermediate-, or small-conductance K+ channels (BKCa, IK, and SK3, respectively). The results of co-immunoprecipitation (co-IP) assays showed an interaction of TRPV4 and IP3R1 with NCXs. Taken together, these findings support a physical and functional interaction of TRPV4 and IP3R1 with NCXs as a novel TRPV4-mediated Ca2+ signaling mechanism and suggest a potential target for regulation of ASM tension and treatment of respiratory diseases, especially tracheal spasm.

Extracellular vesicles from endothelial progenitor cells prevent steroid-induced osteoporosis by suppressing the ferroptotic pathway in mouse osteoblasts based on bioinformatics evidence.

Abnormal antioxidative capabilities were observed in the pathogenesis of steroid-induced osteoporosis (SIOP). Ferroptosis is a recently discovered type of cell death that is characterized by the overproduction of ROS in response to GPX4 and system Xc- downregulation, which is mediated by an Fe2+ fenton reaction. However, investigations focusing on the relationship between ferroptosis and steroid-induced bone disease remain limited. In the present study, high-dose dexamethasone was used to establish a mouse SIOP model, and extracellular vesicles extracted from bone marrow-derived endothelial progenitor cells (EPC-EVs) alleviated the pathological changes in SIOP via microtomography (micro-CT), with elevations in bone volume (BV), bone surface (BS), trabecular thickness (Tb.Th), and trabecular connectivity density (Conn-D) and decreases in trabecular separation (Tb.sp) and the structure model index (SMI). Histopathological analysis, such as haematoxylin and eosin (HE) and Masson staining, showed that EPC-EVs treatment increased the volume and density of the trabecular bone and bone marrow. RNA sequencing (RNA-seq) and bioinformatics analysis revealed subcellular biological alterations upon steroid and EPC-EVs treatment. Compared with the control, high-dose dexamethasone downregulated GPX4 and system XC-, and the Kyoto Encyclopedia of Genes and Genomes (KEGG)-based gene set enrichment analysis suggested that the ferroptotic pathway was activated. In contrast, combination treatment with EPC-EVs partly reversed the KEGG-mapped changes in the ferroptotic pathway at both the gene and mRNA expression levels. In addition, alterations in ferroptotic marker expression, such as SLC3A2, SLC7A11, and GPX4, were further confirmed by RNA-seq. EPC-EVs were able to reverse dexamethasone treatment-induced alterations in cysteine and several oxidative injury markers, such as malondialdehyde (MDA), glutathione (GSH), and glutathione disulphide (GSSG) (as detected by ELISA). In conclusion, EPC-EVs prevented mouse glucocorticoid-induced osteoporosis by suppressing the ferroptotic pathway in osteoblasts, which may provide a basis for novel therapies for SIOP in humans.

Resveratrol reduces store-operated Ca2+ entry and enhances the apoptosis of fibroblast-like synoviocytes in adjuvant arthritis rats model via targeting ORAI1-STIM1 complex.

BACKGROUND: Resveratrol was reported to trigger the apoptosis of fibroblast-like synoviocytes in adjuvant arthritis rats but the subcellular mechanism remains unclear. Since ER stress, mitochondrial dysfunction and oxidative stress were involved in the effects of resveratrol with imbalance of calcium bio-transmission, store operated calcium entry (SOCE), a novel intracellular calcium regulatory pathway, may also participate in this process. RESULTS: In the present study, Resveratrol was found to suppress ORAI1 expression of a dose dependent manner while have no evident effects on STIM1 expressive level. Besides, resveratrol had no effects on ATP or TG induced calcium depletion but present partly dose-dependent suppression of SOCE. On the one hand, microinjection of ORAI1 overexpressed vector in sick toe partly counteracted the therapeutic effects of resveratrol on adjuvant arthritis and serum inflammatory cytokine including IL-1, IL-6, IL-8, IL-10 and TNF-α. On the other hand, ORAI1 SiRNA injection provided slight relief to adjuvant arthritis in rats. In addition, ORAI1 overexpression partly diminished the alleviation of hemogram abnormality induced by adjuvant arthritis after resveratrol treatment while ORAI1 knockdown presented mild resveratrol-like effect on hemogram in rats model. CONCLUSION: These results indicated that resveratrol reduced store-operated Ca2+ entry and enhanced the apoptosis of fibroblast-like synoviocytes in adjuvant arthritis rats model via targeting ORAI1-STIM1 complex, providing a theoretical basis for ORAI1 targeted therapy in future treatment with resveratrol on rheumatoid arthritis.

Resveratrol alleviates inflammatory injury and enhances the apoptosis of fibroblast­like synoviocytes via mitochondrial dysfunction and ER stress in rats with adjuvant arthritis.

Resveratrol, a bioactive compound predominantly found in grapes and red wine, provides a wide range of properties that are beneficial for health, including anticancer and anti­inflammatory activities. Previously published studies have addressed the potential therapeutic effects of resveratrol on rheumatoid arthritis (RA); however, the subcellular mechanism remains to be fully elucidated. In the present study, the therapeutic effects of resveratrol on adjuvant arthritis (AA) in Sprague­Dawley rats were investigated, and the mechanisms of resveratrol­induced apoptosis in fibroblast­like synoviocytes (FLSs) were further examined. Based on the findings, resveratrol treatment over a 12­day period led to a reduction in paw swelling and arthritis scores at the macroscopic level, and an attenuation of inflammatory cell infiltration and synovial hyperplasia, upon a histopathological examination of the AA rats. Furthermore, the administration of resveratrol triggered decreases in the expression of interleukin (IL)­1, IL­6, IL­8 and tumor necrosis factor­α (TNF­α) and an increase in the expression of IL­10, alleviating inflammatory injury in AA rats in a dose­dependent manner. In addition, resveratrol was revealed to induce the apoptosis of FLSs when administered with 5 µM H2O2 as determined by elevated levels of Bax, caspase­3, caspase­12 and C/EBP­homologous protein, and the downregulation of B­cell lymphoma 2 (Bcl­2), suggesting that resveratrol is able to induce apoptosis in FLSs via the mitochondrial pathway and endoplasmic reticulum (ER) stress in a milieu containing 5 µM H2O2. Furthermore, JC­1 was used as a fluorescent probe to detect the mitochondrial membrane potential (Δψm), and resveratrol was shown to reduce the Δψm in FLSs in the presence of 5 µM H2O2. However, resveratrol was not able to trigger intracellular calcium overload, although it did suppress ATP­ and thapsigargin­induced calcium release from the ER. In conclusion, the present study revealed that resveratrol was able to alleviate inflammatory injury in AA rats, triggering the apoptosis of FLSs via the mitochondrial pathway and ER stress. These results provide a theoretical basis for future treatments using resveratrol for RA.

Resveratrol reduces store-operated Ca2+ entry and enhances the apoptosis of fibroblast-like synoviocytes in adjuvant arthritis rats model via targeting ORAI1-STIM1 complex

BACKGROUND: Resveratrol was reported to trigger the apoptosis of fibroblast-like synoviocytes In adjuvant arthritis rats but the subcellular mechanism remains unclear. Since ER stress, mitochondrial dysfunction and oxidative stress were involved in the effects of resveratrol with imbalance of calcium bio-transmission, store operated calcium entry (SOCE), a novel intracellular calcium regulatory pathway, may also participate in this process. RESULTS: In the present study, Resveratrol was found to suppress ORAI1 expression of a dose dependent manner while have no evident effects on STIM1 expressive level. Besides, resveratrol had no effects on ATP or TG induced calcium depletion but present partly dose-dependent suppression of SOCE. On the one hand, microinjection of ORAI1 overexpressed vector in sick toe partly counteracted the therapeutic effects of resveratrol on adjuvant arthritis and serum inflammatory cytokine including IL-1, IL-6, IL-8, IL-10 and TNF-α. On the other hand, ORAI1 SiRNA injection provided slight relief to adjuvant arthritis in rats. In addition, ORAI1 overexpression partly diminished the alleviation of hemogram abnormality induced by adjuvant arthritis after resveratrol treatment while ORAI1 knockdown presented mild resveratrol-like effect on hemogram in rats model. CONCLUSION: These results indicated that resveratrol reduced store-operated Ca2+ entry and enhanced the apoptosis of fibroblast-like synoviocytes in adjuvant arthritis rats model via targeting ORAI1-STIM1 complex, providing a theoretical basis for ORAI1 targeted therapy in future treatment with resveratrol on rheumatoid arthritis.

Detection of Mitochondria Membrane Potential to Study CLIC4 Knockdown-induced HN4 Cell Apoptosis In Vitro.

Depletion of the mitochondrial membrane potential (MMP, ΔΨm) is considered the earliest event in the apoptotic cascade. It even occurs ahead of nuclear apoptotic characteristics, including chromatin condensation and DNA breakage. Once the MMP collapses, cell apoptosis will initiate irreversibly. A series of lipophilic cationic dyes can pass through the cell membrane and aggregate inside the matrix of mitochondrion, and serve as fluorescence marker to evaluate MMP change. As one of the six members of the Cl- intracellular channel (CLIC) family, CLIC4 participates in the cell apoptotic process mainly through the mitochondrial pathway. Here we describe a detailed protocol to measure MMP via monitoring the fluorescence fluctuation of Rhodamine 123 (Rh123), through which we study apoptosis induced by CLIC4 knockdown. We discuss the advantages and limitations of the application of confocal laser scanning and normal fluorescence microscope in detail, and also compare it with other methods.

Reducing-Autophagy Derived Mitochondrial Dysfunction during Resveratrol Promotes Fibroblast-Like Synovial Cell Apoptosis.

In rheumatoid arthritis patients, the fibroblast-like synovial cells (FLS) growth is not controlled normally, but is similar to the tumor cells proliferation in histology. Our previous studies have shown that resveratrol inhibits the proliferation of FLS and promotes FLS apoptosis. However, the molecular mechanisms involved in resveratrol-induced FLS apoptosis have not been determined yet. Here, we showed that the FLS cell viability (following pretreatment with 5 µM H2 O2 for 24 hr) exhibited better proliferation performance than at other concentrations via the CCK-8 assay. The cell apoptotic rate increased with the increasing concentration of resveratrol (0, 40, 80, 160, 320 µM), as detected by TdT-mediated dUTP nick-end labeling (TUNEL) staining and western blotting. Furthermore, the expression level of autophagy-related proteins (LC3A/B, ATG-5) decreased with the increased concentration of resveratrol, as determined by immunofluorescence and western blot analysis. We also showed that resveratrol induced FLS mitochondrial morphology change. Moreover, mitochondrial function detection showed that the mitochondrial membrane potential was lost with the increased concentration of resveratrol as examined by the JC-1 assay. The production of ATP in cells was positively and negatively correlated with the resveratrol concentration. Simultaneously, the intracellular calcium release and calcium influx decreased gradually with the increase in resveratrol concentration. Therefore, we proposed that resveratrol can reduce the level of autophagy in FLS. The decrease in the autophagy level can lead to the accumulation of reactive oxygen species, which may result in mitochondrial dysfunction and promotion of FLS apoptosis. Anat Rec, 301:1179-1188, 2018. © 2018 Wiley Periodicals, Inc.

Knockdown of CLIC4 enhances ATP-induced HN4 cell apoptosis through mitochondrial and endoplasmic reticulum pathways.

BACKGROUND: Human head and neck squamous carcinoma is the 6th most prevalent carcinoma worldwide. Although many novel therapies have been developed, the clinical treatment for patients remains non-ideal. Chloride intracellular channel 4 (CLIC4), one of the seven members of the CLIC family, is a newly found Cl(-) channel that participates in various biological processes, including cellular apoptosis and differentiation. Accumulating evidence has revealed the significant role of CLIC4 in regulating the apoptosis of different cancer cells. Here, we investigated the functional role of CLIC4 in the apoptosis of HN4 cells, a human head and neck squamous carcinoma cell line. RESULTS: In the present study, we used immunohistochemical staining to demonstrate that the expression level of CLIC4 is elevated in the tissue of human oral squamous carcinoma compared with healthy human gingival tissue. Specific CLIC4 small interfering RNA was used to knockdown the expression of CLIC4. The results showed that knockdown of CLIC4 with or without 100 µM adenosine triphosphate (ATP) treatment significantly increased the expression of Bax, active caspase 3, active caspase 4 and CHOP but suppressed Bcl-2 expression in HN4 cells. Moreover, the results from the TdT-mediated dUTP nick end labeling assay indicated that CLIC4 knockdown induced a higher apoptotic rate in HN4 cells under the induction of ATP. In addition, knockdown of CLIC4 dramatically enhanced ATP-induced mitochondrial membrane depolarization in HN4 cells. Moreover, intracellular Ca(2+) measurement revealed that Ca(2+) release induced by ATP and thapsigargin, a Ca(2+)-ATPase inhibitor of the endoplasmic reticulum, was significantly enhanced by the suppression of CLIC4 in HN4 cells. CONCLUSIONS: Knockdown of CLIC4 enhanced ATP-induced apoptosis in HN4 cells. Both the pathways of mitochondria and endoplasmic reticulum stress were involved in CLIC4-mediated cell apoptosis. Based on our finding, CLIC4 may be a potential and valuable target for the clinical treatment of head and neck squamous carcinoma.

Interferon-stimulated gene factor 3 complex is required for the induction of sterile α motif and HD domain-containing protein 1 expression by interferon-α in SMMC-7721 cells.

Sterile α motif and HD domain-containing protein 1 (SAMHD1) is a novel intrinsic restriction factor that inhibits the replication of certain retroviruses and DNA viruses through its deoxynucleoside triphosphate triphosphohydrolase activity. A previous study by our group showed that SAMHD1 restrained hepatitis B virus replication and interferon (IFN)­α induced SAMHD1 expression in liver cells. However the mechanisms of SAMHD1 upregulation by IFN­α in liver cells have remained elusive. The present study demonstrated that IFN­α treatment increased SAMHD1 mRNA levels in SMMC­7721 cells in a time­dependent manner. Knockdown of STAT1 inhibited the induction of SAMHD1 expression by IFN­α in SMMC­7721 cells. STAT2 silencing also suppressed the induction of SAMHD1 expression by IFN­α in SMMC­7721 cells. Furthermore, the induction of SAMHD1 expression in SMMC­7721 cells by IFN­α was found to be dependent on IFN­regulatory factor 9 (IRF9). In conclusion, these results suggested that the interferon­stimulated gene factor 3 complex, which consists of STAT1, STAT2 and IRF9, is required for the induction of SAMHD1 expression by IFN-α in SMMC-7721 cells.

Inhibition of Hepatitis B virus replication by SAMHD1.

Sterile alpha motif and HD-domain containing protein 1 (SAMHD1) is a newly identified intracellular antiviral factor. By depleting the dNTPs pool of host cells to a low level that cannot support the efficient synthesis of viral cDNA, it restricts replication of some retroviruses. As a DNA virus, Hepatitis B virus (HBV) experiences a process of reverse transcription in its life cycle akin to that of retroviruses. However, whether SAMHD1 can restrict HBV replication in liver cells is unknown. Here, we reported that SAMHD1 expression was detectable in four liver cell lines. Exogenous expression of SAMHD1 in SMMC-7721 cells restrained HBV replication. Similarly, SAMHD1 impeded HBV replication in another liver cell line, BEL-7402. Remarkably, the catalytically inactive mutant, SAMHD1 HD/AA also hampered HBV replication. Additionally, HBV replication reduced SAMHD1 expression in HepG2 cells. Moreover, it was found that IFN-α induced expression of SAMHD1 in liver cells. Together, these findings suggested that IFN-α-inducible SAMHD1 inhibited HBV replication in liver cells.