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Growth of prostate cancer cells is dependent upon androgen stimulation of the androgen receptor (AR). Dihydrotestosterone (DHT), the most potent androgen, is usually synthesized in the prostate from testosterone secreted by the testis. Following chemical or surgical castration, prostate cancers usually shrink owing to testosterone deprivation. However, tumors often recur, forming castration-resistant prostate cancer (CRPC). Here, we show that CRPC sometimes expresses a gain-of-stability mutation that leads to a gain-of-function in 3ß-hydroxysteroid dehydrogenase type 1 (3ßHSD1), which catalyzes the initial rate-limiting step in conversion of the adrenal-derived steroid dehydroepiandrosterone to DHT. The mutation (N367T) does not affect catalytic function, but it renders the enzyme resistant to ubiquitination and degradation, leading to profound accumulation. Whereas dehydroepiandrosterone conversion to DHT is usually very limited, expression of 367T accelerates this conversion and provides the DHT necessary to activate the AR. We suggest that 3ßHSD1 is a valid target for the treatment of CRPC.
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3-Hidroxiesteroide Desidrogenases/genética , Di-Hidrotestosterona/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/genética , 3-Hidroxiesteroide Desidrogenases/metabolismo , Androgênios/metabolismo , Animais , Humanos , Masculino , Camundongos , Neoplasias da Próstata/metabolismo , Proteólise , UbiquitinaçãoRESUMO
mRNA translation relies on identifying translation initiation sites (TISs) in mRNAs. Alternative TISs are prevalent across plant transcriptomes, but the mechanisms for their recognition are unclear. Using ribosome profiling and machine learning, we developed models for predicting alternative TISs in the tomato (Solanum lycopersicum). Distinct feature sets were predictive of AUG and nonAUG TISs in 5' untranslated regions and coding sequences, including a novel CU-rich sequence that promoted plant TIS activity, a translational enhancer found across dicots and monocots, and humans and viruses. Our results elucidate the mechanistic and evolutionary basis of TIS recognition, whereby cis-regulatory RNA signatures affect start site selection. The TIS prediction model provides global estimates of TISs to discover neglected protein-coding genes across plant genomes. The prevalence of cis-regulatory signatures across plant species, humans, and viruses suggests their broad and critical roles in reprogramming the translational landscape.
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Eucariotos , Iniciação Traducional da Cadeia Peptídica , Humanos , Iniciação Traducional da Cadeia Peptídica/genética , Eucariotos/genética , Plantas/genética , Regiões 5' não Traduzidas , RNA Mensageiro/genética , Códon de IniciaçãoRESUMO
Observations show robust near-surface trends in Southern Hemisphere tropospheric circulation towards the end of the twentieth century, including a poleward shift in the mid-latitude jet1,2, a positive trend in the Southern Annular Mode1,3-6 and an expansion of the Hadley cell7,8. It has been established that these trends were driven by ozone depletion in the Antarctic stratosphere due to emissions of ozone-depleting substances9-11. Here we show that these widely reported circulation trends paused, or slightly reversed, around the year 2000. Using a pattern-based detection and attribution analysis of atmospheric zonal wind, we show that the pause in circulation trends is forced by human activities, and has not occurred owing only to internal or natural variability of the climate system. Furthermore, we demonstrate that stratospheric ozone recovery, resulting from the Montreal Protocol, is the key driver of the pause. Because pre-2000 circulation trends have affected precipitation12-14, and potentially ocean circulation and salinity15-17, we anticipate that a pause in these trends will have wider impacts on the Earth system. Signatures of the effects of the Montreal Protocol and the associated stratospheric ozone recovery might therefore manifest, or have already manifested, in other aspects of the Earth system.
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Atmosfera/química , Política Ambiental/legislação & jurisprudência , Cooperação Internacional/legislação & jurisprudência , Ozônio/análise , Vento , Regiões Antárticas , Atividades Humanas/legislação & jurisprudência , Oceanos e Mares , Chuva , Salinidade , Movimentos da ÁguaRESUMO
BACKGROUND: Ubiquitous presence of short extrachromosomal circular DNAs (eccDNAs) in eukaryotic cells has perplexed generations of biologists. Their widespread origins in the genome lacking apparent specificity led some studies to conclude their formation as random or near-random. Despite this, the search for specific formation of short eccDNA continues with a recent surge of interest in biomarker development. RESULTS: To shed new light on the conflicting views on short eccDNAs' randomness, here we present DeepCircle, a bioinformatics framework incorporating convolution- and attention-based neural networks to assess their predictability. Short human eccDNAs from different datasets indeed have low similarity in genomic locations, but DeepCircle successfully learned shared DNA sequence features to make accurate cross-datasets predictions (accuracy: convolution-based models: 79.65 ± 4.7%, attention-based models: 83.31 ± 4.18%). CONCLUSIONS: The excellent performance of our models shows that the intrinsic predictability of eccDNAs is encoded in the sequences across tissue origins. Our work demonstrates how the perceived lack of specificity in genomics data can be re-assessed by deep learning models to uncover unexpected similarity.
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DNA Circular , DNA , Humanos , Genoma , Células Eucarióticas , BiomarcadoresRESUMO
The involvement of nuclear factor Y (NF-Y) in transcriptional reprogramming during arbuscular mycorrhizal symbiosis has been demonstrated in several plant species. However, a comprehensive picture is lacking. We showed that the spatial expression of NF-YC3 was observed in cortical cells containing arbuscules via the cis-regulatory element GCC boxes. Moreover, the NF-YC3 promoter was transactivated by the combination of CYCLOPS and autoactive calcium and calmodulin-dependent kinase (CCaMK) via GCC boxes. Knockdown of NF-YC3 significantly reduced the abundance of all intraradical fungal structures and affected arbuscule size. BCP1, SbtM1, and WRI5a, whose expression associated with NF-YC3 levels, might be downstream of NF-YC3. NF-YC3 interacted with NF-YB3a, NF-YB5c, or NF-YB3b, in yeast (Saccharomyces cerevisiae) and in planta, and interacted with NF-YA3a in yeast. Spatial expression of three NF-YBs was observed in all cell layers of roots under both mock and mycorrhizal conditions. Simultaneous knockdown of three NF-YBs, but not individually, reduced the fungal colonization level, suggesting that there might be functional redundancy of NF-YBs to regulate AM symbiosis. Collectively, our data suggest that NF-YC3 and NF-YBs positively regulate AM symbiosis in tomato, and arbuscule-related NF-YC3 may be an important downstream gene of the common symbiosis signaling pathway.
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SignificanceWe introduce an approach to identify latent topics in large-scale text data. Our approach integrates two prominent methods of computational text analysis: topic modeling and word embedding. We apply our approach to written narratives of violent death (e.g., suicides and homicides) in the National Violent Death Reporting System (NVDRS). Many of our topics reveal aspects of violent death not captured in existing classification schemes. We also extract gender bias in the topics themselves (e.g., a topic about long guns is particularly masculine). Our findings suggest new lines of research that could contribute to reducing suicides or homicides. Our methods are broadly applicable to text data and can unlock similar information in other administrative databases.
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Bases de Dados Factuais , Homicídio , Modelos Teóricos , Violência , Humanos , Estados UnidosRESUMO
We elucidate the flexoelectricity of semiconductors in the high strain gradient regime, the underlying mechanism of which is less understood. By using the generalized Bloch theorem, we uncover a strong flexoelectric-like effect in bent thinfilms of Si and Ge due to a high-strain-gradient-induced band gap closure. We show that an unusual type-II band alignment is formed between the compressed and elongated sides of the bent film. Therefore, upon the band gap closure, electrons transfer from the compressed side to the elongated side to reach the thermodynamic equilibrium, leading to a pronounced change of polarization along the film thickness dimension. The obtained transverse flexoelectric coefficients are unexpectedly high with a quadratic dependence on the film thickness. This new mechanism is extendable to other semiconductor materials with moderate energy gaps. Our findings have important implications for the future applications of flexoelectricity in semiconductor materials.
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The Dzyaloshinskii-Moriya interaction (DMI) is understood to be forbidden by the symmetry of centrosymmetric systems, thus restricting the candidate types for investigating many correlated physical phenomena. Here, we report the hidden DMI existing in centrosymmetric magnets driven by the local inversion symmetry breaking of specific spin sublattices. The opposite DMI spatially localized on the inverse spin sublattice favors the separated spin spiral with opposite chirality. Furthermore, we elucidate that hidden DMI widely exists in many potential candidates, from the first-principles calculations on the mature crystal database. Interestingly, novel topological spin configurations, such as the anti-chirality-locked merons and antiferromagnetic-ferromagnetic meron chains, are stabilized as a consequence of hidden DMI. Our understanding enables the effective control of DMI by symmetry operations at the atomic level and enlarges the range of currently useful magnets for topological magnetism.
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Recently discovered as an intrinsic antiferromagnetic topological insulator, MnBi2Te4 has attracted tremendous research interest, as it provides an ideal platform to explore the interplay between topological and magnetic orders. MnBi2Te4 displays distinct exotic topological phases that are inextricably linked to the different magnetic structures of the material. In this study, we conducted electrical transport measurements and systematically investigated the anomalous Hall response of epitaxial MnBi2Te4 films when subjected to an external magnetic field sweep, revealing the different magnetic structures stemming from the interplay of applied fields and the material's intrinsic antiferromagnetic (AFM) ordering. Our results demonstrate that the nonsquare anomalous Hall loop is a consequence of the distinct reversal processes within individual septuple layers. These findings shed light on the intricate magnetic structures in MnBi2Te4 and related materials, offering insights into understanding their transport properties and facilitating the implementation of AFM topological electronics.
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A prominent theoretical framework spanning philosophy, psychology, and neuroscience holds that selective attention penetrates early stages of perceptual processing to alter the subjective visual experience of behaviorally relevant stimuli. For example, searching for a red apple at the grocery store might make the relevant color appear brighter and more saturated compared with seeing the exact same red apple while searching for a yellow banana. In contrast, recent proposals argue that data supporting attention-related changes in appearance reflect decision- and motor-level response biases without concurrent changes in perceptual experience. Here, we tested these accounts by evaluating attentional modulations of EEG responses recorded from male and female human subjects while they compared the perceived contrast of attended and unattended visual stimuli rendered at different levels of physical contrast. We found that attention enhanced the amplitude of the P1 component, an early evoked potential measured over visual cortex. A linking model based on signal detection theory suggests that response gain modulations of the P1 component track attention-induced changes in perceived contrast as measured with behavior. In contrast, attentional cues induced changes in the baseline amplitude of posterior alpha band oscillations (â¼9-12 Hz), an effect that best accounts for cue-induced response biases, particularly when no stimuli are presented or when competing stimuli are similar and decisional uncertainty is high. The observation of dissociable neural markers that are linked to changes in subjective appearance and response bias supports a more unified theoretical account and demonstrates an approach to isolate subjective aspects of selective information processing.SIGNIFICANCE STATEMENT Does attention alter visual appearance, or does it simply induce response bias? In the present study, we examined these competing accounts using EEG and linking models based on signal detection theory. We found that response gain modulations of the visually evoked P1 component best accounted for attention-induced changes in visual appearance. In contrast, cue-induced baseline shifts in alpha band activity better explained response biases. Together, these results suggest that attention concurrently impacts visual appearance and response bias, and that these processes can be experimentally isolated.
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Potenciais Evocados , Córtex Visual , Humanos , Masculino , Feminino , Incerteza , Cognição , Sinais (Psicologia) , Córtex Visual/fisiologia , Percepção Visual/fisiologia , Estimulação Luminosa/métodos , EletroencefalografiaRESUMO
BACKGROUND: Left prefrontal intermittent theta-burst stimulation (iTBS) has emerged as a safe and effective transcranial magnetic stimulation (TMS) treatment protocol in depression. Though network effects after iTBS have been widely studied, the deeper mechanistic understanding of target engagement is still at its beginning. Here, we investigate the feasibility of a novel integrated TMS-fMRI setup and accelerated echo planar imaging protocol to directly observe the immediate effects of full iTBS treatment sessions. OBJECTIVE/HYPOTHESIS: In our effort to explore interleaved iTBS-fMRI feasibility, we hypothesize that TMS will induce acute BOLD signal changes in both the stimulated area and interconnected neural regions. METHODS: Concurrent TMS-fMRI with full sessions of neuronavigated iTBS (i.e. 600 pulses) of the left dorsolateral prefrontal cortex (DLPFC) was investigated in 18 healthy participants. In addition, we conducted four TMS-fMRI sessions in a single patient on long-term maintenance iTBS for bipolar depression to test the transfer to clinical cases. RESULTS: Concurrent TMS-fMRI was feasible for iTBS sequences with 600 pulses. During interleaved iTBS-fMRI, an increase of the BOLD signal was observed in a network including bilateral DLPFC regions. In the clinical case, a reduced BOLD response was found in the left DLPFC and the subgenual anterior cingulate cortex, with high variability across individual sessions. CONCLUSIONS: Full iTBS sessions as applied for the treatment of depressive disorders can be established in the interleaved iTBS-fMRI paradigm. In the future, this experimental approach could be valuable in clinical samples, for demonstrating target engagement by iTBS protocols and investigating their mechanisms of therapeutic action.
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Imageamento por Ressonância Magnética , Estimulação Magnética Transcraniana , Humanos , Estimulação Magnética Transcraniana/métodos , Imageamento por Ressonância Magnética/métodos , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiologia , Giro do Cíngulo , Córtex Pré-Frontal DorsolateralRESUMO
The chapter on the thiol-related hydrogen bond (H-bond) and its excited-state intramolecular proton-transfer (ESIPT) reaction was recently opened where compound 4'-diethylamino-3-mercaptoflavone (3NTF) undergoes ESIPT in both cyclohexane solution and solid, giving a 710 nm tautomer emission with an anomalously large Stokes shift of 12,230 cm-1. Considering the thiol H-bond to be unconventional compared to the conventional Pauling-type -OH or -NH H-bond, it is thus essential and timely to probe its fundamental difference between their ESIPT. However, thiol-associated ESIPT tends to be nonemissive due to the dominant nπ* character of the tautomeric lowest excited state. Herein, based on the 3-mercaptoflavone scaffold and π-elongation concept, a new series of 4'-substituted-7-diethylamino-3-mercaptoflavones, NTFs, was designed and synthesized with varied H-bond strength and 690-720 nm tautomeric emission upon ultraviolet (UV) excitation in cyclohexane. The order of their H-bonding strength was experimentally determined to be N-NTF < O-NTF < H-NTF < F-NTF, while the rate of -SH ESIPT measured by fluorescence upconversion was F-NTF (398 fs)-1 < H-NTF (232 fs)-1 < O-NTF (123 fs)-1 < N-NTF (101 fs)-1 in toluene. Unexpectedly, the strongest H-bonded F-NTF gives the slowest ESIPT, which does not conform to the traditional ESIPT model. The results are rationalized by the trend of carbonyl oxygen basicity rather than -SH acidity. Namely, the thiol acidity relevant to the H-bond strength plays a minor role in the driving force of ESIPT. Instead, the proton-accepting strength governs ESIPT. That is to say, the noncanonical thiol H-bonding system undergoes an unconventional type of ESIPT.
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There are limited therapeutic options for patients with Dravet syndrome (DS). The equilibrative nucleoside transporters 1 (ENT1) mediate both the influx and efflux of adenosine across the cell membrane exerted beneficial effects in the treatment of epilepsy. This study aimed to evaluate the anticonvulsant effect of the ENT1 inhibitor in an animal model of DS (Scn1aE1099X/+ mice). J7 (5 mg/kg) treatment was efficacious in elevating seizure threshold in Scn1aE1099X/+ mice after hyperthermia exposure. Moreover, the J7 treatment significantly reduced the frequency of spontaneous excitatory post-synaptic currents (sEPSCs, ~35% reduction) without affecting the amplitude in dentate gyrus (DG) granule cells. Pretreatment with the adenosine A1 receptor (A1R) antagonist, DPCPX, abolished the J7 effects on sEPSCs. These observations suggest that the J7 shows an anticonvulsant effect in hyperthermia-induced seizures in Scn1aE1099X/+ mice. This effect possibly acts on presynaptic A1R-mediated signaling modulation in granule cells.
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Epilepsias Mioclônicas , Epilepsia , Humanos , Camundongos , Animais , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Nucleosídeos/uso terapêutico , Epilepsias Mioclônicas/tratamento farmacológico , Epilepsias Mioclônicas/genética , Epilepsias Mioclônicas/metabolismo , Neurônios/metabolismo , Modelos Animais de Doenças , Canal de Sódio Disparado por Voltagem NAV1.1/genéticaRESUMO
Spherical nucleic acids (SNAs) with exceptional colloidal stability, multiple modularity, and programmability are excellent candidates to address common molecular delivery-related issues. Based on this, the higher targeting accuracy and enhanced controllability of stimuli-responsive SNAs render them precise nanoplatforms with inestimable prospects for diverse biomedical applications. Therefore, tailored diagnosis and treatment with stimuli-responsive SNAs may be a robust strategy to break through the bottlenecks associated with traditional nanocarriers. Various stimuli-responsive SNAs are engineered through the incorporation of multifunctional modifications to meet biomedical demands with the development of nucleic acid functionalization. This review provides a comprehensive overview of prominent research in this area and recent advancements in the utilization of stimuli-responsive SNAs in biosensing, bioimaging, and therapeutics. For each aspect, SNA nanoplatforms that exhibit responsive behavior to both internal stimuli (including sequence, enzyme, redox reactions, and pH) and external stimuli (such as light and temperature) are highlighted. This review is expected to offer inspiration and guidance strategies for the rational design and development of stimuli-responsive SNAs in the field of biomedicine.
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Técnicas Biossensoriais , Ácidos Nucleicos , Técnicas Biossensoriais/métodos , Ácidos Nucleicos/química , Humanos , AnimaisRESUMO
High power conversion efficiencies (PCEs) in perovskite solar cells (PSCs) have always been awe-inspiring, but perovskite films scalability is an exacting precondition for PSCs commercial deployment, generally unachievable through the antisolvent technique. On the contrary, in the two-step sequential method, the perovskite's uncontrolled crystallization and unnecessary PbI2 residue impede the device's performance. These two issues motivated to empower the PbI2 substrate with orthorhombic RbPbI3 crystal seeds, which act as grown nuclei and develop orientated perovskites lattice stacks, improving the perovskite films morphologically and reducing the PbI2 content in eventual perovskite films. Thence, achieving a PCE of 24.17% with suppressed voltage losses and an impressive life span of 1140 h in the open air.
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Herein, we report the finding that a naturally sunflower pollen-derived microspheres (HSECs) with hierarchical structures can selectively absorb polyC and polyA with high efficiency and affinity. HSECs exhibit the capability to selectively absorb polyC and polyA ssDNA under neutral and acidic conditions. It has been observed that the presence of metal cations, specifically Ca2+, enhances the absorption efficiency of HSECs. Mechanically, this absorption phenomenon can be attributed to both electrostatic interactions and cation-π interactions. Such an appealing property enables the functionalization of HSECs for broad potential biomedical applications, such as microRNA detection.
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Ferroelastic twin walls in nonpolar materials can give rise to a spontaneous polarization due to symmetry breaking. Nevertheless, the bistable polarity of twin walls and its reversal have not yet been demonstrated. Here, we report that the polarity of SrTiO_{3} twin walls can be switched by an ultralow strain gradient. Using first-principles-based machine-learning potential, we demonstrate that the twin walls can be deterministically rotated and realigned in specific directions under the strain gradient, which breaks the inversion symmetry of a sequence of walls and leads to a macroscopic polarization. The system can maintain polarity even after the constraint is removed. As a result, the polarization of twin walls can exhibit a ferroelectriclike hysteresis loop upon cyclic bending, namely flexoferroelectricity. Finally, we propose a scheme to experimentally detect the polarity of the twin wall by measuring the bulk photovoltaic responses. Our findings suggest a twin-wall-mediated flexoferroelectricity in SrTiO_{3}, which could be potentially exploited as functional elements in nanoelectronic devices design.
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Solving the Hamiltonian of a system yields the energy dispersion and eigenstates. The geometric phase of the eigenstates generates many novel effects and potential applications. However, the geometric properties of the energy dispersion go unheeded. Here, we provide geometric insight into energy dispersion and introduce a geometric amplitude, namely, the geometric density of states (GDOS) determined by the Riemann curvature of the constant-energy contour. The geometric amplitude should accompany various local responses, which are generally formulated by the real-space Green's function. Under the stationary phase approximation, the GDOS simplifies the Green's function into its ultimate form. In particular, the amplitude factor embodies the spinor phase information of the eigenstates, favoring the extraction of the spin texture for topological surface states under an in-plane magnetic field through spin-polarized STM measurements. This work opens a new avenue for exploring the geometric properties of electronic structures and excavates the unexplored potential of spin-polarized STM measurements to probe the spinor phase information of eigenstates from their amplitudes.
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BACKGROUND AND AIMS: Hepatitis B virus (HBV) vaccination programs in Taiwan are one of the earliest programs in the world and have largely reduced the prevalence of HBV infection. We aimed to demonstrate the vaccination efficacy after 35 years and identify gaps toward HBV elimination. METHODS: A total of 4717 individuals aged 1-60 years were recruited from four administrative regions based on the proportion of population distribution. Serum levels of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc) levels were assessed. HBV viral load, genotypes and HBsAg 'É' determinant variants were evaluated if indicated. RESULTS: After 35 years of vaccination, the overall seropositivity rates for HBsAg and anti-HBc in Taiwan were 4.05% and 21.3%, respectively. The vaccinated birth cohorts exhibited significantly lower seropositivity rates for both markers compared to the unvaccinated birth cohorts (HBsAg: 0.64% vs. 9.78%; anti-HBc: 2.1% vs. 53.55%, respectively; p < 0.0001). Maternal transmission was identified as the main route of HBV infection in breakthrough cases. Additionally, increased prevalences of genotype C and HBsAg escape mutants were observed. CONCLUSION: The 35-year universal HBV vaccination program effectively reduced the burden of HBV infection, but complete eradication of HBV infection has not yet been achieved. In addition to immunization, comprehensive screening and antiviral therapy for infected individuals, especially for pregnant women, are crucial strategies to eliminate HBV.
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Anticorpos Anti-Hepatite B , Antígenos de Superfície da Hepatite B , Vacinas contra Hepatite B , Vírus da Hepatite B , Hepatite B , Humanos , Taiwan/epidemiologia , Feminino , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Masculino , Antígenos de Superfície da Hepatite B/sangue , Adulto , Vírus da Hepatite B/imunologia , Vírus da Hepatite B/genética , Anticorpos Anti-Hepatite B/sangue , Pessoa de Meia-Idade , Criança , Lactente , Adolescente , Adulto Jovem , Pré-Escolar , Carga Viral , Genótipo , Prevalência , Vacinação/estatística & dados numéricos , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Programas de Imunização , Estudos SoroepidemiológicosRESUMO
BACKGROUND: The use of antiviral agents, specifically tenofovir disoproxil fumarate (TDF), in pregnant women to prevent mother-to-child HBV transmission is a key step towards hepatitis elimination. However, data on using tenofovir alafenamide (TAF) is insufficient. The frequent occurrence of postpartum ALT flares may impact the clinical implementation. METHODS: The maternal and infant outcomes were compared in multi-centre trials of high viral load HBsAg/HBeAg+ pregnant women receiving TAF or TDF from the third trimester until 2 weeks postpartum with intensive follow-ups. To explore the dynamic pre- and postpartum changes in ALT levels, we used a group-based trajectory model for analysing data of 332 women from three prospective studies. RESULTS: After treatment, the maternal HBV DNA levels significantly decreased from baseline to delivery: 7.87 ± 0.59 to 3.99 ± 1.07 Log10 IU/mL TAF (n = 78) and 8.30 ± 0.36 to 4.47 ± 0.86 Log10 IU/mL (TDF, n = 53), with viral load reductions of 3.87 versus 3.83 Log10 IU/mL. The HBsAg-positive rates among 12-month-old infants were 1.28% (1/78) versus 1.82% (1/55) respectively (p = 1.00). Of the TAF or TDF-treated mothers, 25.64% versus 16.98% experienced ALT > 2X ULN, and 11.54% versus 1.89% received extended antiviral treatment. Our model revealed four distinct ALT patterns: stable ALT (87.2%), moderate (8.0%) or marked (2.4%) postpartum flares, or prepartum elevations (2.4%). CONCLUSIONS: TAF effectively reduces mother-to-child HBV transmission, but prophylaxis failure still occurred in few cases. Postpartum ALT flares are common in women receiving TAF or TDF during pregnancy. Approximately 12.8% of mothers may require extended postpartum antiviral treatment. CLINICAL TRIAL NUMBER: NCT03695029 (ClinicalTrials.gov).