Search Results (22)

Background: Influenza remains a significant public health challenge, with vaccination being a substantial way to prevent it. Cell-cultured influenza vaccines have emerged to improve on the drawbacks of egg-based vaccines, but there are few studies focusing on T cell immunity with both types of vaccines. Therefore, we studied the following 2022–2023 seasonal influenza vaccines with a standard dose and high dose: cell-based (C_sd and C_hd) and egg-based (E_sd and E_hd) vaccines. Methods: Along with a saline control group, C_sd, C_hd, E_sd, and E_hd vaccines were administered to BALB/c mice, followed by a challenge with the A/Victoria/2570/2019 (H1N1) strain. Results: After the challenge, four out of five mice in the saline group died by day 7 post-infection (P.I.). None of the vaccinated groups experienced over 20% weight loss or any deaths. On day 7 P.I., the lung viral load in the saline group (mean log value of 4.17) was higher than that in the vaccinated groups, with the C_sd group showing the lowest viral load (mean log value of 3.47). The C_sd group showed a significantly high response in macrophage 1 (M1), IFN-γ+ T cells, and tissue-resident memory (T_RM) T cells compared with the E_sd group on day 2 P.I. These M1, IFN-γ+ T cells, and T_RM cells showed similar trends (p < 0.01). In terms of humoral immunity, only the E_hd group showed HAI titers above 40 for all four strains before and after the challenge. Conclusions: The high levels of T cells in the cell-cultured vaccines suggest, pending further real-world research, that these vaccines may offer advantages. Full article

Pear black spot, caused by A. gaisen during fruit growth, is a disease that significantly reduces pear yield. Biological control using antagonistic microorganisms is regarded as a viable alternative to chemical agents. The discovery of TRM76147, a novel species of Streptomyces isolated from the Taklamakan Desert, has demonstrated promising potential in addressing this issue. This study was conducted to determine the potential of crude extract of Streptomyces sp. nov., strain TRM76147, for control of A. gaisen. TRM76147 is closely related to Streptomyces griseoviridis NBRC 12874^T, exhibiting an average nucleotide identity (ANI) value of 82.13%. Combined with the polyphasic taxonomic identification, this suggests that TRM76147 is a potentially new species. Through analyses using BigSCAPE and antiSMASH, it was determined that the TRM76147 genome contains 19 gene clusters. The ethyl acetate extract of this strain demonstrates antifungal activity, with the active substance remaining stable at temperatures up to 70 °C, achieving an activity level of 16.23 ± 0.22 mm. Furthermore, the crude extract maintains its antifungal efficacy across a pH range of 2 to 12. Notably, the antifungal diameter was recorded at 16.53 ± 0.12 mm following 80 min of UV irradiation. Under different treatment conditions, TRM76147 fermentation crude extract caused A. gaisen spore crumpling and spore number reduction. In addition, this study also found that the TRM76147 fermentation broth could control the production of pear black spot disease, which initially revealed the inhibition mechanism. The abundant actinomycete resources in this study have good application and development value in the discovery of new species and the study of bioactive substances and biological control. Full article

Tyramine (TRM) is a biogenic catecholamine neurotransmitter, which can trigger migraines and hypertension. TRM accumulated in foods is reduced and detected using additive cyclodextrins (CDs) while their association characteristics remain unclear. Here, single-crystal X-ray diffraction and density functional theory (DFT) calculation have been performed, demonstrating the elusive pseudopolymorphs in β-CD inclusion complexes with TRM base/HCl, β-CD·0.5TRM·7.6H₂O (1) and β-CD·TRM HCl·4H₂O (2) and the rare α-CD·0.5(TRM HCl)·10H₂O (3) exclusion complex. Both 1 and 2 share the common inclusion mode with similar TRM structures in the round and elliptical β-CD cavities, belong to the monoclinic space group P2₁, and have similar herringbone packing structures. Furthermore, 3 differs from 2, as the smaller twofold symmetry-related, round α-CD prefers an exclusion complex with the twofold disordered TRM–H⁺ sites. In the orthorhombic P2₁2₁2 lattice, α-CDs are packed in a channel-type structure, where the column-like cavity is occupied by disordered water sites. DFT results indicate that β-CD remains elliptical to suitably accommodate TRM, yielding an energetically favorable inclusion complex, which is significantly contributed by the β-CD deformation, and the inclusion complex of α-CD with the TRM aminoethyl side chain is also energetically favorable compared to the exclusion mode. This study suggests the CD implications for food safety and drug/bioactive formulation and delivery. Full article

Macrophages play multiple roles in innate immunity including phagocytosing pathogens, modulating the inflammatory response, presenting antigens, and recruiting other immune cells. Tissue-resident macrophages (TRMs) adapt to the local microenvironment and can exhibit different immune responses upon encountering distinct pathogens. In this study, we generated induced macrophages (iMACs) derived from human pluripotent stem cells (hPSCs) to investigate the interactions between the macrophages and various human pathogens, including the hepatitis C virus (HCV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and Streptococcus pneumoniae. iMACs can engulf all three pathogens. A comparison of the RNA-seq data of the iMACs encountering these pathogens revealed that the pathogens activated distinct gene networks related to viral response and inflammation in iMACs. Interestingly, in the presence of both HCV and host cells, iMACs upregulated different sets of genes involved in immune cell migration and chemotaxis. Finally, we constructed an image-based high-content analysis system consisting of iMACs, recombinant GFP-HCV, and hepatic cells to evaluate the effect of a chemical inhibitor on HCV infection. In summary, we developed a human cell-based in vitro model to study the macrophage response to human viral and bacterial infections; the results of the transcriptome analysis indicated that the iMACs were a useful resource for modeling pathogen–macrophage–tissue microenvironment interactions. Full article

In the presented study, a novel approach for thermal atomic layer deposition (ALD) of Al₂O₃ thin films using plasma-activated water (PAW) as a co-reactant, replacing traditionally employed deionized (DI) water, is introduced. Utilizing ex situ PAW achieves up to a 16.4% increase in the growth per cycle (GPC) of Al₂O₃ films, consistent with results from plasma-enhanced atomic layer deposition (PEALD). Time-resolved mass spectrometry (TRMS) revealed disparities in CH₄ partial pressures between TMA reactions with DI water and PAW, with PAW demonstrating enhanced reactivity. Reactive oxygen species (ROS), namely H₂O₂ and O₃, are posited to activate Si(100) substrate sites, thereby improving GPC and film quality. Specifically, Al₂O₃ films grown with PAW pH = 3.1 displayed optimal stoichiometry, reduced carbon content, and an expanded bandgap. This study thus establishes “PAW-ALD” as a descriptor for this ALD variation and highlights the significance of comprehensive assessments of PAW in ALD processes. Full article

Disruption of mitochondrial structure/function is well-recognized to be a determinant of cell death in cardiomyocytes subjected to lethal episodes of ischemia-reperfusion (IR). However, the precise mitochondrial event(s) that precipitate lethal IR injury remain incompletely resolved. Using the in vitro HL-1 cardiomyocyte model, our aims were to establish whether: (1) proteolytic processing of optic atrophy protein-1 (OPA1), the inner mitochondrial membrane protein responsible for maintaining cristae junction integrity, plays a causal, mechanistic role in determining cardiomyocyte fate in cells subjected to lethal IR injury; and (2) preservation of OPA1 may contribute to the well-documented cardioprotection achieved with ischemic preconditioning (IPC) and remote ischemic conditioning. We report that HL-1 cells subjected to 2.5 h of simulated ischemia displayed increased activity of OMA1 (the metalloprotease responsible for proteolytic processing of OPA1) during the initial 45 min following reoxygenation. This was accompanied by processing of mitochondrial OPA1 (i.e., cleavage to yield short-OPA1 peptides) and release of short-OPA1 into the cytosol. However, siRNA-mediated knockdown of OPA1 content did not exacerbate lethal IR injury, and did not attenuate the cardioprotection seen with IPC and a remote preconditioning stimulus, achieved by transfer of ‘reperfusate’ medium (TRM-IPC) in this cell culture model. Taken together, our results do not support the concept that maintenance of OPA1 integrity plays a mechanistic role in determining cell fate in the HL-1 cardiomyocyte model of lethal IR injury, or that preservation of OPA1 underlies the cardioprotection seen with ischemic conditioning. Full article

The production of syngas with optimal energy usage, a minimal environmental impact, and an adjustable H₂/CO molar ratio is possible using tri-reforming of methane (TRM). Despite the number of studies dedicated to the TRM process, this process is still in its infancy, with many technical obstacles to overcome. Except for its kinetics and catalysts, which have been reviewed elsewhere, the TRM process is evaluated thoroughly in this work. First, feasibility studies of TRM and the TRM process are presented. Second, the impacts of various operating conditions on the rate of gas conversions, syngas production, and coke formation are discussed. Third, different reactor configurations are compared. This review then goes through the energy and energetic efficiency, economic, environmental, and safety aspects of the TRM process. Finally, a research path for the future is suggested. Full article

Extreme typhoon rainfall can lead to damaging floods near the coastal region in mainland China. In the present study, we calibrate the parameters for a parametric hurricane rain model by using the precipitation radar (PR) data from the Tropical Rainfall Measuring Mission (TRMM) (i.e., PR-TRMM) and the TRMM microwave imager (TMI) data (i.e., TMI-TRMM). To show the applicability of the model for the tropical cyclone (TC) rain hazard assessment, we combine the developed rainfall intensity model with historical and synthetic TC tracks to estimate the T-year return period value of the accumulated rainfall in 24 h, Q_A24-T. We map Q_A24-100 for part of the coastal region in mainland China, showing that the spatial variation of Q_A24-100 is relatively smooth. It was found that the estimated Q_A24-100 using the model developed, based on the snapshots from PR-TRMM, is about 60% of that obtained using the model developed based on the snapshots from TMI-TRMM. This reflects the differences in the rainfall intensities reported in TMI-TRMM and PR-TRMM. As part of verification, we compare the estimated return period value to that obtained by using the record from surface meteorological stations at a few locations. The comparison indicates that, on average, Q_A24-100 based on gauge data is about 1.4 and 2.3 times that obtained using the model developed based on the snapshots from PR-TRMM and TRM-TRMM, respectively. This suggests that, for TC rain hazard estimation, one may consider the empirical scaling factor of 1.4 and 2.4 for the rainfall intensity models developed based on snapshots from PR-TRMM and TMI-TRMM, respectively. Full article

Background: Cryopreservation of PBSC for allogenic hematopoietic stem cell transplantation (allo-HSCT) was implemented due to the current Coronavirus 2019 pandemic. The impact of match unrelated donor (MUD) graft freezing on the outcome of allo-HSCT in terms of hematological recovery, graft versus host disease (GVHD), and survival are still controversial. Methods: In this study, we compared graft composition, clinical characteristics, and outcome of 31 allo-HSCT from MUD cryopreserved PBSC (Cryo Group) with 23 matched-pair allo-HSCT from fresh MUD PBSC (Fresh Group) performed in our center between January 2020 and July 2021. Results: No significant differences were recognized in clinical characteristics of patients, donors, and transplants between the Cryo and Fresh groups except for a better prognostic comorbidity index (HCT-CI) of the Cryo group. In the Cryo Group, the median time from apheresis to cryopreservation was 46.0 h (range 23.8–53.5), while the median time from cells collection and reinfusion was 13.9 days (range 5.8–28.1). In the Fresh Group, median time from apheresis to reinfusion was 35.6 h (range 21.4–51.2). The number of viable (7-AAD negative) CD34+ cells per kg patient infused was significantly lower in the Cryo Group (5.2 ± 1.9 × 10⁶/kg vs. 7.0 ± 1.3 × 10⁶/kg; p < 0.001). Indeed, there was a 36% (11–70) median loss of viable CD34+/kg cells after freezing. All patients engrafted: median time to neutrophil engraftment (>0.5 × 10⁹/L) was 13.5 days (range 12–15) for Cryo Group and 14 days (range 13–16) days for Fresh Group (p = 0.522), while the median time to platelet engraftment (>20 × 10⁹/L) was, respectively, 14 (range 12–18) and 15 (range 12–17) days (p = 0.904). The incidence of grade ≥ 2 acute GVHD was similar in the two groups (56.5% Cryo Group vs. 60.0% Fresh Group; p = 0.832) and no differences in terms of OS (p = 0.090), PFS (p = 0.200) and TRM (p = 0.970) were observed between the Cryo and Fresh groups. Conclusions: In our series, no differences between the Cryo and Fresh groups were found in engraftment, grade ≥ 2 acute GVHD incidence, OS, PFS, and TRM despite a lower CD34+ infused dose in the Cryo Group. Frozen PBSCs could be considered a safe option also for allo-HSCT from MUD but a higher amount of PBSC should be collected to warrant an adequate viable CD34+ post-thawing. Full article

6-Heteryl-5-methylthieno[2,3-d]pyrimidin-2,4(1H,3H)-diones are of great interest as the promising objects for the search of antibacterials. In this communication, we obtained 6-(imidazo[1,2-a]pyridin-2-yl)-5-methyl-3-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione by interaction of 6-(bromoacetyl)-5-methyl-3-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione with 2-aminopyridine. The obtained heterocyclic hybrid was further modified by alkylation with 2-chloroarylacetamides. Antimicrobial activity studies for the synthesized compounds using the agar well diffusion method revealed their moderate activity against S. aureus, E. coli and B. subtilis. According to the double dilution assay MIC value results for 6-(imidazo[1,2-a]pyridin-2-yl)-5-methyl-3-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dioneagainst P. aeruginosa was less than the value determined for the reference drug streptomycin. The docking study of the synthesized compounds to the active site of TrmD isolated from P. aeruginosa did not show their effective inhibitory activity. Full article

Limited research has focused on the effect of high temperatures on the textile-reinforced mortar (TRM)-to-masonry bond. In this study, masonry prisms that were furnished with double-layered TRM strips were tested under shear bond conditions after their exposure to 200 °C and 400 °C for 1 h using the single-lap/single-prism setup. A total of four TRM systems were applied sharing the same type of textile –a dry AR glass fiber one– and different matrices: two cementitious matrices, namely a normal-weight (TRCNM) and a lightweight (TRCLM) one, and two counterpart alkali-activated matrices (TRAANM and TRAALM) based on metakaolin and fly ash. Specimens’ exposure to elevated temperatures did not alter their failure mode which was due to the sleeve fibers’ rupture along with core fibers’ slippage from the mortar. The residual bond capacity of the TRM systems decreases almost linearly with increasing exposure temperature. The alkali-activated textile reinforced mortars outperformed their cement-based counterparts in terms of bond strength at every temperature. All systems retained close to 50% of their original shear bond strength after heating at 400 °C. Per the type of binder, lightweight matrices resulted in either comparable (cement-based systems) or better (alkali-activated systems) heat protection at the TRM/masonry interface. Full article

Comparative structural/molecular biology by single-molecule analyses combined with single-cell dissection, mass spectroscopy, and biochemical reconstitution have been powerful tools for elucidating the mechanisms underlying genome DNA folding. All genomes in the three domains of life undergo stepwise folding from DNA to 30–40 nm fibers. Major protein players are histone (Eukarya and Archaea), Alba (Archaea), and HU (Bacteria) for fundamental structural units of the genome. In Euryarchaeota, a major archaeal phylum, either histone or HTa (the bacterial HU homolog) were found to wrap DNA. This finding divides archaea into two groups: those that use DNA-wrapping as the fundamental step in genome folding and those that do not. Archaeal transcription factor-like protein TrmBL2 has been suggested to be involved in genome folding and repression of horizontally acquired genes, similar to bacterial H-NS protein. Evolutionarily divergent SMC proteins contribute to the establishment of higher-order structures. Recent results are presented, including the use of Hi-C technology to reveal that archaeal SMC proteins are involved in higher-order genome folding, and the use of single-molecule tracking to reveal the detailed functions of bacterial and eukaryotic SMC proteins. Here, we highlight the similarities and differences in the DNA-folding mechanisms in the three domains of life. Full article

The rapid development in bacterial resistance to many groups of known antibiotics forces the researchers to discover antibacterial drug candidates with previously unknown mechanisms of action, one of the most relevant being the inhibition of tRNA (Guanine37-N1)-methyltransferase (TrmD). The discovery of selective TrmD inhibitors in the series of carboxamide derivatives of thienopyrimidines became a background for further modification of the similar structures aimed at the development of promising antibacterial agents. As part of this research, we carried out the construction of heterocyclic hybrids bearing the moieties of thieno[2,3-d]pyrimidine and benzimidazole starting from 3,5-dimethyl-4-oxo-2-thioxo-1H-thieno[2,3-d]pyrimidine-6-carboxylic acid, which was used as the pivotal intermediate. The hybrid molecule of 6-(1H-benzimidazol-2-yl)-3,5-dimethyl-2-thioxo-1H-thieno[2,3-d]pyrimidin-4-one prepared via condensation of the carboxylic acid with ortho-phenylenediamine was further alkylated with aryl/hetaryl chloroacetamides and benzyl chloride to produce the series of S-alkyl derivatives. The results of molecular docking studies for the obtained series of S-alkyl benzimidazole-thienopyrimidines showed their high affinity to the TrmD isolated from the P. aeruginosa. The results of antimicrobial activity screening revealed the antimicrobial properties for all of the studied molecules against both Gram-positive and Gram-negative bacteria and the Candida albicans fungal strain. The highest antimicrobial activity was determined for 2-{[6-(1H-benzimidazol-2-yl)-3,5-dimethyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-2-yl]thio}-N-(4-isopropylphenyl)acetamide, which also had the highest affinity to the TrmD inhibitor’s binding site according to the docking studies results. Full article

Immunological memory is a cardinal feature of the immune system. The intestinal mucosa is the primary exposure and entry site of infectious organisms. For an effective and long-lasting safeguard, a robust immune memory system is required, especially by the mucosal immunity. It is well known that tissue-resident memory T cells (Trms) provide a first response against infections reencountered at mucosal tissues surfaces, where they accelerate pathogen clearance. However, their function in intestinal immunization remains to be investigated. Here, we report enhanced local mucosal and systemic immune responses through oral administration of H9N2 influenza whole inactivated virus (H9N2 WIV) plus Bacillus subtilis spores. Subsequently, H9N2 WIV plus spores led to the generation of CD103⁺ CD69⁺ Trms, which were independent of circulating T cells during the immune period. Meanwhile, we also found that Bacillus subtilis spores could stimulate Acrp30 expression in 3T3-L1 adipocytes. Moreover, spore-stimulated adipocyte supernatant also upregulated the expression of intercellular adhesion molecule-1 (ICAM1) in dendritic cells (DCs). Furthermore, the proportion of HA-tetramer⁺ cells was severely curtailed upon suppressed ICAM1 expression, which also depended on HA-loaded DCs. Taken together, our data demonstrated that spore-promoted H9N2 WIV induced an immune response by enhancing Trms populations, which were associated with the activation of ICAM1 in DCs. Full article

The main scope of this work is to develop nano-carbon-based mixed matrix cellulose acetate membranes (MMMs) for the potential use in both gas and liquid separation processes. For this purpose, a variety of mixed matrix membranes, consisting of cellulose acetate (CA) polymer and carbon nanotubes as additive material were prepared, characterized, and tested. Multi-walled carbon nanotubes (MWCNTs) were used as filler material and diacetone alcohol (DAA) as solvent. The first main objective towards highly efficient composite membranes was the proper preparation of agglomerate-free MWCNTs dispersions. Rotor-stator system (RS) and ultrasonic sonotrode (USS) were used to achieve the nanofillers’ dispersion. In addition, the first results of the application of the three-roll mill (TRM) technology in the filler dispersion achieved were promising. The filler material, MWCNTs, was characterized by scanning electron microscopy (SEM) and liquid nitrogen (LN₂) adsorption-desorption isotherms at 77 K. The derivatives CA-based mixed matrix membranes were characterized by tensile strength and water contact angle measurements, impedance spectroscopy, gas permeability/selectivity measurements, and water permeability tests. The studied membranes provide remarkable water permeation properties, 12–109 L/m²/h/bar, and also good separation factors of carbon dioxide and helium separations. Specifically, a separation factor of 87 for 10% He/N₂ feed concentration and a selectivity value of 55.4 for 10% CO₂/CH₄ feed concentration were achieved. Full article