Establishment of an in vitro model of monocyte-like THP-1 cells for trained immunity induced by bacillus Calmette-Guérin.

BACKGROUND: Mycobacteria bloodstream infections are common in immunocompromised people and usually have disastrous consequences. As the primary phagocytes in the bloodstream, monocytes and neutrophils play critical roles in the fight against bloodstream mycobacteria infections. In contrast to macrophages, the responses of monocytes infected with the mycobacteria have been less investigated. RESULTS: In this study, we first established a protocol for infection of non-adherent monocyte-like THP-1 cells (i.e. without the differentiation induced by phorbol 12-myristate 13-acetate (PMA) by bacillus Calmette-Guérin (BCG). Via the protocol, we were then capable of exploring the global transcriptomic profiles of non-adherent THP-1 cells infected with BCG, and found that NF-κB, MAPK and PI3K-Akt signaling pathways were enhanced, as well as some inflammatory chemokine/cytokine genes (e.g. CCL4, CXCL10, TNF and IL-1ß) were up-regulated. Surprisingly, the Akt-HIF-mTOR signaling pathway was also activated, which induces trained immunity. In this in vitro infection model, increased cytokine responses to lipopolysaccharides (LPS) restimulation, higher cell viability, and decreased Candida albicans loads were observed. CONCLUSIONS: We have first characterized the transcriptomic profiles of BCG-infected non-adherent THP-1 cells, and first developed a trained immunity in vitro model of the cells.

Multi-omics analysis reveals that linoleic acid metabolism is associated with variations of trained immunity induced by distinct BCG strains.

Trained immunity is one of the mechanisms by which BCG vaccination confers persistent nonspecific protection against diverse diseases. Genomic differences between the different BCG vaccine strains that are in global use could result in variable protection against tuberculosis and therapeutic effects on bladder cancer. In this study, we found that four representative BCG strains (BCG-Russia, BCG-Sweden, BCG-China, and BCG-Pasteur) covering all four genetic clusters differed in their ability to induce trained immunity and nonspecific protection. The trained immunity induced by BCG was associated with the Akt-mTOR-HIF1α axis, glycolysis, and NOD-like receptor signaling pathway. Multi-omics analysis (epigenomics, transcriptomics, and metabolomics) showed that linoleic acid metabolism was correlated with the trained immunity-inducing capacity of different BCG strains. Linoleic acid participated in the induction of trained immunity and could act as adjuvants to enhance BCG-induced trained immunity, revealing a trained immunity-inducing signaling pathway that could be used in the adjuvant development.

Confined growth of Ultrathin, nanometer-sized FeOOH/CoP heterojunction nanosheet arrays as efficient self-supported electrode for oxygen evolution reaction.

Self-supported electrodes, featuring abundant active species and rapid mass transfer, are promising for practical applications in water electrolysis. However, constructing efficient self-supported electrodes with a strong affinity between the catalytic components and the substrate is of great challenge. In this study, by combining the ideas of in-situ construction and space-confined growth, we designed a novel self-supported FeOOH/cobalt phosphide (CoP) heterojunctions grown on a carefully modified commercial Ni foam (NF) with three-dimensional (3D) hierarchically porous Ni skeleton (FeOOH/CoP/3D NF). The specific porous structure of 3D NF directs the confined growth of FeOOH/CoP catalyst into ultra-thin and small-sized nanosheet arrays with abundant edge active sites. The active FeOOH/CoP component is stably anchored on the rough pore wall of 3D NF support, leading to superior stability and improved conductivity. These structural advantages contributed to a highly facilitated oxygen evolution reaction (OER) activity and enhanced durability of the FeOOH/CoP/3D NF electrode. Herein, the FeOOH/CoP/3D NF electrode afforded a low overpotential of 234 mV at 10 mA cm-2 (41 mV smaller than FeOOH/CoP grown on unmodified Ni foam) and high stability for over 90 h, which is among the top reported OER catalysts. Our study provides an effective idea and technique for the construction of active and robust self-supported electrodes for water electrolysis.

A multistage Sendai virus vaccine incorporating latency-associated antigens induces protection against acute and latent tuberculosis.

One-quarter of the world's population is infected with Mycobacterium tuberculosis (Mtb). After initial exposure, more immune-competent persons develop asymptomatic latent tuberculosis infection (LTBI) but not active diseases, creates an extensive reservoir at risk of developing active tuberculosis. Previously, we constructed a novel recombinant Sendai virus (SeV)-vectored vaccine encoding two dominant antigens of Mtb, which elicited immune protection against acute Mtb infection. In this study, nine Mtb latency-associated antigens were screened as potential supplementary vaccine candidate antigens, and three antigens (Rv2029c, Rv2028c, and Rv3126c) were selected based on their immune-therapeutic effect in mice, and their elevated immune responses in LTBI human populations. Then, a recombinant SeV-vectored vaccine, termed SeV986A, that expresses three latency-associated antigens and Ag85A was constructed. In murine models, the doses, titers, and inoculation sites of SeV986A were optimized, and its immunogenicity in BCG-primed and BCG-naive mice were determined. Enhanced immune protection against the Mtb challenge was shown in both acute-infection and latent-infection murine models. The expression levels of several T-cell exhaustion markers were significantly lower in the SeV986A-vaccinated group, suggesting that the expression of latency-associated antigens inhibited the T-cell exhaustion process in LTBI infection. Hence, the multistage quarter-antigenic SeV986A vaccine holds considerable promise as a novel post-exposure prophylaxis vaccine against tuberculosis.

Natural products in anti-tuberculosis host-directed therapy.

Given that the disease progression of tuberculosis (TB) is primarily related to the host's immune status, it has been gradually realized that chemotherapy that targets the bacteria may never, on its own, wholly eradicate Mycobacterium tuberculosis, the causative agent of TB. The concept of host-directed therapy (HDT) with immune adjuvants has emerged. HDT could potentially interfere with infection and colonization by the pathogens, enhance the protective immune responses of hosts, suppress the overwhelming inflammatory responses, and help to attain a state of homeostasis that favors treatment efficacy. However, the HDT drugs currently being assessed in combination with anti-TB chemotherapy still face the dilemmas arising from side effects and high costs. Natural products are well suited to compensate for these shortcomings by having gentle modulatory effects on the host immune responses with less immunopathological damage at a lower cost. In this review, we first summarize the profiles of anti-TB immunology and the characteristics of HDT. Then, we focus on the rationale and challenges of developing and implementing natural products-based HDT. A succinct report of the medications currently being evaluated in clinical trials and preclinical studies is provided. This review aims to promote target-based screening and accelerate novel TB drug discovery.

Identifying global research trends on inflammation associated with traumatic brain injury by bibliometric and visualized analysis.

Background: Traumatic brain injury (TBI) is a catastrophic disease involving complex inflammatory processes. This study aimed to quantitatively analyze and visualize the global research trends on inflammation associated with TBI. Methods: All publications concerning TBI and inflammation published from 2007 to 2021 were retrieved from the Web of Science Core Collection database. Key visualization and statistical analysis were calculated and evaluated using VOSviewer, CiteSpace, R package "bibliometrix," and an online bibliometric analysis platform. Results: From 2007 to 2021, 15,138 authors from 2860 institutions in 77 countries/regions published 3154 articles on inflammation associated with TBI in 786 academic journals. The research output has significantly increased over the years despite a minor fluctuation. Among the countries, the United States showed the highest output (43.50%) with the most total citations (62,791). The author with the most published articles was Cox CS (30 articles with h-index = 20), and the most popular journal in the field was the Journal of Neurotrauma (190 papers, cited 6433 times). The high-frequency keywords were "post-traumatic brain injury," "brain edema," and "glial activation." Moreover, high-frequency keywords analysis indicated that various inflammatory cells contributed to neuroinflammation, neuroprotection, and oxidative stress after TBI. Conclusion: This study revealed the research trends, hotspots, and emerging topics in inflammation associated with TBI by quantitative and visualized analysis. The current research focuses on the crosstalk between various inflammatory cells and the brain and the associated mechanisms. This study presents the research landscape and inspires future research on inflammation associated with TBI.

Simulation and Experimental Study of Solid-Liquid Extraction of Coal Tar Residue Based on Different Extractants.

Coal tar residue (CTR) is recognized as a hazardous industrial waste with a high carbon content and coal tar consisting mainly of toxic polycyclic aromatic hydrocarbons (PAHs). The coal tar in CTR can be deeply processed into high-value-added fuels and chemicals. Effective separation of coal tar and residue in CTR is a high-value-added utilization method for it. In this paper, ethyl acetate, ethanol, and n-hexane were chosen as extractants to study the extraction process of coal tar from CTR, considering the mass transfer in the liquid phase outside the CTR particles and the diffusion inside the CTR particles, and a mathematical model of the solid-liquid extraction process of CTR was established based on Fick's second law. First, the mass-transfer coefficients (kf) and effective diffusion coefficients (De) of ethyl acetate, ethanol, and n-hexane in solid-liquid extraction at 35 °C were determined to be 1.54 × 10-5 and 4.99 × 10-10 m2·s-1, 1.14 × 10-5 and 3.57 × 10-10 m2·s-1, and 1.01 × 10-5 and 3.48 × 10-10 m2·s-1, respectively. Furthermore, the simulated values obtained by the model also maintained a high degree of agreement with the experimental results, which indicates the high accuracy prediction of the model. Finally, the model was used to investigate the effects of the solvent-solid ratio, temperature, and stirring speed on the extraction rates with the three extractants. According to the analysis with gas chromatography-mass spectrometry (GC-MS), among the three solvents, n-hexane extracted the highest content of aliphatic hydrocarbons (ALHs), ethyl acetate extracted the highest content of oxygenated compounds (OCs), and ethanol extracted the highest content of aromatic hydrocarbons (ARHs). The model and experimental data can be used to provide accurate predictions for industrial utilization of CTR.

Substrate DNA Promoting Binding of Mycobacterium tuberculosis MtrA by Facilitating Dimerization and Interpretation of Affinity by Minor Groove Width.

In order to deepen the understanding of the role and regulation mechanisms of prokaryotic global transcription regulators in complex processes, including virulence, the associations between the affinity and binding sequences of Mycobacterium tuberculosis MtrA have been explored extensively. Analysis of MtrA 294 diversified 26 bp binding sequences revealed that the sequence similarity of fragments was not simply associated with affinity. The unique variation patterns of GC content and periodical and sequential fluctuation of affinity contribution curves were observed along the sequence in this study. Furthermore, docking analysis demonstrated that the structure of the dimer MtrA-DNA (high affinity) was generally consistent with other OmpR family members, while Arg 219 and Gly 220 of the wing domain interacted with the minor groove. The results of the binding box replacement experiment proved that box 2 was essential for binding, which implied the differential roles of the two boxes in the binding process. Furthermore, the results of the substitution of the nucleotide at the 20th and/or 21st positions indicated that the affinity was negatively associated with the value of minor groove width precisely at the 21st position. The dimerization of the unphosphorylated MtrA facilitated by a low-affinity DNA fragment was observed for the first time. However, the proportion of the dimer was associated with the affinity of substrate DNA, which further suggested that the affinity was actually one characteristic of the stability of dimers. Based on the finding of 17 inter-molecule hydrogen bonds identified in the interface of the MtrA dimer, including 8 symmetric complementary ones in the conserved α4-ß5-α5 face, we propose that hydrogen bonds should be considered just as important as salt bridges and the hydrophobic patch in the dimerization. Our comprehensive study on a large number of binding fragments with quantitative affinity values provided new insight into the molecular mechanism of dimerization, binding specificity and affinity determination of MtrA and clues for solving the puzzle of how global transcription factors regulate a large quantity of target genes.

Miniaturized fiber Bragg grating accelerator sensors for low-frequency vibration monitoring.

Acceleration monitoring is an important technical means of seismic monitoring, oil exploration, deep well observation, etc. A miniaturized fiber Bragg grating (FBG) acceleration sensor with three cantilever beams is proposed against the fact that it is difficult for fiber-optic sensors to meet the requirements for low-frequency vibration monitoring. First, the model of the FBG acceleration sensor was built and theoretically analyzed; second, the effect of structural parameters on sensor sensitivity and natural frequency was analyzed, and the sensors were subjected to static stress analysis and modal simulation analysis through the ANSYS finite element analysis software; finally, the real sensors were developed and subjected to performance tests with a low-frequency vibration test system. According to the result, the natural frequency of the sensor is about 64 Hz, and its sensitivity is 201.3 pm/g; favorable linearity is observed at the working frequency band of 0.1-40 Hz, and the transverse interference is less than 2.51%. The research findings offer a reference for the development of like sensors and the further exploration of the lower limit of low frequency.

A topochemical reaction induced the formation of Bi2S3 micro-straws from a Bi-MOF for an ultra-long Zn storage life.

Aqueous zinc ion batteries (ZIBs) are considered as promising energy storage devices in the post-lithium-ion era, due to their high energy density, low cost, high safety, and environmental benignity, however their commercialization is hindered by the sluggish diffusion kinetics of cathode materials due to the large hydrate Zn2+ radius. In this work, we propose a unique structure inheritance strategy for preparing Bi2S3 micro-straws in which a metal-organic framework (MOF) denoted as Bi-PYDC (PYDC2- = 3,5-pyridinedicarboxylate) with a string of [Bi2O2]2+ chains is judiciously selected as the structure-directing template to induce the formation of micro-straws based on a topochemical reaction. The distinctive hollow structure significantly enhances the ionic storage kinetics. Impressively, the obtained battery exhibits an ultra-long cycle life of more than 10 000 cycles at a current density of 1 A g-1 while maintaining a capacity of more than 153.4 mA h g-1. In addition, the Zn2+ insertion/extraction mechanism of Bi2S3 micro-straws is also investigated by multiple analytical methods, revealing the involvement of Zn2+ rather than H+ in the electrochemical storage process. This work may lead a new direction for constructing high performance cathodes of Zn-ion batteries through a MOF-based structure-directing template.

Proteinase K-pretreated ConA-based ELISA assay: a novel urine LAM detection strategy for TB diagnosis.

Objectives: Lipoarabinomannan (LAM), an abundant cell wall glycolipid of mycobacteria including Mycobacterium tuberculosis (Mtb), is a promising TB diagnostic marker. The current commercially available urine LAM assays are not sufficiently sensitive, and more novel detection strategies are urgently needed to fill the current diagnostic gap. Methods: A proteinase K-pretreated Concanavalin A (ConA)-based ELISA assay was developed. Diagnostic performance was assessed by several bacterial strains and clinical urine samples. Results: The limit of detection (LoD) of the assay against ManLAM was 6 ng/ml. The assay reacted strongly to Mtb H37Rv and M. bovis BCG, intermediately to M. smegmatis mc2155, and weakly to four non-mycobacteria pathogens. This method could distinguish TB patients from healthy controls (HCs) and close contacts (CCs) in 71 urine samples treated with proteinase K, which increases urine LAM antibody reactiveness. In TB+HIV+ and TB+HIV- patients, the sensitivity was 43.8 and 37.5%, respectively, while the specificity was 100.0%. The areas under ROC curves (AUCs) were 0.74 and 0.82, respectively. Conclusion: This study implies that ConA can be paired with antibodies to detect LAM. Proteinase K treatment could effectively enhance the sensitivity by restoring the reactiveness of antibodies to LAM.

Advances in protein subunit vaccines against tuberculosis.

Tuberculosis (TB), also known as the "White Plague", is caused by Mycobacterium tuberculosis (Mtb). Before the COVID-19 epidemic, TB had the highest mortality rate of any single infectious disease. Vaccination is considered one of the most effective strategies for controlling TB. Despite the limitations of the Bacille Calmette-Guérin (BCG) vaccine in terms of protection against TB among adults, it is currently the only licensed TB vaccine. Recently, with the evolution of bioinformatics and structural biology techniques to screen and optimize protective antigens of Mtb, the tremendous potential of protein subunit vaccines is being exploited. Multistage subunit vaccines obtained by fusing immunodominant antigens from different stages of TB infection are being used both to prevent and to treat TB. Additionally, the development of novel adjuvants is compensating for weaknesses of immunogenicity, which is conducive to the flourishing of subunit vaccines. With advances in the development of animal models, preclinical vaccine protection assessments are becoming increasingly accurate. This review summarizes progress in the research of protein subunit TB vaccines during the past decades to facilitate the further optimization of protein subunit vaccines that may eradicate TB.

Study on the Hydroconversion Law of Coal-Based Heavy Fractions with Different Catalyst Contents Based on an Improved Separation Method.

Heavy fractions (e.g., asphaltene and resin) can easily be subjected to physical aggregation and chemical coking reaction through molecular force in the process of lightweight processing and use of coal tar (CT), such that the normal processing and use can be affected. In this study, hydrogenation experiments were performed by regulating the catalyst to oil ratio (COR), while the heavy fractions of the hydrogenated products were extracted based on a novel separation method (e.g., the resin with a poor separation effect and rare existing research). The samples were analyzed through Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, nuclear magnetic resonance spectroscopy, and thermogravimetric analysis. On that basis, the composition and structure characteristics of heavy fractions and the law of hydrogenation conversion were investigated. As indicated by the results, with the rise of the COR, the saturates, aromatics, resins, and asphaltenes (SARA) contents indicated the law of increasing the content of saturate, decreasing the content of other fractions, as well as sharply decreasing the content of asphaltene. Moreover, with the increase of the reaction condition, the relative molecular weight, the content of the hydrogen bonded functional groups and C-O groups, the carbon skeleton properties, the number of aromatic rings, and the stacking structure parameters were progressively reduced. In comparison with resin, asphaltene was characterized by large aromaticity and more aromatic rings, short and less alkyl side chains, as well as more complex heteroatoms on the surface of the heavy fractions. The results achieved in this study are expected to lay a solid basis for the relevant theoretical research and facilitate the industrial use process of CT processing.

Electron-Rich Triazine-Conjugated Microporous Polymers for the Removal of Dyes from Wastewater.

Conjugated microporous polymers (CMP) as porous functional materials have received considerable attention due to their unique structures and fascinating properties for the adsorption and degradation of dyes. Herein, a triazine-conjugated microporous polymer material with rich N-donors at the skeleton itself was successfully synthesized via the Sonogashira-Hagihara coupling by a one-pot reaction. These two polymers had Brunauer-Emmett-Teller (BET) surface areas of 322 and 435 m2g-1 for triazine-conjugated microporous polymers (T-CMP) and T-CMP-Me, respectively. Due to the porous effects and the rich N-donor at the framework, it displayed a higher removal efficiency and adsorption performance compared to cationic-type dyes and selectivity properties for (methylene blue) MB+ from a mixture solution of cationic-type dyes. Furthermore, the T-CMP-Me could quickly and drastically separate MB+ and (methyl orange) MO- from the mixed solution within a short time. Their intriguing absorption behaviors are supported by 13C NMR, UV-vis absorption spectroscopy, scanning electron microscopy, and X-ray powder diffraction studies. This work will not only improve the development of porous material varieties, but also demonstrate the adsorption or selectivity of porous materials for dyes from wastewater.

Diagnosis of extrapulmonary tuberculosis by ultrasound-guided biopsy: A retrospective comparison study.

Objective: To compare the diagnostic performance of laboratory assays on the ultrasound-guided core needle biopsy samples for diagnosis of extra-pulmonary tuberculosis (EPTB) in HIV-positive and HIV-negative patients. Methods: A total of 217 patients suspected to have EPTB underwent lesion biopsy from 2017 to 2020. Results of laboratory tests on the biopsy and non-biopsy samples were collected with clinical data for retrospective analysis of test utility. The calculated diagnostic accuracy of the tests was stratified according to the specimen types and HIV status. Results: The cohort contained 118 patients with a final positive diagnosis of extrapulmonary tuberculosis (EPTB group, 54.4%) and 99 finally diagnosed as without TB (non-EPTB group, 45.6%). The risk factor for EPTB was HIV co-infection (OR 2.22, 95% CI 1.17-4.28, p = 0.014). In biopsy samples, GeneXpert (Xpert) showed higher sensitivity (96.6% [91.6-98.7], p < 0.0001) than culture (56.1% [47.0-64.9]). Regardless of HIV status, Xpert had the highest sensitivity (>95%) and specificity (nearly 100%) of any methods. In non-biopsy samples, only T-SPOT.TB (T-SPOT) showed higher sensitivity than culture (90.9% [62.3-99.5] vs 35.3% [17.3-58.7], p = 0.0037). Furthermore, the sensitivities of Xpert were lower in non-biopsy samples (60.0% [23.1-92.9], p = 0.022) than in biopsy samples (100% [86.7-100]). Even in smear-negative biopsy samples, Xpert still had higher sensitivity than culture and retained high specificity (100% [95.7-100]). Conclusion: Superior performance of Xpert in diagnosing EPTB was observed regardless of HIV status and specimen types. Nevertheless, the biopsy samples still substantially facilitated the accurate diagnosis of extrapulmonary tuberculosis.

Trisodium citrate as a modulation additive to increase the cycling capability of a Bi2S3 cathode in a zinc-ion battery.

3D Bi2S3 materials were prepared by the trisodium citrate (Na3Cit)-assisted solvothermal method and applied to aqueous zinc ion batteries (AZIBs) to explore the effect of the electrode material morphology on the electrochemical performance. As the concentration of Na3Cit increases, the 3D assembly morphology evolves from coral-like to sphere-like to snowflake-like structures. The electrochemical test results show that the electrode materials of various morphologies possess excellent cycle life, but the specific capacity varies greatly depending on the morphology. Impressively, the Bi2S3-1.2 electrode has the best electrochemical performance, with a capacity of 203.5 mA h g-1 after 4000 charge/discharge cycles at 0.5 A g-1. Furthermore, the Bi2S3-1.2 electrode delivers an ultralong lifetime of over 10 000 cycles with a capacity of 150.2 mA h g-1 at 1 A g-1. This work demonstrates a feasible route to prepare ultra-long cycle life AZIBs.

Bi-MOF Modulating MnO2 Deposition Enables Ultra-Stable Cathode-Free Aqueous Zinc-Ion Batteries.

The Mn-based materials are considered as the most promising cathodes for zinc-ion batteries (ZIBs) due to their inherent advantages of safety, sustainability and high energy density, however suffer from poor cyclability caused by gradual Mn2+ dissolution and irreversible structural transformation. The mainstream solution is pre-adding Mn2+ into the electrolyte, nevertheless faces the challenge of irreversible Mn2+ consumption results from the MnO2 electrodeposition reaction (Mn2+  â†’ MnO2 ). This work proposes a "MOFs as the electrodeposition surface" strategy, rather than blocking it. The bismuth (III) pyridine-3,5-dicarboxylate (Bi-PYDC) is selected as the typical electrodeposition surface to regulate the deposition reaction from Mn2+ to MnO2 . Because of the unique less hydrophilic and manganophilic nature of Bi-PYDC for Mn2+ , a moderate MnO2 deposition rate is achieved, preventing the electrolyte from rapidly exhausting Mn2+ . Simultaneously, the intrinsic stability of deposited R-MnO2 is enhanced by the slowly released Bi3+ from Bi-PYDC reservoir. Furthermore, Bi-PYDC shows the ability to accommodate H+ insertion/extraction. Benefiting from these merits, the cathode-free ZIB using Bi-PYDC as the electrodeposition surface for MnO2 shows an outstanding cycle lifespan of more than 10 000 cycles at 1 mA cm-2 . This electrode design may stimulate a new pathway for developing cathode free long-life rechargeable ZIBs.