Steering the Selectivity of Carbon Dioxide Electroreduction from Single-Carbon to Multicarbon Products on Metal-Organic Frameworks via Facet Engineering.

Although metal-organic frameworks (MOFs) have attracted more attention for the electrocatalytic CO2 reduction reaction (CO2RR), obtaining multicarbon products with a high Faradaic efficiency (FE) remains challenging, especially under neutral conditions. Here, we report the controlled synthesis of stable Cu(I) 5-mercapto-1-methyltetrazole framework (Cu-MMT) nanostructures with different facets by rationally modulating the reaction solvents. Significantly, Cu-MMT nanostructures with (001) facets are acquired using isopropanol as a solvent, which favor multicarbon production with an FE of 73.75% and a multicarbon:single-carbon ratio of 3.93 for CO2RR in a neutral electrolyte. In sharp contrast, Cu-MMT nanostructures with (100) facets are obtained utilizing water, promoting single-carbon generation with an FE of 63.98% and a multicarbon: single-carbon ratio of only 0.18. Furthermore, this method can be extended to other Cu-MMT nanostructures with different facets in tuning the CO2 reduction selectivity. This work opens up new opportunities for the highly selective and efficient CO2 electroreduction to multicarbon products on MOFs via facet engineering.

Percent duration of heart rate acceleration within the respiratory cycle: a novel approach to assess heart rate asymmetry.

Accelerations and decelerations of heart rate are nonsymmetrical in the magnitude and number of beat-to-beat changes. The asymmetric features of heart rate variability are related to respiratory durations. To explore the link between respiration and heart rate asymmetry (HRA), we evaluated 14 seated, healthy young adults who breathed with nine combinations of inspiration duration (TI) and expiration duration (TE), chosen respectively from 2, 4, and 6 s. A 5-min R-R interval (RRI) time series was obtained from each study period to construct an averaged pattern waveform relative to the respiratory cycle. We observed that the time interval between inspiration onset and RRI minimum progressively lengthened as TI and TE increased. The time interval between expiration onset and RRI maximum also lengthened when TE increased but shortened when TI increased. Consequently, TI and TE had different effects on the acceleration time (AT; from RRI maximum to RRI minimum) and deceleration time (DT; from RRI minimum to RRI maximum). The percentage of AT within the respiratory cycle showed a strong correlation with traditional Guzik's (r = 0.862, P < 0.001) and Porta's (r = 0.878, P < 0.001) indexes of HRA assessed in a Poincaré plot analysis. These findings suggest that, in addition to considering the magnitude and number of beat-to-beat changes, HRA can also be assessed based on another aspect: the duration of consecutive changes. The stepwise link between the duration of heart rate change and respiratory duration provides insight into the mechanisms connecting respiration to HRA.NEW & NOTEWORTHY In healthy adults who regulated their breathing across nine combinations of inspiration and expiration durations, we used averaged pattern waveform technique to quantify the durations of heart rate acceleration and deceleration within the respiratory cycle. The percent duration of acceleration showed a strong correlation with traditional heart rate asymmetry indexes, which evaluate the magnitude and number of beat-to-beat changes. This new approach opens a window to explore the asymmetric features of heart rate variability.

Different effects of inspiratory duration and expiratory duration on heart rate deceleration capacity and heart rate asymmetry.

PURPOSE: Low values of heart rate deceleration capacity (DC) and heart rate asymmetry (HRA) are associated with cardiovascular risks. Slow respiration has been proven to enhance the magnitudes of these indexes, but individual inspiratory (TI) and expiratory (TE) durations were not controlled in most studies. This study aims to examine whether the effects of TI and TE on these indexes would be the same and, if not, how to adjust TI and TE to maximize the effect of slow respiration. METHODS: We evaluated 14 seated healthy young adults who randomly controlled their breathing to nine combinations of TI and TE, each chosen respectively from 2, 4, and 6 s. A 5-min R-R interval time series was obtained from each study period for further analysis. RESULTS: The magnitude of DC increased when TI or TE increased, while that of acceleration capacity (AC) remained almost unchanged by TI. We further defined a new index as 100 × DC2/(DC2 + AC2) and found it to be correlated with conventional Guzik's (r = 0.94) and Porta's (r = 0.99) indexes of HRA during different combinations of TI and TE. Increasing TI and increasing TE both enhanced the magnitudes of HRA indexes, with TI taking effect when ≤ 4 s, and TE taking effect when > 4 s. DC and HRA indexes were maximized with a TI of 4 s and a TE of 6 s. CONCLUSION: We suggest that a TI of 3-4 s with a TE of 7-6 s is an appropriate standard for slow respiration.

Sensitivity, Specificity, and Safety of a Novel ESAT6-CFP10 Skin Test for Tuberculosis Infection in China: 2 Randomized, Self-Controlled, Parallel-Group Phase 2b Trials.

BACKGROUND: Diagnostics to identify tuberculosis infection are limited. We aimed to assess the diagnostic accuracy and safety of ESAT6-CFP10 (EC) skin test for tuberculosis infection in Chinese adults. METHODS: We conducted 2 randomized, parallel-group clinical trials in healthy participants and tuberculosis patients. All participants were tested with the T-SPOT.TB test, then received an EC skin test and tuberculin skin test (TST). The diameter of skin indurations and/or redness at injection sites were measured at different time periods. A bacillus Calmette Guerin (BCG) model was established to assess the diagnosis of tuberculosis infection using an EC skin test. RESULTS: In total, 777 healthy participants and 96 tuberculosis patients were allocated to receive EC skin test at 1.0 µg/0.1 mL or 0.5 µg/0.1 mL. The area under the curve was 0.95 (95% confidence interval [CI], .91-.97) for the EC skin test at 1.0 µg/0.1 mL at 24-72 hours. Compared with the T-SPOT.TB test, the EC skin test demonstrated similar sensitivity (87.5, 95% CI, 77.8-97.2 vs 86.5, 95% CI, 79.5-93.4) and specificity (98.9, 95% CI, 96.0-99.9 vs 96.1, 95% CI, 93.5-97.8). Among BCG vaccinated participants, the EC skin test had high consistency with the T-SPOT.TB test (96.3, 95% CI, 92.0-100.0). No serious adverse events related to the EC skin test were observed. CONCLUSIONS: The EC skin test demonstrated both high specificity and sensitivity at a dose of 1.0 µg/0.1 mL, comparable to the T-SPOT.TB test. The diagnostic accuracy of the EC skin test was not impacted by BCG vaccination. CLINICAL TRIALS REGISTRATION: NCT02389322 and NCT02336542.

A Formaldehyde Sensor Based on Self-Assembled Monolayers of Oxidized Thiophene Derivatives.

High-performance formaldehyde sensors play an important role in air quality assessment. Herein, a self-assembled monolayer (SAM) sensor for trace formaldehyde (FA) is fabricated based on the fluorescence enhancement of oxidized thiophene derivatives. In the primary SAM molecules, the functional backbone trithiophene (3T) links to the anchor through an n-propyl group. The anchor with an active Si-Cl bond can form a covalent bond with the SiO2 substrate by solution incubation, which ensures good stability against organic solvents and high sensitivity via monolayer structures. With the alkyl chain's leading, a dense 3T SAM can be obtained on SiO2. Upon exposure to UV light in the presence of oxygen, 3T can be oxidized into a nonfluorescent but coordination-active product with abundant carbonyl groups, which can be doped with FA and induce a blueshifted fluorescence. With this mechanism, we proposed an SAM-based FA sensor by detecting the enhancement of the blueshifted fluorescence. Reliable reversibility, selectivity, stability, and detection limit lower than 1 ppm are achieved in this system. The work provides an experimental basis for developing a cheap, efficient, and flexible sensor for trace FA detection.

An AIE-Active Ultrathin Polymeric Self-Assembled Monolayer Sensor for Trace Volatile Explosive Detection.

This work has prepared polymeric self-assembled monolayer (SAM) sensors for the detection of trace volatile nitroaromatic compound (NAC) explosives by fluorescence quenching. A typical aggregation-induced emission (AIE) luminogen 1,1,2,2-tetraphenylethene (TPE) polymerizes into PTPE to increase the fluorescence intensity in the SAMs, and the phosphoric acid acts as the anchor group to form stable covalent bonds with the Al2 O3 substrate. This design takes advantage of the high sensitivity and good stability of SAMs, and high fluorescence intensity, and "wire effect" of the conjugated polymers. The polymeric SAM sensors are prepared on the Al2 O3 silicon wafer and testing paper. Both of them show good response speed, reversibility, selectivity, and sensitivity. The detection limits down to 0.07, 0.35, and 4.11 ppm for TNT, DNB, and NB, respectively, are achieved on the inorganic testing paper. Furthermore, due to the higher fluorescence intensity by interlacing and overlapping of fibers, the detection of the paper can be distinguished by naked eyes even with a low-power handheld UV lamp, which provides an experimental basis for the development of cheap and easy trace NAC explosive sensors.

Crystallization Mechanism of 9,9-Diphenyl-dibenzosilole from Solids.

Organic semiconductor (OSC) crystals have great potential to be applied in many fields, as they can be flexibly designed according to the demands and show an outstanding device performance. However, OSCs with the capacity of solid-state crystallization (SSC) are developing too slowly to meet demands in productions and applications, due to their difficulties in molecular design and synthesis, unclear mechanism and high dependence on experimental conditions. In this work, in order to solve the problems, we synthesized an organic semiconductor capable of SSC at room temperature by adjusting the relationship between conjugated groups and functional groups. The thermodynamic and kinetic properties have been studied to discover the model of film SSC. Moreover, it can be purposefully controlled to prepare the high-quality crystals, and their corresponding organic electronic devices were further fabricated and discussed.

Active Self-Assembled Monolayer Sensors for Trace Explosive Detection.

Trace explosives can be detected with the help of a portable device using a flexible active self-assembled monolayer (SAM). 9,10-diphenyl anthracene with aggregation-induced emission enhancement (AIEE) properties is selected as the fluorophore. Phosphoric acid as the anchor group is linked to the fluorophore through an alkyl chain and able to self-assemble into a dense monolayer on the HfO2 adhesion layer on a flexible substrate. The dense SAMs show high fluorescence intensity, which can be quenched by nitroaromatic compounds (NACs), and have advantages of high response rate, sensitivity, reversibility, and selectivity.

Tuberculosis vaccine development: from classic to clinical candidates.

Bacillus Calmette-Guérin (BCG) has been in use for nearly 100 years and is the only licensed TB vaccine. While BCG provides protection against disseminated TB in infants, its protection against adult pulmonary tuberculosis (PTB) is variable. To achieve the ambitious goal of eradicating TB worldwide by 2050, there is an urgent need to develop novel TB vaccines. Currently, there are more than a dozen novel TB vaccines including prophylactic and therapeutic at different stages of clinical research. This literature review provides an overview of the clinical status of candidate TB vaccines and discusses the challenges and future development trends of novel TB vaccine research in combination with the efficacy of evaluation of TB vaccines, provides insight for the development of safer and more efficient vaccines, and may inspire new ideas for the prevention of TB.

[Utility value of a T-cell interferon-γ release assay based on recombinant Mycobacterium tuberculosis 11kD protein in the diagnosis of tuberculosis].

OBJECTIVE: To evaluate the diagnostic efficiency of a T-cell interferon-γ release assay based on recombinant Mycobacterium tuberculosis (MTB) 11kD protein for diagnosing tuberculosis. METHODS: This prospective study enrolled inpatients with suspected tuberculosis at PUMCH to examine the diagnostic sensitivity, specificity, predictive value (PV) and likelihood ratio (LR) of T-cell interferon-γ release assays based on recombinant MTB-11kD protein, early antigenic target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10) peptides (T-SPOT. TB). Test results were compared with final clinical and microbiological diagnoses. RESULTS: Among 151 inpatients with suspected tuberculosis, 33 (21.9%) were microbiologically or clinically diagnosed as tuberculosis and 107 (70.9%) ruled out. And the remaining 11 (7.3%) patients were clinically indeterminate. The sensitivities of recombinant MTB-11kD-ELISPOT assay and T-SPOT. TB were 60.6%and 81.8%respectively (P = 0.057).Whereas, the specificity of recombinant MTB-11kD-ELISPOT assay was significantly higher than that of T-SPOT. TB (84.1%vs 72.9%, P = 0.046). The parallel testing increased the sensitivity to 84.9% and serial testing increased the specificity to 86.9%. CONCLUSION: The recombinant MTB-11kD-ELISPOT assay is more specific than T-SPOT. TB. And its combination with T-SPOT. TB may improve the diagnostic efficiency for tuberculosis.

Long-read sequencing-based transcriptomic landscape in longissimus dorsi and transcriptome-wide association studies for growth traits of meat rabbits.

Rabbits are an attractive meat livestock species that can efficiently convert human-indigestible plant biomass, and have been commonly used in biological and medical researches. Yet, transcriptomic landscape in muscle tissue and association between gene expression level and growth traits have not been specially studied in meat rabbits. In this study Oxford Nanopore Technologies (ONT) long-read sequencing technology was used for comprehensively exploring transcriptomic landscape in Longissimus dorsi for 115 rabbits at 84 days of age, and transcriptome-wide association studies (TWAS) were performed for growth traits, including body weight at 84 days of age and average daily gain during three growth periods. The statistical analysis of TWAS was performed using a mixed linear model, in which polygenic effect was fitted as a random effect according to gene expression level-based relationships. A total of 18,842 genes and 42,010 transcripts were detected, among which 35% of genes and 47% of transcripts were novel in comparison with the reference genome annotation. Furthermore, 45% of genes were widely expressed among more than 90% of individuals. The proportions (±SE) of phenotype variance explained by genome-wide gene expression level ranged from 0.501 ± 0.216 to 0.956 ± 0.209, and the similar results were obtained when explained by transcript expression level. In contrast, neither gene nor transcript was detected by TWAS to be statistically significantly associated with these growth traits. In conclusion, these novel genes and transcripts that have been extensively profiled in a single muscle tissue using long-read sequencing technology will greatly improve our understanding on transcriptional diversity in rabbits. Our results with a relatively small sample size further revealed the important contribution of global gene expression to phenotypic variation on growth performance, but it seemed that no single gene has an outstanding effect; this knowledge is helpful to include intermediate omics data for implementing genetic evaluation of growth traits in meat rabbits.

Radiographic chest wall abnormalities in primary spontaneous pneumothorax identified by artificial intelligence.

Primary spontaneous pneumothorax (PSP) primarily affects slim and tall young males. Exploring the etiological link between chest wall structural characteristics and PSP is crucial for advancing treatment methods. In this case-control study, chest computed tomography (CT) images from patients undergoing thoracic surgery, with or without PSP, were analyzed using Artificial Intelligence. Convolutional Neural Network (CNN) model of EfficientNetB3 and InceptionV3 were used with transfer learning on the Imagenet to compare the images of both groups. A heatmap was created on the chest CT scans to enhance interoperability, and the scale-invariant feature transform (SIFT) was adopted to further compare the image level. A total of 2,312 CT images of 26 non-PSP patients and 1,122 CT images of 26 PSP patients were selected. Chest-wall apex pit (CAP) was found in 25 PSP and three non-PSP patients (p < 0.001). The CNN achieved a testing accuracy of 93.47 % in distinguishing PSP from non-PSP based on chest wall features by identifying the existence of CAP. Heatmap analysis demonstrated CNN's precision in targeting the upper chest wall, accurately identifying CAP without undue influence from similar structures, or inappropriately expanding or minimizing the test area. SIFT results indicated a 10.55 % higher mean similarity within the groups compared to between PSP and non-PSP (p < 0.001). In conclusion, distinctive radiographic chest wall configurations were observed in PSP patients, with CAP potentially serving as an etiological factor linked to PSP. This study accentuates the potential of AI-assisted analysis in refining diagnostic approaches and treatment strategies for PSP.

Site-Selective Growth of fcc-2H-fcc Copper on Unconventional Phase Metal Nanomaterials for Highly Efficient Tandem CO2 Electroreduction.

Copper (Cu) nanomaterials are a unique kind of electrocatalysts for high-value multi-carbon production in carbon dioxide reduction reaction (CO2RR), which holds enormous potential in attaining carbon neutrality. However, phase engineering of Cu nanomaterials remains challenging, especially for the construction of unconventional phase Cu-based asymmetric heteronanostructures. Here the site-selective growth of Cu on unusual phase gold (Au) nanorods, obtaining three kinds of heterophase fcc-2H-fcc Au-Cu heteronanostructures is reported. Significantly, the resultant fcc-2H-fcc Au-Cu Janus nanostructures (JNSs) break the symmetric growth mode of Cu on Au. In electrocatalytic CO2RR, the fcc-2H-fcc Au-Cu JNSs exhibit excellent performance in both H-type and flow cells, with Faradaic efficiencies of 55.5% and 84.3% for ethylene and multi-carbon products, respectively. In situ characterizations and theoretical calculations reveal the co-exposure of 2H-Au and 2H-Cu domains in Au-Cu JNSs diversifies the CO* adsorption configurations and promotes the CO* spillover and subsequent C-C coupling toward ethylene generation with reduced energy barriers.

Efficacy and safety of recombinant Mycobacterium tuberculosis ESAT-6 protein for diagnosis of pulmonary tuberculosis: a phase II trial.

BACKGROUND: This study aimed to determine the efficacy and safety of recombinant Mycobacterium tuberculosis ESAT-6 protein for diagnosis of pulmonary tuberculosis (TB). MATERIAL AND METHODS: A phase II trial was performed in 158 patients with pulmonary TB (145 initially-treated and 13 re-treated) and 133 healthy subjects. Skin testing was carried out by injecting purified protein derivative (PPD) (on left forearm) or recombinant ESAT-6 protein at a dosage of 2, 5, or 10 µg/mL (on the right forearm) in each subject. Reaction activity and adverse events were monitored at 24, 48, and 72 h following the injection. Receiver operating characteristic curves were plotted to determine the areas under the curves (AUCs) and the cut-off induration diameters for the optimal diagnostic performance. RESULTS: The reaction activity was significantly increased upon recombinant ESAT-6 injection in pulmonary TB patients compared with healthy subjects. In pulmonary TB patients, the reaction was dose-dependent, and at 48 h, 10 µg/mL recombinant ESAT-6 produced a reaction similar to that produced by PPD. The AUCs for a 10 µg/mL dosage were 0.9823, 0.9552, and 0.9266 for 24 h, 48 h, and 72 h, respectively, and the induration diameters of 4.5-5.5 mm were the optimal trade-off values between true positive rates and false positive rates. No serious adverse events occurred in any subjects. CONCLUSIONS: Recombinant ESAT-6 protein is efficacious and safe for diagnosing pulmonary TB. Based on the reaction, performance, safety, and practicability, we recommend that 10 µg/mL at 48 h with an induration cut-off value of 5.0 mm be used.

Metal functionalization of two-dimensional nanomaterials for electrochemical carbon dioxide reduction.

With the mechanical exfoliation of graphene in 2004, researchers around the world have devoted significant efforts to the study of two-dimensional (2D) nanomaterials. Nowadays, 2D nanomaterials are being developed into a large family with varieties of structures and derivatives. Due to their fascinating electronic, chemical, and physical properties, 2D nanomaterials are becoming an important type of catalyst for the electrochemical carbon dioxide reduction reaction (CO2RR). Here, we review the recent progress in electrochemical CO2RR using 2D nanomaterial-based catalysts. First, we briefly describe the reaction mechanism of electrochemical CO2 reduction to single-carbon (C1) and multi-carbon (C2+) products. Then, we discuss the strategies and principles for applying metal materials to functionalize 2D nanomaterials, such as graphene-based materials, metal-organic frameworks (MOFs), and transition metal dichalcogenides (TMDs), as well as applications of resultant materials in the electrocatalytic CO2RR. Finally, we summarize the present research advances and highlight the current challenges and future opportunities of using metal-functionalized 2D nanomaterials in the electrochemical CO2RR.

Comparison of the Immune Responses to Different Formulations of BC02-Adjuvanted HPV Types 16 and 18 Bivalent Vaccines in Mice.

To achieve maximum efficacy, vaccines, such as subunit, recombinant, and conjugate vaccines, necessitate the incorporation of immunostimulators/adjuvants. Adjuvants play a vital role in bolstering and extending the strength of the immune response while also influencing its type. As antigen and adjuvant formulations become more intricate, it becomes imperative to establish a well-characterized and robust formulation to ensure consistent and reproducible outcomes in preclinical and clinical studies. In the present study, an HPV bivalent vaccine was developed using a BC02 adjuvant in conjunction with HPV 16 and 18 L1 VLP antigens produced from an E. coli expression system. The study involved evaluating the adjuvant formulation and in vivo immunogenicity in mice. Remarkably, a medium-dose of BCG-CpG-DNA combined with a low-dose of aluminum hydroxide substantially enhanced the immunogenicity of HPV16 and 18 VLPs, resulting in improved cellular and humoral immune responses.

A genome-wide association study of coat color in Chinese Rex rabbits.

Coat color is an important phenotypic characteristic of the domestic rabbit (Oryctolagus cuniculus) and has specific economic importance in the Rex rabbit industry. Coat color varies considerably among different populations of rabbits, and several causal genes for this variation have been thoroughly studied. Nevertheless, the candidate genes affecting coat color variation in Chinese Rex rabbits remained to be investigated. In this study, we collected blood samples from 250 Chinese Rex rabbits with six different coat colors. We performed genome sequencing using a restriction site-associated DNA sequencing approach. A total of 91,546 single nucleotide polymorphisms (SNPs), evenly distributed among 21 autosomes, were identified. Genome-wide association studies (GWAS) were performed using a mixed linear model, in which the individual polygenic effect was fitted as a random effect. We detected a total of 24 significant SNPs that were located within a genomic region on chromosome 4 (OCU4). After re-fitting the most significant SNP (OCU4:13,434,448, p = 1.31e-12) as a covariate, another near-significant SNP (OCU4:11,344,946, p = 7.03e-07) was still present. Hence, we conclude that the 2.1-Mb genomic region located between these two significant SNPs is significantly associated with coat color in Chinese Rex rabbits. The well-studied coat-color-associated agouti signaling protein (ASIP) gene is located within this region. Furthermore, low genetic differentiation was also observed among the six coat color varieties. In conclusion, our results confirmed that ASIP is a putative causal gene affecting coat color variation in Chinese Rex rabbits.

Modeling Methodology for Site Selection Evaluation of Underground Coal Gasification Based on Combination Weighting Method with Game Theory.

The lack of systematic geological work is an essential reason why underground coal gasification (UCG) has not been industrialized for a long time. Building a scientific index system and favorable area evaluation technology for the UCG site selection is the key to breaking through the geological bottleneck. Aiming at the problems of the single index weight determination method, intense subjectivity, and poor reliability of current evaluation models, we put forward an evaluation modeling methodology for the UCG site selection using the combination weighting method with the game theory. The factors of coal resource conditions associated with the potential risk of UCG are systematically analyzed. From the six dimensions of the geological structure, hydrogeology, seam occurrence, coal properties, reserves, and roof lithology, 23 key factors were selected as evaluation indexes to construct a hierarchical model composed of the target layer, category index layer, and index layer. The influence of each index on UCG and its reasonable value range were systematically analyzed. The evaluation index system for UCG site selection was formed. The improved analytic hierarchy process (AHP) was adopted to sequence indices and determine their subjective weight. And the variability, conflict, and information amount of the index data were analyzed by the CRiteria Importance Through Intercriteria Correlation (CRITIC) method to calculate the objective weight. Then, the subjective and objective weights were combined through game theory. On this basis, fuzzy theory was employed to calculate the membership of indices and construct the fuzzy comprehensive judgment matrix. The evaluation model of the UCG site selection was applied to the suitability evaluation of resource conditions of UCG pilot projects at Zhongliangshan (ZLS), Huating (HT), and Shanjiaoshu (SJS) mines in China. The result shows that the resource conditions of HT are the best, followed by ZLS and, finally, SJS, which are consistent with the actual running effects of the three UCG pilot projects. It indicates that the evaluation model can provide a scientific theoretical basis and reliable technical support for the UCG site selection.

High accuracy of recombinant fusion protein early secretory antigenic target protein 6-culture filtrate protein 10 skin test for the detection of tuberculosis infection: a phase III, multi-centered, double-blind, hospital-based, randomized controlled trial.

OBJECTIVES: To verify the diagnostic utility of recombinant fusion protein ESAT6-CPF10 (EC), a novel skin test reagent to detect Mycobacterium tuberculosis infection. METHODS: A multi-centered, double-blind, randomized controlled trial was conducted from December 17, 2015, to March 2, 2018. Participants involved in this study included those with active tuberculosis (TB), suspected pulmonary TB, or non-TB pulmonary disease. Each participant received three tests simultaneously, TB-specific enzyme-linked immunospot assay (T-SPOT.TB), tuberculin skin test (TST), and EC skin test (ECST), and adverse events were reported. RESULTS: Diagnostic accuracy was analyzed using data from 1085 protocol-compliant participants. The sensitivities of the ECST, TST, and T-SPOT.TB were 91.2% (95% CI, 89.0-93.2%), 91.4% (95% CI, 89.1-93.3%), and 92.1% (95% CI, 89.9-93.9%), respectively. The specificities of the ECST (69.7%, 95% CI, 64.5-74.5%) and T-SPOT.TB (76.1%, 95% CI, 71.2-80.5%) were significantly higher than the TST (54.4%, 95% CI, 48.9-59.7%). The agreements between ECST and TST (kappa = 0.632) and between ECST and T-SPOT.TB (kappa = 0.780) were substantial. No severe adverse event was reported. CONCLUSION: The diagnostic performance of the ECST was close to the T-SPOT.TB assay in the detection of TB infection and indicated good potential for clinical application in common scenarios.

Enhanced Potency and Persistence of Immunity to Varicella-Zoster Virus Glycoprotein E in Mice by Addition of a Novel BC02 Compound Adjuvant.

Herpes zoster (HZ) is one of two distinct syndromes caused by Varicella-zoster virus (VZV). A primary infection with VZV causes varicella in susceptible young children. After resolution of the primary infection, VZV establishes a lifelong latency within the cranial or dorsal root ganglia. With increasing age, family history of shingles, immunosuppression or other risk factors, there is a decline in the virus-specific T-cell-mediated immune (CMI) response which allows reactivation of latent VZV in the root ganglia resulting in HZ. There are currently two vaccines that have been approved to prevent HZ and postherpetic neuralgia (PHN) but one is a live attenuated vaccine, the protective effect of which is considered to decrease significantly with the age of the recipient. However, a recombinant subunit vaccine may provide targeted VZV-specific cellular and humoral immunity, giving it a more potent and longer-lasting protective effect against HZ. The current study reports the development of a novel adjuvant, BC02 (BCG CpG DNA compound adjuvants system 02), composed of Al(OH)3 inorganic salt adjuvant and BC01 (BCG CpG DNA compound adjuvants system 01), a Toll-like receptor 9 (TLR9) agonist. Immunogenicity and compatibility with recombinant VZV glycoprotein E (gE) in mice were studied. The BC02-adjuvanted gE experimental vaccine was highly effective in eliciting both humoral and cellular immune responses to the recombinant gE glycoprotein and VZV-Oka in a mouse model. The efficient production and long-term persistence of gE and VZV-Oka-specific IFN-γ, IL-2-specific T cells and memory B cells in the early (1W), middle (7W), middle-late (15W), and final (27W) immune stages were established. Results of fluorescent antibody to membrane antigen (FAMA) and serum antibody plaque reduction tests also showed that the BC02 adjuvanted-gE experimental vaccine induced mice to secrete neutralizing antibodies against clinically isolated VZV strains. In combination, the current data suggest that the BC02 compound adjuvant offers a strategy to induce an appropriately strong cellular and humoral immunity against the VZV gE protein subunit to improve vaccine efficacy.