Low-dose metformin targets the lysosomal AMPK pathway through PEN2.

Metformin, the most prescribed antidiabetic medicine, has shown other benefits such as anti-ageing and anticancer effects1-4. For clinical doses of metformin, AMP-activated protein kinase (AMPK) has a major role in its mechanism of action4,5; however, the direct molecular target of metformin remains unknown. Here we show that clinically relevant concentrations of metformin inhibit the lysosomal proton pump v-ATPase, which is a central node for AMPK activation following glucose starvation6. We synthesize a photoactive metformin probe and identify PEN2, a subunit of γ-secretase7, as a binding partner of metformin with a dissociation constant at micromolar levels. Metformin-bound PEN2 forms a complex with ATP6AP1, a subunit of the v-ATPase8, which leads to the inhibition of v-ATPase and the activation of AMPK without effects on cellular AMP levels. Knockout of PEN2 or re-introduction of a PEN2 mutant that does not bind ATP6AP1 blunts AMPK activation. In vivo, liver-specific knockout of Pen2 abolishes metformin-mediated reduction of hepatic fat content, whereas intestine-specific knockout of Pen2 impairs its glucose-lowering effects. Furthermore, knockdown of pen-2 in Caenorhabditis elegans abrogates metformin-induced extension of lifespan. Together, these findings reveal that metformin binds PEN2 and initiates a signalling route that intersects, through ATP6AP1, the lysosomal glucose-sensing pathway for AMPK activation. This ensures that metformin exerts its therapeutic benefits in patients without substantial adverse effects.

Physiology and transcriptome analysis of Artemisia argyi adaptation and accumulation to soil cadmium.

The soil pollution caused by cadmium (Cd) poses a significant threat to the environment. Therefore, identifying plants that can effectively remediate Cd-contaminated soils is urgently needed. In this study, physiological, cytological, and transcriptome analyses were performed to comprehensively understand the changes in Artemisia argyi under Cd stress. Physiological and cytological analyses indicated that A. argyi maintained normal growth with intact cell structure under Cd stress levels up to 10 mg/kg. Cytological analysis showed that Cd precipitation in leaf cells occurred in the cytoplasm and intercellular spaces. As the levels of Cd stress increased, proline accumulation in leaves increased, whereas soluble protein and soluble sugar initially increased, followed by a subsequent decline. The translocation factor was above 1 under 0.6 mg/kg Cd stress but decreased when it exceeded this concentration. Transcriptome analyses revealed several crucial Cd-influenced pathways, including amino acid, terpenoid, flavonoid, and sugar metabolisms. This study not only proved that A. argyi could enrich Cd in soil but also revealed the response of A. argyi to Cd and its resistance mechanisms, which provided insight into the cleaner production of A. argyi and the remediation of Cd-contaminated soil.

An Improved Method for Accurate Radiation Measurement Based on Dark Output Noise Drift Compensation.

This paper verified through experiments that change in ambient temperature are the main cause of dark output noise drift. Additionally, the impact of dark output noise drift in fiber optic spectrometers on emissivity measurements has been investigated in this work. Based on an improved fiber optic spectrometer, two methods were proposed for characterizing and correcting the dark output noise offset in fiber optic spectrometers: the mean correction scheme and the linear fitting correction scheme. Compared to the mean correction scheme, the linear fitting correction scheme is more effective in solving the problem of dark output noise drift. When the wavelength is greater than 1600 nm, the calibration relative error of silicon carbide (SIC) emissivity is less than 0.8% by the mean correction scheme, while the calibration relative error of silicon carbide emissivity is less than 0.62% by the linear fitting correction scheme. This work solves the problem of dark output noise drift in prolonged measurement based on fiber optic spectrometers, improving the accuracy and reliability of emissivity and quantitative radiation measurement.

IR-Based Novel Device for Real-Time Online Acquisition of Fish Heart ECG Signals.

We developed an infrared (IR)-based real-time online monitoring device (US Patent No: US 10,571,448 B2) to quantify heart electrocardiogram (ECG) signals to assess the water quality based on physiological changes in fish. The device is compact, allowing us to monitor cardiac function for an extended period (from 7 to 30 days depending on the rechargeable battery capacity) without function injury and disturbance of swimming activity. The electrode samples and the biopotential amplifier and microcontroller process the cardiac-electrical signals. An infrared transceiver transmits denoised electrocardiac signals to complete the signal transmission. The infrared receiver array and biomedical acquisition signal processing system send signals to the computer. The software in the computer processes the data in real time. We quantified ECG indexes (P-wave, Q-wave, R-wave, S-wave, T-wave, PR-interval, QRS-complex, and QT-interval) of carp precisely and incessantly under the different experimental setup (CuSO4 and deltamethrin). The ECG cue responses were chemical-specific based on CuSO4 and deltamethrin exposures. This study provides an additional technology for noninvasive water quality surveillance.

FACT and Ash1 promote long-range and bidirectional nucleosome eviction at the HO promoter.

The Saccharomyces cerevisiae HO gene is a model regulatory system with complex transcriptional regulation. Budding yeast divide asymmetrically and HO is expressed only in mother cells where a nucleosome eviction cascade along the promoter during the cell cycle enables activation. HO expression in daughter cells is inhibited by high concentration of Ash1 in daughters. To understand how Ash1 represses transcription, we used a myo4 mutation which boosts Ash1 accumulation in both mothers and daughters and show that Ash1 inhibits promoter recruitment of SWI/SNF and Gcn5. We show Ash1 is also required for the efficient nucleosome repopulation that occurs after eviction, and the strongest effects of Ash1 are seen when Ash1 has been degraded and at promoter locations distant from where Ash1 bound. Additionally, we defined a specific nucleosome/nucleosome-depleted region structure that restricts HO activation to one of two paralogous DNA-binding factors. We also show that nucleosome eviction occurs bidirectionally over a large distance. Significantly, eviction of the more distant nucleosomes is dependent upon the FACT histone chaperone, and FACT is recruited to these regions when eviction is beginning. These last observations, along with ChIP experiments involving the SBF factor, suggest a long-distance loop transiently forms at the HO promoter.

Proteomic Analysis of Roots Response to Potassium Deficiency and the Effect of TaHAK1-4A on K+ Uptake in Wheat.

Potassium (K+) is essential for plant growth and stress responses. A deficiency in soil K+ contents can result in decreased wheat quality and productivity. Thus, clarifying the molecular mechanism underlying wheat responses to low-K+ (LK) stress is critical. In this study, a tandem mass tag (TMT)-based quantitative proteomic analysis was performed to investigate the differentially abundant proteins (DAPs) in roots of the LK-tolerant wheat cultivar "KN9204" at the seedling stage after exposure to LK stress. A total of 104 DAPs were identified in the LK-treated roots. The DAPs related to carbohydrate and energy metabolism, transport, stress responses and defense, and post-translational modifications under LK conditions were highlighted. We identified a high-affinity potassium transporter (TaHAK1-4A) that was significantly up-regulated after the LK treatment. Additionally, TaHAK1-4A was mainly expressed in roots, and the encoded protein was localized in the plasma membrane. The complementation assay in yeast suggested that TaHAK1-4A mediates K+ uptake under extreme LK conditions. The overexpression of TaHAK1-4A increased the fresh weight and root length of Arabidopsis under LK conditions and improved the growth of Arabidopsis athak5 mutant seedlings, which grow poorly under LK conditions. Moreover, silencing of TaHAK1-4A in wheat roots treated with LK stress decreased the root length, dry weight, K+ concentration, and K+ influx. Accordingly, TaHAK1-4A is important for the uptake of K+ by roots exposed to LK stress. Our results reveal the protein metabolic changes in wheat induced by LK stress. Furthermore, we identified a candidate gene potentially relevant for developing wheat lines with increased K+ use efficiency.

Disruption of promoter memory by synthesis of a long noncoding RNA.

The yeast HO endonuclease is expressed in late G1 in haploid mother cells to initiate mating-type interconversion. Cells can be arrested in G1 by nutrient deprivation or by pheromone exposure, but cells that resume cycling after nutrient deprivation or cyclin-dependent kinase (CDK) inactivation express HO in the first cell cycle, whereas HO is not expressed until the second cycle after release from pheromone arrest. Here, we show that transcription of a long noncoding RNA (lncRNA) mediates this differential response. The SBF and Mediator factors remain bound to the inactive promoter during arrest due to CDK inactivation, and these bound factors allow the cell to remember a transcriptional decision made before arrest. If the presence of mating pheromone indicates that this decision is no longer appropriate, a lncRNA originating at -2700 upstream of the HO gene is induced, and the transcription machinery displaces promoter-bound SBF, preventing HO transcription in the subsequent cell cycle. Further, we find that the displaced SBF is blocked from rebinding due to incorporation of its recognition sites within nucleosomes. Expressing the pHO-lncRNA in trans is ineffective, indicating that transcription in cis is required. Factor displacement during lncRNA transcription could be a general mechanism for regulating memory of previous events at promoters.

FACT and Asf1 regulate nucleosome dynamics and coactivator binding at the HO promoter.

Transcriptional activators and coactivators overcome repression by chromatin, but regulation of chromatin disassembly and coactivator binding to promoters is poorly understood. Activation of the yeast HO gene follows the sequential binding of both sequence-specific DNA-binding proteins and coactivators during the cell cycle. Here, we show that the nucleosome disassembly occurs in waves both along the length of the promoter and during the cell cycle. Different chromatin modifiers are required for chromatin disassembly at different regions of the promoter, with Swi/Snf, the FACT chromatin reorganizer, and the Asf1 histone chaperone each required for nucleosome eviction at distinct promoter regions. FACT and Asf1 both bind to upstream elements of the HO promoter well before the gene is transcribed. The Swi/Snf, SAGA, and Mediator coactivators bind first to the far upstream promoter region and subsequently to a promoter proximal region, and FACT and Asf1 are both required for this coactivator re-recruitment.

Stochastic expression and epigenetic memory at the yeast HO promoter.

Eukaryotic gene regulation usually involves sequence-specific transcription factors and sequence-nonspecific cofactors. A large effort has been made to understand how these factors affect the average gene expression level among a population. However, little is known about how they regulate gene expression in individual cells. In this work, we address this question by mutating multiple factors in the regulatory pathway of the yeast HO promoter (HOpr) and probing the corresponding promoter activity in single cells using time-lapse fluorescence microscopy. We show that the HOpr fires in an "on/off" fashion in WT cells as well as in different genetic backgrounds. Many chromatin-related cofactors that affect the average level of HO expression do not actually affect the firing amplitude of the HOpr; instead, they affect the firing frequency among individual cell cycles. With certain mutations, the bimodal expression exhibits short-term epigenetic memory across the mitotic boundary. This memory is propagated in "cis" and reflects enhanced activator binding after a previous "on" cycle. We present evidence that the memory results from slow turnover of the histone acetylation marks.

The Rts1 regulatory subunit of PP2A phosphatase controls expression of the HO endonuclease via localization of the Ace2 transcription factor.

The RTS1 gene encodes a subunit of the PP2A phosphatase that regulates cell cycle progression. Ace2 and Swi5 are cell cycle-regulated transcription factors, and we recently showed that phosphorylation of Ace2 and Swi5 is altered in an rts1 mutant. Here we examine expression of Ace2 and Swi5 target genes and find that an rts1 mutation markedly reduces expression of the HO gene. The decreased HO expression in an rts1 mutant is significantly restored by an additional ace2 mutation, a surprising result because HO is normally activated by Swi5 but not by Ace2. Ace2 normally accumulates only in daughter cells, and only activates transcription in daughters. However, in an rts1 mutant, Ace2 is present in both mother and daughter cells. One of the genes activated by Ace2 is ASH1, a protein that normally accumulates mostly in daughter cells; Ash1 is a transcriptional repressor, and it blocks HO expression in daughters. We show that in the rts1 mutant, Ace2 accumulation in mother cells results in Ash1 expression in mothers, and the Ash1 can now repress HO expression in mothers.

Exploring diverse programmed cell-death patterns to develop a novel gene signature for predicting the prognosis of lung adenocarcinoma patients.

Background: Programmed cell death (PCD) plays a critical role in tumor progression and malignancy, and exploring its relationship with lung adenocarcinoma (LUAD)'s survival outcomes is important for personalized diagnosis and treatment. This study aimed to identify survival-related genes and construct an effective prognostic indicator for LUAD based on 12 forms of PCD. Methods: A total of 1,933 candidate genes related to PCD were collected from published studies and public data center. A prognostic gene signature, called the cell death index (CDI), was established based on RNA-Seq and immunohistochemistry (IHC). IHC staining on tissue microarray was applied for the validation of protein level. Moreover, GSE42127, GSE72094 were used as validation datasets. Results: The CDI based on expression level of nine genes (CCNB2, HMGA1, CACNA2D2, BUB1B, BTG2, KIF14, PTGDS, SERPINB5, BRCA1) was highly predictive for overall survival (OS) of LUAD in our cohort [36-month area under the curve (AUC): 0.750, 60-month AUC: 0.809]. The CDI was further validated in independent cohorts (GSE72094, 36-month AUC: 0.717, 60-month AUC: 0.737; GSE42127, 12-month AUC: 0.829, 60-month AUC: 0.663). And the CDI was found to be an independent prognostic factor after adjusting for other clinical characteristics. Furthermore, the high-CDI group was associated with upregulated tumor immune infiltration compared to the low-CDI group. Conclusions: This study identified a 9-gene signature (CDI) based on PCD-related genes that accurately predicted the prognosis of LUAD patients. The CDI could serve as a valuable prognostic indicator and guide personalized therapeutic strategies for LUAD.

Preparation of chitosan photodynamic antibacterial film loaded with VK3 complex in the preservation of chilled mutton.

To effectively utilize the photodynamic antibacterial ability of vitamin K3 (VK3), by solving the photothermal instability of VK3, it was combined with natural polymers to apply the preservation of chilled mutton. We encapsulated VK3 in the (2-Hydroxypropyl)-ß-cyclodextrin (HP-ß-CD) to construct VK3-HP-ß-CD complex and then introduced the complex to chitosan (CS) and polyvinyl alcohol (PVA) to fabricate an antibacterial film (CS/PVA-VK3-HP-ß-CD film). Through the packaging performance test of the film, the content of VK3-HP-ß-CD was an important factor determining the properties of film including tensile strength, elongation at break, water vapor permeability, water content and water contact angle. Meanwhile, CS/PVA-VK3-HP-ß-CD films could continuously release ROS under light and suspended in dark, thus realizing >99 % antibacterial rate for Escherichia coli and Staphylococcus aureus. In the application experiment of chilled mutton, CS/PVA-VK3-1-HP-ß-CD film could significantly inhibit the increase of total viable count (TVC), pH value (pH) and total volatile base nitrogen (TVB-N) of chilled mutton, and extended its shelf life for at least 12 days. These results indicated that the CS/PVA film with the VK3-HP-ß-CD complex might have promising potential as an antibacterial material for packaging and preserving food.

Anti-tumor efficacy of HRS-4642 and its potential combination with proteasome inhibition in KRAS G12D-mutant cancer.

KRAS G12D is the most frequently mutated oncogenic KRAS subtype in solid tumors and remains undruggable in clinical settings. Here, we developed a high affinity, selective, long-acting, and non-covalent KRAS G12D inhibitor, HRS-4642, with an affinity constant of 0.083 nM. HRS-4642 demonstrated robust efficacy against KRAS G12D-mutant cancers both in vitro and in vivo. Importantly, in a phase 1 clinical trial, HRS-4642 exhibited promising anti-tumor activity in the escalating dosing cohorts. Furthermore, the sensitization and resistance spectrum for HRS-4642 was deciphered through genome-wide CRISPR-Cas9 screening, which unveiled proteasome as a sensitization target. We further observed that the proteasome inhibitor, carfilzomib, improved the anti-tumor efficacy of HRS-4642. Additionally, HRS-4642, either as a single agent or in combination with carfilzomib, reshaped the tumor microenvironment toward an immune-permissive one. In summary, this study provides potential therapies for patients with KRAS G12D-mutant cancers, for whom effective treatments are currently lacking.

The E2F functional analogue SBF recruits the Rpd3(L) HDAC, via Whi5 and Stb1, and the FACT chromatin reorganizer, to yeast G1 cyclin promoters.

Regulation of the CLN1 and CLN2 G1 cyclin genes controls cell cycle progression. The SBF activator binds to these promoters but is kept inactive by the Whi5 and Stb1 inhibitors. The Cdc28 cyclin-dependent kinase phosphorylates Whi5, ending the inhibition. Our chromatin immunoprecipitation (ChIP) experiments show that SBF, Whi5 and Stb1 recruit both Cdc28 and the Rpd3(L) histone deacetylase to CLN promoters, extending the analogy with mammalian G1 cyclin promoters in which Rb recruits histone deacetylases. Finally, we show that the SBF subunit Swi6 recruits the FACT chromatin reorganizer to SBF- and MBF-regulated genes. Mutations affecting FACT reduce the transient nucleosome eviction seen at these promoters during a normal cell cycle and also reduce expression. Temperature-sensitive mutations affecting FACT and Cdc28 can be suppressed by disruption of STB1 and WHI5, suggesting that one critical function of FACT and Cdc28 is overcoming chromatin repression at G1 cyclin promoters. Thus, SBF recruits complexes to promoters that either enhance (FACT) or repress (Rpd3L) accessibility to chromatin, and also recruits the kinase that activates START.

Efficient Reflectance Capture With a Deep Gated Mixture-of-Experts.

We present a novel framework to efficiently acquire anisotropic reflectance in a pixel-independent fashion, using a deep gated mixture-of-experts. While existing work employs a unified network to handle all possible input, our network automatically learns to condition on the input for enhanced reconstruction. We train a gating module that takes photometric measurements as input and selects one out of a number of specialized decoders for reflectance reconstruction, essentially trading generality for quality. A common pre-trained latent-transform module is also appended to each decoder, to offset the burden of the increased number of decoders. In addition, the illumination conditions during acquisition can be jointly optimized. The effectiveness of our framework is validated on a wide variety of challenging near-planar samples with a lightstage. Compared with the state-of-the-art technique, our quality is improved with the same number of input images, and our input image number can be reduced to about 1/3 for equal-quality results. We further generalize the framework to enhance a state-of-the-art technique on non-planar reflectance scanning.

Low glucose metabolite 3-phosphoglycerate switches PHGDH from serine synthesis to p53 activation to control cell fate.

Glycolytic intermediary metabolites such as fructose-1,6-bisphosphate can serve as signals, controlling metabolic states beyond energy metabolism. However, whether glycolytic metabolites also play a role in controlling cell fate remains unexplored. Here, we find that low levels of glycolytic metabolite 3-phosphoglycerate (3-PGA) can switch phosphoglycerate dehydrogenase (PHGDH) from cataplerosis serine synthesis to pro-apoptotic activation of p53. PHGDH is a p53-binding protein, and when unoccupied by 3-PGA interacts with the scaffold protein AXIN in complex with the kinase HIPK2, both of which are also p53-binding proteins. This leads to the formation of a multivalent p53-binding complex that allows HIPK2 to specifically phosphorylate p53-Ser46 and thereby promote apoptosis. Furthermore, we show that PHGDH mutants (R135W and V261M) that are constitutively bound to 3-PGA abolish p53 activation even under low glucose conditions, while the mutants (T57A and T78A) unable to bind 3-PGA cause constitutive p53 activation and apoptosis in hepatocellular carcinoma (HCC) cells, even in the presence of high glucose. In vivo, PHGDH-T57A induces apoptosis and inhibits the growth of diethylnitrosamine-induced mouse HCC, whereas PHGDH-R135W prevents apoptosis and promotes HCC growth, and knockout of Trp53 abolishes these effects above. Importantly, caloric restriction that lowers whole-body glucose levels can impede HCC growth dependent on PHGDH. Together, these results unveil a mechanism by which glucose availability autonomously controls p53 activity, providing a new paradigm of cell fate control by metabolic substrate availability.

Repressive chromatin affects factor binding at yeast HO (homothallic switching) promoter.

The yeast HO gene is tightly regulated, with multiple activators and coactivators needed to overcome repressive chromatin structures that form over this promoter. Coactivator binding is strongly interdependent, as loss of one factor sharply reduces recruitment of other factors. The Rpd3(L) histone deacetylase is recruited to HO at two distinct times during the cell cycle, first by Ash1 to the URS1 region of the promoter and then by SBF/Whi5/Stb1 to URS2. SBF itself is localized to only a subset of its potential binding sites in URS2, and this localization takes longer and is less robust than at other SBF target genes, suggesting that binding to the HO promoter is limited by chromatin structures that dynamically change as the cell cycle progresses. Ash1 only binds at the URS1 region of the promoter, but an ash1 mutation results in markedly increased binding of SBF and Rpd3(L) at URS2, some 450 bp distant from the site of Ash1 binding, suggesting these two regions of the promoter interact. An ash1 mutation also results in increased coactivator recruitment, Swi/Snf and Mediator localization in the absence of the normally required Gcn5 histone acetyltransferase, and HO expression even in the presence of a taf1 mutation affecting TFIID activity that otherwise blocks HO transcription. Ash1 therefore appears to play a central role in generating the strongly repressive environment at the HO promoter, which limits the binding of several coactivators at URS2 and TATA region.

Facile synthesis and luminescence characteristics of high-quality CdS: Eu/ZnS core/shell nanocrystals with biocompatibility.

In this paper, we report a facile method to synthesize high quality CdS: Eu nanocrystals (NCs) and CdS: Eu/ZnS NCs with strong photoluminescence (PL). The influence of various experimental variables including the concentration of Eu3+ ions, the reaction time and the reaction temperature were investigated systematically. In addition, the PL properties of CdS: Eu NCs exhibited pH sensitive. Under the acid condition, pH value of the CdS: Eu NCs solution played an important role in determining PL emission intensity. However, under the alkaline condition, the obtained CdS: Eu NCs exhibited a tunable PL emission wavelength (from 490 nm to 610 nm) when pH value was adjusted from pH 7 to 10. After coating with ZnS shell, the CdS: Eu/ZnS NCs showed enhanced PL intensity compare with one of the CdS: Eu NCs. The CdS: Eu NCs and CdS: Eu/ZnS NCs were characterized by X-ray diffraction (XRD) and high-resolution transmission electron microscopy (HRTEM). In addition, the biocompatibility of these NCs was measured by hemolytic test, which indicated that CdS: Eu/ZnS NCs were more biocompatible than CdS: Eu NCs at the same conditions. It can be expected that CdS: Eu/ZnS NCs are promising biolabeling materials.

One-pot aqueous synthesis PbS quantum dots and their Hg2+ sensitive properties.

In this study, we report the synthesis and stability of PbS quantum dots (QDs) using an aqueous route with L-Cysteine (L-Cys) as the capping molecule. The as-synthesized L-Cys-capped PbS QDs were characterized by high resolution transmission electron microscopy (HRTEM), and X-ray diffraction (XRD), the results indicated that the QDs were about 4 nm in size and dispersed well with a rock salt crystalline structure, and there was L-Cys on the surface of QDs, which was confirmed by Fourier transform infrared (FT-IR) spectrometry. The influence of various experimental variables, including amounts of capping ligand, pH value and refluxing time, on the luminescent properties of the obtained QDs have been systematically investigated. The QDs exhibited optimal PL intensity when Pb: L-Cys: S = 1:2.2:0.3. In addition, the as-prepared QDs could be used as fluorescence probes to detect Hg2+ ions in aqueous media. The response of QDs fluorescence probes was linearly proportional to the concentration of Hg2+ ions ranging from 8 x 10(-9) to 2 x 10(-6) mol x L(-1) with a limit of detection of 2 x 10(-9) mol x L(-1). Furthermore, the method was successfully applied to the determine Hg2+ ions in different real samples.

[Efficacy and safety of telbivudine treatment to block mother-to-child transmission of hepatitis B virus: a meta-analysis].

OBJECTIVE: To evaluate the efficacy and safety of telbivudine treatment in pregnant patients with chronic hepatitis B to block mother-to-child transmission of hepatitis B virus (HBV). METHODS: Medline and the Chinese Biomedical Literature Database were searched for studies of HBV, mother-to-child transmission, and telbivudine. Of the 68 potentially relevant publications, eight randomized controlled trials (RCTs) conformed to the inclusion and exclusion criteria. Following data extraction, a meta-analysis was carried out with RevMan5.1 software. RESULTS: Seven of the eight RCTs were in Chinese, and the remaining study was in English but carried out at a Chinese site. The RCTs comprised a total of 678 subjects, including 352 cases and 326 controls. Infants born to telbivudine-treated mothers had a significantly lower rate of HBsAg positivity and HBV DNA positivity at birth than the control group of infants (odds ratio (OR) = 0.27, 95% confidence interval (CI): 0.17, 0.43, P less than 0.00001; OR = 0.14, 95% CI: 0.06, 0.32, P less than 0.00001). Infants born to telbivudine-treated mothers also had significantly lower rates of mother-to-child transmitted HBV at 6 months (OR = 0.06, 95% CI: 0.02, 0.22, P less than 0.00001; OR = 0.05, 95% CI: 0.01, 0.25, P = 0.0003) and 12 months (OR = 0.13, 95% CI: 0.03, 0.56, P = 0.007; OR = 0.08, 95% CI: 0.02, 0.37, P = 0.001) after birth. The pre-telbivudine treatment levels of HBV DNA were not significantly different between pregnant women in the telbivudine-treated group and the control group (OR = 0.12, 95% CI: 0.00, 0.24, P = 0.04), but the HBV DNA levels were significantly lower in the telbivudine-treated group of pregnant women prior to delivery (OR = -3.92, 95% CI: -4.90, -2.95, P less than 0.00001). There was no evidence of telbivudine treatment being associated with more adverse side effects or complications during pregnancy or in the infant (OR = 1.72, 95% CI: 0.68, 4.38, P = 0.25; OR=0.69, 95% CI: 0.04, 11.24, P = 0.80). CONCLUSION: Telbivudine treatment effectively and safely prevents mother-to-child transmission of HBV from chronically infected mothers with a high degree of infectivity late in pregnancy.