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.

Salinity stress results in ammonium and nitrite accumulation during the elemental sulfur-driven autotrophic denitrification process.

In this study, we investigated the effects of salinity on elemental sulfur-driven autotrophic denitrification (SAD) efficiency, and microbial communities. The results revealed that when the salinity was ≤6 g/L, the nitrate removal efficiency in SAD increased with the increasing salinity reaching 95.53% at 6 g/L salinity. Above this salt concentration, the performance of SAD gradually decreased, and the nitrate removal efficiency decreased to 33.63% at 25 g/L salinity. Approximately 5 mg/L of the hazardous nitrite was detectable at 15 g/L salinity, but decreased at 25 g/L salinity, accompanied by the generation of ammonium. When the salinity was ≥15 g/L, the abundance of the salt-tolerant microorganisms, Thiobacillus and Sulfurimonas, increased, while that of other microbial species decreased. This study provides support for the practical application of elemental sulfur-driven autotrophic denitrification in saline nitrate wastewater.

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.

Divalent manganese stimulates the removal of nitrate by anaerobic sludge.

This study investigated the effect of different concentrations of Mn2+ on the removal of nitrate by anaerobic sludge and changes in the microbial communities through batch experiments. The results showed that the addition of Mn2+ promoted nitrate removal by anaerobic sludge; the nitrate was completely removed within 6 d in the treatment group with >5 mM Mn2+. With the increase in Mn2+, the concentration of nitrite and nitrous oxide increased in the first 4 d and then decreased to 0 µM after 8 d of incubation. The increasing tendency of ammonium increased firstly and then decreased with the addition of Mn2+ compared to A. Moreover, the Mn2+ removal efficiency gradually decreased with the increase of Mn2+ concentration. The changes of microflora structure in sludge before and after adding Mn2+ were analyzed, and the results revealed that the microbial communities in the sludge may have evolved towards an energy-efficient association of short-cut nitrification, denitrification, and anaerobic ammonia oxidation after adding Mn2+. Mn2+ stimulated the removal of nitrate by anaerobic sludge mainly by promoting the growth of PHOS-HE36.

Characterization and metabolic pathway of Pseudomonas fluorescens 2P24 for highly efficient ammonium and nitrate removal.

The ammonium and nitrate removal performance and metabolic pathways of a biocontrol strain, Pseudomonas fluorescens 2P24, were investigated. Strain 2P24 could completely remove 100 mg/L ammonium and nitrate, with removal rates of 8.27 mg/L/h and 4.29 mg/L/h, respectively. During these processes, most of the ammonium and nitrate were converted to biological nitrogen via assimilation, and only small amounts of nitrous oxide escaped. The inhibitor allylthiourea had no impact on ammonium transformation, and diethyl dithiocarbamate and sodium tungstate did not inhibit nitrate removal. Intracellular nitrate and ammonium were detectable during the nitrate and ammonium transformation process, respectively. Moreover, the nitrogen metabolism functional genes (glnK, nasA, narG, nirBD, nxrAB, nirS, nirK, and norB) were identified in the strain. All results highlighted that P. fluorescens 2P24 is capable of assimilatory and dissimilatory nitrate reduction, ammonium assimilation and oxidation, and denitrification.

Efficient Mn(II) removal mechanism by Serratia marcescens QZB-1 at high manganese concentration.

Manganese (Mn(II)) pollution has recently increased and requires efficient remediation. In this study, Serratia marcescens QZB-1, isolated from acidic red soil, exhibited high tolerance against Mn(II) (up to 364 mM). Strain QZB-1 removed a total of 98.4% of 18 mM Mn(II), with an adsorption rate of 71.4% and oxidation rate of 28.6% after incubation for 48 h. The strain synthesized more protein (PN) to absorb Mn(II) when stimulated with Mn(II). The pH value of the cultural medium continuously increased during the Mn(II) removal process. The product crystal composition (mainly MnO2 and MnCO3), Mn-O functional group, and element-level fluctuations confirmed Mn oxidation. Overall, strain QZB-1 efficiently removed high concentration of Mn(II) mainly via adsorption and showed great potential for manganese wastewater removal.

Dissimilatory nitrate reduction to ammonium in four Pseudomonas spp. under aerobic conditions.

Dissimilatory nitrate reduction to ammonium (DNRA) has an important role in soil nitrogen retention and is considered to be constrained to anaerobic conditions. However, a recent study found that Pseudomonas putida Y-9 is capable of DNRA under aerobic conditions. In this study, four species of Pseudomonas spp. were found to produce ammonium during the nitrite reduction process under aerobic conditions, similar to the Y-9 strain. The detectable ammonium in the culture supernatant during the nitrite reduction process for each of the four strains originated intracellularly. A subsequent 15N isotope experiment showed that these four strains were able to transform 15NO2 - to 15NH4 + in 3 h under aerobic conditions. The NirBD sequence in each of the four strains showed high similarity with that in the Y-9 strain (approximately 94.61%). Moreover, the nirBD sequences in the four strains and the Y-9 strain were all similar to those of other Pseudomonas spp., while they were relatively distant in terms of their phylogenetic relationship from those of other genera. Overall, these results suggest that these four strains of Pseudomonas spp. are capable of DNRA under aerobic conditions, which might be attributed to the existence of nirBD.

Effects of microorganisms on soil selenium and its uptake by pak choi in selenium-enriched lateritic red soil.

Data on selenium (Se) transformation, specifically the mineralization or activation of Se bound by microorganisms in natural Se-enriched soil, is limited. Therefore, this study investigates the effects of microorganisms on Se availability of Se-enriched lateritic red soil and Se uptake by pak choi. Following the incubation of Stenotrophomonas maltophilia S1 and arbuscular mycorrhizal (AM) fungi agent, the available Se content of soils increased from 35 to 66.69-117.04 µg/kg, corresponding to an increase of 90.50-234.40%. The Se bioconcentration and translocation factors in pak choi increased after adding the AM fungi agent and strain S1. The soil acid phosphatase activity, and pak choi root length, surface area, and diameter also increased. Moreover, the soil acid phosphatase activity showed a significant positive correlation with soil available Se and phosphorus content (p < 0.01). Overall, the AM fungi agent and strain S1 increased Se bioavailability by enhancing soil acid phosphatase and promoting root activity, ultimately increasing pak choi's ability to absorb available Se.

The nitrite reductase encoded by nirBDs in Pseudomonas putida Y-9 influences ammonium transformation.

It is unknown whether nirBDs, which conventionally encode an NADH nitrite reductase, play other novel roles in nitrogen cycling. In this study, we explored the role of nirBDs in the nitrogen cycling of Pseudomonas putida Y-9. nirBDs had no effect on organic nitrogen transformation by strain Y-9. The △nirBD strain exhibited higher ammonium removal efficiency (90.7%) than the wild-type strain (76.1%; P < 0.05) and lower end gaseous nitrogen (N2O) production. Moreover, the expression of glnA (control of the ammonium assimilation) in the △nirBD strain was higher than that in the wild-type strain (P < 0.05) after being cultured in ammonium-containing medium. Furthermore, nitrite noticeably inhibited the ammonium elimination of the wild-type strain, with a corresponding removal rate decreasing to 44.8%. However, no similar impact on ammonium transformation was observed for the △nirBD strain, with removal efficiency reaching 97.5%. In conclusion, nirBDs in strain Y-9 decreased the ammonium assimilation and increased the ammonium oxidation to nitrous oxide.

Selenium nanoparticle rapidly synthesized by a novel highly selenite-tolerant strain Proteus penneri LAB-1.

Microorganisms with high selenite-tolerant and efficient reduction ability of selenite have seldom been reported. In this study, a highly selenite-resistant strain (up to 500 mM), isolated from lateritic red soil, was identified as Proteus penneri LAB-1. Remarkably, isolate LAB-1 reduced nearly 2 mM of selenite within 18 h with the production of selenium nanoparticles (SeNPs) at the beginning of the exponential phase. Moreover, in vitro selenite reduction activities of strain LAB-1 were detected in the membrane protein fraction with or without NADPH/NADH as electron donors. Strain LAB-1 transported selenite to the membrane via nitrate transport protein. The selenite was reduced to SeNPs through the glutathione pathway and the catalysis of nitrate reductase, and the glutathione pathway played the decisive role. P. penneri LAB-1 could be a potential candidate for the selenite bioremediation and SeNPs synthesis.

Highly Selenite-Tolerant Strain Proteus mirabilis QZB-2 Rapidly Reduces Selenite to Selenium Nanoparticles in the Cell Membrane.

The application of biosynthesized nano-selenium fertilizers to crops can improve their nutrient levels by increasing their selenium content. However, microorganisms with a high selenite tolerance and rapid reduction rate accompanied with the production of selenium nanoparticles (SeNPs) at the same time have seldom been reported. In this study, a bacterial strain showing high selenite resistance (up to 300 mM) was isolated from a lateritic red soil and identified as Proteus mirabilis QZB-2. This strain reduced nearly 100% of 1.0 and 2.0 mM selenite within 12 and 18 h, respectively, to produce SeNPs. QZB-2 isolate reduced SeO3 2 - to Se0 in the cell membrane with NADPH or NADH as electron donors. Se0 was then released outside of the cell, where it formed spherical SeNPs with an average hydrodynamic diameter of 152.0 ± 10.2 nm. P. mirabilis QZB-2 could be used for SeNPs synthesis owing to its simultaneously high SeO3 2 - tolerance and rapid reduction rate.

[The mechanism of microbial removal of Mn(â ¡) and its influencing factors: a review].

Manganese is an element essential for living organisms. Development of industrial technologies and exploitation of mineral resources have led to the release of large amount of Mn(Ⅱ) into the environment, posing a serious threat to human health. Bioremediation can remove the Mn(Ⅱ) from the environment rapidly and effectively without generating secondary pollution, thus received increasing attention. This review summarized the diversity and distribution of Mn(Ⅱ) removal microorganisms and the associated mechanisms, followed by discussing the effect of environmental factors on microbial Mn(Ⅱ) removal. Finally, the challenges and prospects for bioremediation of Mn(Ⅱ) polluted wastewater were proposed.

Certain Environmental Conditions Maximize Ammonium Accumulation and Minimize Nitrogen Loss During Nitrate Reduction Process by Pseudomonas putida Y-9.

Realizing the smallest nitrogen loss is a challenge in the nitrate reduction process. Dissimilatory nitrate reduction to ammonium (DNRA) and nitrate assimilation play crucial roles in nitrogen retention. In this study, the effects of the carbon source, C/N ratio, pH, and dissolved oxygen on the multiple nitrate reduction pathways conducted by Pseudomonas putida Y-9 are explored. Strain Y-9 efficiently removed nitrate (up to 89.79%) with glucose as the sole carbon source, and the nitrogen loss in this system was 15.43%. The total nitrogen decrease and ammonium accumulation at a C/N ratio of 9 were lower than that at 12 and higher than that at 15, respectively (P < 0.05). Besides, neutral and alkaline conditions (pH 7-9) favored nitrate reduction. Largest nitrate removal (81.78%) and minimum nitrogen loss (10.63%) were observed at pH 7. The nitrate removal and ammonium production efficiencies of strain Y-9 increased due to an increased shaking speed. The expression patterns of nirBD (the gene that controls nitrate assimilation and DNRA) in strain Y-9 were similar to ammonium patterns of the tested incubation conditions. In summary, the following conditions facilitated nitrate assimilation and DNRA by strain Y-9, while reducing the denitrification: glucose as the carbon source, a C/N ratio of 9, a pH of 7, and a shaking speed of 150 rpm. Under these conditions, nitrate removal was substantial, and nitrogen loss from the system was minimal.

Association Between Assisted Reproductive Technology and White Matter Injury in Premature Infants: A Case-Control Study.

Objectives: Whether there is a link between assisted reproductive technology (ART) and brain damage in premature infants remains unclear. The aim of this study was to determine whether premature infants conceived by ART are at a greater risk of developing white matter injury (WMI), as detected by magnetic resonance imaging (MRI) or diffusion-weighted imaging (DWI) within 14 days, than those naturally conceived (NC). Methods: A retrospective case-control study was conducted on singleton premature infants with a gestational age of ≥28 weeks and <34 weeks delivered between 2017 and 2019 at Shengjing Hospital, China Medical University. This study included 638 live births that were stratified into case group (n = 218) and control group (n = 420), depending on the presence or absence of WMI. The exposure proportion of ART was compared between the case and control groups, and a logistic regression model was used to identify whether ART was an independent risk factor for WMI. Results: In the univariate analysis, the exposure proportion of ART conception was higher in cases than in controls (12.84 vs. 7.38%, p = 0.024). According to the multivariable analysis, after adjustment for other variables, the association between ART and WMI remained significant (1.82; 95% confidence interval, 1.04-3.21; P = 0.038). Conclusions: Singleton premature infants conceived by ART have a higher risk of WMI than NC infants. Given that ART is an independent risk factor for WMI in premature infants, more attention should be paid to neurodevelopmental outcomes in this group.

Low C/N Ratios Promote Dissimilatory Nitrite Reduction to Ammonium in Pseudomonas putida Y-9 under Aerobic Conditions.

The biogeochemical consequences of denitrification and dissimilatory nitrate reduction to ammonium (DNRA) have a significant influence on nitrogen (N) cycling in the ecosystem. Many researchers have explored these two pathways in soil and sediment ecosystems under anaerobic conditions. However, limited information is available regarding the influence of external environmental conditions on these two pathways in a well-defined experimental system under aerobic conditions. In this study, the impacts of the external environmental factors (carbon source, C/N ratio, pH, and dissolved oxygen) on nitrite reduction through the denitrification and DNRA routes in Pseudomonas putida Y-9 were studied. Results found that sodium citrate and sodium acetate favored denitrification and DNRA, respectively. Furthermore, neutral pH and aerobic conditions both facilitated DNRA and denitrification. Especially, low C/N ratios motivated the DNRA while high C/N ratios stimulated the denitrification, which was opposite to the observed phenomena under anaerobic conditions.

The Antibacterial Properties of 4, 8, 4', 8'-Tetramethoxy (1,1'-biphenanthrene) -2,7,2',7'-Tetrol from Fibrous Roots of Bletilla striata.

Biphenanthrene compound, 4, 8, 4', 8'-tetramethoxy (1, 1'-biphenanthrene)-2, 7, 2', 7'-tetrol (LF05), recently isolated from fibrous roots of Bletilla striata, exhibits antibacterial activity against several Gram-positive bacteria. In this study, we investigated the antibacterial properties, potential mode of action and cytotoxicity. Minimum inhibitory concentrations (MICs) tests showed LF05 was active against all tested Gram-positive strains, including methicillin-resistant Staphylococcus aureus (MRSA) and staphylococcal clinical isolates. Minimum bactericidal concentration (MBC) tests demonstrated LF05 was bactericidal against S. aureus ATCC 29213 and Bacillus subtilis 168 whereas bacteriostatic against S. aureus ATCC 43300, WX 0002, and other strains of S. aureus. Time-kill assays further confirmed these observations. The flow cytometric assay indicated that LF05 damaged the cell membrane of S. aureus ATCC 29213 and B. subtilis 168. Consistent with this finding, 4 × MIC of LF05 caused release of ATP in B. subtilis 168 within 10 min. Checkerboard test demonstrated LF05 exhibited additive effect when combined with vancomycin, erythromycin and berberine. The addition of rat plasma or bovine serum albumin to bacterial cultures caused significantly loss in antibacterial activity of LF05. Interestingly, LF05 was highly toxic to several tumor cells. Results of these studies indicate that LF05 is bactericidal against some Gram-positive bacteria and acts as a membrane structure disruptor. The application of biphenanthrene in the treatment of S. aureus infection, especially local infection, deserves further study.

[Effects of wearing a mask on oxygenation of subjects with spontaneous breathing during supplementary oxygen through facemask].

During the COVID-19 epidemic, our national guidelines have suggested that surgical patients should wear a mask to decrease the potential transmission of COVID-19 in the operating room, as long as the condition allows. However, so far, there is no study to discuss the influence of wearing a mask on the ventilation and blood oxygenation status in patients of spontaneous breathing with supplementary oxygen through an anesthetic facemask. This is a before-after study in the same patient, and 10 healthy volunteers were recruited, by testing the arterial blood gas parameters at key time points before and after oxygen inhalation to evaluate the effects of two different supplementary oxygen methods ('disposable medical mask + anesthetic facemask' and 'anesthetic facemask only') on the oxygenation of subjects. Our data demonstrated whether wearing a disposable medical mask or not could effectively increase the oxygen supply of the subjects compared with the basic value before oxygen inhalation; however, compared with the group without mask, the arterial oxygen partial (PaO 2) reduced significantly at each time points when subjects wearing a disposable medical mask. There was no significant difference in other parameters, and our data showed that age growth and smoking had no significant effects on the difference of PaO 2 between the groups with and without masks. This study demonstrates effective oxygen supplementation through anesthetic facemask in subjects with spontaneous breathing who is wearing a disposable medical mask, whose pulse oxygen saturation and arterial oxygen saturation can reach 100% rapidly, and this provides a theoretical basis for the management of patients with disseminated respiratory diseases to wear masks in the operating room; however, the rate and amount of PaO 2 increase are both decreased as compared to those who is not wearing a disposable medical mask during supplementary oxygenation. Whether this difference will affect the clinical outcome needs further study.

Exogenous Fe2+ alleviated the toxicity of CuO nanoparticles on Pseudomonas tolaasii Y-11 under different nitrogen sources.

Extensive use of CuO nanoparticles (CuO-NPs ) inevitably leads to their accumulation in wastewater and toxicity to microorganisms that effectively treat nitrogen pollution. Due to the effects of different mediums, the sources of CuO-NPs-induced toxicity to microorganisms and methods to mitigating the toxicity are still unclear. In this study, CuO-NPs were found to impact the nitrate reduction of Pseudomonas tolaasii Y-11 mainly through the action of NPs themselves while inhibiting the ammonium transformation of strain Y-11 through releasing Cu2+. As the content of CuO-NPs increased from 0 to 20 mg/L, the removal efficiency of NO3 - and NH4 + decreased from 42.29% and 29.83% to 2.05% and 2.33%, respectively. Exogenous Fe2+ significantly promoted the aggregation of CuO-NPs, reduced the possibility of contact with bacteria, and slowed down the damage of CuO-NPs to strain Y-11. When 0.01 mol/L Fe2+ was added to 0, 1, 5, 10 and 20 mg/L CuO-NPs treatment, the removal efficiencies of NO3 - were 69.77%, 88.93%, 80.51%, 36.17% and 2.47%, respectively; the removal efficiencies of NH4 + were 55.95%, 96.71%, 38.11%, 20.71% and 7.43%, respectively. This study provides a method for mitigating the toxicity of CuO-NPs on functional microorganisms.

Nitrate assimilation, dissimilatory nitrate reduction to ammonium, and denitrification coexist in Pseudomonas putida Y-9 under aerobic conditions.

The specific nitrate reduction pathway in Pseudomonas putida Y-9 under aerobic conditions was studied. Strain Y-9 removed 82% of the nitrate accompanied by an accumulation of ammonium and a decrease of total nitrogen. Ammonium inhibited nitrate transformation (removal efficiency was 22.65%), illustrating that nitrate assimilation exists in strain Y-9. The detectable ammonium in the supernatant during the nitrate reduction process came from intracellular locations in strain Y-9. The nirBD that encodes nitrite reductase had an important role in strain growth and ammonium production. A 15N isotope experiment demonstrated that strain Y-9 can conduct dissimilatory nitrate reduction to ammonium (DNRA) and nirBD controls this process. This further indicated that the loss of total nitrogen is due to denitrification. All results highlighted that strain Y-9 performs simultaneous nitrate assimilation, DNRA, and denitrification under aerobic conditions, and nirBD controls the assimilation and DNRA process. Thereinto, nitrate assimilation dominates the removal of nitrate.