Whole-Brain Wiring Diagram of Oxytocin System in Adult Mice.

Oxytocin (Oxt) neurons regulate diverse physiological responses via direct connections with different neural circuits. However, the lack of comprehensive input-output wiring diagrams of Oxt neurons and their quantitative relationship with Oxt receptor (Oxtr) expression presents challenges to understanding circuit-specific Oxt functions. Here, we establish a whole-brain distribution and anatomic connectivity map of Oxt neurons, and their relationship with Oxtr expression using high-resolution 3D mapping methods in adult male and female mice. We use a flatmap to describe Oxt neuronal expression in four hypothalamic domains including under-characterized Oxt neurons in the tuberal nucleus (TU). Oxt neurons in the paraventricular hypothalamus (PVH) broadly project to nine functional circuits that control cognition, brain state, and somatic visceral response. In contrast, Oxt neurons in the supraoptic (SO) and accessory (AN) nuclei have limited central projection to a small subset of the nine circuits. Surprisingly, quantitative comparison between Oxt output and Oxtr expression showed no significant correlation across the whole brain, suggesting abundant indirect Oxt signaling in Oxtr-expressing areas. Unlike output, Oxt neurons in both the PVH and SO receive similar monosynaptic inputs from a subset of the nine circuits mainly in the thalamic, hypothalamic, and cerebral nuclei areas. Our results suggest that PVH-Oxt neurons serve as a central modulator to integrate external and internal information via largely reciprocal connection with the nine circuits while the SO-Oxt neurons act mainly as unidirectional Oxt hormonal output. In summary, our Oxt wiring diagram provides anatomic insights about distinct behavioral functions of Oxt signaling in the brain.SIGNIFICANCE STATEMENT Oxytocin (Oxt) neurons regulate diverse physiological functions from prosocial behavior to pain sensation via central projection in the brain. Thus, understanding detailed anatomic connectivity of Oxt neurons can provide insight on circuit-specific roles of Oxt signaling in regulating different physiological functions. Here, we use high-resolution mapping methods to describe the 3D distribution, monosynaptic input and long-range output of Oxt neurons, and their relationship with Oxt receptor (Oxtr) expression across the entire mouse brain. We found Oxt connections with nine functional circuits controlling cognition, brain state, and somatic visceral response. Furthermore, we identified a quantitatively unmatched Oxt-Oxtr relationship, suggesting broad indirect Oxt signaling. Together, our comprehensive Oxt wiring diagram advances our understanding of circuit-specific roles of Oxt neurons.

Enhanced Stability of All-Inorganic Perovskite Light-Emitting Diodes by a Facile Liquid Annealing Strategy.

Ensuring the stability of all-inorganic halide perovskite light-emitting diodes (LEDs) has become an obstacle that needs to be broken for commercial applications. Currently, lead halide perovskite CsPbX3 (X = Br, I, Cl) nanocrystals (NCs) are considered as alternative materials for future fluorescent lighting devices due to their combination of superior optical and electronic properties. However, the temperature of the surface of the LEDs will increase after long-term power-on work, which greatly affects the optical stability of CsPbX3 NCs. In order to overcome this bottleneck issue, a strategy of annealing perovskite materials in liquid is proposed, and the changes in photoluminescence and electroluminescence (EL) behaviors before and after annealing are studied. The results show that the luminescence stability of the annealed perovskite materials is significantly improved. Moreover, the EL stability of different perovskite LED devices under long-term operation is monitored, and the performance of the annealed materials is particularly outstanding. The results have proved that this convenient and low-cost liquid annealing strategy is suitable for large-scale postprocessing of perovskite materials, granting them stable fluorescence emission, which will bring a new dawn to the commercialization of next-generation optoelectronic devices.

Hard template synthesis of 2D porous Co3O4 nanosheets with graphene oxide for H2O2 sensing.

In this work, we used graphene oxide (GO) as a template that was removed by calcination to finally successfully prepare Co3O4 with 2D porous nanostructure. The results show that 2D porous structure Co3O4 nanosheets were only prepared at pH = 2. After electrochemical tests, the as-prepared Co3O4 nanosheets showed electrochemical properties that are highly suitable for H2O2 detection, such as high current response, short response time (less than 3 s), wide linear range (0.388-44.156 mM), low limit of detection (2.33 µM) and high sensitivity (0.0891 mA mM-1 cm-2). These excellent properties are mainly due to GO, as a 2D template, which connects Co3O4 nanoparticles to each other on a 2D plane, preventing the agglomeration of Co3O4 nanoparticles. The abundant pores between Co3O4 nanoparticles can greatly increase the reaction between the nanoparticles and H2O2 molecules.

Cu2+doped TiO2-SiO2with photonic crystal structure for synergistic enhancement of photocatalytic degradation under visible light irradiation.

The development of visible light photocatalysts with the ability to efficiently degrade pollutants is an important measure to solve environmental problems. In this paper, Cu2+doped TiO2-SiO2(CTS) with photonic crystal structure composite was successfully synthesized via sol-gel strategy and template method. The prepared materials have abundant pore structure and uniform pore diameter, and the pores were arranged in a periodically hexagonal structure. It showed enhancing synergistic effect of adsorption-photodegradation ability for removing Rhodamine B (RhB). The brilliant adsorption capability of the catalyst is not only due to the addition of silica which can increase surface area that results the increase in adsorption ability, but also related to the rich and ordered porous structure provided by the photonic crystal. The catalyst has a narrow band gap ∼2.92 eV which exhibits the excellent photocatalytic activity for RhB degradation (>95% at 30 min) under visible light irradiation, and possesses higher photocatalytic reaction apparent rate constants (k) which is 7 folds higher than that of pure TiO2. The excellent photocatalytic performance is attributed to the Cu2+doping that narrows the band gap, increases light absorption, and promotes charge separation. Besides, the constructed photonic crystal structure not only further enhances charge transport but also provides more surface activity sites for photocatalytic reactions. More importantly, the ordered pore structure-photonic crystal can prolong the interaction time between light and catalyst through the slow photon effect and the porous scattering effect. Eventually, the photocatalytic degradation efficiency of the catalyst was significantly improved by the synergistic effect of the above mechanisms.

Effects of Focal Axonal Swelling Level on the Action Potential Signal Transmission.

Focal axon swelling refers to localized swelling in axons that may occur because of trauma (e.g., traumatic brain injury) or neurodegenerative diseases (e.g., Alzheimer's disease). Since the swelling region can be many times larger than its original axon size, many researchers hypothesize that the swelling can alter the action potential (AP) signal. This article discusses the results of a series of newly developed computational studies to elucidate the possible intervention or blockage of AP signals due to swelling in the brain. We argue that the spherical geometry of the swelling site with its enlarged conducting interior causes the entering electric currents to spread evenly over the entire swelled membrane. As such, when the swelled surface becomes larger than the threshold size, the electric current will spread too thin to trigger the AP to spike. In this study, we have used a hybrid membrane model to simulate AP propagation across axons of different radii and swelling radii. We used an integrated model where a cylindrical symmetric 2D model is used to examine the electric current inside a spherical swelling site. In addition, two 1D models are used to capture the current flows along the upstream and downstream stretch before and after the swelling site. The parameters for this model are obtained from literature dedicated to modeling the experimental outcomes of mammal neurons. We observed two factors, which simultaneously affect AP transmission across a swelled axon: a) the axon radius and b) the ratio of the swelled and unswelled axon radii. In general, a thicker axon needs a smaller swelling size and axon ratio to block AP transmission. On the other hand, a thinner axon will reach the threshold at a larger swelling size and axon ratio. When only swelling size is considered, then thinner axons will block AP transmission at a smaller swelling radius. The AP transmission delay inside the swelled region determines whether the AP transmits forward or not. Notably, the blockage is worse if the AP fires at a high frequency. An increase in the charging and reset time due to swelling appears to be the main reason for the variation in axonal response.

Fabrication of Z-Type TiN@(A,R)TiO2 Plasmonic Photocatalyst with Enhanced Photocatalytic Activity.

Plasmonic effect-enhanced Z-type heterojunction photocatalysts comprise a promising solution to the two fundamental problems of current TiO2-based photocatalysis concerning low-charge carrier separation efficiency and low utilization of solar illumination. A plasmonic effect-enhanced TiN@anatase-TiO2/rutile-TiO2 Z-type heterojunction photocatalyst with the strong interface of the N-O chemical bond was synthesized by hydrothermal oxidation of TiN. The prepared photocatalyst shows desirable visible light absorption and good visible-light-photocatalytic activity. The enhancement in photocatalytic activities contribute to the plasma resonance effect of TiN, the N-O bond-connected charge transfer channel at the TiO2/TiN heterointerface, and the synergistically Z-type charge transfer pathway between the anatase TiO2 (A-TiO2) and rutile TiO2 (R-TiO2). The optimization study shows that the catalyst with a weight ratio of A-TiO2/R-TiO2/TiN of approximately 15:1:1 achieved the best visible light photodegradation activity. This work demonstrates the effectiveness of fabricating plasmonic effect-enhanced Z-type heterostructure semiconductor photocatalysts with enhanced visible-light-photocatalytic activities.

Oxygen Vacancy Mediated Band-Gap Engineering via B-Doping for Enhancing Z-Scheme A-TiO2/R-TiO2 Heterojunction Photocatalytic Performance.

Fabrication of Z-scheme heterojunction photocatalysts is an ideal strategy for solving environmental problems by providing inexhaustible solar energy. A direct Z-scheme anatase TiO2/rutile TiO2 heterojunction photocatalyst was prepared using a facile B-doping strategy. The band structure and oxygen-vacancy content can be successfully tailored by controlling the amount of B-dopant. The photocatalytic performance was enhanced via the Z-scheme transfer path formed between the B doped anatase-TiO2 and rutile-TiO2, optimized band structure with markedly positively shifted band potentials, and the synergistically-mediated oxygen vacancy contents. Moreover, the optimization study indicated that 10% B-doping with the R-TiO2 to A-TiO2 weight ratio of 0.04 could achieve the highest photocatalytic performance. This work may provide an effective approach to synthesize nonmetal-doped semiconductor photocatalysts with tunable-energy structures and promote the efficiency of charge separation.

Aging drives cerebrovascular network remodeling and functional changes in the mouse brain.

Aging is the largest risk factor for neurodegenerative disorders, and commonly associated with compromised cerebrovasculature and pericytes. However, we do not know how normal aging differentially impacts the vascular structure and function in different brain areas. Here we utilize mesoscale microscopy methods (serial two-photon tomography and light sheet microscopy) and in vivo imaging (wide field optical spectroscopy and two-photon imaging) to determine detailed changes in aged cerebrovascular networks. Whole-brain vascular tracing showed an overall ~10% decrease in vascular length and branching density, and light sheet imaging with 3D immunolabeling revealed increased arteriole tortuosity in aged brains. Vasculature and pericyte densities showed significant reductions in the deep cortical layers, hippocampal network, and basal forebrain areas. Moreover, in vivo imaging in awake mice identified delays in neurovascular coupling and disrupted blood oxygenation. Collectively, we uncover regional vulnerabilities of cerebrovascular network and physiological changes that can mediate cognitive decline in normal aging.

epDevAtlas: Mapping GABAergic cells and microglia in postnatal mouse brains.

During development, brain regions follow encoded growth trajectories. Compared to classical brain growth charts, high-definition growth charts could quantify regional volumetric growth and constituent cell types, improving our understanding of typical and pathological brain development. Here, we create high-resolution 3D atlases of the early postnatal mouse brain, using Allen CCFv3 anatomical labels, at postnatal days (P) 4, 6, 8, 10, 12, and 14, and determine the volumetric growth of different brain regions. We utilize 11 different cell type-specific transgenic animals to validate and refine anatomical labels. Moreover, we reveal region-specific density changes in γ-aminobutyric acid-producing (GABAergic), cortical layer-specific cell types, and microglia as key players in shaping early postnatal brain development. We find contrasting changes in GABAergic neuronal densities between cortical and striatal areas, stabilizing at P12. Moreover, somatostatin-expressing cortical interneurons undergo regionally distinct density reductions, while vasoactive intestinal peptide-expressing interneurons show no significant changes. Remarkably, microglia transition from high density in white matter tracks to gray matter at P10, and show selective density increases in sensory processing areas that correlate with the emergence of individual sensory modalities. Lastly, we create an open-access web-visualization (https://kimlab.io/brain-map/epDevAtlas) for cell-type growth charts and developmental atlases for all postnatal time points.

Developmental Mouse Brain Common Coordinate Framework.

3D standard reference brains serve as key resources to understand the spatial organization of the brain and promote interoperability across different studies. However, unlike the adult mouse brain, the lack of standard 3D reference atlases for developing mouse brains has hindered advancement of our understanding of brain development. Here, we present a multimodal 3D developmental common coordinate framework (DevCCF) spanning mouse embryonic day (E) 11.5, E13.5, E15.5, E18.5, and postnatal day (P) 4, P14, and P56 with anatomical segmentations defined by a developmental ontology. At each age, the DevCCF features undistorted morphologically averaged atlas templates created from Magnetic Resonance Imaging and co-registered high-resolution templates from light sheet fluorescence microscopy. Expert-curated 3D anatomical segmentations at each age adhere to an updated prosomeric model and can be explored via an interactive 3D web-visualizer. As a use case, we employed the DevCCF to unveil the emergence of GABAergic neurons in embryonic brains. Moreover, we integrated the Allen CCFv3 into the P56 template with stereotaxic coordinates and mapped spatial transcriptome cell-type data with the developmental ontology. In summary, the DevCCF is an openly accessible resource that can be used for large-scale data integration to gain a comprehensive understanding of brain development.

Comparative Transcriptome-Based Mining of Genes Involved in the Export of Polyether Antibiotics for Titer Improvement.

The anti-coccidiosis agent salinomycin is a polyether antibiotic produced by Streptomyces albus BK3-25 with a remarkable titer of 18 g/L at flask scale, suggesting a highly efficient export system. It is worth identifying the involved exporter genes for further titer improvement. In this study, a titer gradient was achieved by varying soybean oil concentrations in a fermentation medium, and the corresponding transcriptomes were studied. Comparative transcriptomic analysis identified eight putative transporter genes, whose transcription increased when the oil content was increased and ranked top among up-regulated genes at higher oil concentrations. All eight genes were proved to be positively involved in salinomycin export through gene deletion and trans-complementation in the mutants, and they showed constitutive expression in the early growth stage, whose overexpression in BK3-25 led to a 7.20-69.75% titer increase in salinomycin. Furthermore, the heterologous expression of SLNHY_0929 or SLNHY_1893 rendered the host Streptomyces lividans with improved resistance to salinomycin. Interestingly, SLNHY_0929 was found to be a polyether-specific transporter because the titers of monensin, lasalocid, and nigericin were also increased by 124.6%, 60.4%, and 77.5%, respectively, through its overexpression in the corresponding producing strains. In conclusion, a transcriptome-based strategy was developed to mine genes involved in salinomycin export, which may pave the way for further salinomycin titer improvement and the identification of transporter genes involved in the biosynthesis of other antibiotics.

Immunogenicity and safety of 4 intramuscular standard-dose and high-dose hepatitis B vaccine in people living with HIV: a randomized, parallel-controlled trial.

OBJECTIVES: The immunogenicity of hepatitis B vaccine is unsatisfactory in the people living with HIV (PLHIV). Studies evaluating optimal regimens to enhance immunogenicity have heretofore been inconclusive. The study was to compare the immunogenicity and safety of the four standard-dose and high-dose regimens of hepatitis B vaccine among PLHIV. METHODS: A randomized, parallel-controlled trial was conducted between May, 2020, and January, 2021. Patients were randomly assigned to receive 3 or 4 doses of 20 or 60 µg of hepatitis B vaccine. Seroconversion rate, high-level response rate, and geometric mean concentration (GMC) of antibody to hepatitis B surface antigen (anti-HBs) at weeks 12 and 28 were the main outcome measures. RESULTS: At week 28, the seroconversion rate and GMC of anti-HBs in both IM20 × 4 and IM60 × 4 groups were significantly higher than those in the IM20 × 3 group (P < 0.05), and the GMC of anti-HBs was numerically higher in the IM60 × 4 group than that in the IM20 × 4 group. CONCLUSIONS: In PLHIV, both the four standard-dose and high-dose regimens significantly improved immunogenicity. The GMC of anti-HBs was numerically higher in the IM60 × 4 group than that in the IM20 × 4 group. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT03962803).

Quantitative relationship between cerebrovascular network and neuronal cell types in mice.

The cerebrovasculature and its mural cells must meet brain regional energy demands, but how their spatial relationship with different neuronal cell types varies across the brain remains largely unknown. Here we apply brain-wide mapping methods to comprehensively define the quantitative relationships between the cerebrovasculature, capillary pericytes, and glutamatergic and GABAergic neurons, including neuronal nitric oxide synthase-positive (nNOS+) neurons and their subtypes in adult mice. Our results show high densities of vasculature with high fluid conductance and capillary pericytes in primary motor sensory cortices compared with association cortices that show significant positive and negative correlations with energy-demanding parvalbumin+ and vasomotor nNOS+ neurons, respectively. Thalamo-striatal areas that are connected to primary motor sensory cortices also show high densities of vasculature and pericytes, suggesting dense energy support for motor sensory processing areas. Our cellular-resolution resource offers opportunities to examine spatial relationships between the cerebrovascular network and neuronal cell composition in largely understudied subcortical areas.

Duration of immunogenicity of high-dose and prolonged-schedule hepatitis B vaccine among patients with chronic kidney disease: A one year follow-up study in China.

BACKGROUND: Patients with chronic kidney disease (CKD) have immunological defects that result in reduced production and faster decay of anti-HBs after hepatitis B vaccination. We assessed the duration of the immunogenicity after four-standard-dose and four-triple-dose regimens among patients with CKD. METHODS: A randomized controlled trial was conducted between May 2019 and February 2020. Patients were randomly allocated to receive three or four doses of 20 µg    , or four doses of 60 µg   of hepatitis B vaccine. Immunogenicity was assessed for 18 months till February 2021. RESULTS: Between months 7 and 18, the seroconversion rate decreased from 81.7% (58/71) to 64.3% (36/56) in IM20 × 3 group, from 93.0% (66/71) to 77.4% (41/53) in IM20 × 4 group, and from 93.2% (68/73) to 90.7% (49/54) in IM60 × 4 group. Seroconversion was higher in IM60 × 4 group than in IM20 × 3 group at month 18 (P < 0.05). In multivariate analysis, CKD patients without immune suppression or hormone therapy or patients with IM60 × 4 were more likely to have durable immunogenicity at month 18. CONCLUSIONS: Patients receiving four-triple-dose regimen of hepatitis B vaccine showed improved duration of immunogenicity at the one-year follow-up. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT03962881).

Seeing the Forest and Its Trees Together: Implementing 3D Light Microscopy Pipelines for Cell Type Mapping in the Mouse Brain.

The brain is composed of diverse neuronal and non-neuronal cell types with complex regional connectivity patterns that create the anatomical infrastructure underlying cognition. Remarkable advances in neuroscience techniques enable labeling and imaging of these individual cell types and their interactions throughout intact mammalian brains at a cellular resolution allowing neuroscientists to examine microscopic details in macroscopic brain circuits. Nevertheless, implementing these tools is fraught with many technical and analytical challenges with a need for high-level data analysis. Here we review key technical considerations for implementing a brain mapping pipeline using the mouse brain as a primary model system. Specifically, we provide practical details for choosing methods including cell type specific labeling, sample preparation (e.g., tissue clearing), microscopy modalities, image processing, and data analysis (e.g., image registration to standard atlases). We also highlight the need to develop better 3D atlases with standardized anatomical labels and nomenclature across species and developmental time points to extend the mapping to other species including humans and to facilitate data sharing, confederation, and integrative analysis. In summary, this review provides key elements and currently available resources to consider while developing and implementing high-resolution mapping methods.

A cold shock protein promotes high-temperature microbial growth through binding to diverse RNA species.

Endowing mesophilic microorganisms with high-temperature resistance is highly desirable for industrial microbial fermentation. Here, we report a cold-shock protein (CspL) that is an RNA chaperone protein from a lactate producing thermophile strain (Bacillus coagulans 2-6), which is able to recombinantly confer strong high-temperature resistance to other microorganisms. Transgenic cspL expression massively enhanced high-temperature growth of Escherichia coli (a 2.4-fold biomass increase at 45 °C) and eukaryote Saccharomyces cerevisiae (a 2.6-fold biomass increase at 36 °C). Importantly, we also found that CspL promotes growth rates at normal temperatures. Mechanistically, bio-layer interferometry characterized CspL's nucleotide-binding functions in vitro, while in vivo we used RNA-Seq and RIP-Seq to reveal CspL's global effects on mRNA accumulation and CspL's direct RNA binding targets, respectively. Thus, beyond establishing how a cold-shock protein chaperone provides high-temperature resistance, our study introduces a strategy that may facilitate industrial thermal fermentation.

Immunogenicity and safety of a high-dose and prolonged-schedule hepatitis B vaccine among chronic kidney disease patients: a randomized, parallel-controlled trial.

Background: The immunogenicity against hepatitis B vaccine is unsatisfactory in the chronic kidney disease (CKD) patients, and studies evaluating augmented vaccine regimens to enhance immunogenicity have been inconclusive.Objectives: To evaluate the immunogenicity and safety of four-standard-dose and four-triple-dose regimens hepatitis B vaccine among CKD patients in China.Research design and methods: We conducted a multicenter, randomized, parallel-controlled trial including 273 patients with CKD who were randomly allocated to receive 3 or 4 doses of 20 or 60 µg of recombinant hepatitis B vaccine.Main outcome measures: Seroconversion rates, high-level response rates, and geometric mean concentrations (GMCs) of anti-HBs at months 3 and 7.Results: The seroconversion rates and high-level responses in the IM20 × 4 group and the IM60 × 4 group were higher than those in the IM20 × 3 group at months 3 and 7 (P < 0.05). The IM60 × 4 group had better immune responses than the IM20 × 4 group at month 3 (P < 0.05); however, no significant difference was noted at month 7 (P > 0.05).Conclusions: Both the four-standard-dose and four-triple-dose regimens improved immune response compared to the three-standard-dose regimen of hepatitis B vaccination in CKD patients, and the additional effect of higher dose was minimal.Trial registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT03962881).

Immunogenicity, safety, and compliance of high- and standard-strength four-dose hepatitis B vaccination regimens in patients receiving methadone maintenance therapy in China: a randomized, parallel-arm controlled trial.

BACKGROUND: We evaluated the safety and immunogenicity of four doses of 20 or 60 µg, and the immunogenicity and compliance of the short-term vaccination regimen (0, 1, and 2 months) among patients receiving MMT. RESEARCH DESIGN AND METHODS: We conducted a randomized controlled trial among 303 patients receiving MMT who were randomized to receive 3 or 4 doses of 20 or 60 µg of recombinant hepatitis B vaccine. RESULTS: At month 7, the seroconversion rates in both IM20 × 4 and IM60 × 4 groups were numerically higher than the IM20 × 3 group (P > 0.05). The high-level responses and geometric mean concentration (GMC) of anti-HBs in both IM20 × 4 and IM60 × 4 groups were significantly higher than the IM20 × 3 group (P < 0.05). The completion rate of the short-term high-strength vaccination group was significantly higher than the standard vaccination group (P < 0.05), with similar immunogenicity (P > 0.05). CONCLUSIONS: Both the high-strength and standard-strength four-dose hepatitis B vaccine regimens could improve the immune response for patients receiving MMT. The high-strength short-term vaccination regimen could improve compliance and attain comparable immunogenicity with the standard vaccination regimen. The high-strength short-term vaccination regimen is recommended and the fourth dose is encouraged for this population considering the compliance and immunogenicity. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT03962816).

Long-term persistent immunogenicity after successful standard and triple-dosed hepatitis B vaccine in hemodialysis patients: A 3-year follow-up study in China.

BACKGROUND: Although the efficacy of hepatitis B vaccines among hemodialysis patients has been documented, the long-term persistence of immunogenicity in this population remains largely unknown. We explored the long-term persistence of immunogenicity induced by different hepatitis B vaccine regimens in hemodialysis patients. METHODS: In initial study, we conducted a randomized, multicenter, double-blind, parallel-controlled trial among hemodialysis patients in 13 hospitals in Shanxi Province, China. A total of 352 hemodialysis patients were allocated to receive 3-dose 20 µg (IM20 group) and 3-dose 60 µg (IM60 group) recombinant hepatitis B vaccine at months 0, 1, and 6. Vaccine-induced immune responses were measured at month 7. In this study, the responders (anti-HBs ≥ 10 mIU/mL) were followed up at months 18, 24, 30, 36 and 42, respectively. We used the generalized log-rank test and generalized estimating equations (GEE) to analyze the long-term durability of responses and the kinetics of anti-HBs levels, respectively. RESULTS: A total of 284 patients were involved in the extended follow-up period. The duration of vaccine-induced response with 75% of patients maintained protective antibody were 12 months and 18 months in the IM20 group and IM60 group, respectively (P = 0.291). The long-term persistent immunogenicity induced by 3-dose 60 µg was more satisfactory than that by 3-dose 20 µg hepatitis B vaccine in patients with hemodialysis duration ≥ five years (P = 0.023). The peak anti-HBs levels in 100-1000 mIU/mL or ≥ 1000 mIU/mL were more likely to maintain long-term protective antibody compared to anti-HBs levels in 10-100 mIU/mL (P ＜ 0.05). The kinetic profile was similar between the two groups (P = 0.334). CONCLUSION: High-dose 60 µg hepatitis B vaccine could lead a satisfactory long-term durability of immunogenicity among patients with hemodialysis duration of five years or more. Peak anti-HBs level after vaccination was associated with the long-term persistence of immunogenicity.

Immunogenicity and persistence of high-dose recombinant hepatitis B vaccine in adults infected with human immunodeficiency virus in China: A randomized, double-blind, parallel controlled trial.

OBJECTIVES: To explore the immunogenicity and persistence of the 60 µg hepatitis B vaccine in adults infected with human immunodeficiency virus (HIV). METHODS: We conducted a randomised controlled trial for adults infected with HIV. A total of 182 patients were randomly allocated to receive 20 µg (IM20 group) or 60 µg (IM60 group) of recombinant hepatitis B vaccine at months 0, 1, and 6 to assess the immunogenicity and were followed-up from month 7 to 42 to assess long-term immunogenicity. RESULTS: Our data showed that the response rate and geometric mean concentration (GMC) of antibodies to hepatitis B surface antigen (anti-HBs) in the IM60 group at month 7 were higher than those in the IM20 group (P > 0.05). The GMC of anti-HBs among the two groups decreased rapidly during the follow-up period (P > 0.05). Survival analysis showed that 25% of patients with anti-HBs ≥ 10 mIU/mL were 20 months in the IM60 group and 9.3 months in the IM20 group. CONCLUSION: The three-dose 60 µg hepatitis B vaccine showed partially better immunogenicity and persistence than the three-dose 20 µg vaccine. TRIAL REGISTRATION: The trial was registered on clinicaltrials.gov, NCT03316807.