The RNA m6A reader YTHDC1 silences retrotransposons and guards ES cell identity.

The RNA modification N6-methyladenosine (m6A) has critical roles in many biological processes1,2. However, the function of m6A in the early phase of mammalian development remains poorly understood. Here we show that the m6A reader YT521-B homology-domain-containing protein 1 (YTHDC1) is required for the maintenance of mouse embryonic stem (ES) cells in an m6A-dependent manner, and that its deletion initiates cellular reprogramming to a 2C-like state. Mechanistically, YTHDC1 binds to the transcripts of retrotransposons (such as intracisternal A particles, ERVK and LINE1) in mouse ES cells and its depletion results in the reactivation of these silenced retrotransposons, accompanied by a global decrease in SETDB1-mediated trimethylation at lysine 9 of histone H3 (H3K9me3). We further demonstrate that YTHDC1 and its target m6A RNAs act upstream of SETDB1 to repress retrotransposons and Dux, the master inducer of the two-cell stage (2C)-like program. This study reveals an essential role for m6A RNA and YTHDC1 in chromatin modification and retrotransposon repression.

Dihydroartemisinin synergistically enhances the cytotoxic effects of oxaliplatin in colon cancer by targeting the PHB2-RCHY1 mediated signaling pathway.

Dihydroartemisinin (DHA) has recently attracted increasing attention for its low toxicity and high antitumor activity. DHA has been reported to have synergistic anticancer effects with a variety of drugs in the clinic; however, the molecular mechanism by which DHA inhibits tumorigenesis and improves oxaliplatin cytotoxicity in colon cancer cells is still not well understood. In this study, we found that DHA can inhibit cell proliferation and colony formation in a dose-dependent manner. Prohibitin 2 (PHB2) is a potential target by which DHA exerts its antitumor and cytotoxic effects. The function and molecular mechanism of PHB2 in colon cancer tumorigenesis were fully studied to determine the regulatory mechanism between DHA and PHB2. We found that PHB2, a mitochondrial inner membrane scaffold protein, has a higher expression level in colon cancer tissues than in adjacent nontumor tissues and is mainly localized in mitochondria. Overexpression of PHB2 can promote cell proliferation and colony formation in vitro and accelerate tumor growth in vivo. We also found that the expression level of PHB2 was inversely related to the cytotoxicity of DHA and oxaliplatin in colon cancer cells. The molecular mechanism of PHB2 in tumorigenesis and cancer therapy was further studied. The results showed that 20 µM DHA can downregulate PHB2 expression in a ubiquitylation-dependent manner and subsequently block PHB2-induced RCHY1 upregulation and p53 and p21 downregulation. In this process, RCHY1 is necessary for PHB2 to play a tumor-promoting role. Thus, PHB2 and RCHY1 are effective targets for colon cancer therapy, and DHA has synergistic anticancer effects with oxaliplatin via promoting PHB2 degradation in colon cancer cells.

Stabilizing Nitroxide Spin Labels for Structural and Conformational Studies of Biomolecules by Maleimide Treatment.

Nitroxide (NO) spin radicals are effective in characterizing structures, interactions and dynamics of biomolecules. The EPR applications in cell lysates or intracellular milieu require stable spin labels, but NO radicals are unstable in such conditions. We showed that the destabilization of NO radicals in cell lysates or even in cells is caused by NADPH/NADH related enzymes, but not by the commonly believed reducing reagents such as GSH. Maleimide stabilizes the NO radicals in the cell lysates by consumption of the NADPH/NADH that are essential for the enzymes involved in destabilizing NO radicals, instead of serving as the solo thiol scavenger. The maleimide treatment retains the crowding properties of the intracellular components and allows to perform long-time EPR measurements of NO labeled biomolecules close to the intracellular conditions. The strategy of maleimide treatment on cell lysates for the EPR applications has been demonstrated on double electron-electron resonance (DEER) measurements on a number of NO labeled protein samples. The method opens a broad application range for the NO labeled biomolecules by EPR in conditions that resemble the intracellular milieu.

Multiple-Aptamer-Integrated DNA-Origami-Based Chemical Nose Sensors for Accurate Identification of Cancer Cells.

Developing simple, rapid, and accurate methods for cancer cell identification could facilitate early cancer diagnosis and tumor metastasis research. Herein, we develop a novel chemical nose sensor that employs the collective recognition abilities of a set of multiple-aptamer-integrated DNA origami (MADO) probes for discriminative identification of cancer cells. By controlling the types and/or copies of aptamers assembled on the DNA origami nanostructure, we constructed five MADO probes with differential binding affinities (ranging from 3.08 to 78.92 nM) to five types of cells (HeLa, MDA-MB-468, MCF-7, HepG2, and MCF-10A). We demonstrate the utility of the MADO-based chemical nose sensor in the identification of blinded unknown cell samples with a 95% accuracy. This sensing platform holds great potential for applications in medical diagnostics.

Multiple Roles of SIRT2 in Regulating Physiological and Pathological Signal Transduction.

Sirtuin 2 (SIRT2), as a member of the sirtuin family, has representative features of evolutionarily highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase activity. In addition, SIRT2, as the only sirtuin protein colocalized with tubulin in the cytoplasm, has its own functions and characteristics. In recent years, studies have increasingly shown that SIRT2 can participate in the regulation of gene expression and regulate signal transduction in the metabolic pathway mainly through its post-translational modification of target genes; thus, SIRT2 has become a key centre in the metabolic pathway and participates in the pathological process of metabolic disorder-related diseases. In this paper, it is discussed that SIRT2 can regulate all aspects of gene expression, including epigenetic modification, replication, transcription and translation, and post-translational modification, which enables SIRT2 to participate in energy metabolism in life activities, and it is clarified that SIRT2 is involved in metabolic process-specific signal transduction mechanisms. Therefore, SIRT2 can be involved in metabolic disorder-related inflammation and oxidative stress, thereby triggering the occurrence of metabolic disorder-related diseases, such as neurodegenerative diseases, tumours, diabetes, and cardiovascular diseases. Currently, although the role of SIRT2 in some diseases is still controversial, given the multiple roles of SIRT2 in regulating physiological and pathological signal transduction, SIRT2 has become a key target for disease treatment. It is believed that with increasing research, the clinical application of SIRT2 will be promoted.

Concurrent binding to DNA and RNA facilitates the pluripotency reprogramming activity of Sox2.

Some transcription factors that specifically bind double-stranded DNA appear to also function as RNA-binding proteins. Here, we demonstrate that the transcription factor Sox2 is able to directly bind RNA in vitro as well as in mouse and human cells. Sox2 targets RNA via a 60-amino-acid RNA binding motif (RBM) positioned C-terminally of the DNA binding high mobility group (HMG) box. Sox2 can associate with RNA and DNA simultaneously to form ternary RNA/Sox2/DNA complexes. Deletion of the RBM does not affect selection of target genes but mitigates binding to pluripotency related transcripts, switches exon usage and impairs the reprogramming of somatic cells to a pluripotent state. Our findings designate Sox2 as a multi-functional factor that associates with RNA whilst binding to cognate DNA sequences, suggesting that it may co-transcriptionally regulate RNA metabolism during somatic cell reprogramming.

Capturing the interactome of newly transcribed RNA.

We combine the labeling of newly transcribed RNAs with 5-ethynyluridine with the characterization of bound proteins. This approach, named capture of the newly transcribed RNA interactome using click chemistry (RICK), systematically captures proteins bound to a wide range of RNAs, including nascent RNAs and traditionally neglected nonpolyadenylated RNAs. RICK has identified mitotic regulators amongst other novel RNA-binding proteins with preferential affinity for nonpolyadenylated RNAs, revealed a link between metabolic enzymes/factors and nascent RNAs, and expanded the known RNA-bound proteome of mouse embryonic stem cells. RICK will facilitate an in-depth interrogation of the total RNA-bound proteome in different cells and systems.

A rumor reversal model of online health information during the Covid-19 epidemic.

The development of the Internet and social media has expanded the speed and scope of information dissemination, but not all widely disseminated information is true. Especially during the public health emergencies, the endogenous health information demand generated by the lack of scientific knowledge of health information among online users stimulates the dissemination of health information by mass media while providing opportunities for rumor mongers to publish and spread online rumors. Invalid scientific knowledge and rumors will have a serious negative impact and disrupt social order during epidemic outbreaks such as COVID-19. Therefore, it is extremely important to construct an effective online rumor reversal model. The purpose of this study is to build an online rumor reversal model to control the spread of online rumors and reduce their negative impact. From the perspective of internal and external factors, based on the SIR model, this study constructed a G-SCNDR online rumor reversal model by adopting scientific knowledge level theory and an external online rumor control strategy. In this study, the G-SCNDR model is simulated, and a sensitivity analysis of the important parameters of the model is performed. The reversal efficiency of the G-SCNDR model can be improved by properly adopting the isolation-conversion strategy as the external control approach to online rumors with improving the popularization rate of the level of users' scientific knowledge and accelerating the transformation efficiency of official nodes. This study can help provide a better understanding of the process of online rumor spreading and reversing, as well as offering ceritain guidance and countermeasures for online rumor control during public health emergencies.

Catellatospora sichuanensis sp. nov., a novel actinobacterium isolated from soil.

A novel actinobacterium, designated strain H14505T, was isolated from a soil sample collected in Hong Yuan, Sichuan, southwest PR China. The temperature, pH and NaCl ranges for growth were determined to be 15-35 °C (optimum, 28 °C), 6.0-8.0 (optimum, pH 7.0) and 0-2 % (w/v; optimum without NaCl), respectively. The polar lipdis detected for strain H14505T were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, glycolipid and four unidentified lipids. The predominant menaquinones of strain H14505T were MK-9(H4) and MK-9(H6), and the prevalent fatty acids (>10 %) were C18 : 1 ω9c, C17 : 1 ω8c, summed feature 5 (anteiso-C18 : 0/ C18 : 2 ω6,9c) and C16 : 0. Phylogenetic analysis based on 16S rRNA gene and whole-genome sequences indicated that strain H14505T showed high similarity to Catellatospora vulcania NEAU-JM1T (99.0 %) and Catellatospora paridis NEAU-CL2T (99.0 %), and formed a monophyletic clade within the the genus Catellatospora in the phylogenetic trees. However, the average nucleotide indentity and DNA-DNA hybridization values between strain H14505T and closely related Catellatospora species showed that it belonged to a distinct species. Furthermore, the results of morphological, physiological and biochemical tests allowed further phenotypic differentiation of strain H14505T from its closest relatives. Thus, it is proposed that strain H14505T represents a novel species of the genus Catellatospora, for which the name Catellatospora sichuanensis sp. nov. is proposed. The type strain of Catellatospora sichuanensis is H14505T (=JCM 32394T=CICC 11042T).

Study on properties of wooden capillary electrospray ionization mass spectrometry.

RATIONALE: In view of the unique properties of wooden materials as electrospray emitters, a novel wooden capillary electrospray ionization (WC-ESI) device was fabricated. The performance of a wooden capillary as an electrospray emitter was investigated by using a wooden capillary instead of the metal emitter of commercial ESI sources. METHODS: The mass spectrometric measurement of baicalein, emodin and myoglobin was carried out by using wooden capillary (WC) and metal capillary (MC) ESI sources. Contrasting analysis of signal intensity between WC and MC electrospray ionization mass spectrometry (ESI-MS) was implemented at different sample flow rates. The effect of WC-ESI-MS and MC-ESI-MS was evaluated experimentally with electrospray solutions in different solvent ratios. RESULTS: Generally, the signal generated by WC-ESI-MS was much stronger than that obtained by MC-ESI-MS. In particular, the MS signal in negative ion mode was very strong, which may solve the long-standing problem of low MS signals in negative ion mode, and fully improve the detection efficiency of ESI-MS. CONCLUSIONS: The signal intensity produced by WC-ESI-MS is significantly higher than that from MC-ESI-MS, and polymerization and electrolysis are reduced; therefore, the spectra become simpler. In addition, it is also tolerant to high flow rates and high aqueous phase samples.

Organizing End-Site-Specific SWCNTs in Specific Loci Using DNA.

Single-wall carbon nanotubes (SWCNTs) are known to embody many desirable features for nanoelectronic and photonic applications, including excellent electronic and optical properties and mechanical robustness. To utilize these species in a bottom-up nanotechnological approach, it is necessary to be able to place them in precise absolute positions within a larger framework, without disturbing the conduction surface. Although it is well-known how to orient one or two nanotubes on a DNA origami, precise placement has eluded investigators previously. Here, we report a method of attaching a strand of DNA on the reactive end of a SWCNT, and then of using that DNA strand to place the nanotube at a specific site on a 2D DNA origami raft. We demonstrate that it is possible to place one or two nanotubes on such a DNA origami raft.

Stochastic RNA Walkers for Intracellular MicroRNA Imaging.

Nucleic acid-based machines have sparked tremendous attention because of their potential applications in biosensing, drug delivery, and biocomputing. Herein, we construct an enzyme-propelled stochastic RNA walker that autonomously walks on a single wall carbon nanotube (SWCNT)-based one-dimensional (1D) track for miRNA imaging in living cells. Driven by duplex-specific nuclease (DSN) with the capability of selective digestion of DNA in the DNA/RNA heteroduplexes, the RNA walker enables autonomous and progressive walk on the SWCNTs, producing amplified signal outputs. As a result, this DSN-powered stochastic RNA walker with high target-recycling kinetic achieves prominent detection performance of miRNA analysis, showing a linear range from 5 fM to 10 pM with a limit of detection of 1.67 fM and one-base mismatch discrimination. Finally, we demonstrated that this nanomachine can be applied for intracellular miRNA imaging.

PADI3 plays an antitumor role via the Hsp90/CKS1 pathway in colon cancer.

BACKGROUND: CKS1 is highly expressed in colon cancer tissues, and is essential for cancer cell proliferation. The downstream molecular mechanism of CKS1 has been fully studied, but the upstream regulatory mechanism of it is still unclear. Earlier research found that PADI3 plays its anti-tumor roles via suppress cell proliferation, in this study, we found that the expression pattern of PADI3 and CKS1 are negatively correlated in colon cancer tissues, and overexpression of PADI3 can partly reverse CKS1 induced cancer cell proliferation. However, the regulatory mechanism of PADI3 and CKS1 in the tumorigenesis of colon cancer is still unclear and need to do further research. METHODS: Western blot and real-time PCR were used to detect the expression levels of genes. CCK-8 and colony formation assays were used to examine cell proliferation and colony formation ability. Overexpression and rescue experiments were used to study the molecular mechanism of CKS1 in colon cancer cells, BALB/c nude mice were used to study the function of CKS1 in vivo. RESULTS: CKS1 is highly expressed in colon cancer tissues, and the overexpression of CKS1 promotes cell proliferation and colony formation in both HCT116 (originating from primary colon cancer) and SW620 (originating from metastatic tumor nodules of colon cancer) cells. CKS1-expressing HCT116 cells produced larger tumors than the control cells. The expression pattern of PADI3 and CKS1 are negatively correlation in clinical samples of colon cancer, further study indicates that PADI3 can significantly decrease Hsp90 and CKS1 expression, and Hsp90 is essential for PADI3 to downregulate CKS1expression in colon cancer cells. CONCLUSIONS: PADI3 exerts its antitumor activity by inhibiting Hsp90 and CKS1 expression, and Hsp90 is essential for PADI3 to suppress CKS1 expression.

Randomized study of continuous high-dose lenalidomide, sequential azacitidine and lenalidomide, or azacitidine in persons 65 years and over with newly-diagnosed acute myeloid leukemia.

Therapy of acute myeloid leukemia in older persons is associated with poor outcomes because of intolerance to intensive therapy, resistant disease and co-morbidities. This multi-center, randomized, open-label, phase II trial compared safety and efficacy of three therapeutic strategies in patients 65 years or over with newly-diagnosed acute myeloid leukemia: 1) continuous high-dose lenalidomide (n=15); 2) sequential azacitidine and lenalidomide (n=39); and 3) azacitidine only (n=34). The efficacy end point was 1-year survival. Median age was 76 years (range 66-87 years). Thirteen subjects (15%) had prior myelodysplastic syndrome and 41 (47%) had adverse cytogenetics. One-year survival was 21% [95% confidence interval (CI): 0, 43%] with high-dose lenalidomide, 44% (95%CI: 28, 60%) with sequential azacitidine and lenalidomide, and 52% (95%CI: 35, 70%) with azacitidine only. Lenalidomide at a continuous high-dose schedule was poorly-tolerated resulting in a high rate of early therapy discontinuations. Hazard of death in the first four months was greatest in subjects receiving continuous high-dose lenalidomide; hazards of death thereafter were similar. These data do not favor use of continuous high-dose lenalidomide or sequential azacitidine and lenalidomide over the conventional dose and schedule of azacitidine only in patients aged 65 years or over with newly-diagnosed acute myeloid leukemia. (clinicaltrials.gov identifier: 01358734).

DNA-Encoded Raman-Active Anisotropic Nanoparticles for microRNA Detection.

The development of highly sensitive and selective methods for the detection of microRNA (miRNA) has attracted tremendous attention because of its importance in fundamental biological studies and diagnostic applications. In this work, we develop DNA-encoded Raman-active anisotropic nanoparticles modified origami paper analytical devices (oPADs) for rapid, highly sensitive, and specific miRNA detection. The Raman-active anisotropic nanoparticles were prepared using 10-mer oligo-A, -T, -C, and -G to mediate the growth of Ag cubic seeds into Ag nanoparticles (AgNPs) with different morphologies. The resulting AgNPs were further encoded with DNA probes to serve as effective surface-enhanced Raman scattering (SERS) probes. The analytical device was then fabricated on a single piece of SERS probes loaded paper-based substrate and assembled based on the principles of origami. The addition of the target analyte amplifies the Raman signals on DNA-encoded AgNPs through a target-dependent, sequence specific DNA hybridization assembly. This simple and low-cost analytical device is generic and applicable to a variety of miRNAs, allowing detection sensitivity down to 1 pM and assay time within 15 min, and therefore holds promising applications in point-of-care diagnostics.

Signaling Scaffold Protein IQGAP1 Interacts with Microtubule Plus-end Tracking Protein SKAP and Links Dynamic Microtubule Plus-end to Steer Cell Migration.

Cell migration is orchestrated by dynamic interaction of microtubules with the plasma membrane cortex. However, the regulatory mechanisms underlying the cortical actin cytoskeleton and microtubule dynamics are less characterized. Our earlier study showed that small GTPase-activating proteins, IQGAPs, regulate polarized secretion in epithelial cells (1). Here, we show that IQGAP1 links dynamic microtubules to steer cell migration via interacting with the plus-end tracking protein, SKAP. Biochemical characterizations revealed that IQGAP1 and SKAP form a cognate complex and that their binding interfaces map to the WWIQ motif and the C-terminal of SKAP, respectively. The WWIQ peptide disrupts the biochemical interaction between IQGAP1 and SKAP in vitro, and perturbation of the IQGAP1-SKAP interaction in vivo using a membrane-permeable TAT-WWIQ peptide results in inhibition of directional cell migration elicited by EGF. Mechanistically, the N-terminal of SKAP binds to EB1, and its C terminus binds to IQGAP1 in migrating cells. Thus, we reason that a novel IQGAP1 complex orchestrates directional cell migration via coupling dynamic microtubule plus-ends to the cell cortex.

A model with combined viral and metabolic factors effectively predicts HBeAg status under long term entecavir therapy: a prospective cohort study.

BACKGROUND & AIM: The aim was to extract factors from virologic and biochemical profiles at baseline and 24 weeks of treatment to predict HBeAg seroconversion in patients treated with ETV. METHODS: HBeAg positive chronic hepatitis B patients receiving ETV naïve-treatment were enrolled. HBV DNA, ALT, and serological markers were prospectively monitored every 6 months for 240 weeks. The cumulative rates of virologic response (VR), biochemical response (BR), and HBeAg seroconversion were determined, and potential predictors for HBeAg seroconversion were identified through uni/multivariate analysis. RESULT: Two hundred twenty nine patients were eligible for this study. The cumulative rates of VR, BR, and HBeAg seroconversion at 240 weeks were 88.4 %, 100 %, and 36.7 %, respectively. Multivariate analysis showed that HBV DNA (OR, 2.8, p = 0.003), ALT (OR, 2.6, p = 0.005) at baseline, undetectable HBV DNA within 24 weeks (OR = 3.2, p < 0.001), and body mass index (BMI) ≥24kg/m(2) (OR = 0.038, p = 0.013) were associated with HBeAg seroconversion. A prediction model for probability of HBeAg seroconversion was constructed. Patients can be classified into high (>40 %), intermediate (20-40 %), or low (≤20 %) groups based on the calculated probability of HBeAg seroconversion. The cumulative rates of HBeAg seroconversion were different among the three groups (p < 0.001). About 58 % patients in the high probability group achieved HBeAg seroconversion while almost 90 % patients within the low group remained HBeAg positive. CONCLUSION: A combination of HBV DNA, ALT and BMI values at baseline, and undetectable HBV DNA level within 24 weeks can predict HBeAg seroconversion. Both viral and metabolic factors likely determine HBeAg status with ETV treatment. TRIAL REGISTRATION: CTR20132358.

Efficacy and safety of oral branched-chain amino acid supplementation in patients undergoing interventions for hepatocellular carcinoma: a meta-analysis.

Most hepatocellular carcinoma (HCC) patients have complications, including cirrhosis and malnutrition. The efficacy of dietary supplementation with oral branched-chain amino acids (BCAAs) in HCC patients undergoing interventions has not been confirmed. Relevant publications on the efficacy and safety of oral BCAA supplementation for HCC patients undergoing anti-HCC interventions through September, 2014 were searched for identification in the PubMed, Embase, Web of Science, and the Cochrane Library databases. The pooled risk ratio (RR) and standardized mean difference (SMD) were used to assess the supplementation effects. A total of 11 eligible studies (974 patients in total) were evaluated and included in our analysis. Oral BCAA supplementation helped to maintain liver reserve with higher serum albumin (SMD = 0.234, 95% CI: 0.033-0.435, P = 0.022), and lower rates of ascites (RR = 0.545, 95% CI: 0.316-0.938, P = 0.029) and edema (RR = 0.494, 95% CI: 0.257-0.952, P = 0.035) than in the control group. BCAA supplementation seemed to be effective in improving mortality, especially in Child-Pugh class B patients, but the efficacy was not confirmed. Apparent effects were not found in improving HCC recurrence, total bilirubin, ALT, or AST. BCAA supplementation was relatively safe without serious adverse events. BCAA supplementation may be clinically applied in improving liver functional reserve for HCC patients and further improving the quality of life.

Regulation of a dynamic interaction between two microtubule-binding proteins, EB1 and TIP150, by the mitotic p300/CBP-associated factor (PCAF) orchestrates kinetochore microtubule plasticity and chromosome stability during mitosis.

The microtubule cytoskeleton network orchestrates cellular dynamics and chromosome stability in mitosis. Although tubulin acetylation is essential for cellular plasticity, it has remained elusive how kinetochore microtubule plus-end dynamics are regulated by p300/CBP-associated factor (PCAF) acetylation in mitosis. Here, we demonstrate that the plus-end tracking protein, TIP150, regulates dynamic kinetochore-microtubule attachments by promoting the stability of spindle microtubule plus-ends. Suppression of TIP150 by siRNA results in metaphase alignment delays and perturbations in chromosome biorientation. TIP150 is a tetramer that binds an end-binding protein (EB1) dimer through the C-terminal domains, and overexpression of the C-terminal TIP150 or disruption of the TIP150-EB1 interface by a membrane-permeable peptide perturbs chromosome segregation. Acetylation of EB1-PCAF regulates the TIP150 interaction, and persistent acetylation perturbs EB1-TIP150 interaction and accurate metaphase alignment, resulting in spindle checkpoint activation. Suppression of the mitotic checkpoint serine/threonine protein kinase, BubR1, overrides mitotic arrest induced by impaired EB1-TIP150 interaction, but cells exhibit whole chromosome aneuploidy. Thus, the results identify a mechanism by which the TIP150-EB1 interaction governs kinetochore microtubule plus-end plasticity and establish that the temporal control of the TIP150-EB1 interaction by PCAF acetylation ensures chromosome stability in mitosis.

Efficacy and resistance in de novo combination lamivudine and adefovir dipivoxil therapy versus entecavir monotherapy for the treatment-naive patients with chronic hepatitis B: a meta-analysis.

BACKGROUND: Currently, there is no consensus on the efficacy and resistance of de novo combination therapy versus monotherapy for treatment naive patients of chronic hepatitis B (CHB). OBJECTIVES: The aim of this study was to evaluate the effectiveness and resistance of de novo combination of lamivudine (LAM) and adefovir dipivoxil (ADV) compared with entecavir (ETV) monotherapy for nucleos(t)ide-naive patients with CHB. STUDY DESIGN: Publications on the effectiveness and resistance of LAM plus ADV versus ETV monotherapy for nucleos(t)ide-naive patients with CHB were identified by a search of PubMed, Embase, the Cochrane Library, Web of science, OVID, and CBM (Chinese Biological Medical Literature) until May 1, 2013. Biochemical response, hepatitis B e antigen seroconversion, and viroligic response were extracted and combined to obtain an integrated result. Viral resistance and safety were reviewed. RESULTS: Five eligible studies (328 patients in total) were included in the analysis. LAM plus ADV combination therapy produced more rapid HBV DNA reduction rate at 12 weeks than that of ETV monotherapy. At 48 weeks, the combination group had superior viroligic response rates compared with ETV group (90.0% vs. 78.9%, P=0.01). The difference in the ALT normalization and HBeAg seroconversion rates was not found. At week 96, LAM + ADV was more effective than ETV in ALT normalization [RR = 1. 11, 95% CI (1.02, 1.21), P =0.01] and HBeAg seroconversion [RR = 2.00, 95% CI (1.26, 3.18, P=0.003)], and no significant difference was found in the virologic response (P =0.23). No viral resistance occurred in combination therapy and six patients in ETV group were experienced with viral breakthrough. Both groups were well tolerated. CONCLUSION: The de novo LAM plus ADV combination therapy for treatment-naïve patients with CHB was greater than ETV monotherapy in both biochemical response and HBeAg seroconversion rate up to 96 weeks. The rate of emergence of viral resistance in the combination group was less than that in the ETV monotherapy.